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SCIENCE MEMO
APP203766 – Revystar® Fungicide
DECEMBER 2019
Project team
Application lead:
Toxicologist:
Ecotoxicologist:
Peer-reviewer:
Page 2 of 162
Science memo for application to import or manufacture Revystar® Fungicide for release (APP203766)
DECEMBER 2019
Executive Summary
The applicant BASF New Zealand Limited has submitted an application on 29 November 2018 to import or
manufacture Revystar® Fungicide for release. It was given Application Number APP203766 and was
formally received on 01 July 2019 as a Category C application.
The active ingredient contained in Revystar® Fungicide, mefentrifluconazole, has not previously been
approved in New Zealand for use as a fungicide. It has been approved internationally for this use pattern in
Europe, Australia, and the USA. The active ingredient fluxapyroxad has been approved in New Zealand as a
fungicide for cereals.
Mefentrifluconazole is of very low acute toxicity in mammals by oral, dermal, inhalation routes and should not
be classified. It is not a skin or eye irritant. However, mefentrifluconazole was found to be a contact
sensitiser and should be classified as 6.5B. It was found not to be genotoxic, carcinogenic, and does not
cause reproductive or developmental toxicity, or target organ toxicity. Mefentrifluconazole is very ecotoxic in
the aquatic environment (9.1A) and harmful to terrestrial vertebrates (9.3C), it is not ecotoxic in the soil
environment or to terrestrial invertebrates
The proposed toxicity classification of Revystar® Fungicide is: 6.1D acute toxicity (oral and inhalation), 6.3A,
6.4B, and 6.5B for skin and eye irritation, and contact sensitisation, respectively. It is classified 6.9B specific
organ toxicity due to fluxapyroxad.
The proposed ecotoxicity hazard classification of Revystar® Fungicide is: 9.1B (ecotoxic in the aquatic
environment) and 9.3C (harmful to terrestrial vertebrates). The EPA staff classification of Revystar®
Fungicide differed from that of the applicant in that they did not classify it for toxicity to terrestrial vertebrates.
Mefentrifluconazole is considered highly persistent in both the aquatic environment and soil environment
according to Annex D of the HSNO Act . Mefentrifluconazole is considered slightly mobile to immobile in soil
according to the McCall classification system . Mefentrifluconazole is considered to have a low potential for
bioaccumulation.
It is considered that there is potential for significant exposure to people and the environment during the use
phase of the lifecycle of Revystar® Fungicide. As such, quantitative risk assessments have been undertaken
to understand the likely exposures to the substance under the use conditions proposed by the applicant,
using the endpoint data available and the standard risk assessment methodologies used by the EPA (EPA
2018).
It is considered that the risks to human health from the proposed use of Revystar® Fungicide are acceptable
without the use of Personal Protective Equipment (PPE), application of re-entry intervals, or enforcement of
no-spray buffer zones to protect bystanders.
It is considered that the risks to the environment from the proposed use of Revystar® Fungicide are
acceptable with the proposed controls
A set of controls have been proposed for Revystar® Fungicide, and are detailed under section 6.
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Science memo for application to import or manufacture Revystar® Fungicide for release (APP203766)
DECEMBER 2019
Table of Contents
APP203766 – Revystar® Fungicide ..................................................................................................... 1
Executive Summary .............................................................................................................................. 2
Table of Contents .................................................................................................................................. 3
1. Introduction/Background ........................................................................................................... 7
2. Hazardous properties ................................................................................................................. 9
Hazard classification of mefentrifluconazole ................................................................................. 9
Hazard classification of Revystar® Fungicide ............................................................................... 9
Identification of components of concern (CMRs, vPBTs etc) ...................................................... 10
3. Risk assessment context ......................................................................................................... 10
4. Human health risk assessment................................................................................................ 11
5. Environmental risk assessment .............................................................................................. 11
6. Proposed controls ..................................................................................................................... 13
Appendix A: Identity of the active ingredient, use pattern and mode of action ........................... 15
Identity of the active ingredient and metabolites ......................................................................... 15
Regulatory status ........................................................................................................................ 16
Table 5: List of intended uses for Revystar® Fungicide ............................................................. 18
Appendix B: Physico-chemical properties of Revystar® Fungicide .............................................. 20
Appendix C: Mammalian toxicology .................................................................................................. 21
Executive summaries and list of endpoints for Revystar® Fungicide ......................................... 21
Executive summaries and list of endpoints for mefentrifluconazole ........................................... 22
General conclusion about mefentrifluconazole ........................................................................... 26
Appendix D: Environmental fate ........................................................................................................ 28
Executive summaries and list of endpoints ................................................................................. 28
Residues relevant to the environment ......................................................................................... 28
Degradation and fate of mefentrifluconazole in aquatic environments ....................................... 30
Degradation and fate of mefentrifluconazole in soil .................................................................... 31
General conclusion about environmental fate ............................................................................. 33
Appendix E: Ecotoxicity ..................................................................................................................... 35
Executive summaries and list of endpoints ................................................................................. 35
Aquatic toxicity ............................................................................................................................ 35
Metabolites ........................................................................................................................ 43
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DECEMBER 2019
Uncertainties and data gaps ............................................................................................. 43
General conclusion about aquatic toxicity......................................................................... 43
Soil toxicity................................................................................................................................... 44
Uncertainties and data gaps ............................................................................................. 47
General conclusion about soil toxicity ............................................................................... 47
Terrestrial vertebrate toxicity ....................................................................................................... 47
Uncertainties and data gaps ............................................................................................. 48
Ecotoxicity to bees and other terrestrial invertebrates ................................................................ 48
Uncertainties and data gaps ............................................................................................. 50
General conclusion about ecotoxicity to bees and terrestrial invertebrate toxicity 50
Appendix F: Hazard classification of mefentrifluconazole and Revystar® Fungicide ................. 51
Appendix G: Human health risk assessment ................................................................................... 56
Quantitative risk assessment ...................................................................................................... 56
Input values for the human health risk assessment .......................................................... 56
Operator exposure assessment ........................................................................................ 57
Re-entry worker exposure assessment ............................................................................ 59
Quantitative bystander risk assessment ........................................................................... 59
Conclusions of the human health risk assessment ........................................................... 60
Appendix H: Environmental risk assessment .................................................................................. 61
Mixture toxicity ............................................................................................................................. 61
Aquatic risk assessment .............................................................................................................. 64
Calculation of expected environmental concentrations .................................................... 64
Output from the GENEEC2 model .................................................................................... 65
Calculated risk quotients ................................................................................................... 67
Refinement of the aquatic risk assessment ...................................................................... 68
Conclusions of the aquatic risk assessment ..................................................................... 70
Groundwater risk assessment ..................................................................................................... 70
Conclusions of the groundwater risk assessment ............................................................ 71
Sediment risk assessment .......................................................................................................... 71
Terrestrial risk assessment ......................................................................................................... 72
Soil macro-organisms ....................................................................................................... 72
Soil accumulation .............................................................................................................. 75
Conclusions of the soil organism risk assessment ........................................................... 76
Non-target plant risk assessment ................................................................................................ 77
Conclusion for non-target plant risk assessment .............................................................. 77
Bird risk assessment ................................................................................................................... 78
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DECEMBER 2019
Screening assessment ...................................................................................................... 78
Calculation of TERs .......................................................................................................... 78
Conclusions of the bird screening risk assessment .......................................................... 79
Tier 1 assessment ............................................................................................................. 79
Secondary poisoning ......................................................................................................... 80
Conclusions for bird risk assessment ............................................................................... 80
Pollinator risk assessment ........................................................................................................... 80
Conclusions of the pollinator risk assessment .................................................................. 81
Non-target arthropod risk assessment ........................................................................................ 81
Conclusion for non-target arthropod risk assessments .................................................... 82
Conclusions of the ecological risk assessment ........................................................................... 83
Aquatic risk assessment ................................................................................................... 83
Soil organism risk assessment ......................................................................................... 84
Non-target plant risk assessment ..................................................................................... 84
Bird risk assessment ......................................................................................................... 84
Pollinator risk assessment ................................................................................................ 84
Non-target arthropod risk assessments ............................................................................ 84
Appendix I: Proposed controls .......................................................................................................... 86
Prescribed controls ...................................................................................................................... 86
Exposure thresholds .................................................................................................................... 86
Impurity limits............................................................................................................................... 87
Ecotoxicity controls ...................................................................................................................... 87
Application restrictions ................................................................................................................ 87
Application method ...................................................................................................................... 87
Buffer zones ................................................................................................................................ 88
Appendix J: Study summaries ........................................................................................................... 89
Toxicity study summaries ............................................................................................................ 89
Mammalian toxicology - Robust study summaries for Revystar® .................................... 89
Environmental fate studies ........................................................................................................ 101
Abiotic degradation ......................................................................................................... 101
Biological degradation – biodegradation in soil .............................................................. 102
Mobility in soil .................................................................................................................. 108
Bioconcentration/bioaccumulation studies ...................................................................... 110
Ecotoxicity study summaries ..................................................................................................... 113
Aquatic ecotoxicity of the active ingredient ............................................................................... 113
Short-term aquatic toxicity studies .................................................................................. 113
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Chronic toxicity to sediment-dwelling organisms ............................................................ 134
Aquatic ecotoxicity of metabolites of mefentrifluconazole .............................................. 135
Soil toxicity of the active ingredient ........................................................................................... 141
Toxicity to terrestrial plants ............................................................................................. 141
Terrestrial vertebrate toxicity of the active ingredient ..................................................... 145
Acute toxicity to birds (oral) ............................................................................................. 145
Acute toxicity to birds (dietary) ........................................................................................ 148
Chronic toxicity to birds (reproduction) ........................................................................... 150
Toxicity of the active ingredient to terrestrial invertebrates ............................................. 152
Acute toxicity to pollinators ............................................................................................. 152
Chronic toxicity to pollinators .......................................................................................... 156
Appendix K: Standard terms and abbreviations ............................................................................ 157
Appendix L: References ................................................................................................................... 160
Appendix M: Confidential Composition .......................................................................................... 161
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Science memo for application to import or manufacture Revystar® Fungicide for release (APP203766)
DECEMBER 2019
1. Introduction/Background
1.1. This application is to import or manufacture Revystar® Fungicide for release.
1.2. Revystar® Fungicide is intended to be used as fungicide to control various fungal diseases on wheat,
barley, oats, ryecorn, triticale, and ryegrass.
1.3. Revystar® Fungicide contains the active ingredients mefentrifluconazole at 100 g/L and fluxapyroxad
at 50 g/L, plus other components.
1.4. The active ingredient contained in Revystar® Fungicide, mefentrifluconazole, has not previously been
approved in New Zealand for use as a fungicide. It has been approved internationally for this use
pattern in Europe, Australia, and the USA. The active ingredient fluxapyroxad has been approved in
New Zealand as a fungicide for cereals.
1.5. The active ingredient fluxapyroxad, contained in Revystar® Fungicide has previously been approved
in New Zealand for use on cereal grains at a similar application rate (Adexar, application APP201884,
approval HSR100948).
1.6. More details about the use pattern of Revystar® Fungicide and the regulatory status of
mefentrifluconazole can be found in Appendix A.
1.7. It is considered that there is potential for significant exposure to people and the environment during
the use phase of the lifecycle of Revystar® Fungicide. As such, quantitative risk assessments have
been undertaken to understand the likely exposures to the substance under the use conditions
proposed by the applicant, using the endpoint data available and the standard risk assessment
methodologies used by the EPA (EPA 2018). Exposure modelling was only conducted on
mefentrifluconazole as modelling on fluxapyroxad was previously completed as noted in 1.5.
Fungicide Full context related to the risk assessment of Revystar® Fungicide is given in section 3.
1.8. Unless otherwise stated, all endpoint data summarised were fully compliant with the relevant
international test methods. For full details of testing undertaken, reference should be made to the
relevant sections of the overseas review [(EFSA 2018) , (EC 2017)]. The applicant has confirmed they
have access to the studies conducted with mefentrifluconazole contained in Revystar® Fungicide. The
original study reports have been provided.
1.9. Physical and Chemical properties of Revystar® Fungicide can be found in Appendix B.
1.10. Mammalian toxicological properties Revystar® Fungicide and mefentrifluconazole have been reported
in Appendix C.
1.11. Environmental Fate properties of mefentrifluconazole have been reported in Appendix D.
1.12. Ecotoxicological properties of Revystar® Fungicide and mefentrifluconazole have been reported in
Appendix E.
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1.13. Hazard properties and classification determination of Revystar® Fungicide and mefentrifluconazole
derived from their properties can be found under Section 2. Hazardous properties and Appendix F.
1.14. Mammalian toxicological data have subsequently been used to generate human health risk
assessment and this is detailed in Appendix G.
1.15. Environmental Fate, Ecotoxicological and other relevant data have subsequently been used to
generate environmental risk assessment and this is detailed in Appendix H.
1.16. Relevant study summaries can be found in Appendix J.
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DECEMBER 2019
2. Hazardous properties
Hazard classification of mefentrifluconazole
2.1. The hazard classification proposed for mefentrifluconazole is outlined in Table 1.
Table 1: Proposed classification for mefentrifluconazole
Hazard endpoint Classification
Contact sensitisation 6.5B
Aquatic ecotoxicity 9.1A
Toxicity to terrestrial vertebrates 9.3C
2.2. Mefentrifluconazole is of very low acute toxicity in mammals by oral, dermal, inhalation routes and
should not be classified. It is not a skin or eye irritant. However, mefentrifluconazole was found to be a
contact sensitiser and should be classified as 6.5B. It was found not to be genotoxic, carcinogenic,
and does not cause reproductive or developmental toxicity, or target organ toxicity.
