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ERMA New Zealand
Evaluation and Review Report
Application for Approval to Import or
Manufacture Firebird for Release
Application Number: HSR08057
Prepared for the Environmental Risk Management
Authority
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 2 of 140
EXECUTIVE SUMMARY
Background information
Bayer New Zealand Ltd. is seeking approval to import Firebird for release.
Firebird is a herbicide containing 400 g/L flufenacet and 200 g/L diflufenican in the
form of a suspension concentrate.
Firebird is proposed to be used for the control of certain broad-leaf and grass weeds
winter wheat and barley.
Firebird will be applied as a herbicide at a maximum product application rate of
300 mL/ha., once per season.
The applicant advises that the method of application will be ground based
application via mechanical spraying equipment.
Diflufenican is present in other herbicides currently available in New Zealand.
Flufenacet is a new active ingredient to New Zealand.
Key issues
The key issues for this application are:
The Agency and the applicant have independently classified Firebird based on the
available information on Firebird and its components. The classifications are
summarised in the table below:
Hazardous Property Applicant’s Assessment The Agency’s
Assessment
Acute Toxicity (Oral) 6.1D (overall) 6.1D
Dermal Sensitisation 6.5B 6.5B
Target Organ Toxicity 6.9B 6.9B
Aquatic Ecotoxicity 9.1A 9.1A
Soil Ecotoxicity - 9.2A
Ecotoxicity to terrestrial vertebrates - 9.3C
The Agency’s classifications differ from the applicant’s due to plant toxicity and
terrestrial vertebrate classifications generated from formulation test data;
Although no EEL has been set for Firebird, the Agency proposes setting the
application rate of 300 mL Firebird / ha. (flufenacet 126.3 g/ha., diflufenican 61.9
g/ha), once per season as the application rate for Firebird. This application rate was
used in the toxicological and ecological risk assessment;
The flufenacet metabolite, FOE 5043 sulfonic acid, has the potential to leach into
and persist in the aquatic environment and ground water. However, it has been
demonstrated that FOE 5043 sulfonic acid is not of ecotoxicological concern. In
addition, flufenacet does not appear to be associated with any metabolites of
toxicological concern (US EPA Fact Sheet, 1998).
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 3 of 140
The Agency’s ecological risk assessment performed on Firebird has resulted in the
following findings:
o High acute risk for aquatic algae. Based on this risk, the Agency considers it is
appropriate to retain the approved handler control for Firebird when it is used
in a wide dispersive manner, or by a commercial contractor.
o The data on diflufenican gathered in HSNO Chemical Classification
Information Database (CCID) is inadequate for aspects of the ecotoxicological
risk assessment of:
Aquatic (acute and chronic) risk;
Terrestrial (plants) risk;
Avian risk;
Environmental fate.
Quantitative modeling carried out by the Agency indicates that, when applied at a
rate of 300 mL Firebird/ha. and in compliance with HSNO controls, the substance
will not pose any significant risks to the health and safety of operators or bystanders.
On this basis, the Agency considers that any risks to human health and safety will be
adequately managed by the default controls which are triggered by the substance’s
hazard classifications. The Agency notes that this evaluation is consistent with the
findings of the EFSA review of diflufenican and products containing this active
ingredient, which included a similar substance to Firebird.
The Agency proposes that, as required by control T1, the following Acceptable
Daily Exposure (ADE) and Potential Daily Exposure (PDE) values are set for
flufenacet:
o ADE = 0.012 mg/kg bw/day;
o PDEfood = 0.008 mg/kg bw/day; and
o PDEdrinking water = 0.002 mg/kg bw/day.
The Agency also proposes that an acute reference dose (ARfD) of 0.017 mg/kg
bw/day for flufenacet is adopted, in case a value is required by the NZ Food Safety
Authority.
The Agency proposes adopting a WES value for Component C of Firebird (Control
T2) as listed in Appendix 8.
Key issues from current reviews:
The Agency notes that diflufenican and products containing diflufenican have been
recently reviewed by EFSA, 2006 (Draft Assessment Report). This report has
highlighted that;
o under the EU use pattern and conditions a no-spray zone of 5-10 m is required
to protect non-target aquatic and terrestrial plants.
o the AOEL previously identified by the Agency for diflufenican (1mg/kg
bw/day) is significantly greater than that which has been established by EFSA
(0.012 mg/kg bw/day).
The data supplied by the applicant and any new information from other regulatory
agencies, such as EFSA, should diflufenican be reassessed.
The Agency has proposed that the default controls for Firebird be modified, such
that:
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 4 of 140
o no Environmental Exposure Limits (control E1) or maximum application rates
(control E2) are set at the present time and any default values are deleted
(however, a maximum application rate is applied under section 77A);
o an approved handler control is added, but modified to apply to use only;
o further controls regarding stationary containment systems and pipework are
added;
o a control which prohibits application of Firebird onto or into water is added;
o a control which restricts the application method to ground-based only is added.
The Agency’s assessment of the risks posed by Firebird to the environment and to
human health, during the substance’s lifecycle, is based on qualitative assessment
and quantitative modelling using the GENEEC2 and German BBA models.
The Agency considers that the risk assessments indicate that the risks associated
with Firebird are negligible with the proposed controls in place.
The Agency has evaluated information supplied by the applicant about the benefits
of Firebird and considers that significant benefits are likely to be realised through
the release of this substance.
In conclusion, the Agency considers that there are negligible risks to human health
and to the environment and significant benefits associated with the release of
Firebird. Therefore, the Agency considers that it is evident that the benefits of
releasing Firebird outweigh the costs and the application may be approved in
accordance with clause 26.
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 5 of 140
TABLE OF CONTENTS
1 Application Details ........................................................................................................................... 6
2 Legislative Criteria for the Application ....................................................................................... 6
3 Application Process .......................................................................................................................... 6
4 Notification and Consultation ........................................................................................................ 7
5 Application Synopsis and Information Review .......................................................................... 8
6 Hazardous Properties, Thresholds and Classification ............................................................... 9
7 Default Controls .............................................................................................................................. 10
8 Risk Assessment ............................................................................................................................. 10
9 Assessment of Beneficial Effects ................................................................................................ 17
10 Controls ............................................................................................................................................ 18
11 Overall Evaluation of Risks, Costs and Benefits ..................................................................... 20
12 Conclusion ....................................................................................................................................... 21
Appendix 1: Decision Path .................................................................................................................... 22
Appendix 2: Hazard Classification ...................................................................................................... 23
Appendix 3: Risk Assessment ............................................................................................................... 90
Appendix 4: Discussion on Controls ................................................................................................. 117
Appendix 5: List of Proposed Controls for Firebird ...................................................................... 125
Appendix 6: Scales for Qualitative Risk Assessment .................................................................... 131
Appendix 7: Government Departments, Crown Entities and Interested Parties Notified ...... 134
Appendix 8: Confidential Material .................................................................................................... 137
Appendix 9: Confidential Material (not to be disclosed to applicant) ................................... 140
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 6 of 140
1 APPLICATION DETAILS
Application Code HSR08057
Application Type To import or manufacture for release any hazardous
substance under Section 28 of the Hazardous Substances
and New Organisms Act 1996 (“the Act”)
Applicant Bayer New Zealand Ltd.
Date Application Received 28 August 2008
Submission Period 11 September 2008 – 23 October 2008
To be considered by A Committee of the Authority (‘the Committee”)
Purpose of the Application To import or manufacture Firebird, an agricultural
herbicide containing 400 g/l flufenacet, plus 200 g/l
diflufenican, in the form of a suspension concentrate, for
the control of annual grass and broad-leaved weeds in
winter wheat and barley (Category C).
2 LEGISLATIVE CRITERIA FOR THE APPLICATION
2.1 The application was lodged pursuant to section 28.
2.2 This report takes into account matters to be considered in section 29; matters
specified under Part II of the Act; and the relevant provisions of the Hazardous
Substances and New Organisms (Methodology) Order 1998 (“the
Methodology”). Unless otherwise stated, references to section numbers in this
report refer to sections of the Act and clauses to clauses of the Methodology.
3 APPLICATION PROCESS
3.1 Evaluation of the application was undertaken by the ERMA New Zealand
project team (“the Agency”) which comprised the following staff members:
Matthew Allen Advisor (Hazardous Substances)
Elizabeth Morgan Advisor (Hazardous Substances)
Tonderai Kaitano Advisor (Hazardous Substances)
Eugene Georgiades Advisor (Hazardous Substances)
Patrick Gemmell Senior Advisor (Kaupapa Kura Taiao).
3.2 The report was reviewed and signed out by:
Noel McCardle Senior Advisor (Hazardous Substances).
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 7 of 140
3.3 Timeline
Application formally
received
28 August 2008
Application notified 11 September 2008
Submission closing date 23 October 2008.
3.4 Due to delays in completing this E&R Report, the Authority postponed the
consideration under section 58(3) until 28 May 2009.
4 NOTIFICATION AND CONSULTATION
4.1 The Minister for the Environment was advised of the application1 and given the
opportunity to “call-in” the application2. This action was not initiated.
4.2 The Department of Labour (Workplace Group), the New Zealand Food Safety
Authority (Agricultural Compounds and Veterinary Medicines (ACVM) Group)
and the Department of Conservation were identified as having a specific interest
in the application and were provided with a copy of the application (excluding
the confidential information but with the opportunity to access this if necessary).
4.2.1 No comments or submissions were received.
4.3 Other Government departments, Crown agencies and other interested parties, as
listed in Appendix 7, were provided with a copy of the application summary and
given the opportunity to comment or to make a submission.
4.3.1 No comments or submissions were received.
4.4 The application was publicly notified on the ERMA New Zealand website on 11
September 2008 and subsequently advertised in The Dominion Post, the New
Zealand Herald, the Christchurch Press and the Otago Daily Times3.
4.4.1 No submissions were received.
1 section 53(4)(a))
2 section 68
3 section 53
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 8 of 140
5 APPLICATION SYNOPSIS AND INFORMATION
REVIEW
Information supplied by the applicant
5.1 The applicant supplied the following documents:
the application;
a confidential appendix (including full formulation data and a draft
label).
Information review
5.2 The confidential information on the composition of Firebird has been withheld
at the request of the applicant for reasons of commercial sensitivity. The
information is provided for the Committee in Confidential Appendix 8.
5.3 The Agency notes that diflufenican and products containing diflufenican have
been recently reviewed by EFSA, 2006 (Draft Assessment Report). This report
has highlighted that;
under the EU use pattern and conditions a no-spray zone of 5-10 m is
required to protect non-target aquatic and terrestrial plants.
the AOEL previously identified by the Agency for diflufenican (1mg/kg
bw/day) is significantly greater than that which has been established by
EFSA (0.012 mg/kg bw/day).
The data supplied by the applicant and any new information from other
regulatory agencies, such as EFSA, will be assessed by the Agency, should a
reassessment of diflufenican be undertaken at a future time.
5.4 The Agency notes that uncertainties exist in aspects of the aquatic, terrestrial
and avian risk assessment, due to the quality and availability of relevant data in
the HSNO Chemical Classification Inventory Database (CCID) for diflufenican
(see paragraph 8.18). However, the Agency considers that these uncertainties
are not sufficient to influence decision making in the scientific and technical
information relating to the potential adverse effects of Firebird4. Therefore, the
Agency considers that the information constitutes an adequate and appropriate
basis for considering the application5.
Description and use of the substance
5.5 Firebird is a herbicide containing 400 g/L flufenacet, and 200 g/L diflufenican
in the form of an suspension concentrate. Firebird is proposed to be used for the
control of certain broadleaf and grass weeds in winter wheat and barley.
4 clauses 29 and 30
5 clause 8
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Lifecycle
Manufacture/Importation
5.6 The applicant has indicated that Firebird will be imported fully formulated,
packed for retail sale.
5.7 While Firebird will be manufactured overseas, it is possible that the substance
could be manufactured in New Zealand in the future. Consequently, the risks
associated with the manufacture of Firebird have been evaluated, so that
approval of this substance will be applicable to both the import and manufacture
of Firebird.
Transport, storage and packaging
5.8 Firebird will be packaged in UN approved HDPE 3L containers. Firebird will be
stored on arrival by Bayer New Zealand Ltd. at a dedicated chemical storage
facility.
5.9 Firebird will be distributed by agricultural distributors, with expertise in
handling pesticide chemicals, and dedicated pesticide storage facilities.
5.10 Firebird will be stored in facilities which meet the requirements of the Act (e.g.
signage, emergency plans) and the Resource Management Act 1991.
Use
5.11 Firebird will be applied as a herbicide at a product application rate of 300
mL/ha. (active ingredient application rates: flufenacet 120 g /ha; diflufenican 60
g/ha), once per season.
5.12 The applicant advises that the method of application will be ground-based
application via mechanical spraying equipment.
Disposal
5.13 The applicant advises that the normal method of disposal will be via use as
detailed on the product label, unused product can be retained for use in the
following season. Used containers should be triple rinsed and residue added to
the spray tank. Empty containers should be taken to an Agrecovery point.
5.14 In all cases, the substance and its packaging will be disposed of in accordance
with the Hazardous Substances (Disposal) Regulations 2001 and the Resource
Management Act 1991.
6 HAZARDOUS PROPERTIES, THRESHOLDS AND
CLASSIFICATION
6.1 The Agency has evaluated the information supplied by the applicant and also
referred to other data sources in assessing the hazardous properties of Firebird.
This assessment is attached as Appendix 2.
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6.2 The applicant’s and the Agency’s classification of the hazard profiles of Firebird
are listed in Table 6.1.
Table 6.1: Summary of applicant’s and Agency’s HSNO classification of Firebird
Hazardous Property Applicant’s
Assessment
The Agency’s
Assessment
Acute Toxicity (Oral) 6.1D (overall) 6.1D
Dermal Sensitisation 6.5B 6.5B
Target Organ Toxicity 6.9B 6.9B
Aquatic Ecotoxicity 9.1A 9.1A
Soil Ecotoxicity - 9.2A
Ecotoxicity to terrestrial
vertebrates
- 9.3C
6.3 The Agency’s classifications differ from the applicant’s due to plant toxicity and
terrestrial vertebrate classifications generated from formulation test data.
6.4 The risk assessment in Section 8 of this report is based on the Agency’s
classification of Firebird.
7 DEFAULT CONTROLS
7.1 Based on the hazard classification shown in Table 6.1, the set of associated
controls has been identified. These default controls are listed in Appendix 4.
7.2 The Authority is able to vary the default controls and impose controls under
sections 77 and 77A to produce a set of controls relevant to Firebird. Variations
and additional controls for Firebird are considered in Section 10 of this report.
8 RISK ASSESSMENT
Identification of potentially non-negligible risks and costs
8.1 Potentially non-negligible risks were identified for evaluation following clauses
9 and 11, which incorporate sections 5, 6 and 8.
8.2 A “cost” is defined in Regulation 2 of the Methodology as “the value of a
particular adverse effect expressed in monetary or non-monetary terms”. Thus,
these have been assessed in an integrated fashion together with the risks of the
adverse effects in the following assessment.
8.3 The applicant has identified potential sources of risk to the environment and to
human health and safety through release, spillage or exposure throughout the
lifecycle of the substance. The Agency has also identified potential sources of
risk and these, along with those identified by the applicant, are tabulated in
Table 8.1.
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 11 of 140
Table 8.1: Potential sources of risks associated with Firebird
Lifecycle Activity Associated Source of Risk
Manufacture / Import An incident during the manufacture or importation of Firebird resulting
in spillage and subsequent exposure of people or the environment to
the substance.
Packing An incident during the packing of Firebird resulting in spillage and
subsequent exposure of people or the environment to the substance.
Transport or storage An incident during the transport or storage of Firebird resulting in
spillage and subsequent exposure of people or the environment to the
substance.
Use Application of Firebird resulting in exposure of users or bystanders or
the environment; or an incident during use resulting in spillage and
subsequent exposure of users or the environment to the substance.
Disposal Disposal of Firebird or packaging resulting in exposure of people or
the environment to the substance.
Assessment of potentially significant risks 8.4 In accordance with sections 5 and 6 and clauses 9 and 12, the Agency has
assessed the potentially non-negligible risks of this substance in terms of risks to
the environment, to human health and safety, to the relationship of Māori to the
environment, to society and the community, to the market economy, and to New
Zealand’s international obligations.
8.5 The Agency notes that the evidence provided by the applicant and additional
evidence found by the Agency, relating to the hazardous properties of Firebird,
is largely scientific in nature6. However, as some of the evaluation of risks, costs
and benefits has been carried out on a qualitative basis, it is recognised that
there is a degree of uncertainty in the risk analysis.
8.6 The analysis of risk takes into account the controls that derive from the HSNO
Regulations (in particular the default controls identified in Appendix 4) and
from other legislation such as the Resource Management Act 1991 and the
Health and Safety in Employment Act 1992. That is, the analysis assumes
controls are in place.
8.7 A quantitative risk assessment has been carried out to evaluate the level of risk
to operators and the environment arising from the use of Firebird (see
Appendix 3).
8.8 A qualitative assessment has been undertaken for all other stages of the
lifecycle. In these cases, the level of risk has been evaluated on the basis of the
magnitude and likelihood of adverse effects occurring to people or the
environment (see Appendix 3).
6 clause 25(1)
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 12 of 140
Assessment of the risks to human health and safety
8.9 The Agency has classified Firebird as an acute oral toxicant (6.1D), a skin
sensitiser (6.5B) and a target organ toxicant (6.9B).
8.10 In the Agency’s opinion, chronic hazards normally require repeated exposure to
the substance for the adverse effects to occur and are therefore most relevant to
the end-users.
8.11 The Agency assessed the health risk to operators on the basis of the German
BBA model predictions for exposure estimates. The quantitative modelling
indicates that at a product application rate of 300 mL / ha., the exposure to
Firebird, when used as recommended on the label, is not likely to present a high
health risk to the mixers or applicators, even with no personal protective
equipment (PPE). However, the Agency considers that is appropriate to retain
requirements for PPE since the use of PPE when handling agrichemicals is good
practice. the Agency notes that the HSNO PPE requirements are not prescriptive
allowing users to select an appropriate level of PPE.
8.12 The Agency notes that the requirement for PPE is triggered as a default control
for Firebird as a result of its 6.9B classification. The Agency, therefore,
concludes that the health risk to operators, with controls in place, is negligible.
Further details on this quantitative assessment are given in Appendix 3.
8.13 Bystanders may be exposed to Firebird by spray-drift during application and are
likely to be further away from the application area than the operators.
Bystanders should not be exposed to Firebird during mixing and loading. The
Agency notes the levels of risk to bystanders posed by mixing, loading and
ground-based application and considers that it is unlikely that an unacceptable
risk will be posed to bystander health. The Agency, therefore, concludes that the
health risk to bystanders is negligible.
8.14 The risks of Firebird to human health and safety (with controls in place) at
various stages of the lifecycle are summarised below in Table 8.3 and discussed
more fully in Appendix 3.
Table 8.3: Level of risk of Firebird to human health and safety.
Lifecycle stage Potential
Adverse Effect
Likelihood of
Adverse
Effect
Occurring
Magnitude of
Adverse
Effect
Level of Risk
Manufacture/packing Acute oral toxicity
Highly
improbable
Moderate Negligible
Contact sensitiser Highly
improbable
Minor -
Moderate
Negligible
Target organ
toxicity
Quantitative assessment indicates that the chronic risks
to human health and safety are acceptable.
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Lifecycle stage Potential
Adverse Effect
Likelihood of
Adverse
Effect
Occurring
Magnitude of
Adverse
Effect
Level of Risk
Importation,
transport or storage
Acute oral toxicity
Highly
improbable
Moderate Negligible
Contact sensitiser Highly
improbable
Minor -
Moderate
Negligible
Target organ
toxicity
Not addressed
Use Acute effects: operators & bystanders (qualitative assessment)
Acute oral toxicity Highly
improbable
Moderate Negligible
Contact sensitiser
Highly
improbable
Minor -
Moderate
Negligible
Chronic effects: operators (quantitative assessment)
Target organ
toxicity
Quantitative assessment indicated that the chronic risks
to human health and safety are acceptable and the level
of risk is considered to be negligible.
Chronic effects: bystanders (quantitative assessment)
Target organ
toxicity
Quantitative assessment indicated that the chronic risks
to bystander human health and safety are acceptable
and the level of risk is considered to be negligible.
Disposal Acute oral toxicity Highly
improbable
Moderate Negligible
Contact sensitiser Highly
improbable
Minor -
Moderate
Negligible
Target organ
toxicity
Quantitative assessment indicates that the chronic risks
to human health and safety during disposal are
acceptable and the level of risk is considered to be
negligible.
Assessment of the risks to the environment
8.15 The Agency has classified Firebird as being highly toxic in the aquatic
environment (9.1A), highly toxic in the terrestrial environment (9.2A) and
harmful to terrestrial vertebrates (9.3C). Flufenacet is considered to be
persistent in the aquatic and terrestrial environments. Diflufenican is considered
to be bioaccumulative. Thus, a range of organisms in the environment may be
adversely affected over a prolonged period if exposed to Firebird.
8.16 The Agency considers that the likelihood of exposure to the environment is
greatest during use of the substance.
8.17 This quantitative assessment of the environmental risks associated with the use
of Firebird at a rate of 300 mL / ha. shows that it presents a low acute risk to fish
and crustacean, low chronic risk to algae, and a high acute risk to algae. The
Agency considers also that, although the risk to soil invertebrates was quantified
as unacceptable, provided Firebird was applied once a year, at a time where its
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 14 of 140
impact on the positive effects of beneficial invertebrates is minimised, this risk
can be reduced to negligible (see Appendix 3).
8.18 The Agency notes that the quality and availability of the data contained in the
HSNO Chemical Classification Information Database (CCID) for diflufenican
gives rise to a degree of uncertainty in aspects of the aquatic, terrestrial, avian
and environmental fate risk assessment for Firebird. However, the Agency notes
the results of the quantitative modelling and considers that application of the
following controls will address the uncertainty arising from the assessment of
diflufenican, and reduce the level of risk to the environment by use of Firebird
to negligible:
Retaining the approved handler controls will minimise the risks
associated with exposure to the aquatic environment;
Setting a maximum application rate of 300 mL / ha., once per year;
Restricting application of Firebird to ground-based methods only;
and
Prohibiting the application of Firebird into or onto water.
8.19 The risks of Firebird to the environment (with controls in place) at various
stages of its lifecycle are summarised below in Table 8.2 and discussed more
fully in Appendix 3.
Table 8.2: Level of risk of Firebird to the environment.
Lifecycle Stage Potential
Adverse
Effect
Likelihood of
Adverse Effect
Occurring
Magnitude of
Adverse
Effect
Level of Risk
Manufacture/packing,
importation, transport
and storage
Spillage
resulting in
death or
adverse effects
to aquatic or
terrestrial
organisms in
the
environment.
Highly improbable Moderate Negligible
Use
Use resulting
in death or
adverse effects
to aquatic
organisms in
the
environment.
Quantitative assessment indicated that
the acute risk to fish and crustacea in
the aquatic environment is low during
use. Quantitative assessment indicated
that the acute risk to algae is high
during use. Flufenacet is considered to
be persistent in the aquatic
environment.
Quantitative assessment indicated that
the chronic risk to fish and crustacea in
the aquatic environment is low during
use.
The Agency
notes the
results of this
quantitative
assessment
and considers
that the
application of
controls will
reduce this
risk to
negligible.
Use resulting
in death or
adverse effects
to terrestrial
Quantitative assessment indicated an
acceptable risk to beneficial insects
during use. Diflufenican is considered
The Agency
notes the
results of this
quantitative
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Lifecycle Stage Potential
Adverse
Effect
Likelihood of
Adverse Effect
Occurring
Magnitude of
Adverse
Effect
Level of Risk
organisms in
the
environment.
to be persistent in the soil environment. assessment
and considers
this risk to be
negligible
Use resulting
in death or
adverse effects
to beneficial
invertebrates in
the terrestrial
environment
Quantitative assessment indicated an
unacceptable risk to beneficial insects
during use, within the field
environment. Quantitative assessment
indicated an acceptable risk to
beneficial insects during use, outside of
the field environment. Diflufenican is
considered to be persistent in the soil
environment. The application frequency
of once a year, applied early-season
reduces the risk of impacting on the
positive effects of beneficial
invertebrates.
The Agency
notes the
results of this
quantitative
assessment
and considers
this risk to be
negligible.
Use resulting
in death or
adverse effects
to terrestrial
vertebrates.
Highly
improbable
Minor Negligible
Use resulting
in death or
adverse effects
to birds.
Quantitative assessment indicated that Firebird is unlikely
to be an avian chronic toxicant and considers this risk to
be negligible.
Disposal Disposal
resulting in
death or
adverse effects
to aquatic or
terrestrial
organisms in
the
environment
Highly
improbable
Minor Negligible
Relationship of Māori to the Environment
8.20 The Agency has considered this application in accordance with the clauses
9(b)(i) and 9(c)(iv) and sections 6(d) and 8. In addition, the framework
contained in the Agency user guide “Working with Māori under the HSNO Act
1996” has been used to assess the effects of this application on the relationship
of Māori to the environment.
8.21 The Agency notes that Firebird triggers a number of hazardous properties giving
rise to the potential for cultural risk including the deterioration of the mauri of
taonga flora and fauna species, the environment and the general health and well-
being of individuals and the community.
8.22 In addition, the introduction and use of this substance has the potential to inhibit
the ability of iwi/Māori to fulfil their role as kaitiaki, particularly in relation to
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 16 of 140
the guardianship of waterways given the highly ecotoxic nature of the substance
to aquatic species, and potential risks to the mauri ora of human health under
prolonged exposure to this substance.
8.23 On considering the information outlined here and elsewhere in this report, the
Agency considers a minimal impact from Firebird on the relationship of Māori
and their culture and traditions with their ancestral lands, water, sites, wāhi tapu,
valued flora and fauna and other taonga to be highly improbable. In addition
there is no evidence to suggest that the controlled use of Firebird will breach the
principles of the Treaty of Waitangi.
8.24 The overall level of risk is therefore considered to be negligible assuming that
the substance will be handled, stored, transported, used, and disposed of, in
accordance with the explicitly stated default and additional controls proposed in
this report, and any other controls required by other legislation.
8.25 However, the Agency notes that should inappropriate use, or accident, result in
the contamination of waterways or the environment generally, that users notify
the appropriate authorities including the relevant iwi authorities in that region.
This action should include advising them of the contamination and the measures
taken to contain and remediate.
Assessment of the risks to society and the community
8.26 There are not expected to be any significant adverse impacts on the social
environment with the controlled use of Firebird, apart from the health effects
and environmental effects already discussed. Consequently, the Agency
considers that this aspect of potential risk need not be considered further.
Assessment of the risks to the market economy
8.27 Taking into account the level of risk to the environment and to human welfare,
no sources of additional risk have been identified that could result in an adverse
economic impact on a community.
8.28 The Agency notes that direct economic costs will be borne by the applicant and
users of the substance. The HSNO default controls intentionally do not manage
direct economic effects. These are for suppliers and users of the substance to
address.
New Zealand’s international obligations
8.29 The Agency does not anticipate that Firebird will pose any risks to New
Zealand’s international obligations.
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 17 of 140
9 ASSESSMENT OF BENEFICIAL EFFECTS
Potentially non-negligible benefits
9.1 A “benefit” is defined in Regulation 2 of the Methodology as “the value of a
particular positive effect expressed in monetary or non-monetary terms”.
Benefits that may arise from any of the matters set out in clauses 9 and 11 were
considered in terms of clause 13.
9.2 The applicant claims that the approval of Firebird will provide the following
benefits:
9.2.1 Firebird is a unique combination of diflufenican and flufenacet, and
provides an alternative to isoproturon-based herbicides for control of
annual grasses and broadleaf weeds;
9.2.2 Application of Firebird can be carried out from pre-emergence to early
post emergence of crop and weeds, providing flexibility of use;
9.2.3 Firebird is safe to use on all varieties of winter wheat and winter
barley;
9.2.4 The low dose rate, 300 ml Firebird / ha., reduces the environmental
pesticide burden and packaging waste.
9.3 The Agency considers that the economic and related benefits to be derived from
the use of Firebird are potentially significant.
Likely effects of the substance being unavailable
9.4 In accordance with section 29, consideration has been given to the likely effects
of Firebird being unavailable.
9.5 The Agency notes that there are currently no other products containing the same
combination of active ingredients as Firebird. Herbicide products with a similar
hazard profile are available in New Zealand designed to target the grasses and
broadleaf weeds.
9.6 The likely effects of Firebird being unavailable would thus be a reduction in
consumer choice for end-users, and the potential benefits arising from the
introduction of Firebird would not be realised.
Risk reduction implications
9.7 The applicant has indicated that the low use rates required for Firebird will
reduce the chemical burden on the environment, and reduce the amount of
packaging required to be disposed of.
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 18 of 140
10 CONTROLS
Setting of exposure limits and application rates
10.1 Control T1 relates to the requirement to limit public exposure to toxic
substances by the setting of Tolerable Exposure Limits (TELs), which are
derived from Acceptable Daily Exposure (ADE) values. The Agency is not
proposing that any TEL values be set for Firebird until implementation of a
pending review of setting such values under section 77B (See Appendix 4).
However, as flufenacet is a new active to New Zealand, the following
Acceptable Daily Exposure (ADE) and Potential Daily Exposure (PDE) values
have been set for flufenacet:
ADE = 0.012 mg/kg bw/day;
PDEfood = 0.008 mg/kg bw/day; and
PDEdrinking water = 0.002 mg/kg bw/day.
The Agency proposes that an acute reference dose (ARfD) of 0.017 mg/kg
bw/day for flufenacet is adopted, in case a value is required by the New Zealand
Food Safety Authority.
10.2 Control T2 relates to the requirement to limit worker exposure to toxic
substances by the setting of Workplace Exposure Standards (WESs). It is
proposed that WES values for Component C of Firebird are adopted (See
Appendix 4). The Agency considers that the Department of Labour WES values
for components H and I should not be applied, due their low concentrations in
Firebird.
10.3 Control E1 relates to the requirements to limit exposure of non-target organisms
in the environment through the setting of Environmental Exposure Limits
(EELs). It is proposed that no EELs are set at this time for Firebird and the
default values are deleted (see Appendix 4).
10.4 Control E2 relates to the requirement to set an application rate for a class 9
substance that is to be sprayed on an area of land (or air or water) and for which
an EEL has been set. As no EEL has been proposed for Firebird, the Agency is
not able to propose the setting of a maximum application rate under this
regulation. However, the Agency notes that the risk quotient derived from the
environmental exposure modelling indicates that Firebird may cause adverse
environmental effects when used according to the specific parameters of the risk
assessment. The Agency therefore considers it is appropriate to set a maximum
application rate under section 77A (see paragraph 11.8).
Proposed additions and modifications to controls
10.5 The Agency notes that the risk quotients derived from the quantitative
modelling indicate that use of Firebird could cause acute adverse effects to the
aquatic environment if the substance was to move off target, and restrictions on
use are necessary to manage the risks to the environment (refer Appendix 3).
Accordingly, the Agency considers that the application of controls addressing
these risks will be more effective than the specified (default) controls in terms of
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 19 of 140
their effect on the management, use and risks of the substance (section
77A(4)(a)). Consequently, the following additional controls are proposed for
Firebird to restrict the level of risk to the environment:
10.5.1 “Firebird shall not be applied onto or into water.”
10.5.2 “The maximum application rate for Firebird shall be 300 mL/ha., with
a frequency of application of once per year.”
10.5.3 “The method of application shall be limited to ground-based
application only”.
10.6 Controls E7 and AH1 relate to requirements for ecotoxic substances to be under
the control of an approved handler. The Agency considers that these controls
should be modified for Firebird so as to apply only during use. Accordingly, the
Agency is proposing that the following control be substituted for Regulation
9(1) of the Hazardous Substances (Classes 6, 8, and 9 Controls) Regulations
2001:
“(1). Firebird must be under the personal control of an approved handler when
the substance is –
(a) applied in a wide dispersive manner; or
(b) used by a commercial contractor.”
10.7 The Agency notes that the specified controls do not address the risks associated
with stationary container systems, nor do they allow for dispensation where it is
unnecessary for any associated pipework to have secondary containment.
Accordingly, the Agency considers that the application of controls addressing
these risks will be more effective than the specified (default) controls in terms of
their effect on the management, use and risks of the substance7. The proposed
controls are shown in Table 5.1 of Appendix 5.
10.8 Control EM12 relates to the requirements for secondary containment of pooling
substances8. The EM12 secondary containment requirements have been
triggered for Firebird as a result of its 6.1D, 6.5B and 9.1A classifications. The
Agency considers that the risks associated with the containment of substances
which are not class 1 to 5 substances (i.e. do not ignite or explode) are different
to those associated with class 1 to 5 substances. Consequently the Agency
considers that the secondary containment requirements can be reduced. The
Agency considers that these reduced secondary containment measures are
adequate to manage the risks of a spillage of Firebird. Therefore, the proposed
additional control, which varies the EM12 control, is more cost-effective in
terms of managing the risks of the substance. The proposed controls are shown
in Table 5.1 of Appendix 5.
10.9 Control TR1 relates to the requirements for a substance to be tracked and is
triggered for Firebird only by virtue of its ecotoxicity. Consequently, the
Agency considers that tracking the substance would be unduly onerous, as the
key risks can be managed through other controls such as approved handler,
7 section 77A(4)(a)
8 Regulations 35 – 41 of the Hazardous Substances (Emergency Management) Regulations 2001
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 20 of 140
packaging, labelling and emergency management requirements. Thus, this
control may be deleted.
10.10 The Agency considers that the following controls may be combined9 for
Firebird as they relate to the same requirements:
10.10.1 Controls T4 and E6 which relate to requirements for equipment used to
handle hazardous substances.
10.10.2 Controls P13 and P15 which relate to requirements for packaging
hazardous substances.
10.10.3 Controls D4 and D5 which relate to requirements for disposal of
Firebird.
Control precedents
10.11 The Agency considered the Authority’s approvals given to pesticides under Part
5 of the Act as well as those transferred to the Act under the Hazardous
Substances (Pesticides) Transfer Notice 2004 (as amended).
Summary of controls
10.12 The Agency considers that the customised controls listed in Appendix 5 should
apply to Firebird.
Environmental user charges
10.13 Section 96 provides that the Authority may identify and report to the Minister
where it considers that a reduction in the likely occurrence of adverse effects
similar to that achieved by the controls attached to any substance could be
achieved by any environmental user charge, or a combination of an
environmental user charge and controls.
10.14 The Agency considers that use of controls is the most effective means of
managing the risks throughout the lifecycle of Firebird. The imposition of an
environmental user charge instead of, or in combination with controls, is
therefore not required at this time.
11 OVERALL EVALUATION OF RISKS, COSTS AND
BENEFITS
11.1 The Agency considers the risks of Firebird to human health to be negligible.
11.2 While the Agency’s use quantitative and qualitative assessments identified a
high acute risk to the algae during the use of Firebird, the Agency considers that
the use of approved handlers, restricting the method of application to ground-
based only, the setting of a maximum application rate, and prohibiting the
9 section 77(5)
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 21 of 140
application of the substance into or onto water, will be sufficient to manage
these risks, and reduce their level to negligible.
11.3 The Agency does not consider there to be significant risks to Māori cultural
wellbeing, society and the community, the market economy, or to New
Zealand’s international obligations.
11.4 The Agency has taken the type and severity of the risks, and the characteristics
of such risks into account, and considers that the overall level of risk posed by
the substance is negligible.
11.5 The Agency considers that there are potentially significant benefits associated
with the release of Firebird as are specified in Section 9 of this report.
11.6 Thus, the Agency considers that it is evident that the benefits of releasing
Firebird outweigh the costs.
12 CONCLUSION
12.1 Bayer New Zealand Ltd. has applied for approval to import for release in New
Zealand the substance identified as Firebird.
12.2 The Agency considers Firebird triggers the following hazard classifications:
6.1D Acute oral toxicity
6.5B Contact Sensitisation
6.9B Target organ systemic toxicity
9.1A Aquatic ecotoxicity
9.2A Soil ecotoxicity
9.3C Terrestrial vertebrate ecotoxicity.