2.3. Mefentrifluconazole is very ecotoxic in the aquatic environment (9.1A) and harmful to terrestrial
vertebrates (9.3C), it is not ecotoxic in the soil environment or to terrestrial invertebrates.
Hazard classification of Revystar® Fungicide
2.4. The hazard classifications of Revystar® Fungicide determined by the EPA staff are 6.1D for both
acute oral and inhalation toxicity. The substance is irritating to both the skin and eyes, and is a weak
contact sensitiser and is respectively classified 6.3A, 6.4B, and 6.5B for these hazards (Table 2). The
hazard classifications of Revystar® Fungicide were determined based on the information provided by
the applicant (including toxicity and ecotoxicity studies), information on the individual components of
Revystar® Fungicide, mixture rules and other available information (EC 2017). Table 4 in Appendix F
shows the method used for classification and indicates the main component that contributes to each
hazard classification.
Table 2: Hazard classification of Revystar® Fungicide
Hazard EPA classification
Acute toxicity (oral) 6.1D
Acute toxicity (inhalation) 6.1D
Skin irritancy/corrosivity 6.3A
Eye irritancy/corrosivity 6.4A
Contact sensitisation 6.5B
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Hazard EPA classification
Target organ or systemic (oral) 6.9B
Aquatic ecotoxicity 9.1B
Terrestrial vertebrate ecotoxicity 9.3C
2.5. Mammalian toxicity studies with Revystar® Fungicide indicate that the substance is of low acute
toxicity and should be classified 6.1D for acute oral and inhalation toxicity and is not classifiable for
acute dermal toxicity. The substance is irritating to both the skin and eyes, and is a contact sensitiser
(albeit weak) and is respectively classified 6.3A, 6.4B, and 6.5B for these hazards. A 6.9B
classification for target organ specific toxicity is present due to the fluxapyroxad active ingredient.
2.6. The proposed ecotoxicity hazard classification of Revystar® Fungicide is: 9.1B (ecotoxic in the aquatic
environment) and 9.3C (harmful to terrestrial vertebrates). The EPA staff classification of Revystar®
Fungicide differed from that of the applicant in that the applicant did not classify it for toxicity to
terrestrial vertebrates.
Identification of components of concern (CMRs, vPBTs etc)
The following component(s) that are present in Revystar® Fungicide were identified to be of concern as they
are known / suspected to be a CMR / vPBT etc:
a) N,N-dimethylformamide (DMF; 68-12-2); reproductive hazard (6.8A): 0.5 g/kg
b) Toluene (108-88-3); reproductive hazard (6.8B): 1 g/kg
c) 1,2,4-(1H)-triazole (288-88-0); reproductive hazard (6.8A): 1 g/kg
These are considered relevant impurities and the maximum concentrations are expressed in relation to the
content of mefentrifluconazole.
3. Risk assessment context
3.1. It is considered that there is potential for significant exposure to people and the environment during
the use phase of the lifecycle of Revystar® Fungicide. As such, quantitative risk assessments have
been undertaken to understand the likely exposures to the substance under the use conditions
proposed by the applicant, using the endpoint data available and the standard risk assessment
methodologies used by the EPA (EPA 2018).
3.2. During the importation, manufacture, transportation, storage and disposal of this substance, it is
estimated that the proposed controls and other legislative requirements will sufficiently mitigate risks to
a negligible level. This assessment takes into account the existing EPA Notices around packaging,
identification and disposal of hazardous substances. In addition, the Land Transport Rule 45001, Civil
Aviation Act 1990, Maritime Transport Act 1994 and New Zealand’s Health and Safety at Work (HSW)
requirements all have provisions for the safe management of hazardous substances.
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4. Human health risk assessment
4.1. The risks (from the use of mefentrifluconazole are considered as a proxy for Revystar® Fungicide) on
users and operators of the substance, re-entry workers and bystanders. Full details can be found in
Appendix G: Human health risk assessment.
4.2. Operator Exposure:
Predicted operator exposures to mefentrifluconazole are below the Acceptable Operator Exposure
Level (AOEL) for each use pattern, even without the use of personal protective equipment (PPE).
Therefore operator exposures are not expected to result in adverse health effects
Although the quantitative risk assessment indicates that PPE is not required to ensure that exposures
are below the AOEL, the requirements under HSW (HS), and in particular Regulations 13.7 and 13.8,
state that personal protective equipment is to be used to minimise risks to the health and safety of
workers.
4.3. Worker re-entry:
Predicted exposures to mefentrifluconazole for workers re-entering and working in areas where
Revystar® Fungicide has been applied are below the AOEL. No re-entry intervals are necessary
4.4. Bystanders:
Estimated bystander exposure from spray drift after application of Revystar® Fungicide to cereals is
below the AOEL. No buffer zone is required to protect bystanders
4.5. Impurities:
Three impurities of toxicological concern were identified by the EPA (Appendix A). The Certificate of
Analysis (CoA) indicates all are well below the maximum allowable levels.
4.6. Overall human health conclusion:
It is considered that the risks to human health from the proposed use of Revystar® Fungicide are
acceptable without the use of Personal Protective Equipment (PPE), application of re-entry intervals,
or enforcement of no-spray buffer zones to protect bystanders.
5. Environmental risk assessment
5.1. No product-specific ecotoxicity data is available for the formulated substance Revystar® Fungicide
(BAS 752 00 F). The applicant has performed a mixture toxicity assessment, which establishes which
active ingredient mostly contributes to the toxicity for each area of the risk assessment, assuming
additivity, following EFSA Guidance (EFSA 2013). This is based on the individual toxicity endpoints for
each of the active ingredients fluxapyroxad and mefentrifluconazole, and their relative contribution to
the formulation.
5.2. Following publication of the US EPA’s Environmental Fate and Ecological Risk Assessment for
mefentrifluconazole (US EPA 2019) and the Canadian Pest Management Regulatory Agency’s
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(PMRA) Proposed Registration Decision for mefentrifluconazole and related use end products (PMRA
2019), it is apparent that ecotoxicity formulation data are available for other mefentrifluconazole-
containing formulations. The EPA has therefore performed a mixture toxicity assessment, also
following the EFSA guidance (EFSA 2013) based on this information. Full details can be found in
Appendix H.
5.3. Since the active ingredient fluxapyroxad has already been approved in New Zealand in other
formulations for similar uses at similar rates, this environmental risk assessment focusses only on the
active ingredient mefentrifluconazole, which is new to New Zealand. Full details can be found in
Appendix H.
5.4. Aquatic environment:
Estimated Environmental Concentrations (EECs) of mefentrifluconazole applied as the formulated
product Revystar resulted in calculated Risk Quotients (RQs) above the Level Of Concern (LOC) for
the aquatic environment. To mitigate these risks, it is proposed to apply controls to reduce spray-drift
into the aquatic environment.
5.5. Groundwater:
For mefentrifluconazole and its metabolite M750F001 (1,2,4-triazole) the predicted concentration in
groundwater is below the 0.1 µg/L trigger level set by the European regulators. Therefore, risks to
groundwater are considered below the level of concern
5.6. Sediment:
The risk quotients for sediment-dwelling organisms following both ground-based and aerial application
were both identified as potentially being above the level of concern (LOC = 1).
Only one chronic endpoint, which is not an absolute value, was available for sediment-dwelling
organisms, and the risk assessment was performed with this value (28-day NOEC of ≥1.158 mg ai/kg
for Chironomus riparius). The No Observed Effect Concentration (NOEC) determined in this case was
the highest concentration tested, and no significant effects were observed at this concentration. If a
higher concentration had been tested, the NOEC could potentially be higher, thus resulting in a lower
risk.
Using a weight-of-evidence approach, given the uncertainty in the determined NOEC value, the fact
that the active ingredient mefentrifluconazole is a fungicide (and no risks were identified for pollinators
or non-target arthropods), and other regulators (EFSA 2018) concluded that risks to sediment-dwelling
organisms were low, risks to sediment-dwelling organisms are considered to be low.
5.7. Soil organisms:
Acute TERs for soil organisms for the active ingredient mefentrifluconazole following application of
Revystar® Fungicide are below the LOC for non-threatened and threatened species, both in-field and
off-field.
Chronic TERs for soil organisms for the active ingredient mefentrifluconazole following application of
Revystar® Fungicide are above the LOC for threatened species in-field. TERs were below the LOC for
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non-threatened species in-field, as well as for off-field for both non-threatened and threatened species.
Due to the risk identified for threatened earthworm species in-field, chronic TER values were refined,
taking into account interception by the crop (80%). The chronic TER for threatened species in-field is
still above the LOC however. Further evaluation indicated that threatened species are unlikely present
in the application areas of Revystar® Fungicide as a result the risk is considered to be below the LOC.
In regard to soil accumulation, the acute TER values were below the level of concern for both non-
threatened and threatened species. At Tier I (assuming 0% crop interception), chronic risks to
earthworms were above the LOC for both non-threatened and threatened species.
At Tier II (assuming 80% crop interception corresponding to growth stage BBCH 30-39 as described
above, is the earliest growth stage that the substance will be applied), chronic risks were identified
only for threatened species, which are considered unlikely to be exposed to Revystar® Fungicide in-
field.
5.8. Non-target Plants:
Risk Quotients (RQs) to non-target plants calculated for mefentrifluconazole when applied to cereals
as the formulated product Revystar® Fungicide are below the level of concern
5.9. Birds:
TER values for birds calculated for the active ingredient mefentrifluconazole when applied to cereals
as the formulated product Revystar® Fungicide are below the LOC for acute risks, and any risks are
negligible. In the reproductive screening assessment, the TER values indicate a chronic risk above the
LOC to non-threatened and threatened bird species. After the Tier I risk assessment, risks to non-
threatened and threatened species of birds are considered below the LOC. The risks from secondary
poisoning is considered to be low
5.10. Pollinators:
The risks to pollinators are below the LOC and any risks are negligible
5.11. Non-target Arthropods:
Risks to non-target arthropods are below the LOC for both off-field and in-field.
5.12. Overall Ecological risk assessment conclusion:
It is considered that the risks to the environment from the proposed use of Revystar® Fungicide are
acceptable with the proposed controls
6. Proposed controls
6.1. More details about proposed controls are available in Appendix I.
Application rate
6.2. Maximum application rate of 150 g mefentrifluconazole/ha, maximum two applications per year with a
minimum interval between applications of 21 days.
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6.3. Maximum application rate of 75 g fluxapyroxad/ha, maximum two applications per year with a
minimum interval between applications of 21 days.
Maximum impurity limit
6.4. Impurity limits for mefentrifluconazole have been identified by the EU. The EPA has proposed the
following maximum impurity limits: N,N-dimethylformamide (DMF; 68-12-2): 0.5 g/kg; toluene (108-88-
3): 1 g/kg; 1,2,4-(1H)-triazole (288-88-0): 1 g/kg
Application method
6.5. Revystar must not be applied when wind speeds are less than 3 km/hr or more than 20 km/hr as
measured at the application site.
6.6. Apply with ground-based equipment and minimum medium droplets, as defined by the American
Society of Agricultural and Biological Engineers ASABE Standard (S572) or the British Crop
Production Council guideline. This information should be required on the label so that users are aware
of this control.
For aerial application, use minimum coarse droplets, as defined by the American Society of
Agricultural and Biological Engineers ASABE Standard (S572) or the British Crop Production Council
guideline. This information should be required on the label so that users are aware of this control.
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Appendix A: Identity of the active ingredient, use pattern and mode of action
Identity of the active ingredient and metabolites
As this is the first full application under Part 5 of the Hazardous Substances and New Organisms (HSNO)
Act 1996 considered for mefentrifluconazole, general data derived from the application form and from
Barbieri, R.F. (2018); Volume 1: Chemistry & Manufacture BASF Doc ID: 2018/NZ105 are provided in Table
3.
Table 3: Identification of mefentrifluconazole
IUPAC name (2RS)-2-[4-(4-chlorophenoxy)-2-(trifluoromethyl)phenyl]-1-(1H-
1,2,4-triazol-1-yl)propan-2-ol
CAS name alpha-[4-(4-chlorophenoxy)-2-(trifluoromethyl)phenyl]-alpha-
methyl-1H-1,2,4-triazole-1-ethanol
Molecular formula C18H15ClF3N3O2
CAS Number 1417782-03-6
Molecular weight 397.8 g/mol
Structural formula
Purity ≥970 g/kg
Significant
impurities/additives
(% concentration)
2-[4-(4-chlorophenoxy)-2-(trifluoromethyl)phenyl]-1-(4H-1,2,4-
triazol-4-yl)propan-2-ol; (5886575) : ≤23 g/kg
2-[4-(4-chlorophenoxy)-2-(trifluoromethyl)phenyl]-1-(1H-1,2,4-
triazol-1-yl)butan-2-ol; 5832500: ≤ 10 g/kg
1-(4-chlorophenoxy)-3-(trifluoromethyl)benzene; 5958976: ≤ 2.0
g/kg
Other international
classification & labelling
None identified
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Regulatory status
The regulatory history of mefentrifluconazole is summarised in Table 4 below.