12.3 The Agency considers that there are negligible risks to the environment and
human health and significant benefits associated with the release of Firebird.
Therefore, the Agency considers that it is evident that the benefits of releasing
Firebird outweigh the costs and the application may be approved in accordance
with clause 26.
12.4 The Agency considers the controls listed in Appendix 5 should apply to
Firebird.
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 22 of 140
APPENDIX 1: DECISION PATH
1
Review the content of the
application and all relevant
information
2
Is this information sufficient
to proceed?
5
Identify the composition of the substance,
classify the hazardous properties of the
substance, and determine default controls
6
Identify all risks, costs and benefits that are
potentially non-negligible
7
Assess each risk assuming controls in place.
Add, substitute or delete controls in
accordance with clause 35 and sections77,
77A, 77B
8
Undertake combined consideration of all risks
and costs, cognisant of proposed controls
9
Are all risks with controls in place
negligible?
10
Review controls for cost-effectiveness in
accordance with clause 35 and sections 77,
77A, 77B
11
Is it evident that benefits outweigh
costs?
16
Confirm and set controls
Approve
(section 29(1)(a))
3
Seek additional
information
4
Sufficient?
Decline (section 29(1)(c))
12
Establish position on risk averseness
and appropriate level of caution
13
Review controls for cost-effectiveness
in accordance with clause 35 and
sections 77, 77A, 77B
14
Assess benefits
15
Taking into account controls,
do positive effects outweigh adverse
effects?
Decline
(section 29(1)(b))
Clause 27
Clause 26
No
No
No
No
Yes
Yes
Yes
Yes
Yes
No
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 23 of 140
APPENDIX 2: HAZARD CLASSIFICATION
Classification of Firebird
Formulation test data were not provided for all endpoints of Firebird. For endpoints
for which formulation test data were not provided, classification was estimated using
mixture rules based on information on the components. Details of the key substance
components and the methods used to derive the classifications are presented in Table
A2.1. The relevant sections of the User Guide to the Thresholds and Classifications in
the HSNO Act (ERMA 2008a) that describes the mixture rules are listed in Table
A2.2.
The active ingredient, flufenacet, is a new pesticide active ingredient to New Zealand.
The Agency has provided a summary of the toxicity, ecotoxicity and environmental
fate data in Tables A2.5 to A2.12a.
Data quality – overall evaluation
The Agency has adopted the Klimisch et al (2001) data reliability scoring system for
evaluating data used in the hazard classification and risk assessment of flufenacet and
Firebird (section 1.2.4 in ERMA 2008a). Scores for individual studies, as evaluated
by the Agency, are included in the data assessment tables A2.5 to A2.12a. Overall,
data provided for flufenacet and Firebird were of high quality (Klimisch scores 1 or
2). Data on components of Firebird were generally of lower quality (Klimisch scores
3 or 4). However, the effect of the lower quality data on the overall evaluation of the
effects of Firebird was not significant because of the amount of high quality
formulation test data supplied.
The lower quality or absence of chronic data on diflufenican has lead to some data
gaps, which affects the prediction of the long-term effects in the environment.
The Agency acknowledges that there are frequently data gaps in the hazard
classification for chemicals which have been in use internationally for a long time.
International programmes such as the OECD High Production Volume programme
(OECD 1990) and REACH (EU 2006) are progressively working towards filling these
data gaps. As new information becomes available, and resources permit, the Agency
will endeavour to update the HSNO classifications for those substances.
Table A2.0: Physical and chemical properties of Firebird. Test Firebird Method Reference
Appearance Beige white, suspension Visual Güldner (2001).
Report No.
14 1050 5201
GLP
Klimisch score: 1
Disk 13
00000469
Odour weak, characteristic Güldner (2001).
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 24 of 140
Report No.
14 1050 5201
GLP
Klimisch score: 1
Disk 13
00000469
Density at 20°C 1.25 OECD 109 Güldner (2001).
Report No.
14 1050 5201
GLP
Klimisch score: 1
Disk 13
00000469
Surface tension 40.6 mN/m OECD 115 Güldner (2001).
Report No.
14 1050 5201
GLP
Klimisch score: 1
Disk 13
00000469
pH 5.5 According to CIPAC MT
75.3 : Electrometric
determination (pH-meter)
of the sample (undiluted)
under nitrogen atmosphere
and room temperature.
Güldner (2001).
Report No.
14 1050 5201
GLP
Klimisch score: 1
Disk 13
00000469
5.4 According to CIPAC MT
75.3 : Electrometric
determination (pH-meter)
of the sample (1%) in
CIPAC D water under
nitrogen atmosphere and
room temperature.
Güldner (2001).
Report No.
14 1050 5201
GLP
Klimisch score: 1
Disk 13
00000469
Dynamic viscosity η = 185x 10-3
Pa.s OECD 114 Güldner (2001).
Report No.
14 1050 5201
GLP
Klimisch score: 1
Disk 13
00000469
Flash point No flash point up to the
boiling point (105°C)
according to DIN EN
22719
DIN EN 22719 Heitkamp (2002).
Report No.
01/00493
GLP
Klimisch score: 1
Disk 13
00000472
Auto flammability Auto ignition temperature
445°C
DIN EN 51794
EC Guideline A 15
Heitkamp (2002).
Report No.
01/00493
GLP
Klimisch score: 1
Disk 13
00000472
Explosive
properties
Not explosive according to
Guideline A 14
EEC-method A14 Heitkamp (2002).
Report No.
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 25 of 140
01/00493
GLP
Klimisch score: 1
Disk 13
00000472
Table A2.1: Summary of the toxicity and ecotoxicity hazard classifications of
Firebird. Hazardous Property The Agency’s
Classification
Classification Method Component(s) driving
classification
6.1 oral 6.1D Formulation test data N/A
6.1 dermal No Formulation test data N/A
6.1 inhalation No Formulation test data N/A
6.3/8.2 Skin
irritation/corrosion No Formulation test data N/A
6.4/8.2 Eye
irritation/corrosion No Formulation test data N/A
6.5 Respiratory
sensitization ND Mixture rules N/A
6.5 Contact
sensitization 6.5B Formulation test data N/A
6.6 Mutagenicity ND Mixture rules N/A
6.7 carcinogenicity ND Mixture rules N/A
6.8 Reproductive
developmental toxicity ND Mixture rules N/A
6.9 Target organ
systemic toxicity 6.9B Mixture rules Flufenacet
9.1 Aquatic ecotoxicity 9.1A Formulation test data N/A
Aquatic Persistence Yes Mixture Rules Flufenacet
Bioaccumulation Yes Mixture Rules Diflufenican
9.2 Soil ecotoxicity 9.2A Formulation test data N/A
Soil Persistence Yes Metabolite data Flufenacet
9.3 Terrestrial
vertebrate ecotoxicity 9.3C Formulation test data N/A
9.4 Terrestrial
invertebrate ecotoxicity No Formulation test data N/A
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 26 of 140
Table A2.2: Location of mixture rules within the HSNO Thresholds and
Classifications User Guide (V2.0. March 2008).
Hazard User Guide to HSNO
Thresholds and
Classifications Reference
Subclass 6.1 Acute Toxicity Part V, Chapter 10, Page 12
Subclass 6.3/8.2 Skin Irritancy/Corrosivity Part V, Chapter 11, Page 7
Subclass 6.4/8.3 Eye Irritancy/Corrosivity Part V, Chapter 12, Page 9
Subclass 6.5 Contact and Respiratory Sensitisation Part V, Chapter 13, Page 8
Subclass 6.6 Mutagenicity Part V, Chapter 14, Page 5
Subclass 6.7 Carcinogenicity Part V, Chapter 15, Page 8
Subclass 6.8 Reproductive Developmental Toxicity Part V, Chapter 16, Page 11
Subclass 6.9 Target Organ Systemic Toxicity Part V, Chapter 17, Page 10
Subclass 9.1 Aquatic Ecotoxicity Part VI, Chapter 19, Page 18
Subclass 9.2 Soil Ecotoxicity Part VI, Chapter 20, Page 8
Subclass 9.3 Terrestrial Vertebrate Ecotoxicity Part VI, Chapter 21, Page 7
Subclass 9.4 Terrestrial Invertebrate Ecotoxicity Part VI, Chapter 22, Page 5
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 27 of 140
Identity of flufenacet
As this is the first full Part V application considered for this active ingredient, general
data about flufenacet are provided in the Tables A2.3D and A2.4.
Table A2.3D: Identification of flufenacet10
.
CAS number
IUPAC name N-(4-Fluoro-phenyl)-N-isopropyl-2-(5-
trifluoromethyl-[1,3,4]thiadiazol-2-
yloxy)-acetamide
Common name Flufenacet
CAS Number 142459-58-3
Molecular formula C14H13F4N3O2S
Molecular weight 363.3 g/mole
Structural formula See Figure 1
Purity 95.0% (minimum)
Significant impurities/additives
(% concentration)
See Confidential Appendix 8
Known uses Herbicide
HSNO classification 6.1D (oral), 6.1E (inhalation), 6.5B, 6.9B,
9.1A, 9.2A, 9.3C
Other classification & labelling N/A
Figure 1: Structural formula of flufenacet.
Physical and chemical properties of flufenacet relevant to the interpretation of
ecotoxicity tests, environmental fate and exposure assessment are summarized in
Table A2.4.
Table A2.4: Physical and chemical properties of flufenacet. Property Flufenacet Test method Reference
Vapour pressure 9 x 10-7
h Pa (20°C)
2 x 10-6
h Pa (25°C)
OECD 104
EEC method A4
Krohn (1994)
Report No.
14 200 0812
GLP
Klimisch score: 1
Disk 2
00000009
Henry’s Law constant 0.0912 Pa x m3/Mole
(20°C)
Calculated
Krohn (1994)
GLP
Klimisch score: 1
Disk 2
00000010
10
In the Tables below FOE 5043 is the company code name for flufenacet.
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 28 of 140
Thiadone (Metabolite)
0.72 Pa m3/Mole
(25°C)
Calculated using
HenryWIN
Hellpointner
(1995)
GLP
Report No.
107282
Klimisch score: 1
Disk 2
00000153
Melting range Two modifications of FOE
5043 can be observed with a
melting point of 76 – 79°C,
respectively.
OECD 102 Krohn (1992)
Report No.
14 155 0749
GLP
Klimisch score: 1
Disk 2
00000005
Relative Density 1.45 g/mL (20°C)
OECD 109
EEC method A3
Krohn (1995)
Report No.
14 200 0883
GLP
Klimisch score: 1
Disk 2
00000008
Water Solubility pH 4: 56 mg/L (20°C)
pH 7: 56 mg/L
pH 9: 53 mg/L
OECD 105 Krohn (1992)
Report No.
14 410 0746
GLP
Klimisch score: 1
Disk 2
00000016
Solvent Solubility
(20°C)
n-hexane 8700 mg/L
toluene >200000 mg/L
dichloromethane
>200000 mg/L
2-propanol 170000 mg/L
1-octanol 88000 mg/L
polyethylene glycol
74000 mg/L
polyethylene glycol +
ethanol 160000 mg/L
acetone >200000 mg/L
dimethylformamide
>200000 mg/L
acetonitrile
>200000 mg/L
dimethylsulfoxide
>200000 mg/L
OECD 105 (adapted
for organic solvents)
EPA 63-8
Krohn (1992)
Report No.
14 500 0745
GLP
Klimisch score: 1
Disk 2
00000017
pH pH 9.4 (2%)
OECD 112
Method
2005-0002801-91D
Method
2187/5140000/14
Stupp (1992)
Report No.
14 400 0748
GLP
Klimisch score: 1
Disk 2
00000022
Surface tension 60 mN/m
(Weakly surface active)
OECD 115
EC method A5
Krohn (1995)
Report No.
14 442 0870
GLP
Klimisch score: 1
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 29 of 140
Flammability Not highly flammable
(Test substance melted when
approached by ignition
flame)
EC method A10 Mix (1995)
Report No.
95/00139
GLP
Klimisch score: 1
Disk 2
00000024
Autoflammability Does not undergo
spontaneous combustion
EC method A16
Explosive properties Not explosive EC method A14
Oxidizing properties A test according to EC
method A17 was omitted as
the test substance melted in a
test using to EC method 10.
Thermal stability DTA: Exothermic reaction
occurred > 160°C
TGA: Weight loss observed
under air and nitrogen >
150°C
Conclusion
FOE 5043 is thermally stable
at room temperature
OECD 113 Eberz and Berg
(1993)
Report No.
93/10262
GLP
Klimisch score: 1
Disk 2
00000006
Partition Coefficient
log Pow
3.20 (24°C) OECD 107
EEC method A8
Krohn (1992)
Report No.
14 700 0744
GLP
Klimisch score: 1
Disk 2
00000018
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 30 of 140
Biological Hazards: Class 6 Toxicity
Flufenacet is a new pesticidal active ingredient to New Zealand. In addition to acute
and chronic toxicity studies for this active ingredient (summarized in Table A2.5), the
applicant has provided acute toxicity studies on FOE 5043 400 SC & DFF 200 (a
formulation containing flufenacet and diflufenican) which are summarized in Table
A2.6. A summary of the studies taken into consideration in the determination of the
Acceptable Operator Exposure Level (AOEL) and Acceptable Daily Exposure (ADE)
is provided in Table A2.7.
Table A2.5: Summary of toxicity data on flufenacet and its metabolites. ACUTE TOXICITY
Acute oral toxicity Acute dermal toxicity Acute inhalation toxicity
TYPE OF STUDY: Acute oral
toxicity in rats.
SPECIES: Rat
STRAIN: Sprague-Dawley
NUMBER/SEX/GROUP: 5
TEST SUBSTANCE: FOE 5043
DOSE LEVELS: 0, 46, 138,
600, 1146 and 4560 mg/kg bw
for males and 0, 46, 325, 514,
664 and 1294 mg/kg bw for
females.
ENDPOINT: LD50
VALUE: 589 mg/kg females,
1617 mg/kg males
REMARKS: Deaths: 3/5 and
4/5 male rats died in the 1146
and 4560 mg/kg bw doses
respectively, within 5 days after
dosing.
2/5, 4/5 and 5/5 female rats died
in the 514, 664, and 1292 mg/kg
bw doses respectively within 24
hours of dosing.
Clinical signs: ataxia, laboured
breathing, decreased activity,
salivation, clear and red
lacrimation, urine stain, perianal
stain, red nasal stain, red lacrimal
stain, oral stain, red tinged fur on
forelimb.
Evidence of lacrimation,
salivation and nasal stain were
considered treatment-related
gross lesions in males found
dead.
Evidence of salivation, nasal
TYPE OF STUDY: Acute
dermal toxicity in rats.
SPECIES: Rat (Sprague-
Dawley)
ENDPOINT: LD50 (limit dose
test)
VALUE: >2000 mg/kg for
males and females
REMARKS: Clinical signs:
two females out of 5 showed
treatment-related urine stains
that persisted through days 2-5.
No treatment related clinical
signs in males. No deaths.
No treatment-related gross
lesions were observed at
necropsy for consistency.
REFERENCE SOURCE:
Sheets, L.P. (1992). Acute
Dermal Toxicity Study with
Technical Grade FOE 5043 in
Rats. Study Number 90-022-
FN (Unpublished report).
Miles Inc., Agriculture
Division Toxicology, 17745
South Metcalf, Stilwell,
Kansas 66085-9104.
GLP: Yes
TEST GUIDELINES:
US-EPA-FIFRA, Guideline
81-2, Nov 1984.
US-EPA-TSCA, 40 CFR
Section 798.1100, July 1988.
OECD Guideline 402,
February 1987.
Japan, 59 NohSan No 4200,
TYPE OF STUDY: Acute
inhalation toxicity in rats.
SPECIES: Rat (Sprague-
Dawley)
DOSE LEVELS: 3.74 mg/L
under nose-only exposure.
ENDPOINT: LC50
VALUE: 3.74 mg/L for males
and females
REMARKS: LC50 not
specifically identified by study
(no mortalities observed).
Clinical signs: ataxia, tilted
head, lacrimation, moribundity,
Nasal discharge, rales, urine
stain and rough coat.
These signs were first observed
shortly after exposure (Day 0)
and a complete recovery in both
sexes was observed by Day 4.
Gross pathology: no treatment-
related effects observed
following necropsy.
REFERENCE SOURCE:
Warren, D. L. (1990). Acute
Four-Hour Inhalation Toxicity
Study with Technical Grade
FOE 5043 in Rats. Study
Number 90-042-FV
(Unpublished report). Mobay
Corporation Health,
Environment, Safety and Plant
Management; Corporate
Toxicology Department, 17745
South Metcalf, Stilwell, KS
66085-9104.
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 31 of 140
stain, ocular stain, ventral/urine
stain, and reddened lungs were
considered treatment-related
gross lesions in females found
dead.
In the surviving animals there
was no effect on body weight or
body weight gain except for a
slight decrease in the surviving
top dose male. All clinical signs
of toxicity had resolved by day
14except for a red lacrimal stain
in one male animal (600 mg/kg
bw).
No gross lesions were observed
in animals that survived to Day
14 (termination).
GLP: Yes
TEST GUIDELINES:
US-EPA-FIFRA, 81-1, Nov 1984
US-EPA-TSCA, 40 CFR section
798.1175, July 1990
OECD Test Guideline 401, Feb
1987
Japan, 59 NohSan No 4200, Jan
1985.
REFERENCE SOURCE:
Astroff, A. B. and Fitzpatrick,
T. L. (1993). Acute Oral
Toxicity Study with Technical
Grade FOE 5043 in Rats.
(Supplemental Submission to
EPA MRID No. 43441104
(Supplement 1996). Bayer
Corporation, Agriculture
Division. Report No. 102699)
RELIABILITY (KLIMISCH
SCORE): 1
The Agency notes that the
applicant submitted other acute
oral toxicity data for FOE 543 in
rats and mice, but the above
study documents the lowest LD50
value (female rats). The other
values were:
Rats (male) 683 mg/kg
bw
Mice: 1331 and 1756
mg/kg bw for male and
females respectively.
the Agency also notes that
although 3/5 males died at 1146
mg/kg bw, the calculated LD50
was given as 1617 mg/kg bw due
January 1985.
RELIABILITY (KLIMISCH
SCORE): 1
The Agency notes that no
significant toxic effects seen
when tested at 2000 mg/kg bw
so no classification for 6.1
dermal applied.
GLP: Yes
TEST GUIDELINES:
US-EPA-FIFRA,
Guideline 81-3,
November 1984.
US-EPA-TSCA, 40 CFR
Section 798.1150, July 1988.
OECD Guidelines Section 4,
Guideline 403,
May 1981.
Japan, 59 NohSan No. 4200,
January 1985.
10
RELIABILITY (KLIMISCH
SCORE): 1
The Agency’s view is that while
no death occurred at the highest
concentration tested, significant
signs of toxicity occurred at this
concentration which is below
the highest cut off for 6.1D. The
Agency assigned the substance a
6.1E classification in accordance
with the ERMA, 2008 (p10-6)
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 32 of 140
to use of a modified probit
analysis program.
The Agency concluded the
substance classified as 6.1D
based on the female rat data.
Conclusion: Classification of
6.1D for acute oral toxicity
Conclusion: no classification
assigned
Conclusion: Classification for
6.1E for inhalation toxicity
IRRITATION
Eye irritation Skin irritation
TYPE OF STUDY: Eye irritation in rabbits.
SPECIES: Rabbits
STRAIN: New Zealand White
NO./GROUP: 6 males
TEST SUBSTANCE: FOE5043 (flufenacet)
approx 93%
APPLICATION: Instillation of 54 mg (1mL) into
the left eye of each animal.
RESULTS:
Mean Draize Scores:
Corneal opacity: 0/18 = 0
Iritis: 0/18 = 0
Conjunctival redness. 13/18 = 0.72
Conjunctival chemosis: 5/18 = 0.28
Conjunctival oedema not recorded; however
conjunctival discharge was recorded and reported
as 0/18 when calculated using the same method as
applied to the scoring of redness and chemosis.
REVERSIBILITY OF EFFECT: Conjunctival
redness was reported for 2/6 rabbits at 72 hours,
but all observed effects had reversed by 7 days.
GLP; Yes
TEST METHOD:
1) US-EPA-FIFRA, Pesticide Assessment
Guidelines, Subdivision F, Hazard
Evaluation: Human and Domestic Animals,
Guideline 81-4, November 1984.
2) US-EPA-TSCA, Health Effects Testing
Guidelines, 40 CFR Section 798.4500, July 1989.
3) OECD Guidelines for Testing of chemicals,
Section 4, Guideline 405,
February 1987.
4) Japan, Ministry of Agriculture, Forestry and
Fisheries, Guidance on Toxicology Study Data for
Application of Agricultural Chemical
Registration, 59 NohSan No. 4200, January 1985.
REFERENCE SOURCE:
Sheets, L.P. and Philips, S.D. (1992). Primary
Eye Irritation Study with Technical Grade FOE
5043 in Rabbits. Study Number 91-335-IU.
TYPE OF STUDY: Skin irritation in rabbits.
SPECIES: Rabbits
STRAIN: New Zealand White
NO./GROUP: 3 males
TEST SUBSTANCE: FOE5043 (flufenacet)
APPLICATION: Semi-occluded dermal
application of 0.5 g/animal.
RESULTS:
Mean Draize Score for erythema: 0/18 = 0
Mean Draize Score for oedema: 0/18 =0
REVERSIBILITY OF EFFECT: Not applicable
as no effects observed.
GLP: Yes
TEST METHOD:
1) US-EPA-FIFRA, Pesticide Assessment
Guidelines, Subdivision F, Hazard Evaluation:
Human and Domestic Animals, Guideline 81-5,
November 1984.
2) US-EPA-TSCA, Health Effects Testing
Guidelines, 40 CFR Section 798.4470, July 1990.
3) OECD Guidelines for Testing of Chemicals,
Section 4, Guideline 404, May 1981.
4) Japan, Ministry of Agriculture, Forestry and
Fisheries, Guidance on Toxicology Study Data
for Application of Agricultural Chemical
Registration, 59 NohSan No. 4200, January 1985.
REFERENCE SOURCE:
Sheets, L.P. and Philips, S.D. (1992). Primary
Dermal Irritation Study with Technical Grade
FOE 5043 in Rabbits. Study Number 91-325-IV.
Mobay Corporation Health, Environment, Safety
and Plant Management; Corporate Toxicology
Department, 17745 South Metcalf, Stilwell,
Kansas 66085-9104.
RELIABILITY (KLIMISCH SCORE): 1
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 33 of 140
Miles Inc., Agriculture Division, Toxicology;
17745 South Metcalf, Stilwell, Kansas 66085-
9104
RELIABILITY (KLIMISCH SCORE): 1
Conclusion on classification: Flufenacet does
not trigger classification as an eye
irritant/corrosive.
Conclusion on classification: Flufenacet does
not trigger classification as a skin
irritant/corrosive.
SENSITIZATION
Respiratory sensitization Contact sensitization
No information provided. TYPE OF STUDY: Contact sensitization in
guinea pigs (Buehler test).
SPECIES: Guinea Pigs
STRAIN: Hsd Win:DH
NO./GROUP: 15 males in test group, 15 males
in non-induced control group, 5 males in
dichloronitrobenzene DNCB positive control
group and 5 males in DNCB non-induced control
group)
RESULTS: No erythema observed in any of the
FOE5043 test or non-induced control animals or
DNCB non-induced control animals.
Sensitization was observed in the DNCB positive
control group. Therefore, under the conditions of
this study, FOE 5043 does not cause dermal
sensitization.
TEST SUBSTANCE: FOE5043 (0.4g solid
flufenacet moistened with deionised water)
GLP: Yes
TEST METHOD: Buehler Topical Closed-Patch
Technique. This study was conducted in
accordance with:
1) US-EPA-FIFRA, Pesticide Assessment
Guidelines, Subdivision F, Hazard Evaluation:
Human and Domestic Animals, Guideline 81-6,
November 1984.
2) US-EPA-TSCA, Health Effects Testing
Guidelines, 40 CFR Section 798.4100, July 1989.
3) OECD Guidelines for Testing of Chemicals,
Section 4, Guideline 406, May 1981.
4) Japan, Ministry of Agriculture, Forestry and
Fisheries, Guidance on Toxicology Study Data
for Application of Agricultural Chemical
Registration, 59 NohSan No. 4200, January 1985.
REFERENCE SOURCE:
Sheets, L.P. and Philips, S.D. (1992). Dermal
Sensitization Study with Technical Grade FOE
5043 in Guinea Pigs. Miles Inc., Agriculture
Division; Toxicology. 17745 South Metcalf,
Stilwell, KS 66085-9104. Study Number 91-324-
JD
RELIABILITY (KLIMISCH SCORE): 1
TYPE OF STUDY: Contact sensitization in
guinea pigs (Magnusson-Kligman Maximization
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 34 of 140
Method).
SPECIES: Guinea Pigs
STRAIN: Hsd Win:DH
DOSES:
Intradermal induction – 5%
Topical induction – 50%
Challenge – 50% and 25%
The test substance was formulated in sterile
physiological saline containing 2% v/v
Cremophor EL® to yield a suspension.
RESULTS: The 50% formulation caused “slight
localized” to “moderate confluent” redness and in
65% in 65% of the animals, whilst the 25% test
substance formulation caused “slight localized”
redness in 70% of the test animals. No skin
reaction was observed in the control animals.
Therefore, FOE 5043 exhibits skin sensitization
potential under the conditions of this test.
GLP: Yes
TEST SUBSTANCE: FOE5043
TEST METHOD: Magnusson-Kligman
Maximization Method carried out in accordance
with GLP. This study was conducted in
accordance with:
1) OECD Guideline for Testing of Chemicals;
Section 4: Health Effects, No. 406: “Skin
Sensitization”.
2) EC Guideline 92/69 (17th
Adaptation of the
Guideline 67/548/EEC): Classification,
Packaging and Labeling of Hazardous Materials,
“Skin Sensitisation”, Method B.6.
Pesticide Assessment Guidelines, Subdivision F,
Hazard Evaluation: Human Domestic Animals, §
81-6.
REFERENCE SOURCE:
Vohr, H.W. (1994). Study For The Skin
Sensitization Effect In Guinea Pigs
(Maximization Test of Nagnusson and Kligman).
Report No: 23560. BAYER AG, Fachbereich
Toxikologie, Friedrich-Ebert-Strasse 217-333 D-
42096 Wuppertal
RELIABILITY (KLIMISCH SCORE): 1
The Agency notes that although the Buehler test
returned a negative result, FOE 5043 elicited skin
reactions in >30% of the animals in the
Magnusson-Kligmann test. This triggers a 6.5B
classification.
Conclusion on classification: No data provided,
therefore no classification assigned.
Conclusion on classification: Flufenacet
triggers a 6.5B classification.
MUTAGENICITY
In vitro studies
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 35 of 140
STUDY TYPE: Ames test (salmonella/microsome test)
CELL TYPE: Bacteria. Salmonella typhimurium strains TA 1535, TA 1537, TA 100 and TA 98.
TEST SUBSTANCE: Flufenacet (96.8%)
DOSE RATE: 0, 16,50, 158, 500, 1571, 5000 µg/plate with and without S9.
RESPONSE: negative
GLP: Yes
GUIDELINE: OECD Guideline 471
REFERENCE SOURCE:
Herbold, B. (1995). Salmonella/Microsome Test - Plate Incorporation And Preincubation Method.
Study No.: T 4054104. Bayer A G, Fachbereich Toxicology, Friedrich-Ebert-Strafie 217-333, D-
42096 Wuppertal, F.R.G.
RELIABILITY (KLIMISCH SCORE): 1
STUDY TYPE: Mammalian chromosome aberration test
CELL TYPE: Mammalian. Chinese Hamster Ovary Cells
TEST SUBSTANCE: Flufenacet (97.5%)
DOSE RATE: 0, 8, 40, 200 µg/mL (with and without S9mix) applied to the culture medium
RESPONSE: No statistically significant or biologically relevant increases of numbers of metaphases
with aberrations were detected 8, 24 or 30 hours after the beginning of the four hour treatment with the
test substance with and without S9 mix. Authors concluded substance is not clastogenic for
mammalian cells, with and without metabolic activation in vitro.
GLP: Yes
GUIDELINE: OECD Guideline 473
REFERENCE SOURCE:
Gahlmann, R. (1995). In Vitro Mammalian Chromosome Aberration Test With Chinese Hamster
Ovary (CHO) Cells. Study No.: T 2039172. Bayer A G, Fachbereich Toxicology, Friedrich-Ebert-
Strafie 217-333, D-42096 Wuppertal, F.R.G.
RELIABILITY (KLIMISCH SCORE): 1
STUDY TYPE: Unscheduled DNA synthesis study
CELL TYPE: Rat Liver Primary Cells
TEST SUBSTANCE: Flufenacet (97.5%)
DOSE RATE: 2.5, 5.0, 10.0, 20.0, 40.0, 60.0 and 80μg/ml
RESPONSE:
There was no evidence of unscheduled DNA synthesis following treatment with the test article. The
positive control article (2-Acetylaminofluorene) produced a clearly positive effect in the assay.
GUIDELINE:
EEC Directive 87/302/EEC: – Mutagenicity. DNA Damage and Repair - Unscheduled DNA
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 36 of 140
Synthesis -Mammalian Cells - In vitro
OECD Guidelines for Testing of Chemicals. "Genetic Toxicology: DNA Damage and
Repair/Unscheduled DNA Synthesis in Mammalian Cells in vitro". Adopted: 23 Oct 86, No.
482.
New and Revised Health Effects Test Guidelines October 1984. (U.S.) Environmental
Protection Agency, Washington DC (PB 84-233295); HG - DNA - Unsched Syn, October
1983
REFERENCE SOURCE:
Brendler-Schwaab, S. (1992). Test On Unscheduled DNA Synthesis In Rat Liver Primary Cell
Cultures In Vitro. Study No.: T 3039551. Bayer A G, Fachbereich Toxicology, Friedrich-Ebert-Strafie
217-333, D-42096 Wuppertal, F.R.G.
RELIABILITY (KLIMISCH SCORE): 1
STUDY TYPE: V79-HGPRT assay in vitro.
CELL TYPE: Chinese hamster lung cells (V79)
TEST SUBSTANCE: Flufenacet (97.5%)
DOSE RATE: 7.8, 15.6, 31.3, 62.5, 125, 180, 250 and 500 μg/ml with and without S9.
RESPONSE:
No significant dose-related or reproducible increase in mutant frequency above that of the negative
controls. In contrast, the positive controls ethylmethanesulfonate (without S-9 mix) and
dimethylbenzanthracene (with S-9 mix) produced a clearly mutagenic effect in the assay. The test
substance is thus considered to be nonmutagenic in the V79-HGPRT Forward Mutation Assay, both
with and without metabolic activation.
GUIDELINE:
EEC Directive 87/302/EEC – Mutagenicity. In vitro Mammalian Cell - Gene Mutation Test
OECD Guidelines for Testing of Chemicals. "Genetic Toxicology: In vitro Mammalian Cell
Gene Mutation Assay". Adopted: 4 April 84, No. 475.
New and Revised Health Effects Test Guidelines October 1984. (U.S.) Environmental
Protection Agency, Washington DC (PB 84-233295). HG - Gene Muta - Somatic Cells,
October 1984.
Reference Source:
Brendler-Schwaab, S. (1994). Mutagenicity Study For The Detection Of Induced Forward Mutations
In The V79-Hgprt Assay In Vitro. Study No.: T 0044066. Bayer A G, Fachbereich Toxicology,
Friedrich-Ebert-Strafie 217-333, D-42096 Wuppertal, F.R.G.
RELIABILITY (KLIMISCH SCORE): 1
In vivo studies
STUDY TYPE: Bone Marrow Micronucleus Test
SPECIES: Mice
STRAIN: Bor: NMRI (SPF Han)
NO/SEX/DOSE: 5 males and 5 females
TEST SUBSTANCE: Flufenacet (97.5%)
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 37 of 140
DOSE RATE: Pilot study (intraperitoneal administration of 0, 250, 300, 350, 500 m/kg) identified 250
mg/kg as maximum tolerated dose (MTD). This was the dose used in the study
RESPONSE: No significant increase in the number of micronucleated normochromatic erythrocytes in
any of the groups. The ratio of polychromatic to normochromatic erythrocytes was not altered by
treatment.
GLP: Yes
GUIDELINE:
EEC Directive 84/449/EEC B.12. Other Effects – Mutagenicity: Micronucleus Test.
OECD Guidelines for Testing of Chemicals - "Genetic Toxicology: Micronucleus Test", No.
474.
New and Revised Health Effects Test Guidelines October 1984. (U.S.) Environmental
Protection Agency Washington, DC (PB 84-233295). HG - Chromo - Micronuc, October
1983.
REFERENCE SOURCE:
Herbold, B. (1993). Micronucleus Test On The Mouse. Study No.: T 8044217. Bayer A G,
Fachbereich Toxicology, Friedrich-Ebert-Strafie 217-333, D-42096 Wuppertal, F.R.G.
RELIABILITY (KLIMISCH SCORE): 1
Conclusion on classification: No classification for mutagenicity assigned to the substance
CARCINOGENICITY
See carcinogenicity studies reported under the ‘Target Organ Systemic Toxicity’ section of this table.
Conclusion on classification: The Agency considers that the data does not trigger any 6.7
classification.
REPRODUCTIVE/DEVELOPMENTAL TOXICITY
Developmental studies
STUDY TYPE: Developmental toxicity study
SPECIES: Rat
STRAIN: Charles River Crl:CD®(SD)BR rats
NUMBER/GROUP: 30 inseminated dams
DOSE: 0, 5, 25, 125 mg/kg/day (by gavage) once daily from days 6 to 15 of gestation (total of 10
consecutive doses)
TEST SUBSTANCE: FOE5043 (97.2%)
TEST GUIDELINE: U.S. EPA-FIFRA, Section 158.135, Guideline No. 83-3 (a)
REMARKS:
Authors note that for the dams, FOE 5043 promoted a significant reduction in mean body
weight gain, actual body weight gain (terminal body weight minus the weight of the intact
uterus) and overall maternal body weight gain during the study for the 125 mg/kg bw/day
group. There was also a statistically significant reduction in food consumption following the
initiation of treatment for the 125 mg/kg bw/day group. However, food consumption returned
to normal by the end of the study.
Histopathological evaluations of liver and thyroid from control and high-dose animals, as well
as those tissues which exhibited gross anatomical abnormalities, revealed no treatment-related
findings.
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 38 of 140
There were no adverse treatment-related effects on any measured maternal reproductive
parameter. Resorption/postimplantation losses were comparable with the control for the 3
treatment groups. The test article has no teratogenic potential at doses up to and including 125
mg/kg, as the incidence of malformations was comparable between the 3 treatment groups and
the control and well within historical control ranges.
The authors note that the only evidence of developmental toxicity was a decrease in fetal
weights and an increase in delayed ossification and/or increased variation in some skeletal
elements for the 125 mg/kg group. Lower doses did not promote any form of developmental
toxicity.
MATERNAL TOXICITY
NOAEL: 25 mg/kg bw/day
LOAEL: 125 mg/kg bw/day, due to reduced body weight gain and food consumption.
FOETAL TOXICITY
NOAEL: 25 mg/kg bw/day
LOAEL: 125 mg/kg bw/day, due to reduced fetal weight, increase in delay ossification and/or an
increase in some skeletal variations.
REFERENCE SOURCE:
Stewart, P.D. (1997). A Developmental Toxicity Study With Orally Administered FOE 5043
Technical in the Rat. [Supplemental Submission to Bayer Report No. 106835 of the same title by
Clemens, G.R., Leeling, J.L., Rinke, M. and Hartnagel Jr, R.E. 1995]. Toxicology – Healthcare, Miles
Inc., P.O. Box 40, Elkhart, IN 46515.
RELIABILITY (KLIMISCH SCORE): 1
The Agency considers that although treatment-related developmental effects were observed in foetuses
from the high dose group, these findings appear to be secondary to maternal toxicity and do not
support 6.8A/B classification.
STUDY TYPE: Developmental toxicity study in rabbits
TEST SUBSTANCE: FOE5043 (98.5%)
SPECIES: Rabbit.
STRAIN: New Zealand White Rabbits
NO/GROUP: 20 does
DOSE: 0, 5, 25, 125, 200 mg/kg bw/day, administered by oral gavage on days 6 to 18 of gestation.
TEST METHOD: U.S. EPA-FIFRA Section 158.135 Guideline No. 83-3
REMARKS:
Signs of maternal toxicity were observed at 125 and 200 mg/kg bw/day according to
researchers. The main effects related to stool changes, reduction in mean body weight gain
during the treatment interval, and an increase in histopathological changes of the liver.
Histopathological changes characterized by vacuolar change in hepatocytes in liver observed
at 25, 125 and 200 mg/kg bw/day, although no changes to absolute or relative liver weight
were seen. In most cases there were associated changes of hypertrophy and a ground-glass
appearance of the hepatocytic cytoplasm reflective of increased endoplasmic reticulum.
No adverse effects on maternal reproductive parameters were observed.
There was a significant decrease in fetal weight and a consequential increase in incidence of
delayed ossification of the skull for the 200 mg/kg bw/day group. There was an increase in
skeletal variations (e.g., supernumerary ribs) for the 125 and 200 mg/kg bw/day groups, some
of which occurred at incidences above historical control incidences.
There were no statistically significant increases in the foetal and/or litter incidences of
external, soft tissue, skeletal or combined malformations for any group.
There were no statistically significant changes in the sex ratio.
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 39 of 140
MATERNAL
NOAEL: 5 mg/kg bw/day
LOAEL: 25 mg/kg/day due to histopathological changes (vacuolation in the hepatocytes) in the liver
DEVELOPMENTAL
NOAEL: 25 mg/kg bw/day
LOAEL: 125 mg/kg bw/day due to an increase in skeletal variations (supernumerary ribs). (Reduced
fetal weight, increased skeletal ossification delays were seen at higher doses.)
REFERENCE SOURCE:
Clemens, G.R., Jasty, V., Grosso, D.S. and Hartnagel Jr., (1995). A developmental toxicity study
with orally administered FOE 5043 technical in the rabbit. Study report MTD9313. Toxicology –
Healthcare, Miles Inc., P.O. Box 40, Elkhart, IN 46515
RELIABILITY (KLIMISCH SCORE): 1
The Agency considers that developmental effects seen in the foetuses may have been secondary to
maternal toxicity. Therefore, these findings do not support any 6.8 classification.
Reproductive studies
STUDY TYPE: Two-generation dietary reproduction study
SPECIES: Rats
STRAIN: Sprague-Dawley
NO/SEX/GROUP: 30
DOSE: 0, 20, 100, 500 ppm in diet. These dietary intakes are equivalent to 1.4, 7.4 and 37.4 mg/kg
bw/day for males (pre-mating). For females, these intakes are respectively: 1.5, 8.2 and 41.4 mg/kg
bw/day (pre-mating), 1.3, 6.9 and 36.2 mg/kg bw/day (during gestation) and 2.4, 13.3 and 68.7 mg/kg
bw/day during the first two weeks of lactation.
TEST METHOD:
P and F1 animals were fed test compound throughout the course of the study, starting at 7
weeks of age for P generation and from weaning for F1 generation.
During the study, adult animals were evaluated for the effect of the test compound on body
weight, food consumption, clinical signs, estrous cycling, mating, fertility, gestation length,
and litter size.
Offspring were evaluated for compound-related effects on sex ratio, pup viability, body
weight gain, and clinical signs.
Gross necropsy evaluations were performed on all adults and pups. Histopathological
evaluation of reproductive organs, the pituitary, liver, and gross lesions was performed on all
P and F1 adults.
TEST SUBSTANCE: FOE5043 (95.2 – 99% purity)
GUIDELINE: OECD No. 416. US EPA 40 CFR Section 798.4700
REMARKS:
No significant compound-related effects on gestation or lactation in P or F1 dams
No compound-related effects on estrous cycle, insemination length, mating index, fertility
index, gestation index, gestation length, birth index, number of implantation sites
Gross pathology – no compound-related effects in adults or pups
Organ weights – there was increased absolute and relative liver weight and morphologic
evidence of hepatocellular hypertrophy in P high-dose females and F1 mid- and high-dose
females.
Morphological evidence of hepatocellular hypertrophy was noted in the P and F1 high-dose
group males, in the F1 high-dose group females, and in the F1 mid-dose group males (clearing
of cytoplasm, granular texture of cytoplasm and/or enlargement of hepatocytes in
centrilobular region). Authors considered these compound-induced changes to be due to
induction of metabolic enzymes as a result of treatment with FOE 5043. Authors considered
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 40 of 140
this to be an adaptive change. Effects in liver are consistent with observations in general
toxicity (6.9) studies.
PARENTAL TOXICITY
NOAEL: 100ppm (equivalent to pre-mating doses of 7.4 mg/kg bw/day for males and 8.2 mg/kg
bw/day for females) based on the argument that the observed increase in liver weights and
hepatocellular hypertrophy is an adaptive rather than adverse response.
LOAEL: 500ppm (equivalent to pre-mating doses of 37.4 mg/kg bw/day for males and 41.4 mg/kg
bw/day for females)
REPRODUCTIVE EFFECTS
NOAEL: 500ppm (equivalent to pre-mating doses of 37.4 mg/kg bw/day for males and 41.4 mg/kg
bw/day for females)
LOAEL: Not determined as NOAEL was the highest test dose
REFERENCE SOURCE: Eigenberg, D A., 1995 (with a supplement, 1997). A two generation dietary
reproduction study in rats using technical grade FOE 5043. Bayer Corporation, Agriculture Division,
Toxicology, 17745 South Metcalf, Stilwell, KS, USA. Unpublished company report No 106891-2
RELIABILITY (KLIMISCH SCORE): 1
The Agency notes that delayed ossification and an increase in minor variations were found as possibly
compound-related developmental effects in both the rat and rabbit studies, however, this occurred
above maternally toxic doses and no increase malformations were seen. The Agency considers the
findings do not support any 6.8 classification for developmental or reproductive toxicity.
Conclusion on classification: No classification
TARGET ORGAN SYSTEMIC TOXICITY
Sub-chronic toxicity – oral
TYPE OF STUDY: sub-chronic 90-day feeding study
SPECIES: Rat
STRAIN: CDF[F-344]/BR
NO.ANIMALS/SEX/GROUP: 15 animals/dose/sex
TEST SUBSTANCE: FOE5043 (Flufenacet) 94.8%
DOSE LEVELS: 0, 100, 400, 1600, 3000ppm equivalent to 0, 6.0, 24.3, 109.1 and 191.2 mg/kg bw/day
in males and 0, 7.2, 28.8, 127.2 and 224.5 mg/kg bw/day in females.
ROUTE: oral (dietary; in feed). Acetone/corn oil mixture used as vehicle
GLP: Yes
TEST GUIDELINES: OECD Guideline 408
REMARKS:
Decrease in body weight observed in 1,600 ppm females and 3,000 ppm males and females,
but these changes were less than 10%.
Authors considered that the toxicological response of the rat could be broadly categorized as
involving structural and/or functional alternations in liver, kidney, haematological
system/spleen, and thyroid-related endpoints.
Haematological changes observed were as follows:
o increased reticulocyte numbers at 1600-ppm (males and females);
o decreased erythrocyte count and hematocrit at 400 ppm (males) and 1600 and 3000
ppm (males and females);
o decreased hemoglobin at 100 ppm (males) and 400, 1600, and 3000 ppm (males and
females);
o increased platelet count at 3000 ppm (males and females); and
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 41 of 140
o Increased white blood cell count at 400- and 1600-ppm (males) and 3000-ppm (males
and females).
Clinical chemistry changes included:
o increased serum potassium concentration in 3000-ppm females;
o decreased serum glucose concentration in 400- and 1600-ppm females and 3000-ppm
males and females;
o increased serum uric acid concentration in 400-ppm females and 1600-and 3000-
ppm males and females;
o increased serum phosphate concentration in 3000-ppm males;
o increased serum cholesterol concentration in 1600- and 3000-ppm males and
females;
o increased total serum protein, albumin, and globulin concentrations in 3000-ppm
males;
o decreased serum triglyceride concentration in 400-, 1600-, and 3000-ppm males;
o increased serum γ-glutamyltransferase activity in 1600- and 3000-ppm females;
o decreased total serum thyroxine concentration in 100-ppm males and 400-, 1600-,
and 3000-ppm males and females; and
o Decreased total serum triiodothyronine concentration in 400-, 1600-, and 3000-ppm
males and increased total serum triiodothyronine concentration in 3000-ppm females.
Principal organ weight changes following exposure to FOE 5043 included:
o increased liver weight in 400, 1600, and 3000 ppm males and females;
o increased spleen weight in 3000-ppm.males; and
o Increased thyroid weight in 400, 1600 and 3000 ppm males and females.
Histopathological changes were:
o Liver: increased incidence of hepatocellular swelling, characterized by both
cytomegaly and karyomegaly in 400-, 1600-, and 3000-ppm males and females; and
increased incidence of individual liver cell degeneration or necrosis in 400-, 1600-,
and 3000-ppm males and females;
o Spleen: increased incidence and severity of brown granular pigment accumulation
within the red pulp in 400-, 1600-, and 3000-ppm males and females;
o Kidney: increased incidence of mild proximal tubule injury in 400-, 1600-, and
3000-ppm males and females.
Decreased total serum thyroxine was observed at 100ppm in males but this is not considered
to be biologically significant as most of the values for the test subjects are within the ranges
displayed by the control group. Effects at 400 ppm and above in both sexes appear to be
significant however.
The authors proposed a NOEL of 7.2mg /kg bw/day for the female rat at the lowest dose
tested of 100ppm. [A further 3-week study was carried out to examine the effect of the
substance on circulating thyroid hormone concentrations in the male rat at exposure levels
below 100ppm (see details of study below)].
LOAEL: 400ppm (equivalent to 24.3mg/kg bw/day for the male rat and 28.8mg/kg bw/day for the
female rat) based on cellular degeneration and necrosis, changes in haematological and other
parameters as discussed above.
NOAEL: 100ppm (equivalent to 6.0 mg/kg bw/day for the male rat and 7.2 mg/kg bw/day for the
female rat.
REFERENCE SOURCE: Christensen, W.R. and Wahle, B.S. (1995). Technical Grade FOE 5043:
Subchronic Toxicity Testing study in rats. Bayer Corporation, Agriculture Division, Toxicology, 17745
South Metcalf, Stilwell, KS, USA. Unpublished company report No 106857.
RELIABILITY (KLIMISCH SCORE): 1
TYPE OF STUDY: 13-week Range-Finding Toxicity Study in the Mouse
SPECIES: Mouse
STRAIN: CD-1
NO.ANIMALS/SEX/GROUP: 15 animals/dose/sex
TEST SUBSTANCE: FOE5043 (Flufenacet) 94.8%
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 42 of 140
DOSE LEVELS: 0, 100, 400, 1600, or 4000 ppm
ROUTE: Dietary
GLP: Yes
TEST GUIDELINES: None given
REMARKS:
Declines in erythrocyte and platelet count, haemoglobin and haematocrit concentration were observed
in 4000-ppm males and females. Decrease in thyroid hormone (400-4000 ppm), alkaline phosphatase
(1600-4000 ppm), and aspartate transaminase (4000 ppm) activity at 13 weeks. alterations in absolute
and/or relative liver (400-4000 ppm), kidney (100-4000 ppm), ovary (4000 ppm) , and spleen (400-
4000 ppm) weight. Cytomegaly of the liver, pigmentation of the spleen, and thyroid hyperplasia in
400-4000-ppm males and females. A top dose of 400 ppm was thus selected at which to conduct
the follow-up oncogenicity testing study with FOE 5043 in the mouse.
REFERENCE SOURCE:
Christenson, W.R. and Wahle, B.S. (1995). Technical Grade FOE 5043: A 13-week Range-Finding
Toxicity Study in the Mouse. Bayer Corporation, Agriculture Division – Toxicology, 17745 South
Metcalf, Stilwell, KS 66085-9104.
RELIABILITY (KLIMISCH SCORE):
TYPE OF STUDY: 13 week subchronic feeding study in beagles
ROUTE: Oral (dietary).
TEST SUBSTANCE: FOE5043 (flufenacet) 94.8% (3/90); 93.8% (10/90)
SPECIES: Dogs
STRAIN: Beagle
NO.ANIMALS/SEX/GROUP: 4
DOSE LEVELS: 0, 50, 200, 800, 2400 ppm (equivalent to 0, 1.67, 7.20, 27.21 and 96.91 mg/kg
bw/day in males and 0, 1.70, 6.90, 28.00 and 93.23 mg/kg bw/day in females respectively.)
GLP: Yes
TEST GUIDELINES:
1) US-EPA-FIFRA, Pesticide Assessment Guidelines, Subdivision F, Hazard Evaluation: Human and
Domestic Animals, Guideline 82-1, November 1984;
2) OECD Guidelines for Testing of Chemicals, Section 4, Guideline 409, May 1981; and
3) Japan, Ministry of Agriculture, Forestry and Fisheries, Guidance on Toxicology Study Data for
Application of Agricultural Chemical Registration, 59 NohSan No. 4200, January 1985.
REMARKS:
Soft faeces and thin body condition were considered treatment-related clinical signs at the
2400 ppm level in both sexes.
Clinical chemistry changes included increased lactate dehydrogenase (LD) and alkaline
phosphatase (ALP) levels, and decreased alanine aminotransferase (ALT) and aspartate
aminotransferase (AST). LD was increased in male dogs at 2400 ppm and in females at 200,
800 and 2400 ppm. ALP was increased in males and females at 2400 ppm. ALT was
decreased in both sexes at 200, 800 and 2400 ppm. AST was decreased at all doses, but
researchers only considered this compound- related in both sexes at 800 and 2400 ppm
because the decrease at 200 ppm was less clear. There was also a decrease in albumin in males
at 200, 800 and 2400 ppm, and in females at 800 and 2400 ppm. Globulin levels were
considered increased in a compound-related manner in females only at 200, 800 and 2400
ppm.
The authors concluded that hepatic enzyme induction resulted in secondary thyroid organ
changes. A treatment related decrease in serum thyroxine (T4) was found in both sexes at
200, 800 and 2400 ppm. A decreased triiodothyronine (T3) was likely to be compound-related
in both sexes at 800 and 2400 ppm. This decline in both hormones, without corresponding
cholesterol and triglyceride increases, and without accompanying myxedema-like clinical
signs (signs of prolonged hypothyroidism), suggests to the Authors an extrathyroidal
mechanism due to increased hepatic clearance of thyroid hormones. [The Agency notes that
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 43 of 140
with the exception of the top dose females, no histopathology findings were seen in the
thyroid.]
The Authors claim calcium and glucose levels were decreased due to the metabolic effect of
the compound on the liver, and secondary to thyroid hormone loss. Serum glucose was
decreased in males at 800 and 2400 ppm, and females at 200, 800 and 2400 ppm. Calcium
was decreased in males at 2400 ppm, and in females at 800 and 2400 ppm.
Decreased red blood cell count (RBC), haemoglobin (Hgb), haematocrit (Hct), mean cell
volume (MCV), and mean cell haemoglobin concentration (MCHC) in both sexes at the 2400
ppm dose.
There were no urinalysis findings or gross pathology observations related to compound
administration.
There was a compound-related decrease in terminal body weights in the 2400 ppm males and
a similar l trend in females. Treatment-related organ weight increases were found in absolute
and relative liver weights in both sexes at 2400 ppm, and in the 800 ppm females.
The relative kidney weights were increased in the 2400 ppm males and in the 200, 800 and
2400 ppm females.
Principle histological findings consisted of:
a. Bone marrow: hyperplasia in 2400 ppm males and females,
b. Spleen: pigment in 200, 800 and 2400 ppm females and in 800 and 2400 ppm
males,
c. Kidney: hyperplasia of epithelial cells in 800 and 2400 ppm males and in 2400
ppm females, and cytoplasmic vacuolization in collecting tubules in 800 and 2400
ppm females,
d. Liver: Moderate diffuse hepatomegaly in 2400 ppm males and females, and
pigment in liver in 2400 ppm females,
e. Brain: Vacuolization of the cerebral cortex in 2400 ppm males and females;
f. Thyroid: Hypertrophy of thyroid follicular cells in 2400 ppm females.
Authors concluded that a clear NOAEL of 50 ppm was present, intermediate progression of
toxicity was represented at 200 and 800 ppm, and a maximum tolerated dose of 2400 ppm was
defined by this study.
LOAEL: 200ppm (7.2mg/kg bw/day for the male beagle and 6.9mg/kg bw/day for the female
beagle) based on increases in lactate dehydrogenase, alkaline phosphatase and globulin levels,
decreases in alanine aminotransferase, aspartate aminotransferase, albumin and serum thyroxine (T4).
NOAEL: 50 ppm for both sexes (1.67 mg/kg bw/day in the male beagle, 1.7 mg/kg bw/day in the
female beagle).
REFERENCE: Jones, R.D, and Lake S.G. 1995. (Addendum, 1997) FOE 5043: 13 week subchronic
feeding study in beagle dogs. Miles Inc [later: Bayer Corporation], Agriculture Division, Toxicology,
17745 South Metcalf, Stilwell, KS, USA. Unpublished company report No 106851-2.
RELIABILITY (KLIMISCH SCORE): 1
TYPE OF STUDY: Chronic toxicity feeding study in the beagle dog [for one year]
ROUTE: Oral (dietary).
TEST SUBSTANCE: Technical grade FOE5043 (flufenacet)
SPECIES: Dog
STRAIN: Beagle
NO.ANIMALS/SEX/GROUP: 4
DOSE LEVELS: 0, 40, 800, 1600 ppm.(equivalent to 0, 1.29, 27.75, and 62.24 mg/kg bw/day for
males and 0, 1.14, 26.84, and 58.79 mg/kg bw/day for females). [The Agency notes the poorly spaced
dose intervals in this study which makes interpretation difficult. The report indicates that the doses
were selected based on findings of 13-week feeding study in beagles (doses in that study were 0, 50,
200, 800 and 2400 ppm)].
GLP: Yes
TEST GUIDELINES:
1) US-EPA-FIFRA, Pesticide Assessment Guidelines, Subdivision F, Hazard Evaluation: Human and
Domestic Animals, Guideline 83-1, November 1984;
2) US-EPA-TSCA, Health Effects Testing Guidelines, 40 CFR Section 798.3320, July 1988;
3) OECD Guidelines for Testing of Chemicals, Section 4, Guideline 452, May 1981;
4) Japan, Ministry of Agriculture, Forestry and Fisheries, Guidance on Toxicology Study Data for
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 44 of 140
Application of Agricultural Chemical Registration, 59 NohSan No. 4200, January 1985; and
5) US-FDA, Toxicological Principles for the Safety Assessment of Direct Food Additives and Color
Additives Used in Food, Appendix II Guidelines For Toxicological Testing, October 1982.
REMARKS:
There were no significant changes in food consumption or body weight during the study, but
at termination body weight decreases were found at 1,600 ppm (both sexes) and 800 ppm
(females) [The Agency notes the inconsistency regarding the fact that no significant weight
changes were observed in-life and yet significant decreases in terminal weights were
reported].
Clinical observation included head tilting at 1,600 ppm in both sexes.
No ophthalmologic abnormalities were found during in-life examinations (but see effect on
eyes reported at necropsy).
Authors considered the liver to be the primary target organ.
Neurological effects observed primarily the highest dose groups (1600 ppm, both sexes) just
prior to termination [The Agency notes the late investigation of these findings but observes
that histological findings in the nervous system were also seen]: (1) abnormal behaviour -
hypo-reactivity in two high dose animals, reduced reaction to movement and sound (1 animal)
and hyper-reactivity/ hypertonia; (2) postural abnormalities - deficits in wheel-barrowing,
hemi-walking, hemi-hopping, hemi-standing and proprioception (both sexes); (3) gait/body
position - deficits in stride width, being stiff legged and reluctant to walk (both sexes), with
stride width deficits in two mid-dose dogs (what sex) [Note: This is the only finding at 800
ppm.] Body position deficits in the high dose dogs consisted of wide stance, head tilt, being
flat footed and being unsteady; and (4) optic nystagmus/strabismus/ placement - abnormal
physiologic nystagmus.
The authors noted differences in organ weights in the two highest dose groups. The changes
were :
o an increase in relative heart weights (800 and 1,600 ppm in both sexes), an increase in
absolute heart weights (1,600 ppm in both sexes and 800 ppm males)
o an increase in relative kidney weights (800 and 1,600 ppm in both sexes) and increased
absolute kidney weights (1,600 ppm in both sexes and 800 ppm males)
o an increase in relative and absolute liver weights (800 and 1,600 ppm in both sexes)
o increased relative adrenal weights in 1,600 ppm females
o increased relative and absolute thyroid weights (1,600 ppm in both sexes)
Histopathology differences noted at necropsy that were compound-related occurred in the
liver, kidney, eye, brain, spinal column and sciatic nerve, and were limited to 800 and/or 1,600
ppm dose levels in both sexes. The principle observations were:
o Liver: slight hepatocytomegally in 1600 ppm males and in 800 and 1600 ppm females.
Slight hepatocyte vacuolization in 800 and 1600 ppm males and females
o Kidney: minimal to slight hyperplasia of the epithelium lining the renal pelvis in 800 and
1600 ppm male and female dose groups
o Eye: minimal to moderate vacuolization of the ciliary body epithelium and cystic
vacuolization of the peripheral optic retina in both sexes at 800 and 1600 ppm.
o Brain, spinal column and sciatic nerve: minimal to moderate axonopathy. Electron
microscopy identified enlarged myelin and/or non myelinated membrane lining around
the organelles (primarily mitichondria). Effects on the sciatic nerve were at 1,600 ppm
both sexes, whilst the brain and spinal cord effects were present in both sexes at 800 and
1,600 ppm.
The main clinical chemistrychanges that were considered compound related were: (1)
decreased glucose (800 and 1600 ppm, both sexes), (2) increased cholesterol (800 and 1600
ppm, both sexes), (3) decreased thyroxine and triiodothyronine (800 and 1600 ppm, both
sexes), (4) decreased alanine aminotransferase (800 and 1600 ppm, both sexes), increased
alkaline phosphatase (800 and 1600 ppm, both sexes), and (5) decreased albumin (800 ppm,
females; 800 and 1600 ppm, males).
Authors concluded NOEL was 40ppm with intermediate toxic effects at the two highest dose
groups.
LOAEL: 800ppm (27.75 mg/kg bw/day for the males and 26.82 mg/kg bw/day for the females). Based
on a combination of clinical chemistry (liver enzymes), organ weight and histopathology changes with
neurological symptoms at the top two doses. The brain and spinal cord effects were the most
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 45 of 140
significant findings at this level.
NOAEL: 40ppm (1.29 mg/kg bw/day for the male beagle, 1.14 mg/kg bw/day for the female beagle).
REFERENCE: RD Jones (1995)
RELIABILITY (KLIMISCH SCORE): 2 (reliable with restrictions)
The Agency review of this study noted that the ratio between dosage intervals were too high to enable
the accurate identification of the NOAEL and LOAEL in this study, particularly when the dose levels
are compared to those used in the subchronic study in dogs (above).
Chronic toxicity/carcinogenicity
TYPE OF STUDY: Chronic toxicity and Carcinogenicity study (2-year duration).
SPECIES: Rat
STRAIN: CDF[F-344]/BR
NO.ANIMALS/SEX/GROUP: 50 (with additional 20 in control and top dose group, and 10 in mid
dose group for 1 year interim sacrifice).
TEST SUBSTANCE: FOE5043 (flufenacet) 95.2-99% purity
DOSE LEVELS: 0, 25, 400, 800 ppm (equivalent to 0, 1.2, 19.3 and 39.0 mg/kg bw/day in males and
0, 1.5, 24.4 and 49.8 mg/kg bw/day in females respectively)
ROUTE: Oral (dietary)
GLP: Yes
TEST GUIDELINES: FIFRA Guideline No. 83-5 Combined Chronic Toxicity/Oncogenicity Studies
OECD Guideline No. 453 Combined Chronic Toxicity/Oncogenicity Studies
TSCA Guideline No. 798.3320 Combined Chronic Toxicity/Oncogenicity Studies
MAFF Guideline 59 NohSan No. 4200 Combined Chronic Toxicity/Oncogenicity Studies
REMARKS:
For the males, survival rates at termination were as follows: Control group – 70%; 25 ppm
group – 70%; 400 ppm group – 46%; 800 ppm group – 44%.
Female survival rates at termination were as follows: Control group – 72%; 25 ppm group –
70%; 400 ppm group – 50%; 800 ppm group – 50%.
There was an 8% decline in body weight gain in 400-ppm females while 10 and 17% declines
in body weight gain were recorded in 800-ppm males and females, respectively.
Findings at 400ppm dose level appear to be generally consistent with the findings of the 90-
day rat study:
o Haematology observations:
increased methaemoglobin content in 400 and 800 ppm males and females;
increased platelet count in 800 ppm males; and
increased white blood cell count in 400 ppm males and 800 ppm males and
females.
o Clinical chemistry observations:
increased serum cholesterol concentration in 400 and 800 ppm females
(changes observed from 95 days onwards);
increased total serum protein and globulin concentration in 800 ppm females
(from 95 days onwards);
decreased serum triglyceride concentration in 400 and 800 ppm males (from
95 days onwards);
increased serum calcium concentration in 800 ppm animals (from day 179
in males and day 368 onwards in females); and
increased serum γ-glutamyltransferase (GGT) activity in 400 and 800ppm
males at 12 month interim sacrifice and at termination, although statistical
significance was not reached at all time points for these dose levels.
o Organ weight observations:
weight changes in the heart (increase), liver (increase), spleen (increase),
and thyroid (increase) of 1-year 400 and 800-ppm males and females; and
weight changes in the brain (relative weight increase), heart (relative weight
increase), kidney (reduction), liver (increase), lung (increase), ovary
(reduction), spleen (increase), and thyroid (increase) of 2-year 400 and/or
800 ppm males and females. [The Agency notes the report refers to changes
in testis weight, but the Appendix tables do not identify this.]
o Histopathological observations:
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 46 of 140
Liver: increased incidence of hepatocytomegaly in 1- and 2-year 400 and
800 ppm males and females;
Liver: increased incidence of hepatic individual cell necrosis in 1-year
800ppm males and females and 2-year 800-ppm males;
Liver: increased incidence of hepatic biliary hyperplasia/fibrosis in 2-year
400 and 800 ppm males;
Liver: decreased incidence of hepatic tigroid basophilic foci/areas of
alteration in 2-year 400 ppm females and 2-year 800 ppm males and
females;
Eyes: exacerbation of the common background change of ocular sclera
mineralization in 1-year 800 ppm females and 2-year 400 and 800 ppm
males and females; and increased incidence of cataracts in 2-year 800-ppm
females;
Spleen: increased incidence of splenic pigmentation in 1-year 400 ppm
females and 1-year 800 ppm males and females;
Kidney: exacerbation of the common background change of renal pelvic
mineralization in 2-year 25, 400, and 800 ppm males and 2-year 400 and
800-ppm females;
Kidney: exacerbation of the common background change of renal pelvic
epithelial hyperplasia in 2-year 400 and 800 ppm males;
Uterus: increased incidence of uterine cystic endometrial hyperplasia in 2-
year 400- and 800-ppm females;
Lung: increased incidence of granulomatous pneumonia in 2-year 400 ppm
males
Upper Respiratory tract: and 2-year 800 ppm males and females; and
increased incidence of suppurative inflammation of the skull (nasal
turbinates, nasolacrimal duct, and/or middle ear) in 2-year 800 ppm males.
Authors concluded there was no evidence of a chemically-induced neoplastic response in any
tissue examined [The Agency concurs with this conclusion].
Chronic toxicity
LOAEL: 400 ppm (equivalent to 19.3 mg/kg bw/day in males and 24.4 mg/kg bw/day in females)
based primarily on increased incidence of methaemoglobin content, hepatic biliary hyperplasia/fibrosis,
ocular sclera mineralisation and renal pelvic epithelial hyperplasia in both sexes and endometrial
hyperplasia in females.
NOAEL: 25 ppm (equivalent to 1.2 mg/kg bw/day in males and 1.5 mg/kg bw/day in females)
Neoplasia
LOAEL: None established (no increase in tumours seen).
NOAEL 800 ppm (equivalent to 39.0 mg/kg bw/day and 49.8. mg/kg bw/day for male and female rats,
respectively) (the highest dose tested).
REFERENCE SOURCE: Christensen, W. R and Wahle B.S., 1995 (Addendum 1997). Technical
Grade FOE 5043: A combined chronic toxicity/oncogenicity toxicity testing study in the rat. Bayer
Corporation, Agriculture Division, Toxicology, 17745 South Metcalf, Stilwell, KS, USA. Unpublished
company report No 106859-1
RELIABILITY (KLIMISCH SCORE): 1
TYPE OF STUDY: Oncogenicity study in mice over 20 months
SPECIES: Mice
STRAIN: CD 1
NO.ANIMALS/SEX/GROUP: 50
TEST SUBSTANCE: FOE 5043
DOSE LEVELS: 0, 50, 200, 400 ppm in the diet, equivalent to 0, 7.4, 30.4 and 62.2 mg/kg bw/day in
males and 0, 9.4, 38.4 and 77.2 mg/kg bw/day in females.
ROUTE: Oral in diet
GLP: Yes
TEST GUIDELINES: OECD No 451. FIFRA No 83-2.
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 47 of 140
REMARKS:
Food consumption and body weight was unaffected in treated groups in comparison to controls in both
sexes and at all the treated dose levels.
There was no effect on survival in either sex.
Clinical observations: There was an increase in the incidence of opacity of the eye in both males and
females at 400 ppm. There was an increase in the incidence of paleness of the eye in both males and
females at 200 and 400 ppm.
There was an increase in blood methaemoglobin content in 200 and 400 ppm males and females.
There was no evidence of any treatment-related effect on organ weights in the study.
At necropsy there was an increase incidence of ocular cataracts in 50, 200 and 4000 ppm males and
females. The researchers suggest that a possible mechanism for producing the eye effects is related to
the raised methaemoglobin levels, which may be reflected in depletion of glutathione and subsequent
oxidative injury. [The Agency notes that this is at this stage only a hypothesis.]
There was no indication of a treatment-related increase in neoplasia at any site.
Chronic toxicity
LOAEL: 50 ppm, equivalent to 30.4 mg/kg bw/day in males and 38.42 mg/kg bw/day in females, based
on ocular cataracts in both males and females and other eye changes.
NOAEL: No NOAEL determined for chronic toxicity.
Neoplasia
LOAEL: None established (no increase in tumours seen).
NOAEL: 400 ppm equivalent to 62.2 mg/kg bw/day in males and 77.4 mg/kg bw/day in females (Note:
this was the highest dose)
REFERENCE SOURCE: Christensen W.R. and Wahle, B.S, 1995 (amendment 1996). Technical
Grade FOE 5043: An oncogenicity toxicity testing study in the mouse. Bayer Corporation, Agriculture
Division, Toxicology, 17745 South Metcalf, Stilwell, KS, USA. Unpublished company report No
106860-1
RELIABILITY (KLIMISCH SCORE): 1
Further investigations – thyroid effects
TYPE OF STUDY: Supplementary study to investigate the compounds effects on the thyroid
SPECIES: rat
STRAIN: male Fischer rats [CDF (F-344)/B strain]
NO.ANIMALS/SEX/GROUP: 5 per dose group
TEST SUBSTANCE: FOE5043
DOSE LEVELS: 0, 25, 1,000, 3,000 ppm
ROUTE: oral (dietary)
TEST GUIDELINES: supplementary study - no guideline
REMARKS: 3 week study. Authors observed dose-related decline in T4 levels over three weeks; also
alterations on thyroid stimulating hormone as well as total, free and reverse serum T3 but these changes
were less consistent than the T4 changes. Authors conclude that the study supports the conclusion that
the changes in T4 levels (free and total serum levels) in the rat are the result of compound related
effects on the liver. The authors note increased liver size and weight with proliferation of the
endoplasmic reticulum.
REFERENCE SOURCE: Christenson & Wahle (1995) Extrathyroidally Mediated Changes in
Circulating Thyroid Hormone Concentrations in the Male Rat Following Administration of an
Experimental Oxyacetamide (FOE 5043)
RELIABILITY (KLIMISCH SCORE): 2 (supplementary study, not conducted to a guideline)
The Agency’s conclusion is that the thyroid changes in the rat are not relevant to the likely human
toxicological response to the compound.
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 48 of 140
Further investigations – neurotoxicity studies
TYPE OF STUDY: Further investigation to examine potential neurotoxic effects in the rat
SPECIES: rat
STRAIN: Fischer 344
NO.ANIMALS/SEX/GROUP: 12 females/dose group
TEST SUBSTANCE: FOE5043
DOSE LEVELS: 0, 25, 48 mg/kg
ROUTE: Oral by gavage (single dose)
GLP: Yes
TEST GUIDELINES: No guideline (supplemental study)
REMARKS:
Functional Observation Battery testing conducted at least 3 hours after dosing. No
compound-related effects observed at either dose.
NOEL: 48 mg/kg (female)
REFERENCE SOURCE: Sheets L. P. 1995 (Addendum 1998). An acute oral neurotoxicity screening
study with Technical Grade FOE 5043 in Fischer 344 rats. Bayer Corporation, Agriculture Division,
Toxicology, 17745 South Metcalf, Stilwell, KS, USA. Unpublished company report No 106897-1
RELIABILITY (KLIMISCH SCORE): 2 (supplementary study, not conducted to a guideline)
Further investigations – neurotoxicity studies
TYPE OF STUDY: Further investigation to examine potential neurotoxic effects in the rat (sub
chronic, 13 week study)
SPECIES: Rat
STRAIN: Fischer 344
NO.ANIMALS/SEX/GROUP: 12
TEST SUBSTANCE: FOE5043
DOSE LEVELS: 0, 120, 600, 3000 ppm (for 13 weeks)
ROUTE: dietary administration
GLP: Yes
TEST GUIDELINES: No guideline (supplemental study)
REMARKS:
Clinical observations: mortality, body weight, food consumption, automated measurements of
activity (figure-eight maze), functional observational battery, quantitative
electroencephalography (qEEG), brain weight, and a gross necropsy. Skeletal muscle,
peripheral nerves, eyes (with optic nerves) and tissues from the central nervous system were
examined microscopically for lesions
No compound-related effects or clinical signs
Body weight and food consumption reduced for males and females in high treatment dose
group
Function Observation Battery (FOB) test: effects noted in males and females in high dose
group.
o FOB results for males: forelimb grip strength reduction, slightly uncoordinated
righting response.
o FOB results for females: reduced forelimb grip strength, decreased body temperature,
increased hind-limb foot-splay.
Evidence of cumulative neurotoxicity in high dose group from weeks 8 to 13, demonstrated
through effects on motor and locomotor activity
NOAEL for clinical signs: 3000ppm (219 mg/kg bw/day for male rat, 247 mg/kg bw/day female rat)
NOAEL for FOB: 600 ppm (38.1 mg/kg bw/day for male rat, 42.6 mg/kg bw/day female rat)
REFERENCE SOURCE: Sheets L.P. (1995) A Subchronic Dietary Neurotoxicity Screening Study
with Technical Grade Thiafluamide (FOE 5043) in Fischer 344 Rats. Bayer Corporation, Agriculture
Division, Toxicology, 17745 South Metcalf, Stilwell, KS, USA. Unpublished company report No 94-
46-72-YQ
RELIABILITY (KLIMISCH SCORE): 2 (supplementary study, not conducted to a guideline)
Conclusion on classification:
The Agency considers that the short-term feeding studies indicate that the substance does effect the
liver, although over the short-term these effects do not appear to be of toxicological significance. The
2 year feeding study suggests, however, that longer term exposure to the substance may cause
irreversible changes in the liver such as hepatic biliary hyperplasia and increased individual cell
necrosis. The male rat appeared to be more sensitive to these effects over the long term, than the
female rat.