Table 4: regulatory status of mefentrifluconazole and fluxapyroxad
Active ingredient
name
Regulatory history in
New Zealand
International regulatory history
(Australia, Canada, Europe,
Japan, USA)
mefentrifluconazole New to Zealand Europe, Australia, and USA
fluxapyroxad Approved Approved in EU, USA, Canada,
Australia
The active ingredient contained in Revystar® Fungicide, mefentrifluconazole, has not previously been
approved in New Zealand for use as a fungicide. It has been approved internationally for this use pattern in
Europe, Australia, and the USA. The active ingredient fluxapyroxad has been approved in New Zealand as a
fungicide for cereals.
The active ingredient fluxapyroxad, contained in Revystar® Fungicide has previously been approved in New
Zealand for use on cereal grains at a similar application rate (Adexar, application APP201884, approval
HSR100948).
Impurities and or restrictions on purity or composition
Impurity limits for mefentrifluconazole have been identified by the EU (EC 2019)These are:
N,N-dimethylformamide (DMF; 68-12-2): 0.5 g/kg
toluene (108-88-3): 1 g/kg
1,2,4-(1H)-triazole (288-88-0): 1 g/kg
Use pattern and mode of action
Use pattern
Revystar® Fungicide is an emulsifiable concentrate which is diluted in water (150-300 litres of water per
hectare). The applicant seeks to have Revystar® Fungicide approved for ground based and aerial
application.
Application will be at the rate of 1 – 1.5 L of product per hectare (L/ha) which is equivalent to 0.100 – 0.150
kg/ha of mefentrifluconazole and 0.050 - 0.075 kg/ha of fluxapyroxad, with a maximum frequency of 2
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applications per year a minimum of 21 days apart. More details on the intended uses for Revystar®
Fungicide are given in Table 5.
Mode of action
The active mefentrifluconazole is a fungicide belonging to the group of the sterol biosynthesis inhibitors (SBI,
mode of action class G – FRAC). Within the SBIs, it belongs to the sub group of demethylation inhibitor (DMI,
G1) and the chemical group of triazoles. The primary mode of action of DMIs is the blocking of ergosterol
biosynthesis through inhibition of cytochrome P450 sterol 14α-demethylase (CYP51). The depletion of
ergosterol and accumulation of non-functional 14α-methyl sterols results in inhibition of growth and cell
membrane disruption.
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Table 5: List of intended uses for Revystar® Fungicide
Crop
and/or
situation
(a)
Use
patt
ern
(b)
Pests or
group of
pests
controlled
(c)
Mixture Application Application rate per treatment
PHI
Remarks
(l) Type
(d-f)
Conc of ai
(g)
Method
and kind
(h-i)
Growth
stage &
season (j)
Num
ber
Min
max
(k)
Interval
between
applicatio
ns – days
(minimum)
kg ai/hL
min max
water
L/ha
min max
kg ai/ha
max
wheat,
barley,
oats,
ryecorn
triticale
and grass
seed
(ryegrass)
F foliar fungi EC
mefentriflu
conazole:
100 g/L
fluxapyrox
ad: 50 g/L
High
volume
spraying
(boom
spray or
aerial
application
Up to end
of
flowering
(Zadox GS
69)
spring/sum
mer
1 - 2 21 days
mefentrifluconaz
ole: 0.033 –
0.10
fluxapyroxad:
0.0167 – 0.050
150 –
300
ground,
60 air
mefentriflu
conazole:
0.10 –
0.150
fluxapyrox
ad: 0.05 –
0.075
Cereal
feed: 28
days
Cereal
grain: 42
days
Rye
grass
seed
crops: 14
days
NA
a Where relevant, the use situation should be described (eg fumigation of soil) b Outdoor or field use (F), glasshouse application (G) or indoor application (I). c eg biting and sucking insects, soil borne insects, foliar fungi, weeds d eg wettable powder (WP), emulsifiable concentrate (EC), granule (GR) e CropLife international, 2008. Technical Monograph no 2, 6th edition. Catalogue of pesticide formulation types and international coding system f All abbreviations used must be explained
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g g/kg or g/l or others h Method, eg high volume spraying, low volume spraying, spreading, dusting, drench, aerial, etc i Kind, eg overall, broadcast, aerial spraying, row, individual plant, between the plant - type of equipment used must be indicated. If spraying include droplet size spectrum j growth stage at last treatment (BBCH Monograph, Growth Stages of Plants, 1997, Blackwell (ISBN 3-8263-3152-4) , including where relevant, information on season at time of application k Indicate the minimum and maximum number of application possible under practical conditions of use l Remarks may include: Extent of use/economic importance/restrictions
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Appendix B: Physico-chemical properties of Revystar® Fungicide
The physico-chemical properties of Revystar® Fungicide are listed in Table 6.
Table 6: Physical and chemical properties of Revystar® Fungicide
Property Value Reference
Colour Dark yellow Barbieri, R.F. (2018); Volume 1:
Chemistry & Manufacture BASF Doc
ID: 2018/NZ105 and the SDS for
Revystar XL
Odour Mild, aromatic
Physical state Liquid
pH 5-7
Freezing point < -20°C
Flash point 112°C
Flammability Not highly flammable
Ignition temperature 380°C
Vapour pressure ~1 hPa (15°C)
Viscosity ~76 mPa.s (20°C, 100 1/s)
~32 mPa.s (40°C, 100 1/s)
Density ~1.02 g/cm3 (20°C)
Water Solubility (20°C) Emulsifiable
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Appendix C: Mammalian toxicology
Unless otherwise noted, all studies were conducted according to GLP and were fully compliant with the
requirements of the international test guidelines followed. Two in vitro studies assessing skin and eye
irritation were not summarised as they were only considered to be supportive in nature and did not impact
the classification.
The only data summarised in this memo are that for the new active, mefentrifluconazole, and the substance
Revystar. The other active ingredient in the substance, fluxapyroxad, has been previously approved for use
in New Zealand (HSR100948 and others).
Executive summaries and list of endpoints for Revystar® Fungicide
The mammalian toxicology data for Revystar® Fungicide are summarised in Table 7.
Table 7: Summary of mammalian toxicology data for Revystar® Fungicide
Endpoint
(Test Guideline)
Klimisch
score Result
HSNO
Classification Reference
Acute oral toxicity
(OECD 423; Commission
Regulation (EC) No
440/2008; US EPA OPPTS
870.1100)
1 LD50: 300 - 2000
mg/kg bw 6.1D
Appendix J; Table 56;
2014/1170783
Acute dermal toxicity
(OECD 402; Commission
Regulation (EC) No
440/2008; US EPA OPPTS
870.1200)
1 LD50: >5000
mg/kg bw No
Appendix J; Table 57;
2014/1170784
Acute inhalation toxicity
(OECD 403; Commission
Regulation (EC) No
1907/2006 and 440/2008; US
EPA OPPTS 870.1300)
1 LC50: 1.9 - 5.1
mg/L 6.1D
Appendix J; Table 58;
2014/1132774
Acute toxicity (aspiration
hazard) 1
Viscosity:
~76 mPa.s (20°C,
100 1/s)
~32 mPa.s (40°C,
100 1/s)
No
Appendix B; Table 6;
2018/NZ105 and the
SDS for Revystar XL
Skin irritation/corrosion
(OECD 404; Commission
Regulation (EC) No
1
Irritating
Mean score -
Erythema: 3.0
Oedema: 1.6
6.3A Appendix J; Table 59;
2014/1170785
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Endpoint
(Test Guideline)
Klimisch
score Result
HSNO
Classification Reference
440/2008; US EPA OPPTS
870.2500)
Eye irritation/corrosion
(OECD 405; Commission
Regulation (EC) No
440/2008; US EPA OPPTS
870.2400)
1
Irritating
Mean Draize
Score -
Cornea
-Opacity: 1.0
Conjunctiva
-Redness: 1.6
-Chemosis: 1.1
Iris: 0.6
6.4A Appendix J; Table 60;
2014/1170786
Contact sensitisation
(OECD 429; Commission
Regulation (EC) No.
440/2008, B.42)
1
Sensitising
SI at 25% was
4.06; EC3: 19.6%
6.5B (SI >3) Appendix J; Table 61;
2014/1170787
Executive summaries and list of endpoints for mefentrifluconazole
All data for mefentrifluconazole were sourced from the EU Draft Assessment Report [DAR (EC 2017)
Volume 3 – B.6 (AS)] and from study reports submitted from the applicant.
Acute toxicity, skin and eye irritation, contact sensitisation and genotoxicity data for mefentrifluconazole are
summarised in Table 8.
Table 8: Summary of acute toxicity, irritation, sensitisation and genotoxicity data for
mefentrifluconazole (BAS 750F)
Endpoint
(Test Guideline) Klimisch score Result Classification Reference
Acute oral toxicity
(OECD 423; US EPA
OPPTS 870.1100; EC No
440/2008)
1 LD50: >2000
mg/kg bw No
EC DAR (EC 2017)
/1149656
Acute dermal toxicity
(OECD 402; US EPA
OPPTS 870.1200; EC No
440 / 2008)
1 LD50: >5000
mg/kg bw No
EC DAR (EC 2017)
/1149657
Acute inhalation toxicity 1 LC50: >5.3 mg/L No EC DAR (EC 2017)
/1127433
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Endpoint
(Test Guideline) Klimisch score Result Classification Reference
(OECD 403; US EPA
OPPTS 870.1300; EC No
440/2008, B.2)
Skin irritation/corrosion
(OECD 404; US EPA
OPPTS 870.2500; EC No
440/2008)
1
Non-irritating
Mean score -
Erythema: 0.0
Oedema: 0.0
No EC DAR (EC 2017)
1150122
Eye irritation/corrosion
(OECD 405; US EPA
OPPTS 870.2400; EC No
440/2008)
1
Non-irritating
Mean Draize
Score -
Cornea
-Opacity: 0.0
Conjunctiva
-Redness: 0.4
-Chemosis: 0.0
Iris: 0.0
No EC DAR (EC 2017)
/1150121
Contact sensitisation
(OECD 406; US EPA
OPPTS 870.2600; EC No
440/2008, B.6)
1
Sensitisation
(positive
reaction in 6/10
animals)
6.5B
EC DAR (EC 2017)
/1150123
Mutagenicity (3 studies): In
Vitro
Reverse mutation assay in
bacteria (OECD 471; US
EPA OPPTS 870.5100; EC
No. 440/2008, B.13/B.14)
Forward mutation assay in
mammalian cells (OECD
476; US EPA OPPTS
870.5300; EC No. 440/2008,
B.17)
Cytogenicity in mammalian
cells (OECD 487; EC No.
640/2012, B.49)
1 Negative (±S9)
No
EC DAR (EC 2017)
2014/1128030
2015/1116956
2015/1112683
2015/1101908
2013/1375108
2015/1101907
Mutagenicity: In Vivo
Micronucleus test 1 Negative
EC DAR (EC 2017)
/1043159
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Endpoint
(Test Guideline) Klimisch score Result Classification Reference
(OECD 474; US EPA
OPPTS 870.5395; EC No.
440/2008, B.12)
Results of the repeated dose toxicity studies with mefentrifluconazole are summarised in Table 9.
Table 9: Summary of repeated dose studies with mefentrifluconazole (BAS 750F)
Study type
NOAEL
(mg/kg
bw/day)
LOAEL
(mg/kg
bw/day
Key effect Reference
28-day dermal study: rats
(OECD 410; US EPA
OPPTS 870.3200; EC No
440/2008)
1000 NA No effects observed at the
highest dose
EC DAR (EC
2017)
/1170751
90-day oral toxicity: rats
(OECD 408; US EPA
OPPTS 870.3100; EC No
440/2008)
76 males (M) /
91 females (F) 256 / 314
Decreased bw and bw gain,
increased liver wt, impairment
of liver function (clinical
chemistry changes)
EC DAR (EC
2017)
/1198721
90-day oral toxicity: mice
(OECD 408; US EPA
OPPTS 870.3100; EC No
440/2008)
11 M / 15 F 58 / 67 Decreased bw gain, increased
liver wt and cell hypertrophy
EC DAR (EC
2017)
/1046542
90-day oral toxicity: dogs
(OECD 409; US EPA
OPPTS 870.3150; EC No
440/2008, B.27)
90 180
Decreased food intake and bw
gain, increased liver wt and
altered liver function (clinical
chemistry changes)
EC DAR (EC
2017)
/1000530
1-year oral toxicity: dogs
(OECD 452; US EPA
OCSPP 870.4100)
30 M / F 150 M / F
Decreased bw and bw gain,
increased liver wt and altered
liver function (clinical
chemistry changes)
EC DAR (EC
2017)
/1000645
Number on
study report
2016/1273716
18-month dietary chronic
toxicity/carcinogenicity
study: mice
(OECD 451; US EPA
OPPTS 870.4200)
chronic: 3.5 M
/ 4.9 F
carc.: 36 M /
61.5 F
chronic: 36 /
62
carcinogenicity
: not
carcinogenic
Decreased bw and bw gain,
increased relative liver wt, and
increased signs of
(pre)degeneration in liver cells
Not carcinogenic in mice
EC DAR (EC
2017)
1000532
Number on
study report
015/7007530
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Study type
NOAEL
(mg/kg
bw/day)
LOAEL
(mg/kg
bw/day
Key effect Reference
2-year chronic
toxicity/carcinogenicity: rat
(OECD 453; US EPA
OPPTS 870.4300; EC No
440/2008, B.33)
chronic: 4 M /
38 F
carc.: 163 M /
302 F
chronic: 26 /
312
carc.: not
carcinogenic
Altered clinical chemistry
parameters in males
Not carcinogenic in mice
EC DAR (EC
2017)
/1000531
Developmental toxicity: rats
(OECD 414; US EPA
OPPTS 870.3700; EC No
440/2008)
Maternal: 150
Offspring: 400
Maternal: 400
Offspring: NA
Maternal: decreased food
consumption, bw and bw gain
Offspring: No treatment related
effects
EC DAR (EC
2017)
/1170755
Developmental toxicity:
rabbits (OECD 414; US
EPA OPPTS 870.3700; EC
No 440/2008)
Maternal: 25
Offspring: 25 NA
Maternal: No treatment related
effects
Offspring: No treatment related
effects
EC DAR (EC
2017)
/1170757
2-generation reproductive
toxicity: rats
(OECD 416; US EPA
OPPTS 870.3800)
Parental: 25
Fertility: 200
Offspring: 75
Parental: 75
Fertility: No
effects at
highest dose
Offspring: 200
Parental: increases in some
clinical chemistry parameters
and liver wt
Fertility: No effects observed
Offspring: decrease in live
pups, pup wt, and wt gain
during lactation
EC DAR (EC
2017)
/1170754
Toxicokinetics and dermal absorption studies with mefentrifluconazole (BAS 750F) are summarised in Table
10.