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 49 of 140
Compound related effects on thyroid hormones were reported in rats and beagles; however, the authors
have concluded that these are secondary to the compound’s effects on the liver. The Agency considers
that there is sufficient evidence to support this conclusion in the rat, although the mechanism that is
described as the pathway the for secondary thyroid effects in beagles is not correct. Nevertheless, the
Agency considers that the effect is unlikely to be relevant to humans.
Further investigative studies indicate neurotoxic effects in the rat. The NOAEL for these effects
appears to be higher than the NOAEL for the compound-related effects on the liver. In the dog,
neurotoxicity was also seen at high dose, and this was associated with histopathology findings in brain
optic nerve and sciatic nerve and these effects appeared to progress. Finally, the Agency notes that no
NOAEL value was established for the eye effects in mice in the oncogenicity study, but due to the
duration of this study (20 months) did not consider this supports a 6.9A classification.
The Agency considers that there is sufficient evidence of an effect on the liver in the rat and the beagle
to support the 6.9B classification. The LOAEL in the 90 day rat study (24.3 mg/kg bw/day) is below
the threshold for classification (ERMA, 2008, p17-9, Table 17-2), and is supported by the 2 year study
in rats. There is support for the classification in the dog studies from the 13 week study. (The Agency
does not consider the LOAEL in the chronic (1 year) study in dogs reliable). In addition, the substance
may have neurotoxic effects at doses higher than those required to elicit adverse effects on the liver.
The Agency concludes that the substance triggers the 6.9B classification.
Metabolism
TYPE OF STUDY: Metabolism study in rats
SPECIES: Rats
STRAIN: Sprague-Dawley
DOSE: For preliminary and low dose experiments animals received 1 mg/kg bw of the labeled FOE
5043.
GLP: Yes
TEST GUIDELINES: Researchers investigated the metabolism using the molecule with a label in
three separate positions: one on the fluorophenyl (fluorophenyl UL- 14
C) portion and and two involving
the thiadizole ring (thiodiazole 2-14
C and 5-14
C, respectively).
FOE 5043 was rapidly absorbed and metabolized. At all dose levels at least 91% of the administered
radioactivity was recovered in excreta or respired gases within 72 hours. Urinary excretion was the
major route of excretion at all doses tested, with smaller amounts excreted in faeces. A maximum of
7% of the administered dose was found in the tissue and residual carcass.
All unidentified residues in excreta were characterized as polar and being of low molecular weight.
REFERENCE SOURCE: Krolski et al, 1995. The metabolism of FOE 5043 in rats. Miles Inc.
[subsequently Bayer Corporation], Agriculture Division, Toxicology, 17745 South Metcalf, Stilwell,
KS, USA. Unpublished company report No 106665.
RELIABILITY (KLIMISCH SCORE): 1
The Agency notes that the authors used Sprague-Dawley rats here and F344 for all but one of the
toxicological studies. This is not a preferred approach as metabolism can vary between strains;
however, this is considered not to have an impact on the overall toxicity assessment.
Repeat dermal toxicity
TYPE OF STUDY: 21 day dermal toxicity in the rat
SPECIES: Rat
STRAIN: Sprague-Dawley
NO.ANIMALS/SEX/GROUP: 8. (An additional 8 rats of each sex in the top and control groups were
included to assess recovery over 2 weeks.)
TEST SUBSTANCE: Technical grade FOE 5043
DOSE LEVELS: 0, 20, 150, or 1,000 mg/kg bw/day. The substance was applied as a solid softened
with tap water.
ROUTE: Dermal application to the shorn back of the animals.
GLP: Yes
TEST GUIDELINES: US EPA FIFRA 82-2. OECD No 411.
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 50 of 140
REMARKS: There were no compound-related clinical signs or mortality. Body weight gain and
terminal weights and food consumption were not affected by treatment.
Thyroxine (T4) and free thyroxine (FT4) were both significantly decreased at 1,0000 mg/kg bw in both
sexes and reductions in FT4 were seen in males at 150 mg/kg bw. Liver weights were significantly
increased in males treated with either 150 or 1,000 mg/kg bw/day, but no change was seen in females.
Centrilobular hepatocytomegaly was seen as the only histopathological change and was only seen in
females at 1,000 mg/kg bw/day.
The animals previously dosed at 1,000 mg/kg bw/day showed a complete recovery following 2 weeks
without treatment.
LOAEL: The researchers proposed the LOAEL was >1,000 mg/kg bw/day for both sexes.
NOAEL: The researchers proposed a NOAEL of 1,000 mg/kg bw/day for both sexes.
REFERENCE SOURCE: Warren D.L. and Zorbas, M.A. 1995. Repeat dose 21 day dermal toxicity
study with technical grade FOE 5043 in rats. Bayer Corporation, Agriculture Division, Toxicology,
17745 South Metcalf, Stilwell, KS, USA. Unpublished company report No 93-112-SZ
RELIABILITY (KLIMISCH SCORE): 1
The Agency notes that while the researchers propose there were no adverse effects, they proposed the
no observed effect level (NOEL) was 20 mg/kg bw for males and 150 mg/kg bw/day for females,
giving a lowest observed effect level (LOEL) of 150 mg/kg bw/day in males and 1,000 mg/kg bw/day
in females. The cut off for 6.9B by the dermal route is a LOAEL ≤200 mg/kg bw/day (although this is
for a 90 day rather than a 28 day study).
In conclusions, the Agency does not consider that these data demonstrate toxic effects from repeat
dermal exposure which justify classification for 6.9 (dermal). The Agency notes that while the liver
weights were increased in males histological changes were only seen in females and these were
reversible and were not associated with liver enzyme changes. With respect to the disturbance in the
thyroid hormone levels the Agency does not consider these to be of biological importance as there were
no treatment-related effects on T3, TSH or thyroid pathology.
Additional studies: Toxicity of Thiadone (a metabolite)
SPECIES: Rat
STRAIN: Sprague Dawley
NO/SEX/DOSE: 5
TEST SUBSTANCE: FOE 6457 (thiadone, a metabolite of FOE 5043)
ENDPOINT: LD50
VALUE: <1,650 mg/kg (males) and < 600 mg/kg (females)
REMARKS: The substance was administered by gavage at 1,650 mg/kg bw in the male group and 600
mg/kg bw in the female group. These doses were selected based on the proposed LD50 values for the
parent compound. All animals died within 10 minutes of dosing.
The only clinical sign seen was tremors in one female animal prior to death.
The only gross finding at necropsy was white mucosa of the glandular stomach which extended to the
duodenum in male rats.
The metabolite appears more toxic than the parent compound.
GLP: Yes
TEST GUIDELINES: OECD, No 401. US EPA FIFRA Guideline 81-1.
REFERENCE SOURCE: Zorbas, M. A. and Phillips, S,D., 1993. Acute toxicity of FOE 6457
(thiadone, a metabolite of FOE 5043) in rats. Miles Inc. [subsequently Bayer Corporation], Agriculture
Division, Toxicology, 17745 South Metcalf, Stilwell, KS, USA. Unpublished company report No
930012-TC.
RELIABILITY (KLIMISCH SCORE): 1
The Agency notes that though the metabolite appears more toxic than the parent compound, no
classification of the substance is required, since it is a metabolite.
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 51 of 140
Table A2.6: Summary of toxicity data on FOE 5043 400 SC & DFF 200 (a
formulation containing flufenacet and diflufenican). ACUTE TOXICITY
Acute oral toxicity Acute dermal toxicity Acute inhalation toxicity
SPECIES: Rat
STRAIN: Wistar Hsd Cpb: WU
(SPF)
TEST SUBSTANCE: FOE 5043
400 SC & DFF 200
DOSE LEVELS: 3 females at
2000 mg/kg bw, 3 females and 3
males at 500 mg/kg bw.
ENDPOINT: LD50 (limit dose
test)
VALUE: >500 <2,000 mg/kg bw
REMARKS: 2 groups of 3
female rats were tested at doses
of 500 and 2,000 mg/kg bw. 1
group of 3 male rats was tested at
500 mg/kg.
Clinical observations:
3/3 of the female animals dosed
at 2000 mg/kg bw died between 2
and 5 hours after dosing.
Summary noted that at 500
mg/kg gait was uncoordinated
and breathing laboured in both
sexes. Additionally, in males
motility was decreased, and in
females gait high legged.
At 2000 mg/kg in females
motility and reactivity were
decreased, gait uncoordinated
and spastic, position abdominal,
breathing laboured, and in one
female atony and in one
increased salivation were
observed. The signs observed
started 45 minutes after
administration and lasted up to
Day 4.
Body weight and body weight
gain of male rats were not
affected by treatment. The gross
pathology investigations
performed at the end of the post-
treatment observation period did
not afford any treatment-related
findings.
At necropsy the female animals
SPECIES: Rats
STRAIN: Wistar Hsd Cpb:
WU (SPF)
NO/SEX/DOSE: 5
TEST SUBSTANCE: FOE
5043 400 SC & DFF 200
ENDPOINT: LD50
VALUE: >4,000 mg/kg bw
REMARKS: Study tested
males and females at 4,000
mg/kg bw.
Clinical observations: At 4000
mg/kg in two males and two
females gait was
uncoordinated on Day 2. It
was claimed by researchers
this was possibly due to the
occlusive dressing.
Locally, the treatment area had
a yellowish discoloration. The
discoloration started on Day 2
and lasted up to Day 15 (the
end of the study). Body
weight and body weight gain
of males were not affected by
treatment. A slight, transient
decrease in body weight was
observed on Day 8 of the study
in one female, the study
authors considered this to be
probably caused by the
occlusive dressing. The body
weight reduction was
reversible by the end of the
post-treatment period. The
gross pathology investigations
performed at the end of the
post-treatment observation
period did not afford any
treatment-related findings. In
one male (animal no. 8) a
diminution of both testes was
observed.
GLP: Yes
TEST GUIDELINE: OECD
No. 402
REFERENCE SOURCE: Dr F
Krötlinger, F., 2002, “Study
for acute dermal toxicity in
rats” Study number T4071312.
SPECIES: Rats
STRAIN: Wistar Hsd Cpb: WU
(SPF)
NO/SEX/DOSE: 5
TEST SUBSTANCE: FOE
5043 400 SC & DFF 200.
ENDPOINT: LC50
DOSE CONCENTRATION:
2,078 mg/m3 air (2.078 mg/L) as
a nose only exposure for 4
hours.
The mass mean aerodynamic
diameter (MMAD) was < 4 µm
(MMAD 3.58 µm, geometric
standard deviation approx.
2.14)
VALUE: NOAEL and LC50
> 2,078 mg/m3 air (> 2.078
mg/L)
REMARKS: Clinical
observations: Exposure to the
maximum technically attainable
concentration of the formulation
as a mist did not result in any
mortality. The only clinical sign
was hypothermia. Mean rectal
temperature of 33.0°C vs 38.2°C
in males and 34.6° C vs 38.3° C
in females. These temperatures
were taken immediately after
cessation of exposures (within
approximately ½ hour).
Necropsy findings were
unobtrusive. In summary, the
test substance (liquid aerosol)
proved to have essentially no
acute inhalation toxicity to rats.
GLP: Yes
TEST GUIDELINE: OECD No.
403
REFERENCE SOURCE:
Pauluhn, J, 2002. “Study on
acute inhalation toxicity in rats
according to OECD No. 403.”
Study No T7071306. Bayer AG
PH PD T Toxicology Friedrich-
Ebert Str. 217–333. D-42096
Wuppertal.
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 52 of 140
that died had pale discolouration
of the liver and spleen and
slightly collapsed lungs with
spotted dark red discolouration.
GLP: Yes
TEST GUIDELINE: OECD
Guideline No 423. 67/548/EEC
B1. US EPA OPPTS 870.1100.
REFERENCE SOURCE:
Krötlinger, F., 2002, “Study for
acute oral toxicity in rats.” Study
number T5071313. Bayer AG
Toxicology Friedrich-Ebert Str.
217–333. D-42096 Wuppertal.
RELIABILITY (KLIMISCH
SCORE): 2
The Agency notes that the study
used both male and female rats,
but no explanation of this was
given. (No evidence was
presented that males were more
sensitive than females.)
[Guidelines assume that females
are more sensitive.] Also, there
was no justification given for the
use of these doses levels.
[OECD Guideline No 23,
following 2-3 deaths at 2000
mg/kg bw would then test the
substance at 300 mg/kg bw.]
Since 3/3 female animals died
after dosing with 2000 mg/kg bw,
the LD50 is clearly <2000 mg/kg
bw, so the classification is 6.1D.
Bayer AG Toxicology
Friedrich-Ebert Str. 217–333.
D-42096 Wuppertal.
RELIABILITY (KLIMISCH
SCORE): 2
The Agency notes that clinical
signs were reversible by the
end of the study with the
exception of the finding of
discolouration at site of
application, which was not
considered a toxicologically
significant finding. Testicular
abnormalities in a single male
were considered a chance
finding not related to
treatment.
RELIABILITY (KLIMISCH
SCORE): 1
The Agency assigned no
classification on the basis that
the highest achievable
concentration as a mist was not
associated with deaths or
significant toxicity. Although
hypothermia was observed, this
is not considered significant
enough to trigger classification.
Conclusion: 6.1D classification
assigned
Conclusion: No classification
is assigned
Conclusion: No classification is
assigned
IRRITATION
Eye irritation Skin irritation
TEST SUBSTANCE: Flufenacet: 406.52 g/l
Diflufenican: 205.76 g/l
TEST METHOD: EC guideline B.5. and OECD
No 405
ANIMALS: 3 male Himalayan rabbits
APPLICATION: single instillation of 0.1 mL into
the conjunctival sack of the right eye of each
animal.
RESULTS:
One animal showed conjunctival redness one hour
after application (score of 1), but this was not
observed in at subsequent time periods.
TEST SUBSTANCE: Flufenacet: 406.52 g/l
Diflufenican: 205.76 g/l
TEST METHOD: EC guideline B.4.
OECD No. 404
ANIMALS: 3 male Himalayan rabbits
APPLICATION: acute skin irritation, Patch-Test,
in rabbits, semi-occlusive, 0.5mL/animal.
RESULTS:
Mean Draize Score for erythema: 0
Mean Draize Score for oedema: 0
REVERSIBILITY OF EFFECT: Not applicable
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 53 of 140
Mean Draize Scores (at 24, 48 and 72 hours) were:
Corneal opacity: 0/9 = 0
Iritis: 0/9 = 0.
Conjunctival redness. 0/9 = 0
Conjunctival oedema: 0/9 = 0
REVERSIBILITY OF EFFECT: Not applicable as
no effects observed.
REFERENCE: Dr PJ Leuschner (2001)
RELIABILITY (KLIMISCH SCORE): 1
as no effects observed.
REFERENCE: Dr PJ Leuschner (2001)
RELIABILITY (KLIMISCH SCORE): 1
Conclusion on classification: The formulation
does not trigger classification as an eye
irritant/corrosive.
Conclusion on classification: the formulation
does not trigger classification as a skin
irritant/corrosive.
SENSITIZATION
Respiratory sensitization Contact sensitization
No information available.
TEST SUBSTANCE: FOE 5043 (flufenacet) :
409.02 g/l; DFF (diflufenican): 207.00 g/l
TEST METHOD: Guinea pig maximization test
according to Magnusson & Kligman.
OECD Guideline No. 406, EC Guideline
96/54/EC, Health Effects Test Guidelines,
OPPTS 870.2600.
ANIMALS: 30 female guinea pigs (20 in test
group, 10 in control group).
STRAIN: Hsd Poc:DH
DOSES:
Intradermal induction: 2.5% (= 10 mg test
item/animal)
Topical induction: 100% (= 500 mg test
item/animal)
1st challenge: 100% (= 500 mg test item/animal)
2nd
challenge: 50% (= 250 mg test item/animal)
RESULTS: After the intra-dermal induction the
animals in the control group and in the test item
group showed strong effects including
encrustation at the injection sites of the first
induction.
The 1st challenge with the 100% test item
concentration led to skin effects (grade 1- 3) in
20 of 20 animals (100%) in the test item group
and in 6 animals (60%) of the control group
(grade 1). The 2nd challenge with the 50% test
item formulation led to skin effects (grade 1-
3) in 18 of 20 animals (90%) in the test item
group and to no skin effects in the control group.
The authors concluded that test formulation
exhibited skin-sensitisation potential.
REFERENCE: Dr HW Vohr (2002)
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 54 of 140
RELIABILITY (KLIMISCH SCORE): 1
The Agency noted that in the Magnusson &
Kligman test the proportion of test animals
showing skin reactions following the challenge
dose was > 30% and is therefore sufficient to
trigger classification as a 6.5B contact sensitiser.
The effects observed following the second
challenge ranged from slight localised redness to
severe redness and swelling with some test
subjects’ skin squamous in places and showing
hardness and/or encrustation.
Conclusion on classification: No classification. Conclusion on classification: The substance
triggers classification as a contact sensitizer
(6.5B).
Table A2.7 Summary of toxicity studies considered in determining the
Acceptable Operator Exposure Level (AOEL) and Acceptable Daily Exposure
(ADE) for flufenacet
Study NOEL LOAEL Critical effect Developmental study in rats. Maternal
25 mg/kg bw/day
Developmental
25 mg/kg bw/day
Maternal
125 mg/kg bw/day
Developmental
125 mg/kg bw/day
Reduced maternal body
weight gain and food
consumption.
Reduced fetal weight,
increase in delayed
ossification and/or in
some skeletal variations.
Developmental study in
rabbits.
Maternal
5 mg/kg bw/day
Developmental
25 mg/kg bw/day
Maternal
25 mg/kg bw/day
Developmental
125 mg/kg bw/day
Histopathological
changes (vacuolation in
the hepatocytes) in the
liver.
Due to increases in
skeletal variations
(supernumary ribs).
Reduced fetal weight and
ossification delays at
higher dose levels.
2 generation reproductive
toxicity in rats
Parental
100 ppm
(7.4 mg/kg bw/day
males and 8.2
mg/kg bw/day
females)
Reproductive
500 ppm
(37.4 mg/kg
Parental
500 ppm
(37.4 mg/kg
bw/day males and
41.4 mg/kg bw/day
females)
Reproductive
>500 ppm
(37.4 mg/kg
Increased liver weights
and hepatocellular
hypertrophy.
No reproductive or
developmental effects
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 55 of 140
bw/day males and
41.4 mg/kg bw/day
females)
bw/day males and
41.4 mg/kg bw/day
females)
seen.
90 day study in rats 100 ppm
(6.0 mg/kg bw/day
males and 7.2
mg/kg bw/day
females)
400 ppm
(24.3 mg/kg
bw/day males and
28.8 mg/kg bw/day
females)
Increased liver weight
and associated
histological changes
(hypertrophy and
hepatocellular necrosis),
also changes in clinical
chemistry parameters
and histological changes
pigmentation in the
spleen and proximal
tubule injury in the
kidney.
13 week study in dogs 50 ppm
(1.67 mg/kg
bw/day males and
1.7 mg/kg bw/day
females)
200 ppm
(7.2 mg/kg
bw/day males and
6.9 mg/kg bw/day
females)
Effects on lactate
dehydrogenase,
alkaline phosphatase,
globulin, alanine
aminotransferase,
aspartate
aminotransferase,
albumin and serum
thyroxine.
Chronic study in dogs (1 year) 40 ppm
(1.29 mg/kg
bw/day males and
1.14 mg/kg bw/day
females)
800 ppm
(1.29 mg/kg
bw/day males and
1.14 mg/kg bw/day
females)
Clinical chemistry (liver
enzymes) with
neurological symptoms
at the top dose.
2 year rat chronic
toxicity/carcinogenicity
study
Chronic toxicity
25 ppm
(1.2 mg/kg
bw/day males and
1.5 mg/kg bw/day
females)
Neoplastic
800 ppm
(39.0 mg/kg
bw/day males and
49.8 mg/kg
bw/day females)
Chronic toxicity
400 ppm
(19.3 mg/kg
bw/day males and
24.4 mg/kg
bw/day females)
Neoplastic
>800 ppm
(>39.0 mg/kg
bw/day males and
>49.8 mg/kg
bw/day females).
Increased
methaemoglobin
content, hepatic biliary
hyperplasia/fibrosis,
ocular sclera
mineralisation, renal
pelvic epithelial
hyperplasia in both
sexes, and endometrial
hyperplasia in females
No increase in
neoplasia seen.
20 month chronic
carcinogenicity study in mice
Chronic toxicity
No NOAEL
established for
chronic toxicity in
this study. (The
lowest dose was 50
ppm, equivalent to
7.4 and 9.4 mg/kg
bw/day in males
and females
respectively.)
Neoplastic
Chronic toxicity
50 ppm
(30.4 mg/kg
bw/day males and
38.4 mg/kg bw/day
females)
Neoplastic
Ocular cataracts in both
males and females and
other eye changes.
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 56 of 140
400 ppm
(62.2 mg/kg
bw/day males and
77.4 mg/kg bw/day
females)
>400 ppm
(>62.2 mg/kg
bw/day males and
>77.4 mg/kg
bw/day females)
No neoplasia seen.
Acceptable Operator Exposure Level (AOEL)
The NOAEL of 1.67 mg/kg bw/day identified in the male beagle (13 week sub-chronic study) was
selected for derivation of the AOEL and an uncertainty factor (UF) of 100 applied (10 for interspecies
extrapolation, 10 for intraspecies uncertainty). No correction for the percentage of absorption in the
study which is consistent with the rapid absorption of the compound. The calculation (rounding to two
significant figures) gives:
AOEL = {NOAEL x absorption fraction}/UF = {1.67x 1.0}/100
AOEL = 0.017 mg/kg bw/day.
Acceptable Daily Exposure (ADE)
The Agency notes that an ADI (0.005 mg/kg bw/day) has been set by the EFSA for flufenacet. The
EFSA have established this ADI based on their LOAEL of 1.2 mg/kg bw/day established in the two-
year rat study (increased incidence of renal pelvic mineralisation was identified as the critical effect).
A uncertainty factor of 250 was applied in determining the ADI.
The UF of 250 is higher than usual as it takes into account that a LOAEL has been used a no NOAEL
was established in the study. The uncertainty factor consisted of 10 for interspecies extrapolation, 10
for intraspecies uncertainty and 2.5 due to the use of an LOAEL rather than a NOAEL.
The Agency notes that in its review of the data a NOAEL was established, as the Agency did not
consider the renal effects to be of sufficient toxicological significance at this 1.2 mg/kg bw/day dose
level. Therefore, the Agency did not use an additional 2.5 uncertain factor to account for the use of a
LOAEL in place of a NOAEL. The Agency’s calculation is:
ADE = NOAEL/LOAEL/{Uncertain factors} = 1.2/100 = 0.012 mg/kg bw/day
Rounding gives: ADE = 0.012 mg/kg bw/day.
[The Agency also notes that the US EPA (US EPA, 1998) established a chronic reference dose of
0.0004 mg/kg bw/day. The US EPA also considered the value was a LOAEL, but used a factor of 3 to
take into account the use of the LOAEL in place of a NOAEL (so their uncertainty factor was 300).]
The Agency has agreed with the New Zealand Food Safety Authority that we will set an acute
reference dose (ARfD), for new active ingredients. In the case of flufenacet the Agency notes that the
EU has proposed a value of 0.017 mg/kg bw/day which is based on the same calculation as the AOEL
(above). The Agency has proposed that this value is proposed for flufenacet in New Zealand.
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 57 of 140
Class 9 Ecotoxicity and environmental fate
Sub-class 9.1 Aquatic ecotoxicity, fate and degradation Classification under this sub-class requires consideration of the acute and chronic
aquatic toxicity of the substance and the bioaccumulative and persistence properties
of the components of the substance.
Aquatic fate and degradation of flufenacet and its metabolites
Information on aquatic fate and degradation is summarised in Table A2.7.
Table A2.7: Summary of aquatic fate and degradation of flufenacet (FOE 5043)
and its metabolites.
Study type Test results Test method
[reference number] Flufenacet (FOE 5043) Metabolites Abiotic degradation
Hydrolysis
Sterile Aqueous Buffer
pH 5: Stable (25°C)
pH 7: Stable
pH 9: Stable
Zeng and Wood (1992)
EPA 161-1 Hydrolysis
Report No.
102623
GLP
Klimisch score: 1
Disk 2
00000019
Photolysis Sterile Aqueous Buffer
pH 5 (25°C)
GLP
Stable
DT50:
3203 days
(irradiated samples)
DT50:
3237 days
(dark control samples)
Non-GLP (25°C)
Pond water 1 (Howe, IN)
DT50: 433 days
Pond water 2 (Stillwell, KS)
DT50: 1386 days
Pure water + 15 ppm humic
material
(natural photosensitizer)
DT50: 433 days
Pure water + 50 ppm KNO3
(generates hydroxyl radicals)
DT50: 95 days
DT50: 130 - > 365 days
The results of the model
studies indicate that direct
photodegradation in water
contributes to the overall
elimination of FOE5043 to a
low extent only.
Kasper and Shadrick
(1995)
EPA 161-2 Photolysis
Report No.
106246
GLP
Klimisch score: 1
Disk 2
00000020
Hellpointner and Schild
(1993)
ECETOC –method in
polychromatic light
Report No.
M 112 0566 - 1
GLP
Klimisch score: 1
Disk 2
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 58 of 140
Study type Test results Test method
[reference number] Flufenacet (FOE 5043) Metabolites 00000021
Biodegradation (laboratory)
Aerobic
(water and
sediment
systems)
Rate 0.750 kg/ha
Duration 157 days
Temperature: 20°C
System I
Water – Lawrence KS
(pH 7.5)
Silty clay loam
(pH 7.9, OC 0.7%)
DT50 (water): 61.7 days
DT50 (total water/sediment):
84.6 days
DT90 (total water/sediment):
284.5 days
System II
Water – Stilwell KS
(pH 7.5)
Silty clay loam
(pH 7.8, OC 1.4%)
DT50 (water): 47 days
DT50 (total water/sediment):
78.1 days
DT90 (total water/sediment):
260.5 days
Bound residues increased
steadily with each successive
sampling interval. For the
157 - day sampling interval
28.5%, and 46.4% of the
applied radioactivity was
tightly bound to the sediment
in System I, and System II,
respectively.
Kelley et al. (1995)
BBA Guideline Part IV,
5-1
Report No.
106928
GLP
Klimisch score: 1
Disk 5
00000151
Anaerobic Pond water/Sandy loam
(pH 6.2 OM 0.6%)
Temperature: 21°C
DT50: 447 days*
Most abundant metabolite,
thiadone (16%)*
*Calculated from 0 to 99
days as anaerobic conditions
were not maintained for the
study duration (388 days
post-treatment).
Pangilinan and Smith
(1995)
EPA 162-3
Report No.
106440
GLP
Klimisch score: 2*
Disk 5
00000150
Bioaccumulation
Bluegill
Lepomis
macrochirus
Uptake rate constant (k1):
165 ± 23
Depuration Rate Constant
(k2):
Gagliano (1994)
FIFRA Guideline 72-6
FIFRA Guideline 165-4
Report No. 106760
GLP
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 59 of 140
Study type Test results Test method
[reference number] Flufenacet (FOE 5043) Metabolites 2.3 ± 0.3
Time to 50% Clearance:
0.30 ± 0.04 days
Steady State BCF:
71.4 ± 1
Time to 90% of BCF:
0.99 ± 0.13 days
Radioactive residues from
sunfish, exposed to [14C]FOE
5043.
Rate of 100 µg/L
Duration: 21 and 28 days
Total radioactive residues
(Fillet)
21 days: 1.79 ppm
28 days: 1.76 ppm
Total radioactive residues
(Viscera)
21 days: 10.97 ppm
28 days: 10.22 ppm
Major metabolite
cysteine conjugate of 4'-
fluoro-N-isopropyl
acetanilide
Fillet: 37%
Viscera: > 50%
(total radioactivity)
Mercapturic acid conjugate
Fillet: 24%
Viscera: 16%
(total radioactivity)
FOE 5043
Fillet: 4.7%
Viscera: 17.8%
(total radioactivity)
Glucuronide conjugate of
hydroxylated FOE 5043
Viscera: 5%
(total radioactivity)
Minor metabolites
glutathione conjugate of 4'-
fluoro-N-isopropyl
acetanilide and the sulfoxides
of both the cysteine and
mercapturic acid conjugates.
Klimisch score: 1
Disk 5
00000170
Leimkuehler and Moore
(1994)
EPA 165-4
Report No. 106577
GLP
Klimisch score: 1
Disk 5
00000171
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 60 of 140
Conclusion
Flufenacet is not considered bioaccumulative based on the results of the study in fish
(BCF = 71.4) and is considered not rapidly degradable.
Aquatic toxicity
The toxicity of flufenacet and Firebird to aquatic organisms is summarized in Tables
A2.8 and A2.8A.
Table A2.8: Summary of aquatic toxicity data for flufenacet and its metabolites.
Test species
Test type
&
duration
Test resultsa, b
Test methodc
[reference number] Flufenacet
(FOE 5043)
Metabolites
Fish
Rainbow trout
Oncorhynchus
mykiss
96 h Static
96 h Static
96 h Static
LC50
5.84 mg/L
95% CI:
3.84 – 7.14 mg/L
[measured] > 80% of
[nominal]
FOE 5043-Sulfonic
acid
LC50
> 86.7 mg/L
[Lowest lethal]
> 86.7 mg/L
Limit test
[measured] > 80% of
[nominal]
Thiadone
LC50
9.1 mg/L
95% CI:
5.0 – 10.3 mg/L
[measured] > 80% of
[nominal]
Bowers and Frank
(1995)
FIFRA 72-1
Report No. 106673
GLP
Klimisch score: 1
Disk 5
00000162
Dorgerloh (1992)
OECD 203
Report No. 95031
GLP
Klimisch score: 1
Disk 5
00000144
Bowers and Lam
(1998)
FIFRA 72-1
Report No. 108738
GLP
Klimisch score: 1
Disk 5
00000165
Bluegill
Lepomis
macrochirus
96 h Static
96 h Static
LC50
2.13 mg/L
95% CI:
1.84 – 2.49 mg/L
[measured] > 80% of
[nominal]
Temperature below
specified range for 4
h (min 20.7°C)
Thiadone
LC50
18.6 mg/L
Bowers (1995)
FIFRA 72-1
Report No. 106674
GLP
Klimisch score: 1
Disk 5
00000163
Hall and Lam (1999)
FIFRA 72-1
Report No. 108455
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 61 of 140
Test species
Test type
&
duration
Test resultsa, b
Test methodc
[reference number] Flufenacet
(FOE 5043)
Metabolites
95% CI:
14.9 – 28.0 mg/L
[measured] > 80% of
[nominal]
Light intensity below
guideline
Hardness above
guideline
GLP
Klimisch score: 1
Disk 5
00000166
Sheephead Minnow
Cyprinodon
variegatus
96 h Static
renewal
LC50
3.31 mg/L
95%CI:
2.73 – 4.02 mg/L
*[measured] range
79 - 106% [nominal]
[DO] < 60% day 2
Temperature outside
of acceptable range
Gagliano and
Bowers (1994)
FIFRA 72-3 (a)
Report No. 106421
GLP
Klimisch score: 2*
Rainbow trout
Oncorhynchus
mykiss
97 day ELS
Flow-
through
NOEC:
0.179 mg/L
(% swim up)
LOEC:
0.334 mg/L
(% swim up)
[measured]
Problems with
diluter (day 81 for
5.5h)
Hardness above
guideline (day 42)
Gagliano (1995)
FIFRA 72-4
Report No. 106978
GLP
Klimisch score: 1
Disk 5
00000167
Invertebrates
Waterflea
Daphnia magna
48 h Static
48 h Static
EC50:
30.9 mg/L
95%CI:
29.0 – 47.9 mg/L
[measured] > 80% of
[nominal]
FOE 5043-Sulfonic
acid
EC50
> 87.3 mg/L
[Lowest lethal]
> 87.3 mg/L
Limit test
Bowers (1994)
FIFRA Guideline
72-2
Report No.
106597
GLP
Klimisch score: 1
Disk 5
00000172
Heimbach (1995)
OECD 202
Report No.
HBF/Dm 145
GLP
Klimisch score: 1
Disk 5
00000145
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 62 of 140
Test species
Test type
&
duration
Test resultsa, b
Test methodc
[reference number] Flufenacet
(FOE 5043)
Metabolites
48 h Static
[measured] > 80% of
[nominal]
Thiadone
31.7 mg/L
95%CI:
26.5 – 38.2 mg/L
[measured] > 80%
and < 120% of
[nominal]
Bowers and Lam
(1998)
FIFRA 72-2
Report No.
108464
GLP
Klimisch score: 1
Disk 5
00000175
Hyalella azteca 96 h Static LC50
2.45 mg /L
95%CI: 1.80 – 3.15
mg/L
*[measured] lower
than 70% [nominal]
[measured] used to
calculate LC50.
Bowers (1995)
FIFRA 72-2
Report No. 106908
GLP
Klimisch score: 1*
Disk 5
106908
Waterflea
Daphnia magna
21 d Static NOEC:
3.26 mg/L
(mean time to first
brood, no. of
offspring)
LOEC:
6.33 mg/L
[measured] > 90% of
[nominal]
*
Temperature out of
range for 32 h
(21.8°C > 21.0°C).
Daphnids did not
receive specified
feed on day 3.
Hardness out of
range
(184 > 180 mg/L).
Gagliano and
Bowers (1994)
FIFRA 72-4
Report No.
106762
GLP
Klimisch score: 1*
Disk 5
00000176
Algae/Aquatic Plants
Algae
Selenastrum
capricornutum
(Pseudokirchneriella
subcapitata)
96 h Static
120 h
ErC50
0.00310 mg/L
95% CI:
Not determined*
EbC50
0.00306 mg/L
95% CI:
0.00284 – 0.00328
mg/L
[measured] > 95%
Dorgerloh (1998)
OECD 201
Report No.
DOM 98092
GLP
Klimisch score: 2*
Disk 5
00000179
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 63 of 140
Test species
Test type
&
duration
Test resultsa, b
Test methodc
[reference number] Flufenacet
(FOE 5043)
Metabolites
and < 106% of
[nominal]
*pH variance > 1.5
(7.1 – 9.5)
Algae
Scenedesmus
subspicatus
72 h Static FOE 5043-Sulfonic
acid
ErC50
> 86.7 mg/L
LOErC
> 86.7 mg/L
[measured] > 80% of
[nominal]
pH values > than
recommended in all
concentrations.
Anderson (1995)
OECD 201
Report No.
E 323 0971-5
GLP
Klimisch score: 1
Disk 5
00000146
Algae
Pseudokirchneriella
subcapitata
72 h Static
72 h Static
FOE 5043-
Methylsulfide
ErC50
83.8 mg/L
*No 95% CI given
[measured] > 85%
and < 110% of
[nominal]
Thiadone
ErC50
15.0 mg/L
95% CI:
10.7 – 21.0 mg/L
[measured] > 100%
and < 110% of
[nominal]
Dorgerloh (1998)
OECD 201
Report No.
E 323 1346-2
GLP
Klimisch score: *2
Disk 5
00000182
Hall and Lam (1998)
FIFRA 123-2 Tier 2
Report No.
E 108823
GLP
Klimisch score: 1
Disk 5
00000183
Algae
Anabaena
flos-aquae
120 h Static
EbC50
32.5 mg/L
95% CI:
26.9 – 39.3 mg/L
[measured] > 84%
and < 107% of
[nominal]
Hughes and
Alexander (1993)
FIFRA 123-2
Report No.
105199
GLP
Klimisch score: 1
Disk 5
00000180
Freshwater Diatom
Navicula pelliculosa
120 h Static EC50:
2.07 mg/L
95% CI:
0.56 – 3.56 mg/L
(Cell Density)
Bowers and Dobbs
(1995)
USEPA 123-2
Report No.
107113
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 64 of 140
Test species
Test type
&
duration
Test resultsa, b
Test methodc
[reference number] Flufenacet
(FOE 5043)
Metabolites
[measured] > 80%
and < 120% of
[nominal]
GLP
Klimisch score: 1
Disk 5
00000178
Marine Diatom
Skeletonema
costatum
120 h Static EC50:
0.00559 mg/L
95% CI:
0.00547 – 0.00578
mg/L
(Cell Density)
[measured] > 92% of
[nominal]
*pH variation > 1.5
units
Bowers and Dobbs
(1995)
USEPA 123-2
Report No.
107115
GLP
Klimisch score: 1*
Aquatic Plants
Lemna gibba
14 d ErC50:
0.0318 mg/L
95% CI:
0.0160 – 0.154 mg/L
[measured] > 75.6%
of [nominal] day 0
[measured] > 51% of
[nominal] day 14
*pH variation > 1.5
units
FOE 5043-Sulfonic
acid
EC50
> 75.9 mg/L
(no. of fronds)
LOAErC
> 75.9 mg/L
[measured]
concentrations used
Dorgerloh (1998)
USEPA 123-2
Report No.
105198
GLP
Klimisch score: 1*
Disk 5
00000184
Dorgerloh (1995)
USEPA 123-2
Report No.
DOM 95072
GLP
Klimisch score: 1
Disk 5
00000147
Other
Oxygen
Consumption in
Activated Sludge
FOE 5043
EC50
> 10000 mg/L
Kanne (1989)
ISO 8192-1986/B
Report No.
89238067
Non-GLP
Klimisch score: 3*
Disk 5
00000205 a Results are reported on the basis of nominal concentrations except where otherwise stated, Standard
test guidelines provide for reporting of results on a nominal basis where measurements indicate the test
substance remains within 20% of nominal. b 95% confidence intervals are stated where available
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 65 of 140
c Unless otherwise stated, the tests were conducted according to the test method identified
Conclusion
Flufenacet is classified as 9.1A due to its toxicity to algae.
Table A2.8A: Summary of aquatic toxicity data for Firebird.
Test species
Test type
&
duration
Test resultsa, b
Test method
c
[reference number]
Rainbow trout
Onchorynchus
mykiss
Static
96 h
LC50
12.3 mg/L
95% CI:
9.31 – 16.4 mg/L
Measured FOE 5043 (flufenacet): 70% - 85%
Measured diflufenican: 1 and 4%*
(*Low solubility in water)
[Nominal] used.
Dorgerloh (1996)
OECD 203
Report No.
DOM 95081
GLP
Klimisch score: 1
Disk 14
00000553
Waterflea
Daphnia magna
Static
48 h
Limit test
EC50
> 100 mg/L
NOEC:
> 100 mg/L
Measured FOE 5043: 55%*
Measured Diflufenican: 0.87%*
(*Low solubility in water)
[Nominal] used.
Heimbach (1996)
OECD 202
Report No.
HBF/Dm 151
GLP
Klimisch score: 1
Disk 14
00000554
Algae
Selenastrum
capricornutum
Static
72 h
ErC50
0.00663 mg/L
Measured FOE 5043: 45 - 178%*
Measured diflufenican: 0.87%*
(*Low solubility in water)
[Nominal] used.
Dorgerloh and
Sommer (2001)
OECD 203
Report No.
DOM 20073
GLP
Klimisch score: 1
Disk 14
00000555
Algae
Scenedesmus
subspicatus
Static
72 h
ErC50
0.01704 mg/L
[Measured] FOE 5043 > 90% and < 111% of
[Nominal] in cell free culture medium.
*pH above guideline.
Anderson (1996)
OECD 201
Report No.
E 323 0975-9
GLP
Klimisch score: 1*
Disk 14
00000556
Aquatic Plants
Lemna gibba
Static
7 d
ErC50
0.307 mg/L
(frond number)
Test medium modified to reach a sufficient
doubling time.
Dorgerloh and
Sommer (2001)
OECD 221
Report No.
DOM 20074
GLP
Klimisch score: 1
Disk 14
00000557 a Results are reported on the basis of nominal concentrations except where otherwise stated, Standard
test guidelines provide for reporting of results on a nominal basis where measurements indicate the test
substance remains within 20% of nominal. b 95% confidence intervals are stated where available
c Unless otherwise stated, the tests were conducted according to the test method identified
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 66 of 140
Conclusion
Firebird is classified as 9.1A due to its toxicity to algae.
Sub-class 9.2 Soil ecotoxicity and terrestrial fate Classification under this sub-class requires consideration of the persistence of the
components of the substance in soil, and the toxicity of the substance to soil-dwelling
invertebrates (e.g. earthworm), soil microbial function and terrestrial plants resulting
from soil based exposure.
Data on the adsorption, mobility and field dissipation of the active ingredient is used
in the ecological risk assessment for the substance. Refer to Appendix 3.
Terrestrial fate and degradation of flufenacet.
Information of terrestrial fate and degradation is summarised in Tables A2.9 and
A2.9A.
Table A2.9: Terrestrial fate and degradation of flufenacet (FOE 5043) and its
metabolites.
Test type Test results Test method
a
[reference number] Flufenacet Metabolites Abiotic degradation Soil Photolysis
Sandy Loam
(pH 6.4, OC 1.16%)
Rate 6.2 ppm
(1 kg/ha)
Temperature 25°C
Irradiated Samples
DT50: 248 days
(First order kinetics)
Dark control samples
DT50: 167 days
(First order kinetics)
Photolysis is not a
primary route of
degradation
Kasper and Shadrick
(1995).
EPA Guidelines N,
Section 161-3
Report No. 106247
GLP
Klimisch score: 1
Disk 4
00000121
Biodegradation
(Laboratory)
Aerobic
Phenyl Labelled
Sandy Loam
(pH 6.2, OC 0.6%)
Temperature 21°C
Rate: 1 ppm
(1 x application rate)
DT50: 33.8 days
(r = 0.9948, First order)
14 metabolic products
Only FOE oxalate >10%
Aerobic
Thiadiazole Labelled
Sandy Loam
(pH 6.2, OC 0.6%)
Temperature 21°C
Pangilinan and Smith
(1994).
EPA Guidelines N,
Section 162-1
Report No. 106408
GLP
Klimisch score: 1
Disk 4
00000119
Pangilinan and Smith
(1994).
EPA Guidelines N,
Section 162-1
Report No. 106420
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 67 of 140
Test type Test results Test method
a
[reference number] Flufenacet Metabolites Rate: 2.9 ppm
(3 X application rate)
DT50: 63.6 days
(r = 0.9922, First order)
>6 metabolic products
Major metabolite
Thiadone < 4%
Rate: 0.750 kg/ha
Temperature: 20°C
Loamy sand
(pH 6.2, OC 2.58%)
DT50: 25.5 days
DT90: 132 days
1.5 order kinetics
Rate: 0.750 kg/ha
Temperature: 20°C
Silt loam
(Laacherhof)
(pH 7.3, OC 0.9%)
DT50: 10.1 days
DT90: 52.6 days
1.5 order kinetics
Rate: 1.5 kg/ha
Temperature: 20°C
Silt loam
(Hofchen im Tal)
(pH 5.8, OC 2.4%)
DT50: 27.1 days
DT90: 90 days
First order kinetics
FOE – Sulfonic Acid
Temperature 20°C
Rate 750 g/ha.assuming
a 40% transformation
rate to sulfonic acid.
Sand
(pH 5.3, OC 0.57%)
DT50: 270 days
Loamy sand
(pH 6.3, OC 2.48%)
DT50: 189 days
Silt Loam
(Laacherhof)
(pH 7.3, OC 0.9%)
DT50: 247 days
FOE oxalate
Calculated values based
on experimental DT50
values of FOE sulfonic
acid.
Loamy sand
DT50: 5 days
GLP
Klimisch score: 1
Disk 4
00000120
Kelley et al. (1995)
BBA Guidelines Part
IV, 4-1
General Directorate
for Agriculture
VI B II-1
Report No. 106664
GLP
Klimisch score: 1
Disk 4
00000123
Hellpointner (1996)
Report No.
MR-1313/95
BBA Guidelines Part
IV, 4-1
SETAC 1995
Disk 5
00000129
Schafer (1998)
Report No.
MR-037/98
(amendment to report
MR 1085/95)
Calculation method
Disk 5
00000128
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 68 of 140
Test type Test results Test method
a
[reference number] Flufenacet Metabolites Silt loam
(Laacherhof)
DT50: 17 days
Silt loam
(Hofchen im Tal)
DT50: 12 days
Biodegradation
(Field)
Product applied
FOE 5043 60 WG
Without vegetation
D-23881 Breitenfide
Silty sand
(pH 6.2 OC 1.69%)
Rate 0.8 kg/ha
Agrotop Spraying Boom
DT50: 30.5 days
DT90: 101 days
Order of function: 1*
D-96166 Kirchlauter
Heavy sandy loam
(pH 7.1 OC 0.61%)
Rate 0.8 kg/ha
Agrotop Spraying Boom
DT50: 53.1 days
DT90: 177 days
Order of function: 1
D-40789 Monheim
loamy sand
(pH 6.7 OC 1.45%)
Rate 0.8 kg/ha
Agrotop Spraying Boom
DT50: 53.7 days
DT90: 178 days
Order of function: 1
D-51399 Burscheid
heavy loamy silt
(pH 6.5 OC 0.97%)
Rate 0.8 kg/ha
Agrotop Spraying Boom
DT50: 15.4 days
DT90: 51.0 days
Order of function: 1*
With vegetation
F-27700
Fresne-L’Archeveque
Crop: Maize
Loamy silt
(pH 6.0 OC 1.11%)
Rate 1.0 kg/ha
Knapsack
DT50: 16 days
Sommer (1995)
Report No.
RA-2112/93
BBA Guidelines Part
IV, 4-1
GLP
Klimisch score: 1
Disk 5
00000130
The results of
following single trials
are presented in this
report:
Trial No.: 30159/0
Trial No.: 30162/0
Trial No.: 30163/9
Trial No.: 30164/7
Trial No.: 30248/1
Trial No.: 30250/3
Trial No.: 30251/1
Trial No.: 30253/8
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 69 of 140
Test type Test results Test method
a
[reference number] Flufenacet Metabolites DT90: 177 days
Order of function: √1
F-27700
Fresne-L’Archeveque
Crop: Maize
Loamy silt
(pH 5.2 OC 1.86%)
Rate 1.0 kg/ha
Knapsack
DT50: 37.9 days
DT90: 198 days
Order of function: 1.5
F-30290 Laudun
Crop: Sunflower
Sandy loamy silt
(pH 7.6 OC 0.62%)
Rate 1.0 kg/ha
Knapsack
DT50: 29.5 days
DT90: 98.1 days
Order of function: 1*
F-13150
St Etienne du Gres
Crop: Sunflower
Sandy loamy silt
(pH 7.7 OC 0.80%)
Rate 1.0 kg/ha
Knapsack
DT50: 33.7 days
DT90: 112 days
Order of function: 1*,**
*Calculated without values of last sampling days
**Calculated without a value for day 7 of
degradation
During the whole test duration nearly all residues
remained in the 0 - 10 cm layers of soil.
The results of the lower layers of all eight trials
show that all concentrations of FOE 5043, FOE
5043-alcohol, FOE 5043-oxalate and FOE 5043-
sulfonic acid in deeper soil layers (20 - 30 cm) are
below the limit of determination of 10 µg/kg.
No mobility of FOE 5043 or the metabolites FOE
5043-alcohol, FOE 5043-oxalate and FOE 5043-
sulfonic acid was observed.
Product
FOE 5043 60 WG
Rate 0.4 kg/ha
Agrotop Spraying Boom
Sommer (1995)
Report No.
RA-2116/93
BBA Guidelines Part
IV, 4-1
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 70 of 140
Test type Test results Test method
a
[reference number] Flufenacet Metabolites D-51399 Burscheid
Silt Loam
(pH 6.5, OC 0.97%)
DT50: 37.6* days
DT90: 125* days
(First order kinetics)
D-40789 Monheim
Sandy Loam
(pH 6.7, OC 1.45%)
DT50: 43.2 days
DT90: 144 days
(First order kinetics)
*calculated without the values of the last sampling
day.
Product
FOE 5043 60 WG
With vegetation
Rate 0.4 kg/ha
Knapsack
F-27150
Saussay-la-Campagne
Silt Loam
(pH 7.4, OC 0.92%)
DT50: 16 days
DT90: 52 days
(First order kinetics)
F-27700
Fresne-L’Archeveque
Silt Loam
(pH 6.6, OC 1.00%)
DT50: 13 days
DT90: 43 days
(First order kinetics)
*calculated without the values of the last sampling
day.
The results of the lower layers of both trials showed
that all concentrations of FOE 5043, FOE 5043-
alcohol, FOE 5043-oxalate and FOE 5043-sulfonic
acid in deeper soil layers (10-20 cm, 20 - 30 cm, 30
- 40 cm and 40 - 50 cm) are below the limit of
detection of 3 µg/kg corresponding to < 2 % of the
initial concentration of the active ingredient.
No mobility of FOE 5043 or the metabolites FOE
5043-alcohol, FOE 5043-oxalate and FOE 5043-
sulfonic acid was observed.
Product
FOE 5043 60 WG
With vegetation
Rate 1 kg/ha
GLP
Klimisch score: 1
Disk 5
00000131
Sommer (1995)
Report No.
RA-2051/93
BBA Guidelines Part
IV, 4-1
GLP
Klimisch score: 1
Disk 5
00000132
Sommer (1995)
Report No.
RA-2019/94
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 71 of 140
Test type Test results Test method
a
[reference number] Flufenacet Metabolites
F-30290 Laudun
Silty clay loam
0 – 30 cm
(pH 7.7, OC 1.28%)
30 – 50 cm
(pH 7.8, OC 0.70%)
Knapsack
DT50: 36.2 days
DT90: 120 days
(First order kinetics)
F-13103
St. Etienne du Gres
Silty loam
0 – 30 cm
(pH 7.7, OC 0.96%)
30 – 50 cm
(pH 7.8, OC 0.60%)
Knapsack
DT50: 41.8 days*
DT90: 139 days*
(First order kinetics)
I-48100
Ravenna
Sandy loamy silt
0 – 30 cm
(pH 7.8, OC 0.0.98%)
Silty sand
30 – 50 cm
(pH 7.8, OC 0.57%)
Wheelbarrow applicator
DT50: 37.9 days
DT90: 126 days
(First order kinetics)
I-48020
Romauldo
loamy clay
0 – 30 cm
(pH 7.8, OC 1.11%)
30 – 50 cm
(pH 7.8, OC 0.96%)
Wheelbarrow applicator
DT50: 47.5 days
DT90: 158 days
(First order kinetics)
*calculated without the values of the last sampling
day.
The results of the lower layers (10 - 20 cm, 20 - 30
cm, 30 - 40 cm and 40 - 50 cm) of all four trials
showed that, except one value of FOE 5043 in the
10 - 20 cm layer between the limit of detection and
the limit of determination, all concentrations of
FOE 5043, FOE 5043-alcohol, FOE 5043-oxalate
BBA Guidelines Part
IV, 4-1
GLP
Klimisch score: 1
Disk 5
00000133
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 72 of 140
Test type Test results Test method
a
[reference number] Flufenacet Metabolites and FOE 5043-sulfonic acid are below the limit of
detection of 3 μg/kg.
No mobility of FOE 5043 or the metabolites FOE
5043-alcohol, FOE 5043-oxalate and FOE 5043-
sulfonic acid was observed.
Soil accumulation
Adsorption/desorption FOE 5043
Kelley and Wood
(1992)
EPA Guideline 163-1
Report No. 103903
GLP
Klimisch score: 1
Disk 5
00000136
Christensen and Yen
(1994).
Canadian guideline
T-1-225 #6.2, B.
Report No. 106578
GLP
Klimisch score: 2*
Disk 5
00000137
Blumhorst et al. 1994
Canadian guideline
T-1-225 #6.2, B.
Report No. 106578
GLP
Klimisch score: 1
Disk 5
00000137
Soil Kd Koc
Silt loam
pH 5.9 OC 2.9%
Ad 3.2
Des 3.9
Ad 213
Des 254
Clay loam
pH 6.4 OC 2.2%
Ad 2.7
Des 3.1
Ad 233
Des 264
Loamy sand
pH 6.4 OC 0.4%
Ad 1.6
Des 2.1
Ad 742
Des 1016
Sand
pH 5.0 OC 0.3%
Ad 1.0
Des 0.9
Ad 613
Des 554
Sandy loam
pH 6.4 OC 1.4%
Ad 4.8
Des 5.3
Ad 354
Des 395
Kd
Koc
Loam
pH 7.1 OC 4.3%
Ad 4.9
Des 10.5
Ad 113
Des 245
Silt Loam
pH 7.3 OC 2.8%
Ad 4.0
Des 6.6
Ad 144
Des 238
Characterised as mobile in loam and silt loam with
a potential for high mobility in the environment.
*There were some minor deviations from
guidelines such as temperature range and pH
measures.
Metabolites
Kd Koc
FOE Methyl Sulfoxide
Sand
pH 5.8, OC 0.27%
Ad 0.13
Des 0.08
Ad 49
Des 31
Sandy Loam
pH 6.3, OC 0.75%
Ad 0.35
Des 0.29
Ad 46
Des 39
Silty Clay Loam
pH 6.6, OC 2.13%
Ad 2.05
Des 2.59
Ad 96
Des 121
Silty Clay
pH 6.0, OC 1.21%
Ad 5.60
Des 6.12
Ad 463
Des 506
Mobility class
very high/medium
FOE Sulfonic Acid
Sand
pH 5.8, OC 0.27%
Ad 0.05
Des -
Ad 19
Des -
Sandy Loam
pH 6.3, OC 0.75%
Ad 0.11
Des -
Ad 15
Des -
Silty Clay Loam
pH 6.6, OC 2.13%
Ad 0.20
Des -
Ad 10
Des -
Silty Clay
pH 6.0, OC 1.21%
Ad 0.07
Des -
Ad 6
Des -
Mobility class very high
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 73 of 140
Test type Test results Test method
a
[reference number] Flufenacet Metabolites
FOE Oxalate
Sand
pH 5.8, OC 0.27%
Ad 0.06
Des -
Ad 23
Des -
Sandy Loam
pH 6.3, OC 0.75%
Ad 0.1
Des -
Ad 13
Des -
Silty Clay Loam
pH 6.6, OC 2.13%
Ad 0.15
Des -
Ad 7
Des -
Silty Clay
pH 6.0, OC 1.21%
Ad 0.16
Des -
Ad 13
Des -
Mobility class
very high
FOE Alcohol
Sand
pH 5.8, OC 0.27%
Ad 0.23
Des 0.4
Ad 0.35
Des 147
Sandy Loam
pH 6.3, OC 0.75%
Ad 0.78
Des 1.38
Ad 1.42
Des 184
Silty Clay Loam
pH 6.6, OC 2.13%
Ad 2.02
Des 3.20
Ad 1.56
Des 150
Silty Clay
pH 6.0, OC 1.21%
Ad 3.80
Des 3.94
Ad 2.10
Des 326
Mobility class
high/medium
Thiadone
Sand
pH 5.8, OC 0.27%
Ad 0.12
Des 0.35
Ad 43
Des 128
Sandy Loam
pH 6.3, OC 0.75%
Ad 0.33
Des 1.42
Ad 44
Des 189
Silty Clay Loam
pH 6.6, OC 2.13%
Ad 0.61
Des 1.56
Ad 29
Des 73
Silty Clay
pH 6.0, OC 1.21%
Ad 0.71
Des 2.10
Ad 58
Des 174
Mobility class
very high/high
It can be concluded that all metabolites have the
potential to be quite mobile in soil. However, with
regard to the quantities being found in soil, only
FOE oxalate or FOE sulfonic acid are expected to
have a potential to leach into deeper soil layers in
significant amounts.
Table A2.9A: Terrestrial fate (mobility and leaching) of flufenacet and its
metabolites. Mobility/
Leaching
Leaching of Aged 5043 through Soil Columns
Rate: 1.76 mg ai/kg soil
Between 26.7% and 29.0% of the applied radioactivity was collected in
the leachates from 30-day columns and 34.7% to 44.3% was collected
in the leachate from the 90-day columns. Only 17.4% of the applied
radioactivity from the 30-day incubation system was due to
metabolites, whereas 42.3% of the applied radioactivity was due to
metabolites in the 90-day incubation system.
Kelley and Wood
(1993)
BBA Guideline Part
IV, 4-2
Report No. 105018
GLP
Klimisch score: 1
Disk 5
00000139
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 74 of 140
Analysis of the leachates from the 30-day and 90-day incubation
periods indicates that the metabolites leach more readily than the
parent compound.
Comparison of extracts from the 30-day and 90-day incubation periods
with the 30-day and 90-day leachates reveals that all of the identified
metabolites and several unknown radioactive components (maximum
percent = 1.8% combined) moved through the soil columns with the
leachates.
Lysimeter study on the translocation of FOE 5043 into the
underground after 2-year application as pre-emergence herbicide
in corn (1st year of study)
Over a period of 1 year after the application the leaching behaviour of
[phenyl-UL-14C] FOE 5043 and it's degradation products was
investigated under practice-relevant German corn growing field
conditions
Rate: 480 g ai/ha
The preliminary results of this study proved that even under worst case
conditions a contamination of soil layers below 1.2 m or of
groundwater by the parent after recommended use of FOE 5043 can be
precluded with a probability bordering certainty.
One metabolite, FOE sulfonic acid, may be contained in soil pore
water below 1.2 m depth at a peak concentration of about 1.2 µg/L and
a 1st year's annual mean of about 0.5 µg/L.
Lysimeter study on the translocation of FOE 5043 into the
underground after 2-year application as pre-emergence herbicide
in corn (2nd
year of study)
Rate: 480 g ai/ha.(First application – May 1993)
Rate: 480 g ai/ha.(Second application – May 1994)
The measured values of total radioactive residue (TRR) in the
leachates showed a typical break-through curve and comparable results
for both lysimeters. The maximum TRR of 1.04 ug and 0.69 ug a.i.
equivalents/L was each reached in February 1995.
The mean residue of FOE 5043 in total 2nd year's leachate was
measured to be less than 0.005 µg/L, but the parent compound could
not be positively detected. The mean concentration of each known
FOE 5043-metabolite was lower than 0.02 µg/L, except the findings of
sulfonic acid. The mean residues of sulfonic acid in AL-95 were
measured to be 0.24 µg/L (lys. #15) and 0.15 µg/L (lys. #16),
respectively.
These contents were significantly lower than those found in the annual
leachates of the 1st year, despite the repeated application after one
year.
Despite the repeated application after one year, the TRR in the
leachates of the 2nd year was generally lower than that of the 1st year.
These findings indicate that the outflow of radioactivity resulting from
the 1st application of FOE 5043 was more or less completed after one
year. Therefore, a longer lasting leaching of metabolites into deeper
soil layers is not to be expected from a single use of FOE 5043.
Hellpointner (1995)
BBA Guideline Part
IV, 4-3
Report No. PF-4024
GLP
Klimisch score: 1
Disk 5
00000140
Hellpointner (1995)
BBA Guideline Part
IV, 4-3
Report No. PF-4081
GLP
Klimisch score: 1
Disk 5
00000143
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 75 of 140
It is indicated that a lower portion of mobile metabolites (i. e. sulfonic
acid) was able to leach out of the soil cores in the subsequent year after
repeated use. This may partly be due to an enhanced overall
degradation (i. e. mineralization) in the year of repeated application,
probably caused by better adapted soil microorganism populations or
by the slightly higher soil temperatures. The other marginal conditions
of study were not differing so much.
Only a total of 0.50% and 0.32% of the radioactivity applied leached
through each of the two soil cores during the 2nd year of study. These
portions correspond to 0.25% and 0.16% of total applied radioactivity,
only. Only a total of 0.66% and 0.59% of the total applied radioactivity
leached through each of the two soil cores during the 2 years of
lysimeter study.
Again, the residues found in the harvested corn materials of the 2nd
year were at a rather low level (TRR < 6.5 ppb in kernels and TRR <
11.7 ppb in cobs & hulls) and were well comparable to those
determined in the materials of the 1st year. These findings indicate that
a repeated use of FOE 5043 should not cause increasing total residues
in the harvested crop materials.
The preliminary results of this study proved that even under worst case
conditions a contamination of soil layers below 1.2 m depth or of
groundwater by the parent after recommended use of FOE 5043 in
corn can be precluded with a probability bordering certainty. One
metabolite, the 4-fluoro-N- methylethylanilinesulfoacetamide (FOE
5043-sulfonic acid) may be contained for short term in soil pore water
below 1.2 m depth. In this study a peak concentration of about 1.2
µg/L was measured in the 1st winter and the annual mean of the 1st
year's leachate amounted to about 0.5 µg/L . But in the subsequent
year, including a repeated application of FOE 5043, the values were
found to be lower (yearly mean of about 0.2 µg/L).
Lysimeter study on the translocation of FOE 5043 into the
underground after the use as pre-emergence herbicide in a corn /
winter wheat crop rotation
Over a period of 1 year the leaching behaviour of [phenyl-UL-14C]
FOE 5043 and it's degradation products was investigated under
practice-relevant German corn (silage) / winter wheat growing field
conditions.
Rate 480 g ai/ha.(First application – May 1993)
Rate 180 g ai/ha.(Second application – November 1993)
The maximum residue of FOE 5043 in single leachate was measured to
be lower than 0.01 µg/L. The maximum concentration of FOE-
metabolites (including unknowns) was each lower than 0.08 µg/L,
except the findings of FOE-sulfonic acid and, only for lys. #18, the
FOE alcohol.
The maximum residues of FOE-sulfonic acid found in the leachates
were measured to be 3.4 µg/L and 3.7 µg/L. The FOE-alcohol was
positively detected in lys. #18, only (maximum residues of 0.16 µg/L).
The detection of FOE-alcohol in the leachates of lysimeter #18 was the
only significant difference in the two tested soil cores.
The mean residue of FOE 5043 in total 1st year's leachate was lower
than 0.01 µg/L. The mean concentration of FOE-metabolites
Hellpointner (1995)
BBA Guideline Part
IV, 4-3
Report No. PF-4025
GLP
Klimisch score: 1
Disk 5
00000141
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 76 of 140
(including unknowns) was each lower than 0.06 ng/L, except the
findings of FOE sulfonic acid. The mean residues of FOE -sulfonic
acid in the total 1st year's leachates were 1.42 µg/L and 1.69 ng/L,
respectively. A total of 1.43% and 1.56% of applied radioactivity
leached through the two soil cores during 1st year of study.
The preliminary results of this study proved that even under worst case
conditions a contamination of soil layers below 1.2 m or of ground
water by the parent after recommended use of FOE 5043 can be
precluded with a probability bordering certainty.
One metabolite, FOE-sulfonic acid, may be contained in soil pore
water below 1.2 m depth at a peak concentration of about 3.5 µg/L and
a 1st year's annual mean of about 1.6 µg/L.
Lysimeter study on the translocation of FOE 5043 into the subsoil
after use as pre-emergence herbicide in a maize / winter wheat
crop rotation The leaching behaviour of [phenyl-UL-
14C]FOE 5043 and its
degradation products was investigated in a maize-winter wheat crop
rotation under practice-relevant German field conditions.
Rate 480 g ai/ha.(First application – May 1993)
Rate 180 g ai/ha.(Second application – November 1993)
The measured total radioactive residue (TRR) in the individual
leachates showed a typical break-through curve and well comparable
results for both lysimeters. For both lysimeters the TRRmax. was
reached in February 1994 (after 38 weeks) at about 5 ug a.i. equivalent/
L. However, in the subsequent period until February 1995 the TRR
decreased about 20-fold to a range of less than 0.25 ug a.i.
equivalent/L.
These findings indicated that the use of FOE 5043 should not have a
longer-lasting influence on the water relevant for groundwater recharge
below agricultural soils.
A concrete peak of parent compound could not be observed in the
analyses of leachates. The content of FOE 5043 in individual leachate
was found to be lower than 0.01 µg/L. The maximum concentration of
metabolites (including unknowns) was each lower than 0.04 µg/L,
except that of FOE 5043 sulfonic acid (SAC) and, in case of lys. #18,
the FOE 5043 alcohol (ALC). The maximum content of SAC found in
the leachates of Feb. 94 was measured to be 3.4 µg/L (lys. #17) and 3.7
µg/L (lys. #18), respectively. The ALC was observed in lys. #18, only
(maximum content of 0.095 ng/L in an early leachate taken in Oct. 93).
The FOE 5043 in annual leachate of the 1st year was much lower than
0.01 µg/L. The content of metabolites (including unknowns) was each
lower than 0.04 µg/L, except that of SAC. On average, the content of
SAC in annual leachate of the 1st year was 1.5 µg/L. The FOE 5043 in
annual leachate of the 2nd year was significantly lower than 0.005
µg/L and the content of metabolites (including unknowns) was at the
most 0.022 µg/L. Compared to the annual leachate of the 1st year the
mean content of SAC had decreased 100-fold to about 0.015 µg/L,
already. Until the end of study, the leaching of [14C]material out of the
soil monolith was approaching the background level. It is quite
plausible that some radioactivity is passing the soil monoliths further,
because a comparatively high portion of radioactively labelled carbon
was applied to the soil in a quite stable [14C]labelling position
Hellpointner (1996)
BBA Guideline Part
IV, 4-3
Report No. PF-4184
GLP
Klimisch score: 1
Disk 5
00000142
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 77 of 140
(phenyl-UL). It is conceivable that the unknown radioactively labelled
compounds (TRR) in the leachate might consist of humic and/or biotic
substances into which liberated radioactively labelled carbon dioxide
and/or radioactive fragments of the a.i. or metabolites had been
incorporated.
The comparatively low mobility of FOE 5043 and its metabolites in
soil was supported by the measured distribution of radioactivity in the
processed soil monoliths. The main portion of recovered radioactivity
was still located in the upper soil layers.
Furthermore, the main portion of TRR still contained there was not
extractable (bound) residue. The recoveries of parent compound (less
than 0.8% of total applied) and of relevant metabolites in the processed
soil layers were quite low. Obviously, relevant portions (55.6% and
44.8%) of radioactivity once applied to the soil monolith had been
mineralised and released into the air.
The results of this study proved that even under worst case conditions a
contamination of soil layers below 1.2 m depth by the parent (after
recommended use of FOE 5043) can be precluded with a probability
bordering certainty. Most of its relevant degradation products in soil
showed a similar behaviour. It should be considered that only a total
portion of 1.56% and 1.72% of applied radioactivity was extracted
from the soil monoliths of lysimeter #17 and #18 by all the leachates
during 2.5 years of study. One individual metabolite, SAC, may be
contained in soil pore water below 1.2 m depth at a short-term peak
concentration of about 3.5 µg/L, a 1st year's annual mean of at about
1.5 µg/L and a 2nd year's annual mean of about 0.015 µg/L, only. The
SAC represents a metabolite formed in soil from one part (half) of the
parent compound molecule. Furthermore, the data confirmed that the
herbicide FOE 5043 is a well degradable parent compound.
The Agency’s Conclusion
The flufenacet metabolite, FOE 5043 sulfonic acid, has the potential to
leach into and persist in the aquatic environment and ground water.
FOE 5043 sulfonic acid has appeared in mean concentrations
exceeding 0.1 µg/L (designated EU cut-off). However, it has been
demonstrated that FOE sulfonic acid has no toxicological or
ecotoxicological relevance.
a unless otherwise stated, the tests were conducted in accordance with the named test guideline
NA= Not applicable
ND= No data provided
Figure 2: Degradation pathway of FOE 5043 (Schafer 1998, MR-037/98).
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 78 of 140
Conclusion
Based on these data flufenacet is considered to not meet the HSNO criteria for
degradability in soil < 30 days. This is primarily due to the degradability of the major
metabolite FOE 5043-sulfonic acid, DT50 range 189 – 270 days. As a result, Firebird
is considered to be not rapidly degradable in soil.
Soil toxicity
A summary of the toxicity of flufenacet and Firebird to soil dwelling macro-
organisms, soil microbial function and terrestrial plants is provided in Tables A2.10
and A2.10A.
Table A2.10: Summary of terrestrial toxicity data for flufenacet.
Test species Test type &
duration
Test resultsa, b
Test methodc
[reference
number] Flufenacet Metabolites
Soil-dwelling invertebrates
Earthworm
Eisenia fetida
Acute
14 day
Acute
14 day
LC50
226 mg/kg dry weight
95% CI:
208 – 246 mg/kg
EC50
22.6 mg/kg dry
weight
NOEC
< 10 mg/kg dry
weight
[Lowest Lethal]
178 mg/kg dry weight
FOE 5043
- Sulfonic acid
LC50
> 1000 mg/kg dry
weight
NOEC
> 1000 mg/kg dry
weight
*temperature
outside of range for
1 day
(22°C < 22.5°C)
*Humidity outside
of range on 0 – 4
days
(94% > 90%)
FOE 5043
- Oxalate
LC50
> 1000 mg/kg dry
weight
Heimbach (1995)
OECD 207
Report No.
HBF/Rg 202
GLP
Klimisch score: 1
Disk 5
00000197
Heimbach (1999)
OECD 207
Report No.
99-005-1022
GLP
Klimisch score: 2*
Disk 5
00000198
Heimbach (1999)
OECD 207
Report No.
1022.006.630
GLP
Klimisch score: 2*
Disk 5
00000199
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 79 of 140
NOEC
> 1000 mg/kg dry
weight
*temperature
outside of range for
1 day
(22°C < 22.5°C)
*Humidity outside
of range on days 5-6
and days 8-12 (98%
> 90%)
d 6-8 (54% < 60%)
Earthworm
Eisenia fetida
Reproduction
56 days
Reproduction
56 days
FOE 5043 WG 60
Rate:
1 kg/ha.formulation
2 kg/ha.formulation
5 kg/ha.formulation
LC50
> 5 kg/ha
NOEC
2 kg/ha.formulation
(Weight reduction)
*This reduction in
weight was not
considered as
biologically
significant.
(p = 0.043 < 0.050).
The numbers of
offspring were not
reduced.
FOE 5043 WG 60
Rate:
1 kg/ha.formulation
2 kg/ha.formulation
5 kg/ha.formulation
1 kg/ha.formulation
Total biomass of
offspring significantly
higher (36 %).
2 kg/ha.formulation
No. of offspring was
significantly higher
(27%).
5 kg/ha.formulation
Total biomass of
offspring significantly
higher (27%).
It can be anticipated,
Heimbach (1997)
ISO/DIS 11268-2
BBA Part VI, 2-2
Report No.
HBF/Rg 251
GLP
Klimisch score: 1
Disk 5
00000200
Heimbach (1997)
ISO/DIS 11268-2
BBA Part VI, 2-2
Report No.
HBF/Rg 213
GLP
Klimisch score: 1
Disk 5
00000201
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 80 of 140
that FOE 5043 WG
60 did not affect
reproduction of
earthworms up to the
highest tested rate of
5 kg/ha.
Terrestrial plants
Monocotyledons
4 species
Dicotyledons
6 species
Seed
Germination
Seedling
Emergence
21 d
FOE 5043 Dry
Flowable 61.0% ai
No significant
difference between
treated and control
plants.
EC50
Sorghum
0.054 lb ai/A
(0.061 kg ai/ha)
(lowest EC50 of 10
spp.)
NOEC
0.0039 lb ai/A
(0.0044 kg ai/ha)
(Height/Weight)
Johns (1994)
Report No.
106780
EPA 122-1
EPA 123-1
GLP
Klimisch score: 1
Disk 5
00000204
Monocotyledons
4 species
Dicotyledons
6 species
Vegetative
vigour
21 d
Risk
assessment
only
EC50
Sorghum
0.058 lb ai/A
0.065 kg ai/ha
Height
EC50
Sorghum
0.041 lb ai/A
0.046 kg ai/ha
Weight
(lowest EC50 of 10
spp.)
NOEC
0.0078 lb ai/A
0.0087 kg ai/ha
Height/Weight
Johns (1994)
Report No.
106780
EPA 122-1
EPA 123-1
GLP
Klimisch score: 1
Disk 5
00000204
Soil microbial function
Nitrogen
Mineralisation
28 d FOE 5043
Rate:
0.62 kg/ha
(0.83 mg/kg dry wt soil)
3.1 kg/ha
(4.15 mg/kg dry wt soil)
EC25
> 4.15 mg/kg dry wt
soil
FOE 5043 should not
Anderson (1994)
BBA Part VI, 1-1
ISO/DIS 1036-6
Report No.
E 337 0885-4
GLP
Klimisch score: 1
Disk 5
00000202
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 81 of 140
negatively influence the
turnover of Nitrogen in
soil.