Table 10: Summary of toxicokinetics and dermal absorption studies with mefentrifluconazole (BAS
750F)
Study type Results
Toxicokinetics
The absorption, distribution, excretion and metabolism of mefentrifluconazole in
mammals was investigated using a mixture of 14C-radiolabeled, 13C-labeled
mefentrifluconazole and non-labelled mefentrifluconazole.
The plasma kinetics of mefentrifluconazole in rats and mice demonstrated high
absorption (~85%) following oral administration, indicated potential enterohepatic
recirculation of the triazole moiety, and showed fast excretion and a more-or-less linear
correlation of the internal exposure to the oral dose.
The biliary excretion experiments confirmed that excretion was fast, more or less
complete and occurred to a major extent within three days after oral dosing in rats,
predominantly by the faecal route. There was no evidence of accumulation. The
distribution experiments demonstrated that mefentrifluconazole was rapidly and widely
distributed in rats after a single oral administration. The active substance was
extensively and rapidly metabolized resulting in rapid and extensive excretion (biliary
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and urinary routes). Results of a comparative in vitro metabolism study showed that the
metabolite patterns of 14C-BAS 750 F formed after incubation with human, rat and
mouse hepatocytes was quantitatively different but qualitatively the same in rat
hepatocytes compared with human cells. The study did not detect a unique human
metabolite and so the rat metabolism study is concluded to provide results that are
representative of human metabolism.
Dermal absorption
The results of an in vitro dermal absorption study conducted using radio-labelled BAS
750 F active in BAS 752 00 F showed 0.36 ± 0.26% and 2.82 ± 0.98% of the applied
dose of 14C-BAS 750 F was recovered as absorbed dose for the concentrate and as a
1:200 (v/v) spray dilution respectively.
General conclusion about mefentrifluconazole
Acute toxicity, irritation and sensitisation
Mefentrifluconazole exhibits very low acute toxicity by all exposure routes (oral, dermal, and inhalation) and
should not be classified. It is not a skin or eye irritant and should not be classified. It was shown to have the
potential be a contact sensitiser (albeit weak) and should be classified 6.5B.
Mutagenicity
Mefentrifluconazole showed no evidence of mutagenicity in several in vitro and in vivo assays.
Carcinogenicity
Mefentrifluconazole showed no evidence of carcinogenicity in either mice or rats.
Reproductive and developmental toxicity
Mefentrifluconazole showed no evidence of developmental toxicity in rats and rabbits, or reproductive toxicity
in rats in a 2-generation study.
Target organ toxicity
The primary target organ seen in rats, mice and dogs was the liver. All three species exhibited dose
responsive weight increase, hepatocellular hypertrophy, and ultimately morphological and degenerative
effects (mice only) and alterations in clinical chemistries. These effects, in general, were observed at dose
levels greater than 100 mg/kg bw (levels not requiring classification) except in mice (58/67 mg/kg bw
males/females). In mice, this dose was also approximately at the maximum tolerated dose (MTD). The effect
was not deemed of sufficient magnitude to classify as 6.9B, in the absence of similar findings in other animal
models.
Toxicokinetics and dermal absorption
The absorption, distribution, excretion and metabolism of mefentrifluconazole in mammals was investigated
using a mixture of 14C-radiolabeled, 13C-labeled mefentrifluconazole and non-labelled mefentrifluconazole.
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The plasma kinetics of mefentrifluconazole in rats and mice demonstrated high absorption (~85%) following
oral administration, indicated potential enterohepatic recirculation of the triazole moiety, and showed fast
excretion and a more-or-less linear correlation of the internal exposure to the oral dose.
The biliary excretion experiments confirmed that excretion was fast, more or less complete and occurred to a
major extent within three days after oral dosing in rats, predominantly by the faecal route. There was no
evidence of accumulation. The distribution experiments demonstrated that mefentrifluconazole was rapidly
and widely distributed in rats after a single oral administration. The active ingredient was extensively and
rapidly metabolized resulting in rapid and extensive excretion (biliary and urinary routes). Results of a
comparative in vitro metabolism study showed no unique human metabolites such that the rat metabolism
study is concluded to provide results that are representative of human metabolism.
The results of an in vitro dermal absorption study conducted using radio-labelled BAS 750 F active in BAS
752 00 F showed 0.36 ± 0.26 and 2.82 ± 0.98% of the applied dose of 14C-BAS 750 F were recovered as
absorbed dose for the concentrate and as a 1:200 (v/v) spray dilution respectively.
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Appendix D: Environmental fate
The active ingredient fluxapyroxad contained in Revystar® Fungicide has previously been approved in New
Zealand for use on cereal grains at a similar application rate (Adexar, application APP201884, approval
HSR100948 and others) and accordingly will not be reviewed or assessed in the context of this memo.
This section focusses only on the active ingredient mefentrifluconazole, which has not previously been
approved in New Zealand.
Executive summaries and list of endpoints
Unless otherwise noted, all studies were conducted according to GLP and were fully compliant with all
requirements of the standard international test methods used. All data for mefentrifluconazole and its
metabolites were sourced from the mefentrifluconazole DAR unless otherwise stated. Study summaries have
only been included in Appendix J where there are comments in regard to individual studies.
Residues relevant to the environment
In laboratory and field degradation studies in soil and water, four major metabolites of mefentrifluconazole
(ie, those found at ≥10% active radioactivity (AR) at any sample interval) were identified: M750F001 (1,2,4-
triazole), M750F005, M750F006 and M750F007. The major metabolites are listed in Table 11.
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Table 11: Major metabolites of mefentrifluconazole1
Metabolite
code Chemical name (IUPAC)
Molecular
weight (g/mol)
Chemical
formula
Max. % formed1
Reference
Soil Sediment Water
M750F001 1,2,4-triazole 69.1 C2H3N3 - 4.9 10.2 EC DAR (EC 2017): Doc ID
2015/1000941
M750F005
4-{4-[2-hydroxy-1-(1H-1,2,4-
triazol-1-yl)propan-2-yl]-3-
(trifluoromethyl)phenoxy}phenol
379.34 C18H16F3N3O3 - - 32.2
EC DAR (EC 2017): Doc ID
2015/7000233
M750F006
6-(4-chlorophenoxy)-3-methyl-3-
(1H-1,2,4-triazol-1-ylmethyl)-2-
benzofuran-1(3H)-one
355.78 C18H14ClN3O3 - - 30.7
M750F007
6-(4-hydroxyphenoxy)-3-methyl-3-
(1H-1,2,4-triazol-1-ylmethyl)-2-
benzofuran-1(3H)-one
337.34 C18H15N3O4 - - 43.9
1 Only major metabolites defined as per the HSNO Act (“metabolites formed in amounts of equal to or more than 10% of the applied amount of substance and any time-
point evaluated during the degradation studies in the appropriate compartment under consideration (soil or water)”) have been listed. Only the maximum percent formed
of each of these metabolites is reported in this table. Metabolites listed may have been identified in other compartments but since this is not relevant to the
environmental risk assessment as they did not meet the “major metabolite” criteria, the values were not reported here
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Four major metabolites, defined as per the HSNO Act as metabolites, formed in amounts of equal to or more
than 10% of the applied amount of substance and any time-point evaluated during the degradation studies in
the appropriate compartment under consideration (soil or water) were identified.
Three major metabolites were identified in the aqueous photolysis study: M750F005, M750F006 and
M750F007 (Doc ID 2015/7000233). Another major metabolite, M750F001 (1,2,4-triazole) was detected in the
aquatic aerobic metabolism study (15.1% in the whole system).
It is noted that M750F001 (1,2,4-triazole) has a higher chronic toxicity to earthworms than the parent
mefentrifluconazole (NOEC of 1.0 mg ai/kg vs. 4.0 mg ai/kg). M750F001 (1,2,4-triazole) was only formed at a
maximum of 5.2% in the soil metabolism study and then declined, and therefore does not meet the HSNO
Act threshold of 10% for identifying (and thus consideration of) a major metabolite. As such, M750F001
(1,2,4-triazole) is not considered a major metabolite in soil.
M750F001 1,2,4-triazole will be included in the groundwater risk assessment however, due to its higher
mobility in soil than parent mefentrifluconazole.
Degradation and fate of mefentrifluconazole in aquatic environments
Information on the degradation and fate of mefentrifluconazole in the aquatic environment is summarised in
Table 12. Information on bioaccumulation potential is listed in Table 13. Values highlighted in bold are used
in the quantitative risk assessment.
Table 12: Degradation and fate of mefentrifluconazole in aquatic environments
Test type Mefentrifluconazole Reference
Ready biodegradation Not readily biodegradable EC DAR (EC 2017): Doc ID
2014/1239574
Aqueous photolysis half-life (DT50) 2.3 days1
EC DAR (EC 2017): Doc ID
2015/7000233
Aerobic mineralisation in surface
water (DT50)
No significant degradation observed, no
DT50 values could be calculated (pelagic
test system, OECD 309)
EC DAR (EC 2017): Doc ID
2015/1186902
Degradation in aerobic
water/sediment (whole system DT50)
122 days and 213 days
EC DAR (EC 2017): Doc ID
2015/1000941
Water solubility at 20°C [mg/L] 0.81 (water) EC DAR (EC 2017); Doc ID
2013/1397136
Hydrolysis half-life (DT50) Stable at pH 4-9
EC DAR (EC 2017): Doc ID
2015/1046919
1 Note that the aqueous photolysis value is based on continuous radiation. The actual direct photodegradation rate at
different temperatures and for different latitudes does not appear to have been calculated.
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Table 13: Bioaccumulation potential of mefentrifluconazole
Test type Mefentrifluconazole Reference
Partition coefficient octanol/water
[Log Pow]
3.4 (pH 7)1 EC DAR (EC 2017); Doc ID
2013/1382370
Fish bioconcentration (whole fish)
Rainbow trout, Onchorynchus mykiss
(BCF: 14-day uptake, 7-day
depuration)
385 (BCFKLg)2,3 Appendix J, Table 70; Salinas et
al. (2015c) [EC DAR (EC 2017):
Doc ID 2015/1122811]
1 Mefentrifluconazole is considered to be lipophilic (Log Kow >2)
2 BCFKLg: growth-corrected kinetic bioconcentration factor normalised to 5% lipid content
3 BCFKLg value of 385 should be treated with care (also see additional notes in Table 70)
Degradation and fate of mefentrifluconazole in soil
Information on the degradation and fate of mefentrifluconazole in the soil environment is summarised in
Table 14. Values highlighted in bold are used in the quantitative risk assessment.
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Table 14: Degradation and fate of mefentrifluconazole in soil
Test type Mefentrifluconazole Reference
Aerobic half-life in soil (laboratory)
Calculated 80th percentile, lab = ≥1000
days1
NA (calculated)
Range: DT50lab (non-normalised) = 201.9
to >1000 days (n = 4)
EC DAR (EC 2017): Doc ID
2014/1275177
DT50lab (non-normalised) = 433.7 days (n
= 1)
EC DAR (EC 2017): Doc ID
2015/1003306
DT50lab (non-normalised) both values
>1000 days (n = 2)
EC DAR (EC 2017): Doc ID
2014/1275178
Anaerobic degradation in soil
(DT50lab) 349, 780 and 899 days
EC DAR (EC 2017): Doc ID
2014/7003496
Aerobic half-life in soil (field)
Calculated 80th percentile, field = 309 days2 NA (calculated)
Range: DisT50field (non-normalised) = 101 to 292 days (n = 6)
Appendix J, Table 64; Jacobson
et al. (2016a) [EC DAR (EC
2017): Doc ID 2015/7006396]
Range: DegT50field (non-normalised) = 185.5 to 846.6 days (n = 6)
Appendix J, Table 65; Schäufele
(2015d) [EC DAR (EC 2017):
Doc ID 2015/1046920] and EC
DAR (EC 2017): Doc ID
2015/1249176
Accumulation behaviour in soil (field)
Accumulation behaviour of BAS 750 F in
soil under field conditions in the United
Kingdom following repeated application
onto winter wheat over several years.