Glucose
Stimulated
Respiration in
Soil
FOE 5043
Rate:
0.62 kg/ha
(0.83 mg/kg dry wt soil)
3.1 kg/ha
(4.15 mg/kg dry wt soil)
EC25
> 4.15 mg/kg dry wt
soil
FOE 5043 should not
influence the
degradation of organic
carbon in soils.
Anderson (1994)
BBA Part VI, 1-1
ISO/DIS 1036-6
Report No.
E 337 0887-9
GLP
Klimisch score: 1
Disk 5
00000203
a Results are reported on the basis of nominal concentrations except where otherwise stated, Standard
test guidelines provide for reporting of results on a nominal basis where measurements indicate the test
substance remains within 20% of nominal. b 95% confidence intervals are stated where available
cUnless otherwise stated, the tests were conducted according to the test method identified
NA= Not applicable
ND= No data provided
Conclusion
Flufenacet is classified as 9.2A due to it’s’ toxicity to non-target plants and its
degradation half-life in soil.
Table A2.10A: Summary of terrestrial toxicity data for Firebird.
Test species Test type &
duration
Test resultsa, b
Test method
c
[reference
number]
Soil-dwelling invertebrates
Earthworm
Eisenia fetida
Acute
14 d
Reproduction
56 d
LC50
> 1000 mg/kg dry weight
NOEC
32 mg/kg dry weight
(weight)
NOEC
> 4 mg/kg dry weight
(3000 g formulation/ha)
Meisner (2001)
OECD 207
Report No.
MPE/Rg 362/01
GLP
Klimisch score: 1
Disk 5
00000565
Heimbach (1998)
BBA VI, 2-2
Report No.
MPE/Rg 280
GLP
Klimisch score: 1
Disk 5
00000566
Terrestrial plants
Monocotyledons
2 species
Dicotyledons
4 species
Seedling
emergence
21 days after
50%
emergence of
Allium cepa
(Onion)
Survival
EC50
331.52 g/ha
Kalsch (2002)
Report No.
P2PA
OECD 208A
GLP
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 82 of 140
controls 0.44 mg/kg dry soil
NOEC
103.4 g/ha
0.14 mg/kg dry soil
Shoot length
Allium cepa
(Onion)
EC50
308.96 g/ha
0.41 mg/kg dry soil
Brassica napus
(Oilseed rape)
NOEC
3.2 g/ha
0.0043 mg/kg dry soil
Fresh weight
Allium cepa
(Onion)
EC50
190.43 g/ha
0.25 mg/kg dry soil
Brassica napus
(Oilseed rape)
NOEC
3.2 g/ha
0.0043 mg/kg dry soil
Klimisch score: 1
Disk 5
00000570
Monocotyledons
2 species
Dicotyledons
4 species
Vegetative
vigour
21 days after
50%
emergence of
controls
Risk
assessment
only
Fresh weight
Cucumis sativus
(Cucumber)
EC50
27.75 g/ha
Glycine max
(Soybean)
Cucumis sativus
(Cucumber)
NOEC
3.2 g/ha
Kalsch (2002)
Report No.
P3PB
OECD 208A
GLP
Klimisch score: 1
Disk 14
00000570
Soil microbial function
Nitrogen
Mineralisation
Rate:
0.6 kg product /ha.
(0.80 mg product/kg dry wt soil)
3.0 kg product/ha
(4.00 mg product/kg dry wt soil)
EC25
> 4.00 mg/kg dry wt soil
Anderson (1995)
BBA Part VI, 1-1
ISO/DIS 1036-6
Report No.
E 337 1025-1
GLP
Klimisch score: 1
Disk 5
00000569
Glucose
Stimulated
Respiration in
Soil
Rate:
0.6 kg product /ha.
(0.80 mg product/kg dry wt soil)
3.0 kg product/ha
(4.00 mg product/kg dry wt soil)
Anderson (1995)
BBA Part VI, 1-1
ISO/DIS 1036-6
Report No.
E 330 1024-3
GLP
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 83 of 140
EC25
> 4.00 mg/kg dry wt soil
Klimisch score: 1
Disk 5
00000568
a Results are reported on the basis of nominal concentrations except where otherwise stated, Standard
test guidelines provide for reporting of results on a nominal basis where measurements indicate the test
substance remains within 20% of nominal. b 95% confidence intervals are stated where available
cUnless otherwise stated, the tests were conducted according to the test method identified
Conclusion
Firebird is classified as 9.2A due to its’ toxicity to non-target plants.
Sub-class 9.3 Terrestrial vertebrate ecotoxicity The mammalian toxicity of flufenacet has been addressed under sub-class 6. Key
endpoints for both mammalian and avian toxicity are summarized in Table A2.11.
Table A2.11: Summary of terrestrial vertebrate toxicity data for flufenacet.
Test
species
Test type
&
duration
Test resultsa, b
Test method
c
[reference number]
Mammals
Rat
(Sprague
Dawley)
Acute oral LD50:
589 mg/kg body weight (females)
Astroff and
Fitzpatrick
US FIFRA 81-1
OECD 401
Report No.
102699
Klimisch score: 1
Birds
Bobwhite
quail
Colinus
virginianus
Acute oral
14 day
observation
LD50:
1608 mg ai/kg
body weight
NOEC:
125 mg/kg body weight
LOEC:
250 mg/kg body weight
Stafford (1992)
FIFRA 71-1
Report No.
102642
GLP
Klimisch score: 1
Disk 5
00000156
Mallard
duck
Anas
platyrhynchos
Acute oral
14 day
observation
LD50:
>2000 mg ai/kg
body weight
NOEC:
500 mg/kg body weight
LOEC:
1000 mg/kg body weight
(mortality)
*Two females at the 1000 mg a.i./kg dose level
and one female at the 2000 mg a.i./kg dose level
were found dead the day after dosing.
Downs and Hancock
(1997)
FIFRA 71-1
Report No.
107700
GLP
Klimisch score: 2*
Disk 5
00000157
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 84 of 140
Postmortem examinations revealed no
compound related findings. No consistent, dose
related symptoms were noted in any birds. None
of the birds that died exhibited any toxic
symptoms. No effects on bodyweight or feed
consumption were noted at any dose level.
Bobwhite
quail
Colinus
virginianus
Subacute
dietary
5 day
exposure
3 day
observation
LC50:
> 5317 ppm
NOEC:
1280 ppm
(Symptoms of intoxication –
ataxia, hyporeactivity)
LOEC:
2469 ppm
(Symptoms of intoxication –
ataxia, hyporeactivity)
Feed aversion observed at 4970 ppm. Death
attributed to food avoidance rather than direct
effect of compound.
Toll (1994)
FIFRA 71-2
OECD 205
Report No.
106583
GLP
Klimisch score: 1
Disk 5
00000159
Mallard
duck
Anas
platyrhynchos
Subacute
dietary
5 day
exposure
3 day
observation
LC50:
> 4970 ppm
NOEC:
<164 ppm
(Symptoms of intoxication - diarrhoea)
LOEC:
164 ppm
(Symptoms of intoxication - diarrhoea)
Feed aversion observed at 4970 ppm. Death
attributed to food avoidance rather than direct
effect of compound.
Stafford (1994)
FIFRA 71-2
Report No.
103814
GLP
Klimisch score: 1
Disk 5
00000158
Bobwhite
quail
Colinus
virginianus
Reproduction
Study
NOEC
(number of eggs laid per hen)
1890 ppm
NOEL
291.58 mg ai/kg bw/day
NOEC
(mean eggshell thickness)
1890 ppm
NOEL
288.66 mg ai/kg bw/day
NOEC
(proportion of fertile eggs per eggs set per hen
or number viable embryos over number of eggs
set)
1890 ppm
NOEL
291.58 mg ai/kg bw/day
NOEC
Schmuck (1994)
OECD 206
FIFRA 71-4
Report No.
SXR/REP 03
GLP
Klimisch score: 1
Disk 5
00000160
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 85 of 140
(proportion of hatching per fertile eggs per hen
or percent hatching of viable embryos)
441 ppm
NOEL
66.92 mg ai/kg bw/day
(% of self hatched chicks, rel. to viable 18-d
embryos)
NOEC
(proportion of 14-day old juveniles per number
of hatchlings)
1890 ppm
NOEL
288.66 mg ai/kg bw/day
NOEC
(14-day juvenile weights per hen)
1890 ppm
NOEL
288.66 mg ai/kg bw/day
Mallard
duck
Anas
platyrhynchos
Reproduction
Study
NOEC
(number of eggs laid per hen)
211 ppm
NOEL
26.98 mg ai/kg bw/day
NOEC
(mean eggshell thickness)
544 ppm
NOEL
74.34 mg ai/kg bw/day
NOEC
(proportion of fertile eggs per eggs set per hen
or number viable embryos over number of eggs
set)
211 ppm
NOEL
26.98 mg ai/kg bw/day
(Viable eggs of eggs set)
NOEC
(proportion of hatching per fertile eggs per hen
or percent hatching of viable embryos)
88 ppm
NOEL
10.20 mg ai/kg bw/day
(Normal hatchlings of live 3-week embryos)
NOEC
(proportion of 14-day old juveniles per number
of hatchlings)
544 ppm
NOEL
74.34 mg ai/kg bw/day
(14-day old survivors of normal hatchlings)
NOEC
(14-day juvenile weights per hen)
Hancock and
Reynolds (1994)
FIFRA 71-4
Report No.
106594
GLP
Klimisch score: 1
Disk 5
00000161
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 86 of 140
88 ppm
NOEL
12.02 mg ai/kg bw/day a Results are reported on the basis of nominal concentrations except where otherwise stated, Standard
test guidelines provide for reporting of results on a nominal basis where measurements indicate the test
substance remains within 20% of nominal. b 95% confidence intervals are stated where available
cUnless otherwise stated, the tests were conducted according to the test method identified
Conclusion
Flufenacet is classified as 9.3C due to its toxicity to mammals and birds.
Table A2.11A: Summary of terrestrial vertebrate toxicity data for Firebird.
Test
species
Test type
&
duration
Test resultsa, b
Test method
c
[reference number]
Mammals
Rat
(Wistar)
Acute oral LD50:
> 500 < 2000 mg/kg body weight
Krötlinger
OECD 423
Report No.
T5071313
Klimisch score: 2
Conclusion
Firebird is classified as 9.3C due to its toxicity to mammals.
Sub-class 9.4 Terrestrial invertebrate ecotoxicity A summary of the data on the toxicity of flufenacet and Firebird to honeybees and
other non-target terrestrial invertebrates is provided in Tables A2.12 and A2.12A,
respectively.
Table A2.12: Summary of terrestrial invertebrate toxicity data for flufenacet.
Test
species
Test type &
duration
Test resultsa, b
Test methodc
[Reference number]
Flufenacet Metabolites
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 87 of 140
Honey bee
Apis
mellifera
Contact
24 h
Contact
48 h
Contact
48 h
LD50
> 25 µg/Bee
LD50
> 200 µg/Bee
LD50
> 400 µg/Bee
Mayer (1996)
FIFRA 141-1
Study no.
107517
GLP
Klimisch score: 1
Disk 5
00000189
Nengel (1995)
EPPO Guideline 170
Study no.
B-94137/01-BLEU
GLP
Klimisch score: 1
Disk 5
00000188
Tornier (1994)
EPPO Guideline 170
Study no.
B-958264
Non-GLP
Klimisch score: 3
Disk 5
00000187
Honey bee
Apis
mellifera
Oral
48 h
Oral
48 h
LD50
> 175.56 µg/Bee
LD50
> 340.4 µg/Bee
Nengel (1995)
EPPO Guideline 170
Study no.
B-94137/01- BLEU
GLP
Klimisch score: 1
Disk 5
00000188
Tornier (1994)
EPPO Guideline 170
Study no.
B-958264
Non-GLP
Klimisch score: 3
Disk 5
00000187 a Results are reported on the basis of nominal concentrations except where otherwise stated, Standard
test guidelines provide for reporting of results on a nominal basis where measurements indicate the test
substance remains within 20% of nominal. b 95% confidence intervals are stated where available
cUnless otherwise stated, the tests were conducted according to the test method identified
Conclusion
Based on the information (Table A2.12), flufenacet does not trigger the threshold for
toxicity to terrestrial invertebrates.
Table A2.12A: Summary of terrestrial invertebrate toxicity data for Firebird.
Test species
Test type
&
duration
Test resultsa, b
Test method
c
[reference number]
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 88 of 140
Honey bee
Apis mellifera
48 h Oral
48 h Contact
72 h
Respiration
LD50
> 198 µg/bee
(40% mortality observed)
LD50
> 200 µg/bee
(0% mortality observed)
LD50
> 0.6 kg/ha.in 200 L/ha
(0% mortality observed)
Heimbach (1996)
EPPO 170
BBA VI 23-1
Report No.
95 10 48 508
GLP
Klimisch score: 1
Disk 14
00000558
Honey bee
Apis mellifera
48 h Oral
48 h Contact
LD50
> 199 µg/bee
(0% mortality observed)
LD50
> 200 µg/bee
(0% mortality observed)
Hennig-Pusch (1996)
EPPO 170
Report No.
95 10 48 508
GLP
Klimisch score: 1
Disk 14
00000559 a Results are reported on the basis of nominal concentrations except where otherwise stated, Standard
test guidelines provide for reporting of results on a nominal basis where measurements indicate the test
substance remains within 20% of nominal. b 95% confidence intervals are stated where available
cUnless otherwise stated, the tests were conducted according to the test method identified
Conclusion
Based on the information (Table A2.12A), Firebird does not trigger the threshold for
toxicity to terrestrial invertebrates.
Table A2.13: Summary of ecotoxicity classifications for flufenacet, diflufenican
and Firebird
Sub-class Flufenacet Diflufenican Firebird 9.1 Aquatic ecotoxicity 9.1A highly
ecotoxic to the
aquatic
environment
9.1A highly
ecotoxic to the
aquatic
environment
9.1A highly ecotoxic to
the aquatic environment
9.2 Soil ecotoxicity 9.2A highly
ecotoxic to the
soil environment
9.2C harmful
to the soil
environment
9.2A highly ecotoxic to
the soil environment
9.3 Terrestrial vertebrate
ecotoxicity
9.3C harmful
to terrestrial
vertebrates
No Data 9.3C harmful
to terrestrial
vertebrates
Note: the Agency’s classifications differ from the applicant’s due to plant toxicity and
terrestrial vertebrate classifications generated from both flufenacet and formulation
(Firebird) data.
References
ERMA New Zealand 2008a. User Guide to HSNO Thresholds and Classifications.
ERMA New Zealand, Wellington.
European Union 2006. Regulation (EC) No 1907/2006 of the European Parliament
and of the Council of 18 December 2006 concerning the Registration, Evaluation,
Authorisation and Restriction of Chemicals (REACH), establishing a European
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 89 of 140
Chemicals Agency, amending Directive 1999/45/EC and repealing Council
Regulation (EEC) No 793/93 and Commission Regulation (EC) No 1488/94 as well as
Council Directive 76/769/EEC and Commission Directives 91/155/EEC, 93/67/EEC,
93/105/EC and 2000/21/EC. http://reach.jrc.it/
Klimisch, HJ, Andreae, E, Tillman, U 1997. A systematic approach for evaluating the
quality of experimental and ecotoxicological data. Regulatory Toxicology and
Pharmacology 25: 1–5.
OECD 1990. Manual for Investigation of HPV Chemicals.
http://www.oecd.org/document/21/0,3343,en_2649_34379_1939669_1_1_1_1,00.htm
l Retrieved 23 January 2008.
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 90 of 140
APPENDIX 3: RISK ASSESSMENT
Introduction
Quantitative risk assessments have been carried out to evaluate the level of risk to operators,
bystanders and the environment arising from the use of Firebird.
Qualitative assessments have been undertaken for all other stages of the lifecycle. In these
cases, the level of risk has been evaluated on the basis of the magnitude and likelihood of
adverse effects occurring to people or the environment (see Appendix 6 for a description of
the scales used for qualitative assessment).
Human health risk assessment
Assessment of risks to human health - manufacture
The Agency has qualitatively assessed the risks of Firebird to human health and safety during
manufacture and considers the risks to be negligible.
This assessment is based on the following considerations:
The Agency considers that, while Firebird has the potential to cause a major adverse
effect through its oral toxicity, workers handling the substance will be aware of the
hazards and the measures that need to be undertaken to ensure their own safety and
will not ingest sufficient substance to result in a major adverse effect. Even a
moderate effect is highly improbable.
The Agency considers that it is highly improbable that workers will suffer contact
sensitisation from exposure to Firebird, given requirements for personal protective
equipment (PPE), and compliance with HSNO information provisions (e.g. labels,
advertising, Safety Data Sheets (SDS)). The magnitude of skin sensitisation is
considered minor to moderate, based on the sensitivity of the exposed parties.
Quantitative assessment of the chronic risks to human health associated with exposure
to Firebird during use, indicated an acceptable level of risk as long as PPE was used.
As workers involved in manufacture of Firebird will be required to comply with the
requirements for PPE as well as comply with Department of Labour (DoL)
requirements for health and safety, the Agency considers the level of risk to workers
to be negligible.
The Agency considers the risk of repeated exposure to bystanders during manufacture
is sufficiently remote that it is not necessary to address, given that the general public
are normally excluded from manufacturing facilities.
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 91 of 140
Assessment of risks to human health – importation, storage and transport
The Agency has qualitatively assessed the risk of Firebird to human health and safety during
importation, transportation and storage and considers the risks to be negligible.
This assessment is based on the following considerations:
Workers and bystanders could only be exposed to the substance during transport and
storage in isolated incidents where spillage occurs.
In these circumstances, the Agency considers it highly improbable that workers or
bystanders will ingest sufficient Firebird to result in a moderate adverse effect.
The Agency considers that it is highly improbable that a spillage of Firebird will
occur during importation, transport or storage and workers or bystanders will suffer
contact sensitisation, given adherence to the HSNO controls (e.g. packaging,
identification and emergency management) and the Land Transport Rule 45001, Civil
Aviation Act 1990 and Maritime Transport Act 1994 (as applicable). The magnitude
of skin sensitisation is considered minor to moderate, based on the sensitivity of the
exposed parties.
The Agency considers the risk of target organ effects from Firebird during
importation, transport or storage to be sufficiently remote that it is not necessary to
address, given that exposure could only occur in isolated spillage incidents.
Assessment of risks to human health - disposal
The Agency has qualitatively assessed the risk to human health and safety during disposal of
Firebird, and considers the risks to the health and safety of people to be negligible.
This assessment is based on the following considerations:
If Firebird is disposed of by means other than use, this will be in accordance with the
requirements of the Hazardous Substances (Disposal) Regulations 2001 and the
Resource Management Act 1991.
The Agency considers that it is highly improbable that users or bystanders could
inadvertently ingest sufficient Firebird during disposal to result in an acute moderate
effect, given that Firebird will generally be disposed of by use or in accordance with
HSNO controls for disposal (e.g. disposal information requirements on labels and
SDS).
The Agency considers that it is highly improbable that workers will suffer contact
sensitisation from exposure to Firebird during disposal, given that Firebird will
generally be disposed of by use. The Agency considers it even less likely that workers
or bystanders will suffer contact sensitisation from exposure to Firebird, disposed of
by means other than use. The magnitude of skin sensitisation is considered minor to
moderate, based on the sensitivity of the exposed parties.
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 92 of 140
The Agency notes that a quantitative assessment of the chronic risks to operators
associated with exposure to Firebird during use indicated an acceptable level even if
PPE was not used. This assessment includes the possibility of prolonged and repeated
exposure to Firebird during use. The Agency considers it is even less likely that users
or bystanders could be repeatedly exposed to Firebird during disposal to such an
extent that target organ toxicity effects occur and therefore considers the chronic risk
to human health during disposal of Firebird to be negligible.
Assessment of risks to human health - use
The Agency has qualitatively assessed the acute risks of Firebird to human health and safety
during use and considers the risks to be negligible.
This assessment is based on the following considerations:
The Agency considers that it is highly improbable that users or bystanders could
inadvertently ingest sufficient Firebird during use to result in an acute moderate
effect, given that Firebird will be used in accordance with HSNO controls (e.g. PPE,
approved handlers).
The Agency considers that it is highly improbable that users will suffer contact
sensitisation from Firebird, given the HSNO requirements for PPE, approved handlers
and provision of hazard and precautionary information on the product label. The
magnitude of skin sensitisation is considered minor to moderate, based on the
sensitivity of the exposed parties.
Operator exposure assessment
The Agency has undertaken an assessment of risks to operator health using the United
Kingdom Pesticide Safety Directorate’s interpretation of the German BBA Model to estimate
operator exposure to the active ingredients flufenacet and diflufenican, during the use of
Firebird. This model estimates the exposure of workers to a pesticide during mixing, loading
and spray application, in mg/kg person/day (http://www.pesticides.gov.uk/index.htm). The
derived values consider both dermal and inhalation exposure routes.
The BBA model can use either the geometric mean or the 95th percentile model - the
geometric mean was used for assessing Firebird. The BBA model provides for a range of
different spray applications (tractor-mounted/trailed sprayers and hand-held sprayers) and
formulation types (liquid, wettable powder and wettable granule). Additionally, the BBA
model also allows flexibility to vary protective clothing (hands, head and body and respiratory
protection).
Five different scenarios were modelled for each of the two active ingredients, as shown in
Table A3.6.
The applicant has indicated that Firebird will be applied at a maximum rate of 300 mL
product/ha.(equivalent to 126.3 g/ha. flufenacet; 61.9g/ha. diflufenican)
The Agency has used this maximum application rate for conducting an operator exposure
assessment.
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 93 of 140
The applicant has provided modelling to estimate operators exposure to Firebird, using the
BBA model; however, this modelling is based on an application rate of 600 mL/ha. i.e. twice
the rate proposed for Firebird.
Table A3.6 details the estimated exposure for each scenario modelled. The following points
have been taken into account for the purposes of calculating the estimated exposure. For each
model only the conservative scenario as described below, has been addressed:
the concentration of active ingredients in Firebird (400g/L flufenacet and 200 g/L
diflufenican)
0.3 L of Firebird is applied per hectare
the substance is sprayed using a tractor mounted/trailed broadcast sprayer with
hydraulic nozzles;
a work rate of 20 hectares per day (the default value for boom sprayers used in the
German BBA model) is used in the absence of specific work rate data in the New
Zealand context;
a 10% percutaneous absorption value was used (the default value for the German BBA
model, and the value which has been used in the applicant’s modeling) in the absence
of specific value for flufenacet; and
the bodyweight for operators is set at 70 kg.
Table A3.6a: Estimated exposure to flufenacet for 70 kg operator under five different
exposure scenarios as predicted from the UK PSDs interpretation of the BBA Model
Exposure scenario Estimated operator Exposure (mg/kg
bw/day)
No personal protective clothing and
equipment (PPE) during mixing, loading
and application
0.016
Gloves only during mixing and loading 0.008
Gloves only during application 0.015
Full PPE during mixing, loading and
application (excluding respirator)
0.00046
Full PPE during mixing, loading and
application (including respirator)
0.00040
Table A3.6b: Estimated exposure to diflufenican for 70 kg operator under five different
exposure scenarios as predicted from the UK PSDs interpretation of the BBA Model
Exposure scenario Estimated operator Exposure (mg/kg
bw/day)
No personal protective clothing and
equipment (PPE) during mixing, loading
and application
0.0079
Gloves only during mixing and loading 0.0037
Gloves only during application 0.0072
Full PPE during mixing, loading and
application (excluding respirator)
0.00022
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 94 of 140
Full PPE during mixing, loading and
application (including respirator)
0.00020
Calculation of Acceptable Operator Exposure Level (AOEL)
The toxicological endpoint for assessment of occupational (worker) and bystander risks is the
AOEL (Acceptable Operator Exposure Level). The AOEL is the maximum daily dose
considered to be without adverse health effect for operators, workers and bystanders. It is
based on the most appropriate NOAEL/NOEL from relevant studies and is calculated by
dividing the NOAEL/NOEL by one or more uncertainty (safety) factors selected on the basis
of the extent and quality of the available data, the species for which data are available and the
nature of the effects observed.
AOEL = NOAEL (most relevant study)
Safety Factors
Selection of NOAEL:
With respect to assigning an appropriate NOAEL to calculate the AOEL, the Agency has
taken the likely duration and frequency of worker exposure into consideration. The Agency
has applied a NOAEL of 1.67 mg/kg bw/day for flufenacet. This value was obtained from the
13 week sub-chronic toxicity study in the beagle. Selection of this value as the NOEL for
flufenacet is indicated in the EFSA Draft Assessment Report (2006).
In calculating the AOEL, the Agency has used a combined safety factor of 100 to account for
intra- and interspecies variation. In the absence of specific oral absorption data for flufenacet,
the Agency has assumed 100% oral absorption.
AOEL [flufenacet] = 1.67 mg/kg bw/day x 100% = 0.017 mg/kg bw/day.
100
The active ingredient diflufenican is currently approved in several formulations. The Agency
notes that the substance has previously undergone full Part 5 assessment (refer to application
HSR04066) and an AOEL of 1 mg/kg bw/day was established. The Agency notes that this
AOEL is significantly greater than that which has been established by the EFSA (0.12 mg/kg
bw/day). The Agency has applied the more conservative AOEL, established by ESFA, to
calculate the risk quotients given below for diflufenican. The AOEL was based on highest
NOAEL of 1.6 – 1.9 mg/kg bw/day for 13 week study in rats (rounded to 2 mg/kg bw/day)
with the use of an uncertainty factor of 100 and using the lower absorption percentage of 58%
in male. (PSD, 2005).
AOEL [diflufenican] = 2.00 mg/kg bw/day x 0.58 = 0.0116 mg/kg bw/day.
100
= 0.012 mg/kg bw/day
Calculation of Risk Quotients and operator risk assessment
To assess the risks to operators the Agency has divided the estimated exposure values as
calculated from the exposure modeling by the AOEL to derive a risk quotient (RQ) for each
exposure scenario modeled (Tables A3.7a and A3.7b). A 10% percutaneous absorption value
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 95 of 140
was used (the default value for the German BBA model, and the value which has been used in
the applicant’s modeling) in the absence of specific value for diflufenican. (The other model
parameters are given above.)
RQ = Estimated Operator (or Bystander) Exposure
AOEL
A RQ > 1 indicates the likelihood of a risk to the operator (or bystander).
Table A3.7a: Risk quotients determined for each exposure scenario for flufenacet.
Exposure scenario Estimated operator
exposure (mg/kg
bw/day)
RQ
No PPE during mixing, loading and application 0.016 0.94
Gloves only during mixing and loading 0.008 0.47
Gloves only during application 0.015 0.88
Full PPE during mixing, loading and
application (excluding respirator)
0.00046 0.027
Full PPE during mixing, loading and
application (including respirator)
0.00040 0.024
Table A3.7b: Risk quotients determined for each exposure scenario for diflufenican.
Exposure scenario Estimated operator
exposure (mg/kg
bw/day)
RQ
No PPE during mixing, loading and application 0.0079 0.66
Gloves only during mixing and loading 0.0037 0.31
Gloves only during application 0.0072 0.605
Full PPE during mixing, loading and
application (excluding respirator)
0.00022 0.0018
Full PPE during mixing, loading and
application (including respirator)
0.00020 0.0016
The Agency notes that in all exposure situations modelled, risks to operators are considered to
be at acceptable levels (RQ < 1) for both active ingredients, although for flufenacet the RQ
estimate for use without PPE is close to 1.0. The Agency considers that, while the ‘no PPE’
exposure model leads to an acceptable level of risk, it is appropriate to retain requirements for
PPE since the use of PPE when handling agrichemicals is good practice. The Agency notes
that the HSNO PPE requirements are not prescriptive allowing users to select an appropriate
level of PPE.
The applicant has indicated that Firebird is intended to be applied using ground-based
methods only, therefore any human health risks associated with aerial application of the
substance have not been assessed.
Exposure for re-entry workers has not been estimated because even with no PPE operator
exposures do not indicate a risk for operators. Re-entry workers are not exposed to mixing
and loading operations so their exposures are likely to be lower that those of operators. The
Agency also notes that the nature of the use for Firebird (for winter cereals early in the growth
cycle) is an application type not likely to be associated with re-entry activity.
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 96 of 140
Public health exposure and risk assessment
The main potential source of exposure to the general public from Firebird (other than via food
residues which will be considered as part of the registration of this substance under the
Agricultural Compounds and Veterinary Medicines (ACVM) Act 1997) is via spray drift.
Given the results of the modelling as outlined above, the Agency considers that the use of
Firebird will not pose a significant risk to bystanders. The modeling above suggests that
bystanders may be at risk from the application of Firebird as they will not be wearing PPE,
however, the Agency notes that bystanders are not exposure during mixing loading and are
likely to be further away from the application area than operators. Therefore, the risk to
bystanders is estimated as acceptable for both active ingredients.
Environmental exposure and risk assessment
Assessment of environmental risks – manufacture/packing, importation, transport and
storage
The Agency has qualitatively assessed the risks to the environment of Firebird during
manufacture, importation, transportation and storage and considers the risks to be negligible.
This assessment is based on the following considerations:
The magnitude of adverse effects on the environment from a spillage during
manufacture, importation, transport or storage are considered by the Agency to be
moderate, as although the substance is toxic to the aquatic and terrestrial
environments, and harmful to terrestrial vertebrates, any spill would involve small
quantities which would lead to localised effects only.
The Agency also considers such an event to be highly improbable given adherence to
the HSNO controls (e.g. packaging, identification and emergency management) and
the Land Transport Rule 45001, Civil Aviation Act 1990 and Maritime Transport Act
1994 (as applicable).
Assessment of environmental risks – disposal
The Agency has qualitatively assessed the risks to the environment of disposal of Firebird and
considers the risks to be negligible.
This assessment is based on the following considerations:
Firebird will generally be disposed of by normal use as a herbicide.
If Firebird is disposed of by means other than use, this will be in accordance with the
requirements of the Hazardous Substances (Disposal) Regulations 2001 and the
Resource Management Act 1991. The Agency considers the likelihood of adverse
effects to the environment arising from disposal to be highly improbable and the
magnitude of such effects minor.
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 97 of 140
Assessment of environmental risks - use
For Class 9 substances, irrespective of the intrinsic hazard classification, the ecological risk
can be assessed for a substance by calculating a risk quotient based on an estimated exposure
concentration. Such calculations incorporate toxicity values, exposure scenarios (including
spray drift, application rates and frequencies), and the half lives of the component(s) in soil
and water. The calculations provide an Estimated Environmental Concentration (EEC) which,
when divided by the LC50 or EC50, gives a risk quotient (RQ).
Acute RQ = EECshort term Chronic RQ = EEClong term
LC50 or EC50 NOEC
If the RQ exceeds a predefined level of concern, this suggests that it may be appropriate to
refine the assessment or to apply the approved handler control (AH) control and/or other
controls to ensure that appropriate matters are taken into account to minimize off-site
movement of the substance. Conversely, if a worst-case scenario is used, and the level of
concern is not exceeded, then in terms of the environment, there is a presumption of low risk
which is able to be adequately managed by such things as label statements (warnings,
disposal). The AH control can then be removed on a selective basis.
Levels of concern (LOC) developed by the USEPA (Urban and Cook 1986) and adopted by
the Agency, to determine whether a substance poses an environmental risk are provided in
Table A3.1.
Table A3.1: Levels of concern as adopted by the Agency.
Endpoint LOC Presumption
Aquatic (fish, invertebrates)
Acute RQ≥ 0.5 High acute risk
Acute RQ 0.1-0.5 Risk can be mitigated through restricted use
Acute RQ< 0.1 Low risk
Chronic RQ≥ 1 High chronic risk
Plants (aquatic and terrestrial)
Acute RQ≥ 1 High acute risk
Birds (EU Guideline, 2008)
Acute dietary
TER ≤
10 High acute risk
Chronic TER ≤ 5 High chronic risk
The Toxicity Exposure Ratios (TER) values are compared with assessment factors (trigger
values, levels of concern) which according EFSA (2008) are < 10 for the acute and short-term
scale and < 5 for the long-term scale. If either of these triggers is met imposition of controls to
reduce exposure or further steps to improve the risk assessment should be considered.
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 98 of 140
Aquatic risk - Flufenacet
Assessment of Expected Environmental Concentration
The Agency has used the Generic Estimated Environmental Concentration Model v2
(GENEEC2) surface water exposure model (USEPA 2001) to estimate the EEC of flufenacet
in surface water which may potentially arise as a result of spray drift and surface runoff from
the applicant’s proposed New Zealand use pattern.
The parameters used in the GENEEC2 modelling are listed in Table A3.2 and represent the
recommended use on winter wheat (highest rate) as a conservative estimate.
Table A3.2: Input parameters for GENEEC2 analysis. Flufenacet Reference
Application rate 300 mL (0.1263 g) Product label
Application frequency Once per season Product label
Application interval NA
Kd * 3.1 Kelley and Wood (1992)
Report No. 103903
GLP, Klimisch score: 1
Disk 5, 00000136
Aerobic soil DT50** 45.51 days Pangilinan and Smith (1994).
Report No. 106408
GLP, Klimisch score: 1
Disk 4, 00000119
Pangilinan and Smith (1994).
Report No. 106420
GLP, Klimisch score: 1
Disk 4, 00000120
Kelley et al. (1995)
Report No. 106664
GLP, Klimisch score: 1
Disk 4, 00000123
Pesticide wetted in? No Product label
Methods of application Ground-based only Product-label
‘No spray’ zone NA
Water solubility 56 mg/L Krohn (1992) Report No. 14 410 0746
GLP, Klimisch score: 1
Disk 2, 00000016
Aerobic aquatic DT50*** 84.6 days Kelley et al. (1995)
Report No. 106928
GLP, Klimisch score: 1
Disk 5, 00000151
Aqueous photolysis DT50 Stable Kasper and Shadrick (1995)
Report No. 106246
GLP, Klimisch score: 1
Disk 2, 00000020
*The lowest of the Kd values measured in a non-sand textured soil (i.e. not sand, coarse sand,
fine sand, loamy sand) (USEPA, 2001).
**The soil DT50 value of 45.51 for flufenacet follows the GENEEC2 calculation of the upper
90% confidence limit on the mean value (n≥2) of the five aerobic laboratory values measured
at 20°C (USEPA, 2001).
***Longest value taken in accordance with GENEEC2 guidance document (USEPA, 2001).
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 99 of 140
Output from the GENEEC2 model. RUN No. 1 FOR flufenacet ON Winter whe * INPUT VALUES *
--------------------------------------------------------------------
RATE (#/AC) No.APPS & SOIL SOLUBIL APPL TYPE NO-SPRAY INCORP
ONE(MULT) INTERVAL Kd (PPM ) (%DRIFT) ZONE(FT) (IN)
--------------------------------------------------------------------
.112( .112) 1 1 3.1 56.0 GRHIFI( 6.6) .0 .0
FIELD AND STANDARD POND HALFLIFE VALUES (DAYS)
--------------------------------------------------------------------
METABOLIC DAYS UNTIL HYDROLYSIS PHOTOLYSIS METABOLIC COMBINED
(FIELD) RAIN/RUNOFF (POND) (POND-EFF) (POND) (POND)
--------------------------------------------------------------------
45.51 2 N/A .00- .00 84.60 84.60
GENERIC EECs (IN MICROGRAMS/LITER (PPB)) Version 2.0 Aug 1, 2001
--------------------------------------------------------------------
PEAK MAX 4 DAY MAX 21 DAY MAX 60 DAY MAX 90 DAY
GEEC AVG GEEC AVG GEEC AVG GEEC AVG GEEC
--------------------------------------------------------------------
4.55 4.51 4.31 3.88 3.60
The Estimated Environmental Concentration (EEC) for flufenacet as estimated by GENEEC2
are:
Peak EEC: 4.55 µg/L 0.00455 mg/L
Chronic EEC (21 days): 4.31 µg/L 0.00431 mg/L
Table A3.3: Aquatic ecotoxicity endpoints to be used in risk assessment
(formulation test data was used where possible). Exposure Species LC50 or EC50
(mg formulation/L)
LC50 or EC50
(mg a.i./L)
Acute Onchorynchus mykiss 12.3 4.18
Daphnia magna > 100 > 33.95
Selenastrum capricornutum 0.00663 (ErC50) 0.00225 (ErC50)
Chronic Onchorynchus mykiss* 0.18
Daphnia magna* 3.26
* data from active ingredient
Assessment of acute risk
The Estimated Environmental Concentration (EEC) for flufenacet as estimated by GENEEC2
are shown in Table 3.4, along with the aquatic data for flufenacet for the most sensitive
species tested (further details on these toxicity data are included in Table A2.7).