This study is ongoing; no residue data is
presented within the interim report. Only
the study design.
Appendix J, Table 67; Schäufele
(2015b) [EC DAR (EC 2017):
Doc ID 2015/1076325]
Accumulation behaviour of BAS 750 F in
soil under field conditions in Germany
following repeated application onto winter
barley over several years
This study is ongoing; no residue data is
presented within the interim report. Only
the study design.
Appendix J, Table 68; Schäufele
(2015c) [EC DAR (EC 2017):
Doc ID 2015/1076326]
Soil photolysis half-life (DT50) 93 days (chlorophenyl-label) and 170
days (triazole-label)
Appendix J, Table 63; Hassink
and Delgado (2014a) [EC DAR
(EC 2017): Doc ID
2014/1181666]
Sorption to soil (Kd)3 Range: 29.75 to 121.5 mL/g
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Test type Mefentrifluconazole Reference
Lowest value non-sand soil: 30.63 mL/g Appendix J, Table 69; Sacchi
(2016) [EC DAR (EC 2017): Doc
ID 2016/3003661] Sorption to soil (Koc)3
Range: 2511 to 4958 mL/g
Lowest value non-sand soil: 2511 mL/g
Metabolites sorption to soil (Koc)
M750F005 = 7863 mL/g
M750F006 = 4919 mL/g
M750F007 = 3938 mL/g
[Note values are QSAR estimates]
EC DAR (EC 2017): Doc ID
2015/1260816
1 Non-normalised upper 80% lab DT50 of >1000, 543, 201.9, 474.5 (Doc ID 2014/1275177), 433.7 (Doc ID
2015/1003306.), >1000 and >1000 days (Doc ID 2014/1275178)
2 Non-normalised upper 80% field DT50 of 281, 286, 286, 266, 292, 101 (Appendix J, Table 64; Jacobson et al., 2016a),
185.5, 350.6, 267.6, 204.4, 846.6 and 313 days (Appendix J, Table 65; Schäufele, 2015d and Doc ID 2015/1249176)
3 Lowest value non-sandy soil used for risk assessment (Kd/Koc values measured in soils classified as “sand”, “coarse
sand”, “fine sand” or “loamy sand” are excluded as per the GENEECE2 guidance)
General conclusion about environmental fate
Mefentrifluconazole
Degradation and fate in the aquatic environment
Mefentrifluconazole does not meet the criteria to be considered rapidly degradable under the HSNO Act ie
degraded by at least 70% within 28 days, equivalent to a DT50 of 16 days (Doc ID 2014/1239574).
The aerobic mineralisation in surface water study (Doc ID: 2015/1186902) indicates that mefentrifluconazole
degrades extremely slowly in a pure water environment; no significant degradation was observed was
observed for the duration of the study (63 days). Total system DT50 values measured in the aerobic aquatic
metabolism study (water and sediment) were 122 days and 213 days, for the Berghäuser Altrhein system
and Ranschgraben systems, respectively (Doc ID: 2015/1000941). Mefentrifluconazole dissipated rapidly
(maximum DT50 = 1.7 days) from the water phase (likely due to sorption to sediment) and degraded at a
moderate rate in the sediment (maximum DT50 = 396 days).
Rapid photodegradation of mefentrifluconazole was observed in irradiated samples with a DT50 of 2.3 days;
no degradation was observed in the dark control samples (Doc ID 2015/7000233). Hydrolysis was
determined to play no role in the degradation of mefentrifluconazole (Doc ID: 2015/1046919).
Mefentrifluconazole is considered to have a low potential for bioaccumulation with a growth-corrected kinetic
bioconcentration factor (BCFKLG) of 385 (Appendix J, Table 70; Salinas et al., 2015c), which is below the
≥500 L/kg threshold in accordance with the HSNO Act. This value should be treated with care however,
since it was observed in the DAR that if a further concentration had been tested, the BCF value would
potentially increase to 655, which meets the HSNO criteria for the active ingredient to have potential for
bioaccumulation (>500).
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Degradation and fate in the soil environment
In the laboratory, aerobic soil half-lives for mefentrifluconazole range from 202 to >1000 days, with a non-
normalised 80% percentile DT50 of ≥1000 days (Doc IDs 2014/1275177, 2015/1003306 and 2014/1275178).
The exact 80% percentile DT50 could not be determined as some values were indicated as greater than 1000
days. In a field study carried out in the USA, half-lives were shorter and ranged from 101 to 292 days
(Appendix J, Table 64, Jacobson et al., 2016). In a field study performed in Europe DT50 values ranged from
186 to 847 days (Appendix J, Table 65; Schäufele, 2015d, and Doc ID: 2015/1249176). In conclusion
mefentrifluconazole is considered persistent in the soil environment (DT50 > 6 months).
Anaerobically, mefentrifluconazole degrades with half-lives ranging from 349 to 899 days (Doc ID
2014/7003496). Photolysis also plays a role in the degradation of mefentrifluconazole in soil with half-lives of
93 and 170 days measured using a chlorophenyl- and triazole-label, respectively (Appendix J, Table 63;
Hassink and Delgado, 2014a).
Mefentrifluconazole is considered slightly mobile to immobile in soil according to the McCall classification
system (McCall et al. 1981). As such, potential for leaching is considered to be low. This was confirmed in
the field dissipation study by Jacobson et al. (2016, Appendix J Table 64) where there was no significant
movement of mefentrifluconazole residues through the soil profile.
Mefentrifluconazole is considered highly persistent in both the aquatic environment and soil environment
according to Annex D of the HSNO Act (Information requirements and screening criteria), a substance is
considered persistent “if the half-life of the chemical in water is greater than two months, or that its half-life in
soil is greater than six months, or if its half-life in sediment is greater than six months”.
Metabolites
Four major metabolites, defined as per the HSNO Act as metabolites formed in amounts of equal to or more
than 10% of the applied amount of substance and any time-point evaluated during the degradation studies in
the appropriate compartment under consideration (soil or water) were identified.
Three major metabolites were identified in the aqueous photolysis study: M750F005, M750F006 and
M750F007 (Doc ID 2015/7000233). Another major metabolite, M750F001 (1,2,4-triazole) was detected in the
aquatic aerobic metabolism study (Doc ID: 2015/1000941).
It is noted that M750F001 (1,2,4-triazole) has a higher chronic toxicity to earthworms than the parent
mefentrifluconazole (NOEC of 1.0 mg ai/kg vs. 4.0 mg ai/kg). M750F001 (1,2,4-triazole) was only formed at a
maximum of 5.2% in the soil metabolism study and then declined, and therefore does not meet the HSNO
Act threshold of 10% for identifying (and thus consideration of) a major metabolite. As such, M750F001
(1,2,4-triazole) is not considered a major metabolite in soil.
M750F001 1,2,4-triazole will be included in the groundwater risk assessment however, due to its higher
mobility in soil than parent mefentrifluconazole.
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Appendix E: Ecotoxicity
The active ingredient fluxapyroxad contained in Revystar® Fungicide has previously been approved in New
Zealand for use on cereal grains at a similar application rate (Adexar, application APP201884, approval
HSR100948) and accordingly will not be reviewed or assessed in the context of this memo.
This section focusses only on the active ingredient mefentrifluconazole, which has not previously been
approved in New Zealand.
Executive summaries and list of endpoints
Unless otherwise noted, all studies were conducted according to GLP and were fully compliant with all
requirements of the standard international test methods used. All data for mefentrifluconazole and its
metabolites were sourced from the mefentrifluconazole DAR unless otherwise stated. Study summaries have
only been included in Appendix J where there are comments in regard to individual studies.
Aquatic toxicity
Table 15 contains the acute and chronic aquatic toxicity test results for the active ingredient
mefentriflucoanzole, and Table 16 contains the acute and chronic aquatic toxicity test results for the major
metabolites of mefentrifluconazole.
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Table 15: Summary of aquatic toxicity data for the active ingredient mefentrifluconazole
Test species Test type and duration Value Reference
Fish Acute
Rainbow trout, Oncorhynchus mykiss 96-hr LC50, flow-through 0.532 mg/L (mean measured) Appendix J, Table 71; Salinas
(2014a) [EC DAR (EC 2017): Doc
ID 2014/1036951]
Zebrafish, Danio rerio 96-hr LC50, flow-through 0.906 mg/L (mean measured) Appendix J, Table 72; Rzodeczko
(2015a) [EC DAR (EC 2017): Doc
ID 2015/1001581]
Sheepshead minnow, Cyprinodon variegates 96-hr LC50, static 0.761 mg/L (mean measured) EC DAR (EC 2017): Doc ID
2014/7002810
Common carp, Cyprinus carpio 96-hr LC50, semi-static 1.126 mg/L (mean measured) EC DAR (EC 2017): Doc ID
2015/1249071
Chronic
Zebrafish, Danio rerio NOEC 36-day, ELS, flow-through 0.027 mg ai/L (mean measured) Appendix J, Table 81; Salinas et al.
(2015a) [EC DAR (EC 2017): Doc
ID 2014/1262160]
NOEC, 140-day full life-cycle,
flow-through
0.022 mg ai/L (mean measured) Appendix J, Table 82; Salinas
(2017a) [Not in DAR. Doc ID
2016/1042889]
Sheepshead minnow, Cyprinodon variegates NOEC 35-day, ELS, flow-through 0.147 mg ai/L (mean measured)1 EC DAR (EC 2017): Doc ID
2015/70000619
Endocrine disruption to fish
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Zebrafish, Danio rerio NOEC 69-day, flow-through ≥0.045 mg ai/L (mean measured) Appendix J, Table 83; Salinas et al.
(2015b) [EC DAR (EC 2017): Doc
ID 2015/1099093]
Invertebrates Acute
Daphnia magna 48-hr EC50 0.944 mg/L (geometric mean
measured)
Appendix J, Table 73; Brzozowska
(2014a) [EC DAR (EC 2017): Doc
ID 2013/1250866]
Americamysis bahia 96-hr EC50, flow-through 1.30 mg/L (mean measured)
Appendix J, Table 74; VanHooser
(2014a) [EC DAR (EC 2017): Doc
ID 2014/7002845]
Eastern oyster, Crassostrea virginica 96-hr EC50, flow-through 0.947 mg ai/L (mean measured) EC DAR (EC 2017): Doc ID
2015/7000021
Chronic
Daphnia magna
NOEC, 21-day, semi-static 0.0091 mg ai/L (time-weighted mean) Appendix J, Table 84; Janson
(2014a) [EC DAR (EC 2017): Doc
ID 2014/1098028]
Mysid shrimp, Americamysis bahia NOEC, 28-day, flow-through 0.0132 mg ai/L (mean measured) EC DAR (EC 2017): Doc ID
2016/7001293
Daphnia pulex
NOEC, 21-day, semi-static 0.0276 mg ai/L (mean measured)2 Appendix J, Table 86; Janson
(2015a) [EC DAR (EC 2017): Doc
ID 2015/1003913]
Daphnia longispina
NOEC, 21-day, semi-static 0.0342 mg ai/L (time-weighted
mean)3
Appendix J, Table 85; Janson
(2015b) [EC DAR (EC 2017): Doc
ID 2015/1003912] and Amendment
Janson (2015c) [EC DAR (EC
2017): Doc ID 2015/1251197]4
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Sediment-dwelling aquatic invertebrates Acute
Chironomus dilutus (spiked sediment) NOEC, 10-day, semi-static 7.08 mg ai/kg dry sediment
(geometric mean measured)
Appendix J, Table 87; Clark
(2015a) [EC DAR (EC 2017): Doc
ID 2015/7000621]
Hyalella azteca (spiked sediment) NOEC, 10-day, semi-static ≥100 mg ai/kg dry sediment (mean
measured)
Appendix J, Table 88; Clark
(2015b) [EC DAR (EC 2017): Doc
ID 2015/7000622]
Leptocheirus plumulosus (spiked sediment) NOEC, 10-day, semi-static >95 mg ai/kg dry sediment (mean
measured)
Appendix J, Table 89; Clark
(2015c) [EC DAR (EC 2017): Doc
ID 2015/7000623]
Chronic
Chironomus riparius (spiked sediment) NOEC, 28-day, semi-static ≥1.158 mg/kg dry sediment (initial
measured)
Appendix J, Table 90; Backfisch
and Weltje (2015a) [EC DAR (EC
2017): Doc ID 2014/1243181]
Algae and aquatic macrophytes
Green alga, Pseudokirchneriella subcapitata 72-hr ErC50, static 1.352 mg/L (geometric mean
measured)
Appendix J, Table 75; Brzozowska
(2014b) [EC DAR (EC 2017): Doc
ID 2013/1250865]
Cyanobacterium, Anabaena flos-aquae 72-hr ErC50, static >3.08 mg/L (geometric mean
measured)5
Appendix J, Table 80; Bergfield
(2015c) [EC DAR (EC 2017): Doc
ID 2015/7000617]
Marine diatom, Skeletonema costatum 72-hr ErC50, static 0.679 mg/L (geometric mean
measured)6
Appendix J, Table 76; Bergfield
(2015a) [EC DAR (EC 2017): Doc
ID 2015/7000620] and Table 77;
Horn (2016a) [EC DAR (EC 2017):
Doc ID 2016/1292092]
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Freshwater diatom, Navicula pelliculosa 72-hr ErC50, static 1.347 mg/L (geometric mean
measured)7
Appendix J, Table 78; Bergfield
(2015b) [EC DAR (EC 2017): Doc
ID 2015/7000618] and Table 79;
Horn (2016b) [EC DAR (EC 2017):
Doc ID 2016/1292093]
Duckweed, Lemna gibba 7-day ErC50, static >1.894 mg/L (time-weighted mean)8 EC DAR (EC 2017): Doc ID
2014/1001322
1 Note this endpoint is reported as 0.16 mg/L (nominal) in the BASF list of ecotoxicity endpoints 2 Note this endpoint is reported as 0.0282 mg/L (nominal) in the BASF list of ecotoxicity endpoints 3 Note this endpoint is reported as 0.0338 mg/L (nominal) in the BASF list of ecotoxicity endpoints 4 Amendment (Appendix J, Table 85; Janson, 2015c) only relates to alkalinity and hardness value table where the decimal place was previously in the wrong place 5 Note this endpoint is reported as >3.20 mg/L (initial measured) in the BASF list of ecotoxicity endpoints 6 Note this endpoint is reported as 0.723 mg/L in the BASF list of ecotoxicity endpoints. This value is from the original study (Appendix J, Table 76; Bergfield, 2015a)
rather than the recalculation of endpoints (Appendix J, Table 77; Horn, 2016a) 7 Note this endpoint is reported as 1.57 mg/L in the BASF list of ecotoxicity endpoints, which is the 96-hr value. Typically the 72-hr endpoints are used. 8 Note this endpoint is reported as 2.017 mg/L (initial measured) in the BASF list of ecotoxicity endpoints
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Table 16: Summary of aquatic toxicity data for metabolites of mefentrifluconazole
Test species Test type and duration Value Reference
M750F001 (1,2,4-triazole)
Fish Acute
Rainbow trout, Oncorhynchus mykiss 96-hr LC50 760 mg/L (nominal)1 EC DAR (EC 2017): Doc ID
1983/1000494
Chronic
Rainbow trout, Oncorhynchus mykiss NOEC, 28-days 3.20 mg/L (nominal)1
Appendix J, Table 91; Dorgerloh and
Sommer (2002) [EC DAR (EC 2017):
Doc ID 2002/1007850]
Invertebrates Acute
Daphnia magna 48-hr EC50 >100 mg/L (nominal)1 EC DAR (EC 2017): Doc ID
1995/1001851
Algae and aquatic macrophytes
Green alga, Pseudokirchneriella subcapitata 72-hr ErC50 >31 mg/L1 (mean measured) EC DAR (EC 2017): Doc ID
2001/1022266
M750F005
Invertebrates Acute
Daphnia magna 48-hr EC50 >8.58 mg/L (geometric mean
measured)
EC DAR (EC 2017): Doc ID
2015/1001490
Algae and aquatic macrophytes
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Test species Test type and duration Value Reference
Green alga, Pseudokirchneriella subcapitata 72-hr ErC50 >8.572 mg/L (geometric mean
measured)
Appendix J, Table 92; Rzodeczko
(2016b) [EC DAR (EC 2017): Doc ID
2015/1184816]
M750F006
Fish Acute
Rainbow trout, Oncorhynchus mykiss 96-hr LC50 6.20 mg/L (geometric mean
measured)
Appendix J, Table 93, Rzodeczko
(2016c) [EC DAR (EC 2017): Doc ID
2016/1128152]
Invertebrates Acute
Daphnia magna 48-hr EC50 4.42 mg/L (geometric mean
measured)
Appendix J, Table 94; Rzodeczko
(2015c) [EC DAR (EC 2017): Doc ID
2015/1001492]
Algae and aquatic macrophytes
Green alga, Pseudokirchneriella subcapitata 72-hr ErC50 1.424 mg/L (geometric mean
measured)
Appendix J, Table 95; Rzodeczko
(2016c) [EC DAR (EC 2017): Doc ID
2015/1184815]
M750F007
Fish Acute
Rainbow trout, Oncorhynchus mykiss 96-hr LC50 >7.20 mg/L (geometric mean
measured)
EC DAR (EC 2017): Doc ID
2015/1001489
Invertebrates Acute
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Test species Test type and duration Value Reference
Daphnia magna 48-hr EC50 >10 mg/L (analytically confirmed
nominal)
Appendix J, Table 96; Backfisch and
Härthe (2015a) [EC DAR (EC 2017):
Doc ID 2015/1003915]
Algae and aquatic macrophytes
Green alga, Pseudokirchneriella subcapitata 72-hr ErC50 >10 mg/L (nominal) EC DAR (EC 2017): Doc ID
2015/1003914
1 Note that the majority of 1,2,4-triazole studies come from the Epoxiconazole DAR
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Metabolites
Based on the aquatic toxicity endpoints for mefentrifluconazole, as listed in Table 16 above, the parent
mefentrifluconazole is of higher toxicity to aquatic organisms than its major metabolites. As such, metabolites
M750F005, M750F006 and M750F007 have not been considered further in the aquatic risk assessment
since any controls for the parent will be protective of any risks from the metabolites. Metabolites M750F005,
M750F006 and M750F007 all exhibit lower mobility in soil than the parent active ingredient.
Although metabolite M750F001 (1,2,4-triazole) has lower aquatic toxicity than the parent, it will still be
assessed in the groundwater risk assessment due to its higher mobility.
Uncertainties and data gaps
No uncertainties or data gaps were identified in regard to aquatic toxicity of the active ingredient
mefentrifluconazole or its metabolites. It should be noted that no aquatic toxicity data for the formulated
substance Revystar Fungicide were available however. The additive toxicity calculations performed for
Daphnia magna showed that mefentrifluconazole was the driver of toxicity (99% contribution) and therefore,
the risk assessment performed for the active constituent alone can be used to conclude on risk to the end
use product.
General conclusion about aquatic toxicity
The active ingredient mefentrifluconazole triggers a 9.1A HSNO classification (very ecotoxic in the aquatic
environment) based on a 96-hr LC50 for the rainbow trout (Onchorhynchus mykiss) of 0.532 mg/L (Appendix
J, Table 71; Salinas, 2014a), a 48-hr EC50 for Daphnia magna of 0.944 mg/L (Appendix J, Table 73;
Brzozowska, 2014a) and a 96-hr ErC50 for the marine diatom (Skeletonema costatum) of 0.679 mg/L
(Appendix J, Table 76 and Table 77; Bergfield, 2015a and Horn, 2016a).
The formulation Revystar Fungicide triggers a 9.1B HSNO classification (ecotoxic in the aquatic
environment) based on mixture rules.
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Soil toxicity
Table 17 contains the acute and chronic soil toxicity test results for the active ingredient mefentrifluconazole.
Values in bold are those toxicity endpoints used for the risk assessment. Underlined values are those used
to determine the classification.
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Table 17: Summary of soil toxicity data for the active ingredient mefentrifluconazole
Test species Test type and duration Value Reference
Soil organisms
Earthworm, Eisenia fetida Acute, 14-day LC50 (artificial soil, 10% peat) >500 mg ai/kg1
[Uncorrected value >1000 mg ai/kg]
EC DAR (EC 2017): Doc
ID 2015/1003342
NOEC, 56-days, reproduction (artificial soil,
10% peat)
4 mg ai/kg dry soil1
[Uncorrected value = 8 mg ai/kg dry soil]
EC DAR (EC 2017): Doc
ID 2013/1235075
Springtail, Folsomia candida NOEC (reproduction and mortality), 28-days
(artificial soil, 5% peat)
≥200 mg ai/kg dry soil1
[Uncorrected value >400 mg ai/kg dry soil]
EC DAR (EC 2017): Doc
ID 2013/1235081
Soil mite, Hypoaspis aculeifer NOEC (reproduction and mortality), 14-days
(artificial soil, 5% peat)
≥500 mg ai/kg dry soil1
[Uncorrected value >1000 mg ai/kg dry soil]
EC DAR (EC 2017): Doc
ID 2013/1235082
Terrestrial plants
Six dicot and four monocot crop
species
Vegetative vigour, 21 days
Foliar application to seedling plants, 10
species
ER25 >150 g ai/ha2
[derived from an ER25 of >1500 Tl/ha for BAS 750
01 F, containing 100 g/L mefentrifluconazole]
NOER >150 g ai/ha2
[derived from a NOER of >1500 Tl/ha for BAS 750
01 F, containing 100 g/L mefentrifluconazole]
Appendix J, Table 97;
Marquardt (2015b) [EC
DAR (EC 2017): Doc ID
2014/1242738]
Seedling emergence, 21 days
Application to soil surface, 10 species
ER25 >150 g ai/ha2
[derived from an ER25 of >1500 Tl/ha for BAS 750
01 F, containing 100 g/L mefentrifluconazole]
NOER = 75 g ai/ha2,3
Appendix J, Table 98;
Marquardt (2015a) [EC
DAR (EC 2017): Doc ID
2016/7010990]
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Test species Test type and duration Value Reference
[derived from a NOER of >1500 Tl/ha for BAS 750
01 F, containing 100 g/L mefentrifluconazole]
Soil microbial function
Soil microflora NOEC, nitrogen mineralisation, 28 days 2.53 mg ai/kg dry soil EC DAR (EC 2017): Doc
ID 2015/1108623
NOEC, carbon mineralisation, 28 days 2.53 mg ai/kg dry soil EC DAR (EC 2017): Doc
ID 2016/1042889
1 Original toxicity endpoints from the artificial soil tests have been divided by 2 to account for different soil characteristics and the possibility of reduced bioavailability for
soil organisms of lipophilic substances (Log Pow >2) as per the EFSA Technical Report (EFSA 2015)
2 Note that the test item applied in this study was not Revystar Fungicide but formulation BAS 750 01 F. Whilst this also an emulsifiable concentrate formulation
containing the same concentration of mefentrifluconazole as Revystar Fungicide (100 g/L), formulation BAS 750 01 F does not contain fluxapyroxad however.
3 Note that the NOER value should be treated with caution as the large deviation from the control suggest that the study lacks sensitivity and there is some uncertainty
regarding the NOER value derived.
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Uncertainties and data gaps
No uncertainties or data gaps were identified in regard to soil toxicity for the active ingredient
mefentrifluconazole with the exception of a reliable mefentrifluconazole NOEC value for seedling
emergence as there was some uncertainty regarding the value derived in the study provided
(Marquardt, 2015a).
It should be noted that no soil toxicity data for the formulated substance Revystar Fungicide were
available however. The results of the applicant’s additive toxicity calculations of the end use product
however indicate additive toxicity is not expected due to a lack of toxicity from one or both active
constituents to soil macro-organisms.
General conclusion about soil toxicity
The active ingredient mefentrifluconazole does not trigger the HSNO thresholds for toxicity to the soil
environment based on the data available. The formulation Revystar Fungicide does not trigger a 9.2
HSNO classification based on mixture rules.
Terrestrial vertebrate toxicity
For effects on terrestrial vertebrates other than birds, refer to the mammalian toxicity section.
Table 18 contains the acute and chronic avian toxicity test results for the active ingredient
mefentrifluconazole.
Table 18: Summary of terrestrial vertebrate toxicity data for mefentrifluconazole
Test species Test type and
duration Value Reference
Bobwhite quail,
Colinus virginianus
Acute oral LD50 816 mg ai/kg bw
Appendix J, Table 99; Zok
(2014a) [EC DAR (EC 2017):
Doc ID 2014/1095701]
8-day dietary LC50
[Disregarded study, see
study summary for
comments]
Appendix J, Table 102; Zok
(2014c) [EC DAR (EC 2017):
Doc ID 2014/1127963 plus
amendment; Keller (2015a)
[EC DAR (EC 2017): Doc ID
2015/1223324]
Reproductive 1
generation, 22 weeks
NOEC
285 mg ai/kg diet (25.3 mg
ai/kg bw/day)
Appendix J, Table 104;
Bryden et al. (2014a) [EC
DAR (EC 2017): Doc ID
2013/1281276]
Mallard duck, Anas
platyrhynchos Acute oral LD50
3228 mg ai/kg [extrapolated
from >2000 mg/kg bw1]
Appendix J, Table 100; Zok
(2014b) [EC DAR (EC 2017):
Doc ID 2014/1095700]
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Test species Test type and
duration Value Reference
8-day dietary LDD50
[Disregarded study, see
study summary for
comments]
Appendix J, Table 103; Zok
(2014d) [EC DAR (EC 2017):
Doc ID 2014/1117035]
Reproductive 1
generation, 21 weeks
NOEC
600 mg ai/kg diet (80.5 mg
ai/kg bw/day)
Appendix J, Table 105;
Temple et al. (2015a) [EC
DAR (EC 2017): Doc ID
2015/7005819]
Canary, Serinus
canaria Acute oral LD50
3512 mg ai/kg [extrapolated
from >2860 mg ai/kg bw]2
Appendix J, Table 101; Keller
(2015a) [EC DAR (EC 2017):
Doc ID 2015/1085493]
1 Note that according to EFSA (EFSA 2009)in cases where there is no mortality the LD50 can be extrapolated
using a factor of 1.614 (five birds tested at limit dose) by multiplying the limit dose by the extrapolation factor (ie.
2000 x 1.614 = 3228 mg ai/kg). No significant sub-lethal effects were observed.
2 Note that based on the EFSA guidance (EFSA 2009) in cases where there is a single mortality the LD50 can be
extrapolated using a factor of 1.228 (five birds tested at limit dose) by multiplying the limit dose by the
extrapolation factor (ie. 2860 x 1.228 = 3512 mg ai/kg). No significant sub-lethal effects were observed.