Table A3.4: Acute risk quotients derived from the GENEEC2 model and toxicity data.
Peak EEC from
GENEEC2 (mg/L)
LC50 or EC50
(mg/L)
RQ (Acute)
EEC/ LC50 or EC50
Fish 0.00455 4.18 0.001
Crustacea >33.95 0.0001
Algae 0.00225 2.022
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 100 of 140
When compared against the relevant acute risk quotients (Table A3.1), the acute RQs derived
from the GENEEC2 modelling for flufenacet indicate the following:
For fish and crustacean: the acute risk is low
For algae: the acute risk is high
Assessment of chronic risk
Table A3.5: Chronic risk quotients derived from the GENEEC2 model and chronic
aquatic toxicity data.
21-day EEC from
GENEEC2 (mg/L)
NOEC
(mg/L)
RQ (Chronic)
EEC/ NOEC
Fish 0.00431 0.18 0.024
Crustacea 3.26 0.001
When compared against the relevant chronic risk quotients (Table A3.1), the chronic RQs
derived from the GENEEC2 modelling for flufenacet indicate the following:
For fish and crustacean: the chronic risk is low
For algae: the levels of concern to estimate chronic risks to algae are not
currently defined
Based on the acute RQs for algae, the Agency considers it is appropriate to retain the
approved handler controls for Firebird when it is used in a wide dispersive manner, or by a
commercial contractor. Further, the Agency considers that the application rate proposed by
the applicant and used in the modelling should be set as a maximum application rate.
Avian Toxicity - Flufenacet
The avian toxicity assessment was performed according to “Risk Assessment to Birds and
Mammals (EFSA 2008)”.
For practical reasons it is useful to conduct the risk assessment in two stages. The screening
step contains simple procedures for the calculation of the TERs (Toxicity Exposure Ratios).
These procedures involve standard scenarios and default values for the exposure estimate
which can be performed with a low input of effort. The tier 1 standard scenarios include
intake via feed and represent a realistic worst case assessment where the exposure scenarios
are selected to reflect a situation where the total daily feed is contaminated. The aim is to
exclude, with sufficient certainty, false negatives (= risk remains undetected).
Acute toxicity
Screening step
Step 1 Identify which of the indicator species listed in Table I.1 (Annex I) is relevant to the crop.
Step 2 Calculate the daily dietary dose (DDD) for a single application by multiplying the shortcut value
presented in Table I.1 with the application rate in kg/ha.
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 101 of 140
DDD single application = application rate [kg/ha] x short cut value
Step 3 Multiply the daily dietary dose for a single application with an appropriate multiple application
factor for 90th percentile residue data (MAF90) when the substance is applied two or more times.
Or calculate a specific MAF90 according to Appendix 15 for non-standard application intervals.
DDD multiple applications = DDD single application x MAF90
Step 4 Take the appropriate LD50 (mg/kg bw/d) for birds.
Step 5 Calculate the toxicity-exposure-ratio
TER = LD50 / DDD
Step 6 Compare the TER to the respective trigger value.
TER ≥ 10 No refinement required
TER < 10 Go to first-tier risk assessment (step 7)
Table A3.6: Acute avian risk assessment – screening step.
Crop1
Indicator
Species2
Short-cut
value3
(90th percentile RUD)
LD504
Application
rate (kg/ha)
MAF905
TER6
Trigger
value
Cereal Small
omnivorous
bird
158.8 1833.03 0.1263 1 91.4 <10
1
Crop type Table I.1 (Annex 1) and Appendix 10 2
Species type Table I.1 (Annex 1) and Appendix 10 3
Residue Unit Dose (90th
percentile) Table I.1 (Annex 1) 4 Geometric mean if multiple species tested
5 Multiple application factor (90
th percentile) Table 11 and Appendix 15
6 Toxicity-exposure ratio = LD50 / Estimated environmental concentration
Flufenacet, as a component of Firebird, applied according to the manufacturer’s instructions is
unlikely to be acutely toxic to birds. The first-tier risk assessment is not necessary.
Chronic toxicity
Steps to determine the reproductive risk to birds It should be noted that the initial steps are based on worst-case assumptions and should be used to
identify those substances and associated uses that do not pose a risk to birds and for which hence
no further reproductive risk assessment is required.
Step 1
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 102 of 140
Determine if breeding birds will be exposed to either the active substance or the associated
product.
Step 2 If exposure is possible, the lowest NOAEL from the avian reproduction study/studies should be
determined. It should be noted that the endpoints from the current guidelines are presented as ppm
diet or mg a.s./kg diet. Therefore, it is necessary to convert the endpoints to daily doses, i.e. mg
a.s./kg bw/d. In the first instance a generic factor of 0.1 can be used and applied to the ppm or mg
a.s./kg food endpoint.
Step 3 Identify the appropriate indicator species and mean shortcut value for the crop under assessment
from Table I.1 in Annex 1 and multiply this by the application rate in kg a.s./ha. If multiple
applications are to be made, then the appropriate ‘multiple application factor’ or MAFm should be
used.
DDD = application rate x short-cut value x MAFm
Step 4 Compare the lowest NOAEL to the DDD generated.
TER ≥ 5 No refinement required
TER< 5 Go to phase-specific approach (step 5)
Table A3.7: Chronic avian risk assessment – screening step.
Crop1
Indicator
Species2
Short-cut
value3
(Mean RUD)
NOAEL4
mg ai/kg bw/d Application
rate (kg/ha)
MAFm5
TER6
Trigger
value
Cereal Small
omnivorous
bird
64.8 26.13 0.1263 1 3.19 <5
1
Crop type Table I.1 (Annex 1) and Appendix 10 2
Species type Table I.1 (Annex 1) and Appendix 10 3
Residue Unit Dose (Mean) Table I.1 (Annex 1) 4 Most sensitive reproductive parameter (Geometric mean if multiple species tested)
5 Multiple application factor (Mean) Table 11 and Appendix 15
6 Toxicity-exposure ratio = LD50 / Estimated environmental concentration
Based upon the chronic toxicity screening step, flufenacet as a component of Firebird applied
according to the manufacturer’s instructions, may be chronically toxic to birds. The risk
assessment requires the refinement of a tier 1 assessment.
Chronic avian risk assessment – Refining step (Tier 1)
Step 5
In the phase-specific approach the breeding cycle of birds is divided into five phases,
namely:
1) pair formation and establishing site selection;
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 103 of 140
2) copulation and egg laying ranging from 5 days pre-laying through to the end of the egg-laying
period;
3) incubation and hatching;
4) juvenile growth and survival until fledging; and
5) post-fledging.
Extract the following toxicity endpoints from the avian reproduction studies:
NOAEL for the number of eggs laid per hen;
NOAEL for mean eggshell thickness;
NOAEL for the proportion of fertile eggs per eggs set per hen or number
viable embryos over number of eggs set;
NOAEL for the proportion of hatching per fertile eggs per hen or percent
hatching of viable embryos;
NOAEL for the proportion of 14-day old juveniles per number of hatchlings;
NOAEL for 14-day juvenile weights per hen.
If more than one avian reproduction study is available, then the above endpoints should be
extracted for each study.
Step 6 Once the above endpoints have been extracted then the endpoints need to be converted to daily
dose using the mean value for food consumption over the whole study and average body weight
over the duration of the study at the NOAEL.
Step 7 If more than one study is available, then the datasets can be either merged or the geometric mean
of the endpoints used.
Step 8 In addition to the above reproductive endpoints, it is also necessary to determine an endpoint to
assess the risk to the phases relevant to chick survival. In order to calculate this endpoint, the LD50
value used in the acute assessment (see section 3.1) should be divided by 10.
Step 9 In order to address uncertainty about the appropriate exposure scenario for the phase-specific
approach, two exposure scenarios are assessed, namely:
1) A scenario where the residue on treated food is assumed to be based on a 1- to 3-day
Period;
2) A scenario where the residue on treated food is assumed to be based on a 21-day period.
For the first scenario, it is assumed that a short exposure could lead to reproductive effects,
whereas in the second scenario it is assumed that long-term exposure could lead to reproductive
effects.
Identify the appropriate crop and generic focal species in Tables I.3 (Annex I). Where more
than one generic focal species is highlighted, the one that is relevant in terms of time of
application or growth stage should be selected. Where there is more than one generic focal species
in terms of timing etc, then it is proposed that risk assessment should be carried out with all
relevant generic focal species and then refined as necessary.
Step 10
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 104 of 140
Once an appropriate generic focal species has been selected, then the daily dietary dose (DDD)
based on 1-, 2-, 3- and 21-day exposure should be determined. The 1-day DDD uses the initial
exposure estimate. In order to calculate the 2-, 3- and 21-d DDDs it is necessary to multiply by a
time-weighted average (TWA) factor to the initial exposure. For 2 days, the factor is 0.93; for 3
days 0.90 and for 21 days 0.53.
DDD = application x short-cut x TWA x MAFm
Step 11 In order to have an exposure estimate for chick survival stage, it is necessary to calculate a 3-day
DDD assuming a shortcut value of 22.7 for chicks fed foliar dwelling insects, and 3.8 for those
fed ground dwelling insects. In the first instance both scenarios should be assessed, unless it can
be justified that one scenario is not relevant to the proposed use.
Step 12 Compare the above DDD to the relevant phase-specific NOAEL.
Step 13 Interpret the risk assessment following the below table.
Scenario Assessment outcome
1 to 3-day ETE
(Effects are based
on short-term
exposure)
TER < 5 TER < 5 TER < 5
21-day ETE
scenarios (i.e.,
effects are based on
long-term
exposure)
TER ≥ 5 TER ≥ 5 TER < 5
Next steps No further
refinement
required.
Further refinement is
required. The outcome
of the risk assessment
indicates that one
possible refinement
step is to try to
determine if the effects
are the result of short-
term exposure.
Further refinement is required.
However, the outcomes of the risk
assessment indicates that little will
be gained by additional effects
data and hence trying to determine
if the effects are the result of short-
term exposure. It is recommended
that refinements should
concentrate on refining the
exposure as well as the potential
consequences of effects.
Table A3.8: Summary of values applied in the phase specific approach. Short-cut
value (Mean RUD)
Lark
Short-cut
value (Mean RUD)
Goose
Application
rate (kg/ha)
MAFm TWA
2 days
TWA
3 days
TWA
21 days
Chick
short-cut
value
3 days
Chick
short-cut
value
21 days
10.9 26.7 0.1263 1 0.93 0.90 0.53 3.8 22.7
Table A3.9: Summary of toxicity values applied in the phase specific approach.
LD50 NOAEL1 NOAEL
2 NOAEL
3 NOAEL
4 NOAEL
5 NOAEL
6
Geometric 1833.03 88.70 146.49 88.70 26.13 146.49 58.92
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 105 of 140
Mean
NOAEL1 number of eggs laid per hen
NOAEL2
mean egg shell thickness
NOAEL3
proportion of viable eggs set per hen
NOAEL4
proportion of hatchling per viable eggs per hen
NOAEL5
proportion of 14 day old juveniles per number of hatchlings per hen
NOAEL6
14 day juvenile weights per hen
Note: Geometric mean of data used (where more than one study available).
Table A3.10: Pair formation and establishing site selection.
Short term Long term
LD50/10 and 1 day DDD LD50/10 and 21 day TWA DDD
Lark TER 133.15 251.23
Goose TER 54.36 102.56
Trigger level < 5
Table A3.11: Copulation and egg laying.
Short term Long term
NOAEL1 and 1
day DDD
NOAEL2 and 1
day DDD
NOAEL1 and 21
day TWA DDD
NOAEL2 and 21
day TWA DDD
Lark
TER
64.43 106.41 121.57 200.77
Goose
TER
26.30 43.43 49.63 81.96
Trigger
level
< 5
Table A3.12: Incubation and hatching.
Short term Long term
LD50/10
and 1 day
DDD
NOAEL3
and 1 day
DDD
NOAEL4
and 1 day
DDD
LD50/10
and 21
day TWA
DDD
NOAEL3
and 21
day TWA
DDD
NOAEL4
and 21
day TWA
DDD
Lark
TER
133.15 64.43 21.09 251.23 121.57 35.81
Goose
TER
54.36 26.30 8.61 102.56 49.63 14.62
Trigger
level
< 5
Table A3.13: Juvenile growth and survival. Short term Long term
LD50/10
and 2
day
TWA
DDD
LD50/10
and 1
day
DDD Chick
ground
dwelling
LD50/10
and 1
day
DDD Chick
foliar
dwelling
NOAEL5
and 3
day
TWA
DDD
LD50/10
and 21
day
TWA
DDD
LD50/10
and 21
day
DDD Chick
ground
dwelling
LD50/10
and 21
day
DDD Chick
foliar
dwelling
NOAEL5
and 21
day
TWA
DDD
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 106 of 140
insects
value insects
value insects
value insects
value
Lark
TER
143.17 381.93 63.94 118.23 251.23 720.62 120.63 200.77
Goose
TER
58.45 381.93 63.94 48.27 102.56 720.62 120.63 81.96
Trigger
level
< 5
Table A3.14: Post-fledgling survival.
Short term Long term
LD50/10 and
1 day DDD Chick ground
dwelling insects
value
LD50/10
and 1 day
DDD Chick foliar
dwelling
insects value
NOAEL6
and 3 day
DDD
LD50/10
and 21
day TWA
DDD Chick ground
dwelling
insects value
LD50/10
and 21
day TWA
DDD Chick foliar
dwelling
insects value
NOAEL6
and 21
day TWA
DDD
Lark
TER
381.93 63.94 47.55 720.62 120.63 80.75
Goose
TER
381.93 63.94 19.41 720.62 120.63 32.96
Trigger
level
< 5
Based upon the refined risk assessment for chronic toxicity (Tier 1), flufenacet as a
component of Firebird applied according to the manufacturer’s instructions, is unlikely to be
chronically toxic to birds.
Aquatic risk - Diflufenican
Assessment of Expected Environmental Concentration
The Agency has used the Generic Estimated Environmental Concentration Model v2
(GENEEC2) surface water exposure model (USEPA 2001) to estimate the EEC of
diflufenican in surface water which may potentially arise as a result of spray drift and surface
runoff from the applicant’s proposed New Zealand use pattern.
The parameters used in the GENEEC2 modelling are listed in Table A3.15 and represent the
recommended use on winter wheat (highest rate) as a conservative estimate.
Table A3.15: Input parameters for GENEEC2 analysis. Diflufenican Reference
Application rate 300 mL (0.0619 g/ha) Product label
Application frequency Once per season Product label
Application interval NA
Koc * 27801 Internal database
Aerobic soil DT50** No laboratory data; field data 311-733
days (mean = 522 days)
Internal database
Pesticide wetted in? No Product label
Methods of application Ground based Product label
‘No spray’ zone No Product label
Water solubility 0.05 mg/L Internal database
Aerobic aquatic DT50*** 1044 days Model default
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 107 of 140
Aqueous photolysis DT50 0 days Model default
*if neither the Kd nor the Koc are available, use 0.35 times the Kow value (USEPA, 2001).
**Value previously used in HSR04066 assessment
***If unavailable use the default of 2 x aerobic soil input value (USEPA, 2001).
Output from the GENEEC2 model.
RUN No. 1 FOR diflufenican ON winter whe * INPUT VALUES *
--------------------------------------------------------------------
RATE (#/AC) No.APPS & SOIL SOLUBIL APPL TYPE NO-SPRAY INCORP
ONE(MULT) INTERVAL Koc (PPB ) (%DRIFT) (FT) (IN)
--------------------------------------------------------------------
.055( .055) 1 1 27801.0 50.0 GRHIFI( 6.6) .0 .0
FIELD AND STANDARD POND HALFLIFE VALUES (DAYS)
--------------------------------------------------------------------
METABOLIC DAYS UNTIL HYDROLYSIS PHOTOLYSIS METABOLIC COMBINED
(FIELD) RAIN/RUNOFF (POND) (POND-EFF) (POND) (POND)
--------------------------------------------------------------------
522.00 2 N/A .00- .00 ****** 1044.00
GENERIC EECs (IN NANOGRAMS/LITER (PPTr)) Version 2.0 Aug 1, 2001
--------------------------------------------------------------------
PEAK MAX 4 DAY MAX 21 DAY MAX 60 DAY MAX 90 DAY
GEEC AVG GEEC AVG GEEC AVG GEEC AVG GEEC
--------------------------------------------------------------------
293.25 271.41 174.55 84.80 59.21
The Estimated Environmental Concentration (EEC) for diflufenican as estimated by
GENEEC2 are:
Peak EEC 0.293 µg/L 0.000293 mg/L
Chronic EEC (21 days) 0.175 µg/L 0.000175 mg/L
Table A3.16: Aquatic ecotoxicity endpoints to be used in risk assessment
(formulation test data was used where possible). Exposure Species LC50 or EC50
(mg formulation/L)
LC50 or EC50
(mg a.i./L)
Acute Onchorynchus mykiss 12.3 >2.05
Daphnia magna > 100 > 16.63
Selenastrum capricornutum 0.00663 (ErC50) 0.00110 (ErC50)
Chronic Onchorynchus mykiss* ND
Daphnia magna* 0.03
* data from active ingredient
Assessment of acute risk
The Estimated Environmental Concentration (EEC) for diflufenican as estimated by
GENEEC2 are shown in Table 3.17, along with the aquatic data for diflufenican for the most
sensitive species tested (further details on these toxicity data are included in Table A2.7).
Table A3.17: Acute risk quotients derived from the GENEEC2 model and toxicity data.
Peak EEC from LC50 or EC50 RQ (Acute)
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 108 of 140
GENEEC2 (mg/L) (mg/L) EEC/ LC50 or EC50
Fish 0.000293 >2.05 *
Crustacea >16.63 *
Algae 0.00110 0.27
*risk to fish not calculated due to low water solubility (0.05 mg/L).
When compared against the relevant acute levels of concern (Table A3.1), the acute RQs
derived from the GENEEC2 modelling for diflufenican indicate the following:
For fish and crustacean: the acute risk is low
For algae: the acute risk is low
Assessment of chronic risk
Table A3.18: Chronic risk quotients derived from the GENEEC2 model and chronic
aquatic toxicity data.
21-day EEC from
GENEEC2 (mg/L)
NOEC
(mg/L)
RQ (Chronic)
EEC/ NOEC
Fish 0.000175 ND --
Crustacea 0.03 0.006
When compared against the relevant chronic levels of concern (Table A3.1), the chronic RQs
derived from the GENEEC2 modelling for diflufenican indicate the following:
For fish and crustacean: the chronic risk is low
For algae: the levels of concern to estimate chronic risks to algae are not
currently defined
Avian toxicity – Diflufenican
The acute and chronic avian toxicity values used in EFSA DAR (2006) were the LD50 of >
2150 mg/kg bw and the NOEC of 91.84 mg/kg bw, respectively. However, since other
formulations containing diflufenican have been assessed without assessment of avian risk
they have not been used in the evaluation of this application. These values reported by EFSA,
as well as the original studies supplied by the applicant, will be assessed by the Agency upon
a reassessment of diflufenican.
It is also noted that the assessment of avian risk carried out in the EFSA DAR (2006) was for
a use rate of diflufenican double that to be used in New Zealand. This assessment showed no
acute or chronic risks to birds.
Terrestrial risk - Firebird
Spray Drift Modelling – Phytotoxicity
Firebird is sprayed at a maximum application rate of 0.372 kg/ha.or 37.2 mg/m2.
Soil-based exposure – seedling emergence
If it assumed that the Firebird is dispersed to a depth of 0.05 m and the density of soil is 1500
kg/m3, then the 37.2 mg/m
2 Firebird will be dispersed within 75 kg of soil/m
2 giving 0.496
mg/kg.
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 109 of 140
If it is assumed that 6.6% (fine spray, high boom) of the Firebird will reach directly outside
the target area (an assumption based on GENEEC2 modeling), then the concentration of
Firebird adjacent to a sprayed field would be 0.033 mg/kg soil.
Firebird generates an EC50 value of 0.19043 kg/ha.(0.25 mg/kg, see Table A2.10A for further
details of this study) for all plant species tested. Consequently, Firebird (high boom, fine
spray) results in a risk quotient of 0.132.
Foliar exposure – vegetative vigour
Firebird is sprayed at a maximum application rate of 372 g/ha.(300 mL/ha).
If it is assumed that 6.6% (fine spray, high boom) of the Firebird will reach directly outside
the target area (an assumption based on GENEEC2 modeling), then the concentration of
Firebird adjacent to a sprayed field would be 24.55 g/ha.
Firebird generates an EC50 value of 27.75 g/ha., (see Table A2.10 for further details of this
study) for cucumber. Consequently, Firebird (fine spray, high boom) results in a risk quotient
of 0.885.
According to the risk assessment performed by the Agency, Firebird does not pose a risk to
non-target plants when applied via the high boom, fine spray scenario.
Risk to Terrestrial Invertebrates (Bees) - Firebird
Firebird is not toxic to bees, therefore no risk assessment is required.
Table 3.19: Summary of effects of exposure to flufenacet on beneficial invertebrates.
Test species Results
Test methodc
[Reference
number]
Predaceous mite
Typhlodromus pyri
Juveniles (protonymphs) of T. pyri were exposed to fresh
residues of FOE 5043 WG 60 applied on a glass substrate.
FOE 5043 WG 60 – 60% flufenacet
The three treatments were each applied as five separate
replicates.
Rate 6.0 µg a.i./sqcm.
It was found that exposure to FOE 5043 WG 60 led to 100
% juvenile mortality.
As no individuals survived the juvenile exposure to FOE
5043 WG 60, no effect on reproduction could be assessed.
Reproduction of the individuals exposed to the harmless
reference was normal.
No effect of juvenile exposure to FOE 5043 WG 60 on egg-
MITOX (1995)
lOBC-Working
Group "Pesticides
and Beneficial
Arthropods".
Report No.
MB013
GLP
Klimisch score: 1
Disk 5
00000190
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 110 of 140
Test species Results
Test methodc
[Reference
number]
hatch success has been determined, because of the 100%
juvenile mortality in the treatments with FOE 5043 WG60.
Note: One replicate of the control was not taken into
account, as the numbers of individuals that had escaped,
exceeded 20 %. This did not affect the validity of the whole
test.
Applicant summary:
As predatory mites are not beneficial species relevant to
product use (preemergence/early postemergence herbicide)
there is no risk to affect biological control capacity. Thus,
no further tests under extended laboratory or semi field
conditions have been conducted.
Parasitic Wasp
Aphidius
rhopalosiphi
A. rhopalosiphi were exposed to fresh residues of FOE
5043 WG 60 applied on a glass substrate.
FOE 5043 WG 60 – 60% flufenacet
Rate of 1 kg /ha.(200 L water).
No wasps died during the first 24 h and only three out of 30
wasps (10 %) had died after 48 h following exposure to
FOE 5043 WG 60. None of the 30 wasps died in the control
over 48 h and all of the insects in the toxic standard
treatment were dead within 24 h.
Ten females from both the FOE 5043 WG 60 and the
control treatments were then confined individually over pots
of aphid-infested barley seedlings for 24 h. The numbers of
mummies (parasitised aphids) produced was assessed 9 days
later.
The mean numbers of mummies produced was 22.6/female
in the FOE 5043 WG 60 treatment and 41.5/female in the
control (Difference 46% < 50%).
It was concluded from this study that it is unlikely that FOE
5043 WG 60 would be harmful to A. rhopalosiphi when
used under conditions of good agricultural practice.
Agrochemical
Evaluation Unit,
The University of
Southampton
(1995)
ESCORT 1994.
Report No.
BAY-94-7
GLP
Klimisch score: 1
Disk 5
00000191
Parasitic Wasp
Aphidius
rhopalosiphi
Extended Laboratory Test to Evaluate the Side-Effects
of the Herbicide FOE 5043 WG 60 on Adults of the
Parasitic Wasp when applied to barley plants.
Rate of 1 kg /ha.(200 L water).
FOE 5043 WG 60 – 60% flufenacet
Over the 48 h confinement period, no wasps died in either
the FOE 5043 WG 60 treatment or in the control. With the
toxic standard treatment, all of the wasps died within 24 h.
Behavioural observations suggested that fresh residues of
the FOE 5043 WG 60 were slightly repellent.
Agrochemical
Evaluation Unit,
The University of
Southampton
(1995)
In house protocol.
Report No.
BAY-95-3
GLP
Klimisch score: 1
Disk 5
00000195
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 111 of 140
Test species Results
Test methodc
[Reference
number]
In the fecundity assessments, the FOE 5043 WG 60
treatment did not significantly affect the numbers of
offspring produced, with 12.1 mummies produced per
female compared with 15.1 mummies per female in the
control.
Carabid beetles
Poecilus cupreus
FOE 5043 WG 60
Rate 1 kg/ha.
FOE 5043 WG 60 – 60% flufenacet
Treatment with 1 kg/ha.FOE 5043 WG 60 had no adverse
effects on the tested ground beetles.
The individual feeding activity was statistically also not
affected by the test compound.
Schmuck (1995)
BBA 23-2.1.8
Report No.
E 371 0852-6
GLP
Klimisch score: 1
Disk 5
00000192
Lycosid spiders
Pardosa agrestis
FOE 5043 WG 60
Rate 1 kg/ha.
FOE 5043 WG 60 – 60% flufenacet
The spray treatment with 1 kg/ha.FOE 5043 WG 60 did not
adversely affect the behaviour or survival of exposed
lycosid spiders.
The individual feeding activity was statistically also not
affected by the test compound. If the total number of flies
eaten per viable spider per day in the control plots is used as
a basis for comparison and assumed to be 100%, then the
feeding rates for the 1 kg/ha.FOE 5043 WG 60 treatment
were 89%.
Schmuck (1995)
BBA 23-2.1.9
Report No.
E 382 0854-0
GLP
Klimisch score: 1
Disk 5
00000193
Rove Beetles
Aleochara bilineata
FOE 5043 WG 60
Rate 1 kg/ha.
FOE 5043 WG 60 – 60% flufenacet
The observed mortality rates during the 28 day exposure
period were 3%, 0% and 55% for the control, FOE 5043
WG 60 and the reference treatment, respectively.
The reproductive performance of the exposed rove beetles
was not impeded by the test substance. If the total number
of beetles that emerged from pupae in the control chambers
(= 2428) is used as a basis for comparison and assumed to
be 100%, then the offspring emergence rates for the FOE
5043 WG 60 treatments was 99.6%.
Schmuck (1995)
IOBC/WPRS 5.2.5
Report No.
E 380 0953-8
GLP
Klimisch score: 1
Disk 5
00000194
Ladybird beetle
Coccinella
septempunctata
FOE 5043 WG 60
Rate 1 kg/ha.
FOE 5043 WG 60 – 60% flufenacet
Control larvae as well as larvae exposed to spray deposits of
FOE 5043 WG 60, entered the pupal stage between day 5
and day 8 (average 6.3 days and 6.7 days) after treatment.
Adult beetles emerged in both groups between day 9 and
day 13 (average: 11.1 days and 11.0 days) following the
application.
Schmuck (1995)
BBA VI, 23-2.1.5
Report No.
E 376 0652 - 2
GLP
Klimisch score: 1
Disk 5
00000196
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 112 of 140
Test species Results
Test methodc
[Reference
number]
In the controls, 36 ladybird larvae completed successfully
the metamorphosis (= 75%). In the cages which received a
treatment, 31 out of 50 (= 69%) larvae entered the adult
stage.
The number of eggs laid per female in the treatment group
(mean value: 739.9 eggs per female; n= 2) was statistically
significant higher than in the control (mean value: 525.9
eggs per female; n=2). Hatch rate of the eggs laid in the
treatment group (70.5%; n=2) was also statistically
significant higher than those laid by the controls (65.0%;
n=2). If the total number of offspring per female in the
control chambers (339.5; n=2) is used as a basis for
comparison and assumed to be 100%, then the offspring
emergence rate for females exposed to the FOE 5043 WG
60 treatments was 154% (521.8; n=2).
Table 3.20: Summary of effects of exposure to Firebird on beneficial invertebrates.
Test species Results
Test methodc
[Reference
number]
Predaceous mite
Typhlodromus pyri
Tier 1 testing
Effects of Flufenacet & Diflufenican SC 600 on the
Predatory Mite Typhlodromus pyri Scheuten (Acari,
Phytoseiidae) in the Laboratory -Dose Response Design-
LR50 (7 d)
81.8 mL/ha
95% CI:
71.4 – 93.8 mL/ha
NOER:
45.0 mL/ha.(not significantly different to controls)
The reproduction was statistically not affected at rates up to
of 45 mL/ha.Flufenacet & Diflufenican SC 600/ha.(Student
t-test, α = 0.05).
Higher tier testing
The effects of Flufenacet & Diflufenican SC 600 on
Typhlodromus pyri (Acari: Phytoseiidae) on natural
substrate in laboratory (extended laboratory test).
LR50 (7 d)
110.2 mL/ha
95% CI:
30.2 – 402.2 mL/ha
NOER:
83.2 mL/ha.(not significantly different to controls)
Goβmann (2001)
Louis/Ufer 1995
Blummel et al.
2000
Report No.
9352063
GLP
Klimisch score: 1
Disk 14
00000560
Chauzat (2002)
Blummel et al.
2000
Report No.
01TYBYL12
GLP
Klimisch score: 1
Disk 14
00000561
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 113 of 140
Test species Results
Test methodc
[Reference
number]
The reproduction was statistically not affected at rates up to
of 83.2 mL/ha.Flufenacet & Diflufenican SC
600/ha.(Student t-test, α = 0.05).
Parasitic Wasp
Aphidius
rhopalosiphi
Effects of Flufenacet & Diflufenican SC 600 on the
Parasitoid Aphidius rhopalosiphi in the Laboratory
- Limit Test - LR50 (2 d)
> 700 mL/ha
The reproduction was not affected at rates up to 700
mL/ha.Flufenacet & Diflufenican SC 600/ha.
Moll and Butzler
(2001)
Mead-Briggs et al.
2000
Report No.
9351001
GLP
Klimisch score: 1
Disk 14
00000562
Carabid beetles
Poecilus cupreus
FOE 5043 (40%) + Diflufenican (19%) WG 60: Acute
effects of a spray application on carabid beetles (Poecilus
cupreus) under laboratory conditions
LR50 (14 d)
> 600 g/ha
The spray-application with 600 g FOE 5043 + OFF WG 60 /
ha.caused in no adverse effects on the treated beetles. Only
negligible effects were observed on 3 beetles for 4 - 6 hours
after application.
The individual feeding activity, following a spray
application of 600 g FOE 5043 + OFF WG 60 / ha., was not
statistically (p = 0.05) affected by the test compound.
Hennig-Pusch
(1996)
BBA 23-2.1.8
SETAC 1994
Report No.
HGP/LA PC002
GLP
Klimisch score: 1
Disk 14
00000563
Ladybird beetle
Coccinella
septempunctata
Testing toxicity to beneficial arthropods Ladybird -
Coccinella septempunctata L. / Larvae according to BBA
Guideline VI, 23-2.1.5 (1989): Foe 5043 & Diflufenican
WG 60
Rate: 600 g FOE 5043 + OFF WG 60 / ha
LR50 (18 d)
> 600 g/ha
In the test variant with Foe 5043 & Diflufenican WG 60
there was 2.4 % mortality of the ladybird larvae (corrected
by SCHNEIDER-ORELLI).
A decrease of the fertility was not observed in comparison
with the control. The relative decrease of beneficial
effectivity was E = -49.6 % (i.e., there was an increase).
Hennig-Pusch
(1996)
BBA 23-2.1.5
Report No.
96 10 48 010
GLP
Klimisch score: 1
Disk 14
00000564
Predatory mite
Hypoaspis aculeifer
Flufenacet & Diflufenican SC 600: The effects on
survival and reproduction of the predaceous mite in
standard soil (LUFA 2.1)
LR50:
> 32 mg ai/kg dry soil
Reproduction
Not statistically different from control at 32 mg ai/kg dry
Lechelt-Kunse
(2002).
SECOFASE
Lekke and van
Gestel, 1996
Barrett et al. 1994
Report No.
B094HAE
GLP
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 114 of 140
Test species Results
Test methodc
[Reference
number]
soil (highest concentration tested). Klimisch score: 1
Disk 14
00000567
Table 3.21: Hazard quotients for in-field scenarios from the use of Firebird.
Species Application rate
(mL/ha)
MAF1 LR50
2
(mL/ha)
HQ Trigger
value Typhlodromus pyri (Tier 1 Test) 300 1 81.8 3.67 2 T. pyri (Extended laboratory test) 300 1 110.2 2.72 2
1MAF Multiple application factor (MAF taken from Appendix III, ESCORT 2)
2LR50 application rate that results in 50% mortality of test species
The in-field assessment shows a non-acceptable risk to beneficial invertebrates from both
tier 1 and the higher tier extended laboratory study using natural substrates.
Table 3.22: Hazard quotients for off-field scenarios from the use of Firebird.
Species Application
rate (mL/ha)
MAF
Drift
factor
Off-field
Rate (g/ha)
LR50
(mL/ha)
HQ Trigger
value T. pyri 300 1 2.77 10.3 110.2 0.09 2
1Drift factor = Drift value/100 (Drift values taken from Appendix IV, ESCORT 2)
The off-field assessment shows an acceptable risk to beneficial invertebrates.
Because the substance is an herbicide sprayed once per season with specific efficacy to plants,
the Agency recommends that the application rate not be changed. However, because the
product is to be applied early in the season (from pre-emergence to early post-emergence of
the crop) the risk of impacting the positive effects of beneficial insects is reduced.
Volatilisation
Hellpointner (1995)
Disk 2: 00000023 PF report No. 4069
Calculation of the chemical lifetime of thiafluamide (FOE5043) in the Troposphere.
Summary
Based on the calculation according to Atkinson the chemical lifetime of thiafluamide
(flufenacet) in the air was assessed to be less than 1 day, with respect to the OH radical
reaction, only. The chemical stability of thiafluamide in air is not determined by an attack at
one single site, but by attacks at different parts of the thiafluamide molecule. This should
result in the formation of various primary radicals leading to secondary oxidation products,
which can be eliminated from the air by wet and/or dry deposition. On account of the
relatively short chemical lifetime of thiafluamide in the air it is not to be expected that the
active ingredient can be transported in gaseous phase over large distances or can accumulate
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 115 of 140
in the air. This indicates that there should be no difference hi the behaviour between
thiafluamide and other organic substances which are emitted into the air from natural sources
(e.g. from soil or plants).
Hellpointner (1995)
BBA Guideline IV, 6-1
GLP
Disk 2: 00000154 PF report No. 4091
Determination of the Volatilisation Behaviour of FOE 5043 (60 WG) in a Field Trial.
Under the weather conditions being typical for a pre-emergence application of FOE 5043 on
late seeded corn end of May the volatilisation rate of parent compound (including possible
volatile metabolites and/or wind-eroded particles containing radioactivity) was determined to
average 16 % within 24 hours.
Two of the three trials showed well comparable results. The mean losses amounted to about
10 % within 24 hours and the main portions were lost within the first hour after application.
The observed loss in the other trial amounted to 29 % after 24 hours (highest observed rate)
and was longer lasting (for about 3 hours). Obviously, this was caused by comparatively
lower recoveries by means of the soil extracts. No plausible explanation, i. e. climatic
parameter of exposure or soil moisture, could be given for that deviation to the other two
trials.
On account of the low trend of FOE 5043 to volatilise from soil an exposure to relevant
amounts of parent compound or an emission via contaminated air is not to be expected in the
field.
Summary and conclusions of the ecological risk assessment
Based on the risk assessment for the aquatic and terrestrial environment as set out above, risks
to the following species groups have been identified.