Uncertainties and data gaps
No uncertainties or data gaps in regard to ecotoxicity to terrestrial vertebrates has been identified.
The applicant’s additive toxicity calculations show that acute toxicity from the end use product is
expected to be based on mefentrifluconazole.
General conclusion about ecotoxicity to terrestrial vertebrates
Mefentrifluconazole triggers a 9.3C HSNO classification (harmful to terrestrial vertebrates) based on
an LD50 for bobwhite quail (Colinus virginianus) of 816 mg/kg bw (Appendix J, Table 99; Zok, 2014a).
The formulation Revystar Fungicide triggers a 9.3C HSNO classification (harmful to terrestrial
vertebrates) based on mixture rules.
Ecotoxicity to bees and other terrestrial invertebrates
Table 19 contains the toxicity test results for the active ingredient mefentrifluconazole for pollinators.
Table 20 contains the Tier I toxicity test results for the active ingredient mefentrifluconazole for non-
target arthropods.
Table 21 contains the Tier II toxicity test results for the active ingredient mefentrifluconazole for non-
target arthropods.
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Table 19: Pollinators: summary of toxicity data for mefentrifluconazole
Test species Test type and
duration Value Reference
Honeybee, Apis
mellifera
LD50 (48-hr), acute
oral
>100 µg ai/bee Appendix J, Table 106;
Franke (2015a); [EC DAR
(EC 2017): Doc ID
2015/1128674] LD50 (48-hr), acute
contact
>100 µg ai/bee
Chronic adult oral
toxicity, 10-days
LD50 (10-day, chronic)
>110.5 µg/bee/day
NOED (10-day, chronic) =
110.5 µg/bee/day
EC DAR (EC 2017): Doc ID
2013/1235086
Honeybee larvae, Apis
mellifera
Bee brood, 96-hr
dietary exposure,
8-day test duration,
larvae
LD50 (96-hrs, acute) = 43.9
µg ai/larva
NOED (96-hrs, acute) = 29.7
µg ai/larva
Appendix J, Table 108;
Kleebaum (2015b) [EC DAR
(EC 2017): Doc ID
2013/1235087]
EC50, ED50, NOEC
and NOED (21
days), repeated
exposure
In vitro
[Disregarded study, see
study summary for
comments]
Appendix J, Table 109;
Royer (2015a) [EC DAR (EC
2017): Doc ID 2014/1327676]
Bumble bee, Bombus
terrestris
Acute oral, 96-hr
LD50
>195.4 µg ai/bee1 Appendix J, Table 107;
Amsel (2015a) [EC DAR (EC
2017): Doc ID 2014/1275250] Acute contact, 96-
hr LD50
>200 µg ai/bee1
1 Included as supporting information but not used in risk assessment.
Table 20: Non-target arthropods: summary of toxicity data (Tier I) for mefentrifluconazole
Test species Test type and
duration Value Reference
Parasitic wasp,
Aphidius rhopalosiphi
LR50 (48-hrs),
rate-response
0.954 g ai/ha1
[derived from an LR50 95.4
mL/ha for BAS 750 01 F in
200 L water/ha, containing
100 g/L mefentrifluconazole]
EC DAR (EC 2017): Doc ID
2014/1242743
Predatory mite,
Typhlodromus pyri
LR50 (7-days),
glass plate
7.691 g ai/ha1
[derived from an LR50 769.1
mL/ha for BAS 750 01 F in
200 L water, containing 100
g/L mefentrifluconazole]
EC DAR (EC 2017): Doc ID
2014/1242742
1 Note that the test item applied in this study was not Revystar Fungicide but formulation BAS 750 01 F. Whilst
this also an emulsifiable concentrate formulation containing the same concentration of mefentrifluconazole as
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Revystar Fungicide (100 g/L), formulation BAS 750 01 F does not contain fluxapyroxad and cannot be used as
an indication of mixture toxicity therefore
Table 21: Non-target arthropods: summary of toxicity data (Tier II) for mefentrifluconazole
Test species Test type and
duration Value Reference
Parasitic wasp,
Aphidius rhopalosiphi
LR50 (48-hrs),
extended
laboratory study
>300 g ai/ha1
[derived from an LR50 >3000
mL/ha for BAS 750 01 F in
200 L water/ha, containing
100 g/L mefentrifluconazole]
EC DAR (EC 2017): Doc ID
2015/1020207
Predatory mite,
Typhlodromus pyri
LR50 (48-hrs),
extended
laboratory study
>300 g ai/ha1
[derived from an LR50 >3000
mL/ha for BAS 750 01 F in
200 L water/ha, containing
100 g/L mefentrifluconazole]
EC DAR (EC 2017): Doc ID
2014/1242744
Green lacewing,
Chrysoperla carnea
LR50 (7-days),
extended
laboratory study
(fresh dry
residues)
>300 g ai/ha1
[derived from an LR50 >3000
mL/ha for BAS 750 01 F in
200 L water/ha, containing
100 g/L mefentrifluconazole]
EC DAR (EC 2017): Doc ID
2015/1020206
1 Note that the test item applied in this study was not Revystar Fungicide but formulation BAS 750 01 F. Whilst
this also an emulsifiable concentrate formulation containing the same concentration of mefentrifluconazole as
Revystar Fungicide (100 g/L), formulation BAS 750 01 F does not contain fluxapyroxad and cannot be used as
an indication of mixture toxicity therefore
Uncertainties and data gaps
No uncertainties or data gaps were identified in regard to toxicity to terrestrial invertebrates for the
active ingredient mefentrifluconazole with the exception of chronic toxicity to honey bee larvae since
the study submitted (Appendix J, Table 109; Royer, 2015a) was considered unreliable. It should be
noted that no toxicity to terrestrial invertebrate data for the formulated substance Revystar Fungicide
were available. Additive toxicity for Revystar® Fungicide could not be calculated however due to a
lack of toxicity of the individual active constituents to bees and standard terrestrial invertebrate test
species. The risk of Revystar® Fungicide to these organisms is therefore considered acceptable.
General conclusion about ecotoxicity to bees and terrestrial invertebrate
toxicity
Mefentrifluconazole does not trigger the HSNO thresholds for toxicity to the terrestrial invertebrates
based on the data available. The formulation Revystar Fungicide does not trigger a 9.4 HSNO
classification based on mixture rules.
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Appendix F: Hazard classification of mefentrifluconazole and Revystar® Fungicide
The hazard classifications of mefentrifluconazole and Revystar® Fungicide are listed in Table 22 and
Table 23 respectively.
Table 22: Applicant and Staff classifications of the active ingredient mefentrifluconazole
Hazard Class/Subclass
Active ingredient
classification by:
Method of
classification
Remarks
Ap
plican
t
EP
A S
taff
Test
resu
lts
Read
acro
ss
Class 1 Explosiveness
Applicant did
not self-
classify the
active
Class 2, 3 & 4 Flammability
Class 5 Oxidisers/Organic
Peroxides
Subclass 8.1 Metallic corrosiveness
Subclass 6.1 Acute toxicity (oral) No See Appendix C,
Table 8
Subclass 6.1Acute toxicity (dermal) No See Appendix C,
Table 8
Subclass 6.1 Acute toxicity
(inhalation) No
See Appendix C,
Table 8
Subclass 6.1 Aspiration hazard NA Material is a solid
Subclass 6.3/8.2 Skin
irritancy/corrosion No
See Appendix C,
Table 8
Subclass 6.4/8.3 Eye
irritancy/corrosion No
See Appendix C,
Table 8
Subclass 6.5A Respiratory
sensitisation ND
Subclass 6.5B Contact sensitisation 6.5B See Appendix C,
Table 8
Subclass 6.6 Mutagenicity No See Appendix C,
Table 8
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Subclass 6.7 Carcinogenicity No See Appendix C,
Table 9
Subclass 6.8 Reproductive/
developmental toxicity No
See Appendix C,
Table 9
Subclass 6.8 Reproductive/
developmental toxicity (via
lactation)
No See Appendix C,
Table 9
Subclass 6.9 Target organ systemic
toxicity (oral) No
See Appendix C,
Table 9
Subclass 6.9 Target organ systemic
toxicity (dermal) No
See Appendix C,
Table 9
Subclass 6.9 Target organ systemic
toxicity (inhalation) ND
See Appendix C,
Table 9
Subclass 9.1 Aquatic ecotoxicity 9.1A
Based on a 96-hour
LC50 of 0.532 mg/L
for the rainbow
trout
Onchorhynchus
mykiss (Salinas,
2014a)
Subclass 9.2 Soil ecotoxicity No See Appendix E,
Table 17
Subclass 9.3 Terrestrial vertebrate
ecotoxicity 9.3C
Based on an LD50
of 816 mg/kg bw for
the bobwhite quail
Colinus virginianus
(Zok, 2014a).
Subclass 9.4 Terrestrial
invertebrate ecotoxicity No
See Appendix E,
Table 18
NA: Not Applicable.
ND: No Data or poor quality data [according to Klimisch criteria (Klimisch, Andreae et al. 1997)]. There is a lack
of data for one or more components.
No: Not classified based on actual relevant data available for the substance. The data are conclusive and
indicate the threshold for classification is not triggered.
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Table 23: Applicant and EPA Staff classifications of Revystar® Fungicide1
Hazard Class/Subclass
Mixture
classification by:
Method of
classification
Remarks
Applicant EPA
Staff
Mix
ture
data
Read
acro
ss
Mix
ture
ru
les
Class 1 Explosiveness No No
Class 2, 3 & 4 Flammability No No
Class 5 Oxidisers/Organic
Peroxides No No
Subclass 8.1 Metallic
corrosiveness No No
Subclass 6.1 Acute toxicity
(oral) 6.1D 6.1D See Appendix C, Table 7
Subclass 6.1Acute toxicity
(dermal)
Not
triggered No See Appendix C, Table 7
Subclass 6.1 Acute toxicity
(inhalation) 6.1D 6.1D See Appendix C, Table 7
Subclass 6.1 Aspiration
hazard ND No
See Appendix B, Table 6
(viscosity greater than
the classifiable minimum)
Subclass 6.3/8.2 Skin
irritancy/corrosion 6.3A 6.3A See Appendix C, Table 7
Subclass 6.4/8.3 Eye
irritancy/corrosion 6.4A 6.4A See Appendix C, Table 7
Subclass 6.5A Respiratory
sensitisation ND ND
Subclass 6.5B Contact
sensitisation 6.5B 6.5B See Appendix C, Table 7
Subclass 6.6 Mutagenicity No ND Neither active ingredient
is classified
Subclass 6.7 Carcinogenicity No ND Neither active ingredient
is classified
1 Use of mixture rules may not adequately take into account interactions between different components in some circumstances and must be considered of lower reliability than substance (formulation) data.
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Hazard Class/Subclass
Mixture
classification by:
Method of
classification
Remarks
Applicant EPA
Staff
Mix
ture
data
Read
acro
ss
Mix
ture
ru
les
Subclass 6.8 Reproductive/
developmental toxicity No ND
Neither active ingredient
is classified
Subclass 6.8 Reproductive/
developmental toxicity (via
lactation)
ND ND Neither active ingredient
is classified
Subclass 6.9 Target organ
systemic toxicity (oral) No 6.9B
Fluxapyroxad triggers
classification
Subclass 6.9 Target organ
systemic toxicity (dermal) No ND
Fluxapyroxad and
mefentrifluconazole are
ND
Subclass 6.9 Target organ
systemic toxicity (inhalation) No ND
Fluxapyroxad and
mefentrifluconazole are
ND
Subclass 9.1 Aquatic
ecotoxicity 9.1B 9.1B
Subclass 9.2 Soil ecotoxicity No ND
Subclass 9.3 Terrestrial
vertebrate ecotoxicity No 9.3C
Subclass 9.4 Terrestrial
invertebrate ecotoxicity No ND
NA: Not Applicable. For instance testing for a specific endpoint may be omitted if it is technically not possible to
conduct the study as a consequence of the properties of the substance: eg very volatile, highly reactive or
unstable substances cannot be used, mixing of the substance with water may cause danger of fire or explosion
or the radio-labelling of the substance required in certain studies may not be possible.
ND: No Data or poor quality data [according to Klimisch criteria (Klimisch, Andreae et al. 1997)]. There is a lack
of data for one or more components.
No: Not classified based on actual relevant data available for the substance or all of its components. The data
are conclusive and indicate the threshold for classification is not triggered.
The proposed toxicity classification of Revystar® Fungicide is: 6.1D acute toxicity (oral and
inhalation), 6.3A, 6.4B, and 6.5B for skin and eye irritation, and contact sensitisation, respectively. It is
classified 6.9B specific organ toxicity due to fluxapyroxad.
The proposed ecotoxicity hazard classification of Revystar® Fungicide is: 9.1B (ecotoxic in the
aquatic environment) and 9.3C (harmful to terrestrial vertebrates). The EPA staff classification of
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Revystar® Fungicide differed from that of the applicant in that they did not classify it for toxicity to
terrestrial vertebrates.
The EPA staff classification of Revystar® Fungicide differed from that of the applicant in that the
applicant classified it as “No” for several endpoints, whereas, the EPA classified it as ND as the EPA
took into account the ND classification for sub-components.