Aquatic environment
Algae: Acute risk
See Approved Handler control in Appendix 4.
Terrestrial environment
Beneficial invertebrates: Acute risk (in-field)
However, because the product is to be applied early in the season (from pre-emergence to
early post-emergence of the crop), the risk of impacting the positive effects of beneficial
insects is reduced.
References EFSA 2008. Risk assessment for birds and mammals. Revision of guidance document under
council directive 91/414/EEC (SANCO/4145/2000 – final of 25 September 2002)1. Scientific
opinion of the panel on plant protection products and their residues (PPR) on the science
behind the guidance document on risk assessment for birds and mammals. Question no.
EFSA-Q-2006-064. Adopted on 17 June 2008. The EFSA Journal, 734: 1-181.
EFSA DAR (2006). Draft Assessment Report. Diflufenican.
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 116 of 140
EPPO 2001. Guideline on the test methods for evaluating the side-effects of plant protection
products. No PP 1/170(3)
EPPO 2002. Environmental risk assessment scheme for plant protection products. Chapter 10
honeybees. EPPO Bulletin 33
http://archives.eppo.org/EPPOStandards/PP3_ERA/pp3-10(2).pdf
ERMA New Zealand 2008a. User Guide to HSNO Thresholds and Classifications. ERMA
New Zealand, Wellington.
European Commission, Guidance Document on terrestrial ecotoxicology under Council
Directive 91/414/EEC, SANCO/ 10329/2002 rev. 2 final, 17 October 2002.
http://ec.europa.eu/food/plant/protection/evaluation/guidance/wrkdoc09_en.pdf
HSNO Chemical Classification Information Database
http://www.ermanz.govt.nz/hs/compliance/chemicals.html
Urban DJ, Cook, NJ 1986. Hazard Evaluation Division Standard Evaluation Procedure:
Ecological Risk Assessment. EPA 540/9-85-001. United States Environmental Protection
Agency Office of Pesticide Programs, Washington DC, USA.
USEPA 2001. Generic Estimated Environmental Concentration Model v2 (GENEEC2).
United States Environmental Protection Agency Office of Pesticide Programs, Washington
DC, USA http://www.epa.gov/oppefed1/models/water/index.htm#geneec2
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 117 of 140
APPENDIX 4: DISCUSSION ON CONTROLS
Based on the hazard classification as shown in Table 6.1, the set of associated controls has
been identified. These default controls, expressed as control codes11
, are listed in Table A4.1.
Table A4.1: List of default controls for Firebird
Toxicity Controls
T1 Limiting exposure to toxic substances through the setting of TELs
T2 Controlling exposure in places of work through the setting of WESs.
T4 Requirements for equipment used to handle substances
T5 Requirements for protective clothing and equipment
T7 Restrictions on the carriage of toxic or corrosive substances on passenger service vehicles
Ecotoxicity Controls
E1 Limiting exposure to ecotoxic substances through the setting of EELs
E2 Restrictions on use of substances in application areas
E5 Requirements for keeping records of use
E6 Requirements for equipment used to handle substances
E7 Approved handler/security requirements for certain ecotoxic substances
Identification Controls
I1 Identification requirements, duties of persons in charge, accessibility, comprehensibility,
clarity and durability
I3 Priority identifiers for ecotoxic substances
I8 Priority identifiers for toxic substances
I9 Secondary identifiers for all hazardous substances
I11 Secondary identifiers for ecotoxic substances
I16 Secondary identifiers for toxic substances
I17 Use of generic names
I18 Requirements for using concentration ranges
I19 Additional information requirements, including situations where substances are in
multiple packaging
I20 Durability of information for class 6.1 substances
I21 General documentation requirements
I23 Specific documentation requirements for ecotoxic substances
I28 Specific documentation requirements for toxic substances
I29 Signage requirements
I30 Advertising corrosive and toxic substances
Packaging Controls
P1 General packaging requirements
P3 Criteria that allow substances to be packaged to a standard not meeting Packing Group I,
II or III criteria
P13 Packaging requirements for toxic substances
P15 Packaging requirements for ecotoxic substances
PG3 Packaging requirements equivalent to UN Packing Group III
PS4 Packaging requirements as specified in Schedule 4
11
Control codes are those assigned by ERMA NZ to enable easy cross reference with the regulations. A
detailed list of these codes is contained in the ERMA New Zealand User Guide to the Controls
Regulations.
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 118 of 140
Disposal Controls
D4 Disposal requirements for toxic or corrosive substances
D5 Disposal requirements for ecotoxic substances
D6 Disposal requirements for packages
D7 Information requirements for manufacturers, importers and suppliers, and persons in
charge
D8 Documentation requirements for manufacturers, importers and suppliers, and persons in
charge
Emergency Management Controls
EM1 Level 1 information requirements for suppliers and persons in charge
EM6 Information requirements for toxic substances
EM7 Information requirements for ecotoxic substances
EM8 Level 2 information requirements for suppliers and persons in charge
EM11 Level 3 emergency management requirements: duties of person in charge, emergency
response plans
EM12 Level 3 emergency management requirements: secondary containment
EM13 Level 3 emergency management requirements: signage
Tracking Controls TR1 General tracking requirements
Approved handler Controls AH1 Approved Handler requirements (including test certificate and qualification requirements)
Tank Wagon and Transportable Containers Controls
The Hazardous Substance (Tank Wagons and Transportable Containers) Regulations 2004
prescribe a number of controls relating to tank wagons and transportable containers.
Those controls which require calculations, derivations or extended discussion are considered
in the following sections.
Toxicity Controls
Setting of TELs (Control Code T1)
Tolerable Exposure Limits (TELs) are designed to limit the extent to which the general public
is exposed to hazardous (toxic) substances. A TEL represents the maximum concentration of
a substance legally allowable in a particular medium, and can be set as either a guideline
value or an action level that should not be exceeded. For the purposes of setting TELs, an
environmental medium is defined as air, water, soil or a surface that a hazardous substance
may be deposited onto.
TELs are established from PDE (potential daily exposure) values, which are themselves
established from ADE (acceptable daily exposure) values or reference doses (RfD) which are
similar to ADE but are used to protect against a specific toxic effect of concern.
Human exposure may also occur through food or drinking water. Exposure through food is
managed via the establishment of Maximum Residue Limits (MRLs) as set by the Minister of
Food Safety on the advice of the New Zealand Food Safety Authority (NZFSA). Exposure
through drinking water is managed via the establishment of Maximum Acceptable Values
(MAVs) as set by the Ministry of Health. MRLs and MAVs are also established from ADE
values.
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 119 of 140
Setting of PDEs
If an ADE or RfD value is set for a substance, or component of a substance, a PDE value for
each relevant exposure route must also be set. A PDE is an amount of substance (mg/kg
bodyweight/day), calculated in accordance with Regulation 23, that estimates the relative
likelihood of particular exposures. A PDE for any single exposure route is a fraction of the
ADE or RfD, and the sum of all PDE values from all possible exposures must be less than or
equal to the ADE or RfD.
The main routes of exposure considered are ingestion (food, water, air, soil), inhalation (air)
and skin contact (surface deposition, water, soil).
Setting of ADEs
An ADE is an amount of a hazardous substance (mg/kg bodyweight/day), that, given a
lifetime of daily exposure, would be unlikely to result in adverse human health effects. An
RfD (reference dose) is a similar measure that can be used to protect against a specific toxic
effect of concern.
Regulation 11(1) of the Hazardous Substances (Classes 6, 8 and 9) Controls Regulations 2001
determines when an ADE/RfD is required to be set:
(1) This regulation applies to a class 6 substance if-
(a) it is likely to be present in-
(i) 1 or more environmental media; or
(ii) food; or
(iii) other matter that might be ingested; AND
(b) it is a substance to which a person is likely to be exposed on 1 or more
occasions during the lifetime of the person; AND
(c) exposure to the substance is likely to result in an appreciable toxic
effect.
If all three requirements of regulation 11(1) are met, then an ADE/RfD should be set for the
relevant component(s), and PDE and TEL values subsequently established for each relevant
exposure route.
The toxicity (Class 6) classifications of Firebird that trigger the need to consider setting a
TEL are 6.1D, 6.5B and 6.9B.
The Agency considers that flufenacet meets the requirements of Regulation 11(1)(a), (b) and
(c), and therefore notes that an ADE, and subsequently PDEs and TELs are required to be set
for this component.
However, the Agency is intending to review the setting of ADEs, PDEs and TELs under
section 77B of the Act, and until this review is complete, the Agency proposes not to set
TELs for flufenacet. Noting that Firebird is intended for use on food crops and contains
flufenacet, a new active ingredient to New Zealand, an ADE and PDEfood value are calculated
for this component which will enable the NZFSA to set MRLs if needed.
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 120 of 140
The Agency notes that the EFSA have set an ADI of 0.005 mg/kg bw/day for flufenacet,
established on the basis of the LOAEL of 1.2 mg/kg bw/day (increased incidence of renal
pelvic mineralisation) in the two two-year studies in the rat, using a safety factor of 250. The
Agency considered this dose level in the study to be a NOAEL, so calculated an ADE for
flufenacet using this value as a NOAEL and an uncertainty factor of 100 (see Appendix 2),
which gave an ADE of 0.012 mg/kg bw/day.
If an ADE is set for a substance, a PDE value for each exposure route must also be set. The
main routes of exposure to be considered are ingestion (from food, water etc), inhalation and
dermal (skin) contact. The sum of all PDE values from each possible exposure route must be
less than or equal to the ADE set for the substance, i.e. the PDE is a fraction of the ADE:
PDE = ADE x n, where “n” = a value between 0 and 1
Exposure to Firebird may occur via inhalation, dermal contact or oral ingestion.
The “n” values for flufenacet are set initially by the Agency at 0.7 for food, 0.2 for drinking
water and 0.1 each for inhalation, dermal contact and non-foodstuffs.
Based on an ADE value for flufenacet of 0.012 mg/kg bw/day (5 µg /kg bw/ day), the Agency
proposes that the following PDE values be adopted:
PDEFOOD = 0.0084, rounded to 0.008 mg/kg bw/day
PDEDRINKING WATER = 0.0024, rounded to 0.002 mg/kg bw/day
The Agency has agreed with the New Zealand Food Safety Authority that we will set an acute
reference dose (ARfD), for new active ingredients. This will provide a basis for the NZ Food
Safety Authority to assess shorter term food residues if this should be required. In the case of
flufenacet the Agency notes that the EU has proposed a value of 0.017 mg/kg bw/day which
is based on the same calculation as the AOEL (in Appendix 3). The Agency proposes that
this value applies to flufenacet in New Zealand.
Setting of WES (Control Code T2)
Workplace exposure standards (WES) are designed to protect persons in the workplace from
the adverse effects of toxic substances. A WES is an airborne concentration of a substance
(expressed as mg substance/m3 of air, or ppm in air), which must not be exceeded in a
workplace and only applies to places of work (Regulation 29(2), Hazardous substances
(Classes 6, 8 and 9 Controls) Regulations 2001).
Regulation 29(1) of the Hazardous Substances (Classes 6, 8 and 9 Controls) Regulations 2001
determines when a WES is required to be set. If all three of the requirements of this regulation
are met then a WES is required to be set.
Regulation 29 states:
(1) This regulation and regulation 30 apply to a class 6 substance if,-
(a) under the temperature and pressure the substance is to be used in, it can become
airborne and disperse in air in the form of inspirable or respirable dust, mists,
fumes, gases or vapours; AND
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 121 of 140
(b) human exposure to the substance is primarily through the inhalation or dermal
exposure routes; AND
(c) the toxicological and industrial hygiene data available for the substance is
sufficient to enable a standard to be set.
When setting WES, the Authority must either adopt a value already proposed by the
Department of Labour or already set under HSNO or derive a value by taking into account the
matters described in Regulation 30(2) of the Hazardous Substances (Classes 6, 8 and 9
Controls) Regulations.
The Agency typically adopts WES values listed in the Workplace Exposure Standards
(Effective from 2002) document (refer to the link below).
http://www.osh.govt.nz/order/catalogue/pdf/wes2002.pdf
The Agency notes that Department of Labour has set WES values for Components C, H4 and
I in Firebird.
The Agency considers that the Department of Labour WES value for Component C should be
adopted as the HSNO WES value that applies to Component C in Firebird and this is given in
Appendix 8. The Agency considers that the WES values for Components H and I should not
be applied to Firebird due to their low concentration in the formulated substance.
Ecotoxicity Controls
Setting of EELs (Control code E1)
Regulation 33 of the Hazardous Substances (Classes 6, 8 and 9 Controls) Regulations 2001
specify that an environmental exposure limit (EEL) may be set for a class 9 substance for one
or more environmental media if organisms that live in that environment may be exposed to the
substance. An EEL is the (maximum) concentration of a substance in an environmental
medium that will present a negligible risk of adverse environmental effects to organisms
(excluding humans) in non-target areas.
As specified by regulation 32, a default EEL of 0.1 µg/L water is set for any class 9.1
substance, and 1 µg/kg soil (dry weight) for any class 9.2 substance.
For the purposes of setting EELs, an environmental medium is defined as water, soil or
sediment where these are in the natural environment, or a surface onto which a hazardous
substance may be deposited.
An EEL can be established by one of three means:
Applying the default EELs specified in regulation 32
Adopting an established EEL as provided by regulation 35(a)
Calculating an EEL from an assessment of available ecotoxicological data as
provided by regulation 35(b).
The Hazardous Substances and New Organisms (Approvals and Enforcement) Act 2005
added a new section (s77B) to the HSNO Act, which, amongst other things provided the
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 122 of 140
Authority with the ability to set EELs as guideline values, rather than the previous pass/fail
values.
However, until the Agency has developed formal policy on the implementation of s77B, it
proposes not to set EELs for any components of Firebird at this time. It is also proposed that
the default EEL water and soil values be deleted until the policy has been established.
Approved Handler Controls- Highly ecotoxic substances (AH1, E7)
Approved handler requirements have been triggered for Firebird as a result of its 9.1A and
9.2A classifications. The outcome of the ecological risk assessment (refer Appendix 3)
indicates that there is potential for acute adverse environmental effects on algae if the
substance moves off-target. The Agency considers it is therefore appropriate to retain the
approved handler control.
This approach is consistent with the Authority’s policy on approved handler and tracking
controls for class 9 substances (November 2003).
Tracking control- Highly ecotoxic substances (TR1)
Tracking requirements have been triggered for Firebird as a result of its 9.1A and 9.2A
classifications. However, for substances where the tracking control has been triggered solely
as a result of ecotoxicity, it is considered that any risk that may arise during its life-cycle are
adequately managed by other controls such as approved handler, packaging, labeling and
emergence management requirements. the Agency therefore considers the tracking control
can be deleted as provided by section 77(4)(b).
This approach is consistent with the Authority’s policy on approved handler and tracking
controls for class 9 substances (November 2003).
Setting of Application Rate (Control Code E2) These regulations relate to the requirement to set an application rate for a class 9 substance
that is to be sprayed or applied to an area of land (or air or water) and for which an EEL has
been set.
Although no EEL has been set for Firebird, the Agency proposes setting the application rate
of 300 mL formulated product/ha. (Flufenacet 126.3 g/ha., Diflufenican 61.9 g/ha), once per
season as the application rate for Firebird. This rate was used in the ecological risk
assessment.
Other controls required as a result of the ecological risk assessment.
This substance is not to be applied onto or into water;
Identification controls
Identification of Toxic Components on Labels/Documentation (SDS)
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The Hazardous Substances (Identification) Regulations 2001 specify that certain toxic and/or
corrosive components are required to be specified on the product label and on SDS
documentation.
Identification of toxic components on labels
Regulations 25(e) and 25(f) require that certain toxic components are required to be specified
on the product label.
Regulation 25(e) states:
...a toxic substance must be identified by...
'information identifying, by its common or chemical name, every ingredient, that would,
independently of any other ingredient, give the substance a hazard classification of 6.1A,
6.1B, 6.1C, 6.5, 6.6, 6.7, 6.8 or 6.9, and the concentration of that ingredient in the substance."
Regulation 25(f) states:
...a toxic substance must be identified by...
"information identifying (other than an ingredient referred to in paragraph (E)) that would,
independently of any other ingredient, give the substance a hazard classification of 6.1D, and
the concentration of the ingredient that would contribute the most to that classification."
Identification of toxic components on SDS
Regulation 39(5) of the Hazardous Substances (Identification) Regulations 2001, states that
certain corrosive and toxic components are required to be specified on documentation.
Regulations 39(5) states:
"The requirements of regulation 19(f) or (as the case requires) regulation 25(e) apply to all
documentation; but any ingredient required by that provision to be identified (other than an
ingredient to which regulation 26 applies) must also be identified by any Chemical Abstract
Services number allocated to it."
Concentration cut-offs for component identification
Consistent with the guidance provided by GHS, the Hazardous Substances Standing
Committee (HSSC) agreed that the concentration cut-offs triggering the requirement for
identification of components on labels and documentation are:
HSNO Classification Cut-off for label (% w/w) Cut-off for SDS (% w/w)
6.5A, 6.5B, 6.6A, 6.7A 0.1 0.1
6.6B 1 1
6.7B 1 0.1
6.8A, 6.8C 0.3 0.1
6.8B 3 0.1
6.9A, 6.9B 10 1
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Firebird - Components requiring identification
Under these regulations, as determined by the HSSC (March 2006), the name and
concentration of the following components need to be specified on the label and
documentation:
Label & Documentation
Flufenacet
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APPENDIX 5: LIST OF PROPOSED CONTROLS FOR
FIREBIRD
Table A5.1: Proposed controls for Firebird – codes, regulations and variations.
Control
Code12
Regulation13
Topic Variations
Hazardous Substances (Classes 6, 8, and 9 Controls) Regulations 2001
T1 11-27 Limiting exposure to toxic
substances
No TEL values are set at this time.
The following ADE and PDE values
are set for flufenacet:
ADE = 0.012 mg/kg bw/day
PDEfood = 0.008 mg/kg bw/day
PDEdrinking water = 0.002 mg/kg bw/day
The following Acute Reference Dose is
set for flufenacet:
ARfD = 0.017 mg/kg bw/day.
T2 29, 30 Controlling exposure in places of
work The DoL WES values for Component
C in Firebird are adopted.
T4/E6 7 Requirements for equipment used to
handle hazardous substances
Controls T4 and E6 are combined.
T5 8 Requirements for protective clothing
and equipment
T7 10 Restrictions on the carriage of toxic
or corrosive substance on passenger
service vehicles
E1 32-45 Limiting exposure to ecotoxic
substances
No EEL values are set at this time and
the default EELs are deleted.
E2 46-48 Restrictions on use within
application area
As no EELs have been set, no
application rate is required to be set
under this control at this time.
However, an application rate is set as
an additional control under Section
77A (see below).
E5 5(2), 6 Requirements for keeping records of
use
E7 9 Approved handler/security
requirements for certain ecotoxic
substances
The following control is substituted for
Regulation 9(1) of the Hazardous
Substances (Classes 6, 8, and 9 Controls)
Regulations 2001:
(1). This subsatnce must be under the
personal control of an approved
12 Note: The numbering system used in this column relates to the coding system used in the ERMA New Zealand Controls Matrix. This links the hazard classification categories to the regulatory controls triggered by each category. It is available from the ERMA New Zealand website www.ermanz.govt.nz/resources and is also contained in the ERMA New Zealand User Guide to the HSNO Control Regulations. 13 These Regulations form the controls applicable to this substance. Refer to the cited Regulations for the formal specification, and for definitions and exemptions.
ERMA New Zealand Evaluation and Review Report: Application HSR08057 Page 126 of 140
Control
Code12
Regulation13
Topic Variations
handler when the substance is -
(a) applied in a wide dispersive
manner; or
(b) used by a commercial contractor.
Hazardous Substances (Identification) Regulations 2001
I1 6, 7, 32-35,
36 (1)-(7)
General identification requirements
Regulation 6 – Identification duties
of suppliers
Regulation 7 – Identification duties
of persons in charge
Regulations 32 and 33 –
Accessibility of information
Regulations 34, 35, 36(1)-(7) –
Comprehensibility, Clarity and
Durability of information
I3 9 Priority identifiers for ecotoxic
substances
I8 14 Priority identifiers for toxic
substances
I9 18 Secondary identifiers for all
hazardous substances
I11 20 Secondary identifiers for ecotoxic
substances
I16 25 Secondary identifiers for toxic
substances
I17 26 Use of Generic Names
I18 27 Use of Concentration Ranges
I19 29-31 Alternative information in certain
cases
Regulation 29 – Substances in fixed
bulk containers or bulk transport
containers
Regulation 30 – Substances in
multiple packaging
Regulation 31 – Alternative
information when substances are
imported
I20 36(8) Durability of information for 6.1
substances
I21 37-39, 47- Documentation required in places of
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Control
Code12
Regulation13
Topic Variations
50 work
Regulation 37 – Documentation
duties of suppliers
Regulation 38 – Documentation
duties of persons in charge of places
of work
Regulation 39 – General content
requirements for documentation
Regulation 47 – Information not
included in approval
Regulation 48 – Location and
presentation requirements for
documentation
Regulation 49 – Documentation
requirements for vehicles
Regulation 50 – Documentation to be
supplied on request
I23 41 Specific documentation requirements
for ecotoxic substances
I28 46 Specific documentation requirements
for toxic substances
I29 51-52 Duties of persons in charge of places
with respect to signage
I30 53 Advertising corrosive and toxic
substances
Hazardous Substances (Packaging) Regulations 2001
P1 5, 6, 7 (1), 8 General packaging requirements
Regulation 5 – Ability to retain
contents
Regulation 6 – Packaging markings
Regulation 7(1) – Requirements
when packing hazardous substance
Regulation 8 – Compatibility
Regulation 9A and 9B – Large
Packaging
P3 9 Packaging requirements for
substances packed in limited
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Control
Code12
Regulation13
Topic Variations
quantities
P13
P15
19
21
Packaging requirements for Firebird Controls P13 and P15 are combined.
PG3 Schedule 3 The tests in Schedule 3 correlate to
the packaging requirements of UN
Packing Group III (UN PGIII).
PS4 Schedule 4 This schedule describes the
minimum packaging requirements
that must be complied with when a
substance is packaged in limited
quantities
Hazardous Substances (Disposal) Regulations 2001
D4
D5
8
9
Disposal requirements for Firebird Controls D4 and D5 are combined
D6 10 Disposal requirements for packages
D7 11, 12 Disposal information requirements
D8 13, 14 Disposal documentation
requirements
Hazardous Substances (Emergency Management) Regulations 2001
EM1 6, 7, 9-11 Level 1 emergency management
information: General requirements
EM6 8(e) Information requirements for toxic
substances
EM7 8(f) Information requirements for
ecotoxic substances
EM8 12-16, 18-
20
Level 2 emergency management
documentation requirements
EM11 25-34 Level 3 emergency management
requirements – emergency response
plans
EM12 35-41 Level 3 emergency management
requirements – secondary
containment
The following subclauses shall be
added after subclause (3) of regulation
36:
(4) For the purposes of this regulation,
and regulations 37 to 40, where
this substance is contained in
pipework that is installed and operated so as to manage any loss
of containment in the pipework it— (a) is not to be taken into account
in determining whether a place
is required to have a secondary containment system; and
(b) is not required to be located in
a secondary containment system.
(5) In this clause, pipework— (a) means piping that—
(i) is connected to a stationary
container; and
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Control
Code12
Regulation13
Topic Variations
(ii) is used to transfer a
hazardous substance into or out of the stationary
container; and
(b) includes a process pipeline or a transfer line.
The following subclauses are added at
the end of regulation 37: (2) If pooling substances which do not
have class 1 to 5 hazard
classifications are held in a place
above ground in containers each of
which has a capacity of 60 litres or
less—
(a if the place’s total pooling
potential is less than 20,000
litres, the secondary containment
system must have a capacity of at
least 25% of that total pooling
potential:
(b) if the place’s total pooling
potential is 20,000 litres or
more, the secondary
containment system must have a
capacity of the greater of—
(i) 5% of the total pooling
potential; or
(ii) 5,000 litres.
(3) Pooling substances to which
subclause (2) applies must be
segregated where appropriate to
ensure that leakage of one substance
may not adversely affect the
container of another substance.
The following subclauses are added at
the end of regulation 38: (2) If pooling substances which do not
have class 1 to 5 hazard
classifications are held in a place
above ground in containers 1 or
more of which have a capacity of
more than 60 litres but none of
which have a capacity of more than
450 litres—
(a) if the place’s total pooling
potential is less than 20,000
litres, the secondary
containment system must have a
capacity of either 25% of that
total pooling potential or 110%
of the capacity of the largest
container, whichever is the
greater:
(b) if the place’s total pooling
potential is 20,000 litres or
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Control
Code12
Regulation13
Topic Variations
more, the secondary containment
system must have a capacity of
the greater of—
(i) 5% of the total pooling
potential; or
(ii) 5,000 litres
(3) Pooling substances to which
subclause (2) applies must be
segregated where appropriate to
ensure that the leakage of one
substance may not adversely affect
the container of another substance.
EM13 42 Level 3 emergency management
requirements – signage
Hazardous Substances (Personnel Qualification) Regulations 2001
AH1 4-6 Approved Handler requirements See E7.
Hazardous Substances (Tank Wagons and Transportable Containers) Regulations 2004
Regulations 4 to 43
where applicable
The Hazardous Substances (Tank Wagons and Transportable Containers)
Regulations 2004 prescribe a number of controls relating to tank wagons and
transportable containers and must be complied with as relevant.
Section 77 and 77A Additional Controls
The controls relating to stationary container systems, as set out in Schedule 8 of the Hazardous
Substances (Dangerous Goods and Scheduled Toxic Substances) Transfer Notice 2004 (Supplement to
the New Zealand Gazette, 26 March 2004, No. 35, page 767), as amended, apply to this substance,
notwithstanding clause 1(1) of that schedule.
Addition of subclauses after subclause (3) of Regulation 36, subclause (1) of Regulation 37 and
subclause (1) of Regulation 38 of the Hazardous Substances (Emergency Management Controls)
Regulations, refer control EM12.
Firebird shall not be applied onto or into water.
The maximum application rate for Firebird shall be 300 mL/ha., once per season.
The method of application of Firebird shall be limited to ground-based application only.
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APPENDIX 6: SCALES FOR QUALITATIVE RISK
ASSESSMENT
This section describes how the Agency staff and the Authority address the qualitative
assessment of risks, costs and benefits. Risks and benefits are assessed by estimating the
magnitude and nature of the possible effects and the likelihood of their occurrence. For each
effect, the combination of these two components determines the level of the risk associated
with that effect, which is a two dimensional concept. Because of lack of data, risks are often
presented as singular results. In reality, they are better represented by ‘families’ of data which
link probability with different levels of outcome (magnitude).
The magnitude of effect is described in terms of the element that might be affected. The
qualitative descriptors for magnitude of effect are surrogate measures that should be used to
gauge the end effect or the ‘what if’ element. Tables 1 and 2 contain generic descriptors for
magnitude of adverse and beneficial effect. These descriptors are examples only, and their
generic nature means that it may be difficult to use them in some particular circumstances.
They are included here to illustrate how qualitative tables may be used to represent levels of
adverse and beneficial effect.
Table 1 Magnitude of adverse effect (risks and costs)
Descriptor Examples of descriptions - ADVERSE
Minimal Mild reversible short term adverse health effects to individuals in highly localised area
Highly localised and contained environmental impact, affecting a few (less than ten) individuals
members of communities of flora or fauna, no discernible ecosystem impact
Local/regional short-term adverse economic effects on small organisations (businesses,
individuals), temporary job losses
No social disruption
Minor Mild reversible short term adverse health effects to identified and isolated groups
Localised and contained reversible environmental impact, some local plant or animal communities
temporarily damaged, no discernible ecosystem impact or species damage
Regional adverse economic effects on small organisations (businesses, individuals) lasting less
than six months, temporary job losses
Potential social disruption (community placed on alert)
Moderate Minor irreversible health effects to individuals and/or reversible medium term adverse health
effects to larger (but surrounding) community (requiring hospitalisation)
Measurable long term damage to local plant and animal communities, but no obvious spread
beyond defined boundaries, medium term individual ecosystem damage, no species damage
Medium term (one to five years) regional adverse economic effects with some national
implications, medium term job losses
Some social disruption (e.g. people delayed)
Major Significant irreversible adverse health effects affecting individuals and requiring hospitalisation
and/or reversible adverse health effects reaching beyond the immediate community
Long term/irreversible damage to localised ecosystem but no species loss
Measurable adverse effect on GDP, some long term (more than five years) job losses
Social disruption to surrounding community, including some evacuations
Massive Significant irreversible adverse health effects reaching beyond the immediate community and/or
deaths
Extensive irreversible ecosystem damage, including species loss
Significant on-going adverse effect on GDP, long term job losses on a national basis
Major social disruption with entire surrounding area evacuated and impacts on wider community
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Table 2 Magnitude of beneficial effect (benefits) Descriptor Examples of descriptions -BENEFICIAL
Minimal Mild short term positive health effects to individuals in highly localised area
Highly localised and contained environmental impact, affecting a few (less than ten) individuals
members of communities of flora or fauna, no discernible ecosystem impact
Local/regional short-term beneficial economic effects on small organisations (businesses,
individuals), temporary job creation
No social effect
Minor Mild short term beneficial health effects to identified and isolated groups
Localised and contained beneficial environmental impact, no discernible ecosystem impact
Regional beneficial economic effects on small organisations (businesses, individuals) lasting less
than six months, temporary job creation
Minor localised community benefit
Moderate Minor health benefits to individuals and/or medium term health impacts on larger (but
surrounding) community and health status groups
Measurable benefit to localised plant and animal communities expected to pertain to medium
term.
Medium term (one to five years) regional beneficial economic effects with some national
implications, medium term job creation
Local community and some individuals beyond immediate community receive social benefit.
Major Significant beneficial health effects to localised community and specific groups in wider
community
Long term benefit to localised ecosystem(s)
Measurable beneficial effect on GDP, some long term (more than five years) job creation
Substantial social benefit to surrounding community, and individuals in wider community.
Massive Significant long term beneficial health effects to the wider community
Long term, wide spread benefits to species and/or ecosystems
Significant on-going effect beneficial on GDP, long term job creation on a national basis
Major social benefit affecting wider community
The likelihood applies to the composite likelihood of the end effect, and not either to the
initiating event, or any one of the intermediary events. It includes:
the concept of an initiating event (triggering the hazard), and
the exposure pathway that links the source (hazard) and the area of impact (public
health, environment, economy, or community).
Thus, the likelihood is not the likelihood of an organism escaping, or the frequency of
accidents for trucks containing hazardous substances, but the likelihood of the specified
adverse effect14
resulting from that initiating event. It will be a combination of the likelihood
of the initiating event and several intermediary likelihoods15
. The best way to determine the
likelihood is to specify and analyse the complete pathway from source to impact.
Likelihood may be expressed as a frequency or a probability. While frequency is often
expressed as a number of events within a given time period, it may also be expressed as the
number of events per head of (exposed) population. As a probability, the likelihood is
dimensionless and refers to the number of events of interest divided by the total number of
events (range 0-1).
14
The specified effect refers to scenarios established in order to establish the representative risk, and may
be as specific as x people suffering adverse health effects, or y% of a bird population being adversely
affected. The risks included in the analysis may be those related to a single scenario, or may be defined as a
combination of several scenarios. 15
Qualitative event tree analysis may be a useful way of ensuring that all aspects are included.
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Table 3 Likelihood
Descriptor Description
Highly improbable Almost certainly not occurring but cannot be totally ruled out
Very unlikely Considered only to occur in very unusual circumstances
Unlikely (occasional) Could occur, but is not expected to occur under normal operating conditions.
Likely A good chance that it may occur under normal operating conditions.
Highly likely Almost certain, or expected to occur if all conditions met
Using the magnitude and likelihood tables a matrix representing a level of risk/benefit can be
constructed.
In the example shown in Table 4, four levels of risk/benefit are allocated: A (negligible), B
(low), C (medium), and D (high). These terms have been used to avoid confusion with the
descriptions used for likelihood and magnitude, and to emphasise that the matrix is a tool to
help decide which risks/benefits require further analysis to determine their significance in the
decision making process.
For negative effects, the levels are used to show how risks can be reduced by the application
of additional controls. Where the table is used for positive effects it may also be possible for
controls to be applied to ensure that a particular level of benefit is achieved, but this is not a
common approach. The purpose of developing the tables for both risk and benefit is so that
the risks and benefits can be compared.
Table 4 Level of risk
Magnitude of effect
Likelihood Minor Minor Moderate Major Massive
Highly
improbable A A A B B
Very unlikely A A B B C
Unlikely A B B C C
Likely B B C C D
Highly likely B C C D D
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APPENDIX 7: GOVERNMENT DEPARTMENTS,
CROWN ENTITIES AND INTERESTED PARTIES
NOTIFIED
Aakland Chemicals (1997) Limited
AgBio Research Limited
Agcarm Incorporated
AgResearch Limited
Agronica New Zealand Limited
Ancare Scientific Limited
ARPPA
BASF New Zealand Limited
Bayer New Zealand Limited
BOC Limited
Bomac Laboratories Limited
Caltex New Zealand Limited
Central Hawkes Bay District Council
Chancery Green
Chemagro New Zealand Limited
Chemsafety Limited
Crown Public Health
CSD Consultancy Ltd
Donaghys Industries Limited
Dow AgroSciences (New Zealand) Limited.
DuPont (New Zealand) Limited
Environment Southland
Environment Waikato
Far North District Council
Federated Farmers of New Zealand (Incorporated)
Fish and Game Council of New Zealand
Fish and Game Eastern Region
Franklin District Council
GE Free (Wairarapa)
General Cable New Zealand Limited
Greater Wellington - The Regional Council
Green Party of Aotearoa New Zealand
Horticulture and Food Research Institute (HortResearch)
HQ Joint Forces New Zealand
Human Rights Commission
Hunt Agencies Limited
IMCD New Zealand Limited
Intervet Limited
Jordens Nurseries
Kaipara District Council
Kawerau District Council
Landcorp Farming Limited
Lowndes Associates
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MackeNew Zealandie District Council
MAF Biosecurity New Zealand (MAFBNew Zealand)
Matamata-Piako District Council
Merial New Zealand Limited
Ministry of Research Science and Technology (MoRST)
Muaupoko Co-operative Society
Napier Health Centre - Public Health Unit
National Aquarium of New Zealand
National Institute of Water and Atmospheric Research Limited (NIWA)
New Plymouth District Council
New Zealand Chemical Industry Council Inc
New Zealand Customs Service
New Zealand Meatworkers Union
New Zealand Press Association
New Zealand Society of Gunsmiths Inc
New Zealand Veterinary Association Inc
New Zeland Bee Industry Group - Federated Farmers
Ngati Kahungunu Iwi Incorporated
Northern Chemical Workers Union
Northland Health
Northland Regional Council
Nufarm New Zealand Limited
Nursery and Garden Industry Association of New Zealand Inc
Otago District Health Board
Pacific Growers Supplies Limited
Pesticide Action Network Aotearoa New Zealand
Pfizer New Zealand Limited
PharmVet Solutions
Physicians and Scientists for Global Responsibility (PSGR)
Rangitikei District Council
Reckitt Benckiser
Royal Forest and Bird Protection Society of New Zealand Inc.
Rural and Associated Contractors Federation of New Zealand
South Taranaki District Council
Spraywatchers Group
Sustainability Council of New Zealand
Syngenta Crop Protection Limited
Tairawhiti District Health
Taranaki Regional Council
Tasman District Council
Te Pataka Matauranga Charitable Trust
Technical Strategy Group Limited
Television New Zealand
Thames Coromandel District Council
The Green Party of Aotearoa New Zealand Inc
The National Beekeepers Association of New Zealand
TMP Consultancy
University of Auckland
Veg-Gro Supplies Limited
ViaLactia Biosciences (New Zealand) Limited
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Virbac Laboratories New Zealand Limited
Yates Australia
Zelam Limited
10 Private Individuals
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APPENDIX 8: CONFIDENTIAL MATERIAL
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APPENDIX 9 CONFIDENTIAL MATERIAL
- NOT TO BE DISCLOSED TO APPLICANT