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Appendix G: Human health risk assessment
Quantitative risk assessment
The operator exposure assessment is based on a modification of the approach used by European
regulators, taking into account New Zealand specific factors. The model is based on the results of
actual measurements carried out in the field and has an established history of providing reliable and
reproducible results.
The re-entry worker exposure assessment is based on a modification of the approach used by
European regulators and the US-EPA. The parameters for the modelling are based on empirical data
relating to measurements of dermal exposure of workers from contact with residues on foliage for
various activities and the amount of foliar residues that are dislodgeable.
The bystander exposure assessment is based on a modification of the approaches used by European
regulators and the US-EPA. Spray drift deposition from ground based application is estimated using
the AgDrift model using the curves produced by the Australian Pesticides and Veterinary Medicines
Authority [APVMA, (APVMA 2010)]. The parameters are based on empirical data. Spray drift
deposition from aerial application is estimated using the AGDISP model along with appropriate New
Zealand input parameters.
Full details of the methodology can be found in the EPA risk assessment methodology document
(EPA 2018).
To assess risks the predicted systemic exposures to the active ingredient(s) are compared with an
acceptable operator exposure limit (AOEL) for the active ingredient and a risk quotient (RQ) is
calculated. RQ values greater than one indicate that predicted exposures are greater than the AOEL
and potentially of concern. RQ values below one indicate that predicted exposures are less than the
AOEL and are not expected to result in adverse effects.
Input values for the human health risk assessment
Reference doses for mefentrifluconazole established by internationally reputable regulatory
authorities are summarised in Table 24.
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Table 24: AOEL reference dose for mefentrifluconazole established by the EPA
Active
Ingredient
Key systemic
effect
NOAEL
mg/kg
bw/day
Uncerta
inty
factors
Reference
value
(AOEL)
mg/kg
bw/day
Staff’s
modifications Remarks
mefentrifluco
nazole
increase in blood
parameters,
increase liver wt
and altered liver
cell morphology
11 100 0.11 None
90-day
study in
mice
The reference value for mefentrifluconazole was derived from the NOAEL observed in the 90 day
study in mice summarized in the European Commission Draft Assessment Report (EC 2017) Volume
3 – B.6 (AS).
Other input values for the exposure assessment are summarised in Table 25.
Dermal absorption data were provided for Revystar® Fungicide so default values were not utilised.
The results of this study indicate mefentrifluconazole in Revystar® is poorly absorbed (0.36 ± 0.26%)
through the skin as a concentrate (100 mg/mL) and when diluted 1:200 with water (0.5 mg/ml) into an
in-use spray dilution (2.82 ± 0.98%). Due to variation in the data the values used in the risk
assessment were the average plus one SD and rounded up to 1% for the concentrate and 4% for the
dilution. These were the same values the applicant utilised in their risk assessment.
Table 25: Input values for human exposure modelling
Operator exposure assessment
The results of the operator exposure assessment are shown in Table 26.
Active ingredient Physical
form
Concentration
of each active
(%)
Maximum
application rate
(for each
active, for each
method of
application)
g ai/ha
Dermal absorption (%) AOEL
mg/kg
bw/day
Concentrate Spray
mefentrifluconazole liquid 100 150 1 4 0.11
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Table 26: Output of operator mixing, loading and application exposure assessment for
mefentrifluconazole
Exposure Scenario - cereals
Estimated operator
exposure (mg/kg
bw/day)
Risk
Quotient
Boom
No personal protective equipment (PPE)2 during mixing, loading and
application
0.0115 0.10
Gloves only during mixing and loading 0.0092 0.08
Gloves only during application 0.0100 0.09
Full PPE during mixing, loading and application (excluding respirator) 0.0009 0.01
Full PPE during mixing, loading and application (including FP1, P1 and
similar respirator achieving 75 % inhalation exposure reduction)
0.0008 0.01
Full PPE during mixing, loading and application (including FP2, P2 and
similar respirator achieving 90 % inhalation exposure reduction)
0.0008 0.01
Predicted operator exposures to mefentrifluconazole are below the Acceptable Operator Exposure
Level (AOEL) for each use pattern, even without the use of personal protective equipment (PPE).
Therefore operator exposures are not expected to result in adverse health effects
Although the quantitative risk assessment indicates that PPE is not required to ensure that exposures
are below the AOEL, the requirements under HSW (HS), and in particular Regulations 13.7 and 13.8,
state that personal protective equipment is to be used to minimise risks to the health and safety of
workers.
2 ‘Full PPE’ includes: gloves, hood/visor, coveralls, and heavy boots during application and gloves during mixing and loading.
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Re-entry worker exposure assessment
The results of the re-entry worker exposure assessment are summarised in Table 27.
Table 27: Output of the re-entry worker exposure assessment for mefentrifluconazole
Active
ingredient Crop/activity
Internal
(absorbed)
dose available
for systemic
distribution
(mg/kg bw/8
hours)
AOEL
(mg/kg
bw/day)
Risk
Quotient
immediately
after
application
Re-
entry
interval
without
gloves
Re-
entry
interval
with
gloves
mefentrifluconazole
Cereals (scouting, irrigation, weeding mature/full foliage plants)
0.00 0.11 0.02 0.0 0.0
Predicted exposures to mefentrifluconazole for workers re-entering and working in areas where
Revystar® Fungicide has been applied are below the AOEL. No re-entry intervals are necessary.
Quantitative bystander risk assessment
It is considered that the main potential source of exposure to the general public for substances of this
type (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. In
terms of bystander exposure, toddlers are regarded as the most sensitive sub-population and are
regarded as having the greatest exposures. For these reasons, the risk of bystander exposure is
assessed in this sub-population. The AOEL calculated for the operator and re-entry worker exposure
assessments has been used for the bystander assessment, as the use of an oral chronic reference
dose (CRfD) is usually likely to be over precautionary.
The results of the bystander exposure assessment are summarised in Table 28.
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Table 28: Output of the bystander exposure assessment for mefentrifluconazole
Exposure Scenario – cereal
Estimated exposure of
15 kg toddler exposed
through contact to
surfaces 8 m from an
application area
(µg/kg bw/day)
Risk Quotient
Buffer zone needed
to reduce toddler
exposure to the
AOEL
Boom
High boom, fine droplets 0.30 0.0027 0
High boom, coarse droplets 0.05 0.0004 0
Low boom, fine droplets 0.10 0.0009 0
Low boom, coarse droplets 0.02 0.0002 0
Aerial - agriculture
Swath width 20 m, Med-coarse
droplet size
0.41 0.0038 0
Swath width 20 m, coarse- v.
coarse droplets
0.31 0.0028 0
Swath width 20 m, extremely
coarse droplets
0.21 0.0019 0
Swath width 24 m, v. fine-fine
droplets
1.24 0.0112 0
Swath width 24 m, fine-med.
droplets
0.61 0.0056 0
Swath width 24 m, med.-coarse
droplets
0.41 0.0037 0
Estimated bystander exposure from spray drift after application of Revystar® Fungicide to cereals is
below the AOEL. No buffer zone is required to protect bystanders.
Conclusions of the human health risk assessment
It is considered that the risks to human health from the proposed use of Revystar® Fungicide are
acceptable without the use of Personal Protective Equipment (PPE), application of re-entry intervals,
or enforcement of no-spray buffer zones to protect bystanders.
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Appendix H: Environmental risk assessment
Mixture toxicity
No product-specific ecotoxicity data is available for the formulated substance Revystar® Fungicide
(BAS 752 00 F).
The applicant has performed a mixture toxicity assessment, which establishes which active ingredient
mostly contributes to the toxicity for each area of the risk assessment, assuming additivity, following
EFSA Guidance (EFSA 2013). This is based on the individual toxicity endpoints for each of the active
ingredients fluxapyroxad and mefentrifluconazole, and their relative contribution to the formulation.
This approach does not establish whether toxicity of the mixture as a whole is additive or non-additive
however. As such, whether the formulated product Revystar® Fungicide (BAS 752 00 F) is found to
behave in a more than additive manner (eg synergism) remains an uncertainty and it’s possible that
the conclusions of the risk assessment may underestimate the risks.
Following publication of the US EPA’s Environmental Fate and Ecological Risk Assessment for
mefentrifluconazole (US EPA 2019) and the Canadian Pest Management Regulatory Agency’s
(PMRA) Proposed Registration Decision for mefentrifluconazole and related use end products (PMRA
2019), it is apparent that ecotoxicity formulation data are available for other mefentrifluconazole-
containing formulations. The EPA has therefore performed a mixture toxicity assessment, also
following the EFSA guidance (EFSA 2013) based on this information, and the results are outlined
under the headings below.
Aquatic environment
There are no product-specific aquatic ecotoxicity data available for the formulated substance
Revystar® Fungicide (BAS 752 00 F).
The acute aquatic toxicity (assuming additivity) of the solo mefentrifluconazole formulation (BAS 750
01 F) has been predicted for fish and Daphnia using the toxicity of the pure mefentrifluconazole active
ingredient and the blank formulation (BAS 750 BS F), which contains the same co-formulants as
Revystar® Fungicide (BAS 752 00 F) with the exception of the active ingredients. This prediction was
compared with the actual acute toxicity of the solo mefentrifluconazole formulation (BAS 750 01 F).
For both fish and Daphnia, it was determined that the interactions between the pure technical grade
active ingredient mefentrifluconazole and the other formulation components do not deviate from
additivity (Model Deviation Ratios (MDRs) of 3 and 2, respectively); in other words this is “in
agreement” and is what would be expected based on the sum of the effects of chemicals involved in
the reaction).
It should be noted however that BAS 750 01 F is only a solo (mefentrifluconazole) formulation and
does not contain the active ingredient fluxapyroxad. The effect on the interaction of the components
by adding the second active ingredient fluxapyroxad is unknown. This is an uncertainty as it is not
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possible to predict what the interactions between the components in the mixture with both active
ingredients would be. It is therefore also not possible to conclude that mefentrifluconazole alone is
driving the toxicity as it cannot be determined if the components in the formulation still interact in an
additive manner when fluxapyroxad is added.
In conclusion there is the potential for the actual formulation to deviate from additivity due to the
inclusion of the second active ingredient fluxapyroxad, and the proposed controls may not be
conservative enough therefore (in case of a more than additive interaction).
It is important to note here however that the endpoint selected for use in the refined aquatic risk
assessment is a chronic NOEC of 0.0091 mg/L (21-day) for Daphnia magna obtained for the pure
active ingredient mefentrifluconazole (see the aquatic risk assessment below). This value is between
58 to 104 times lower than the most sensitive mefentrifluconazole acute toxicity endpoints for fish,
aquatic invertebrates and algae, and is considered a worst-case scenario. Although there is the
potential that a synergistic effect may occur on a chronic basis as a result of the addition of
fluxapyroxad, this would not affect the aquatic risk assessment, and would not change the buffer zone
calculation.
Soil environment
EPA conclusion
There is no product-specific soil toxicity data are available for the formulated substance Revystar®
Fungicide (BAS 752 00 F). No toxicity to earthworms has been demonstrated in the two-way mixture
formulation BAS 752 01 F (containing the active ingredients mefentrifluconazole and fluxapyroxad but
this is not Revystar) however, and as such interactions between these two active ingredients are
considered unlikely. There is a very low concern therefore that the toxicity will deviate from additivity
as interactions being very strongly more than additive (eg synergism) would likely have been seen in
toxicity of the mixture.
It should be noted that BAS 752 01 F is not the actual formulation undergoing assessment however,
and different co-formulants can impact overall toxicity and interactions. It is considered likely that the
formulated product Revystar® Fungicide (BAS 752 00 F) behaves in a similar manner to BAS 752 01
F, and therefore the current soil risk assessment is considered acceptable.
Terrestrial vertebrates
EPA conclusion
No product-specific terrestrial vertebrate toxicity data are available for the formulated substance
Revystar® Fungicide (BAS 752 00 F). No toxicity to birds has been demonstrated in the two-way
mixture formulation BAS 752 01 F (containing the active ingredients mefentrifluconazole and
fluxapyroxad but different co-formulants to Revystar® Fungicide (BAS 752 00 F)) however. As such,
more than additive interactions between these two active ingredients are considered unlikely. There is
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a very low concern that the toxicity will deviate from additivity therefore, as interactions being very
strongly more than additive (eg synergism) would likely have been seen in toxicity of the mixture.
It should be noted that BAS 752 01 F is not the actual formulation undergoing assessment however,
and different co-formulants can impact overall toxicity and interactions. It is considered likely that the
formulated product Revystar® Fungicide (BAS 752 00 F) behaves in a similar manner to BAS 752 01
F however, and as such the current terrestrial vertebrate risk assessment is considered acceptable.
Terrestrial invertebrates
EPA conclusion
No product-specific terrestrial invertebrate toxicity data are available for the formulated substance
Revystar® Fungicide (BAS 752 00 F), no toxicity to honey bees has been demonstrated in the two-
way mixture formulation BAS 752 01 F (containing the active ingredients mefentrifluconazole and
fluxapyroxad but different co-formulants to Revystar® Fungicide (BAS 752 00 F)) however, and as
such interactions between these two active ingredients are considered unlikely. There is therefore a
very low concern that the toxicity will deviate from additivity as interactions being very strongly more
than additive (eg synergism) would likely have been seen in toxicity of the mixture.
It should be noted that BAS 752 01 F is not the actual formulation undergoing assessment however,
and different co-formulants can impact overall toxicity and interactions. It is considered likely that the
formulated product Revystar® Fungicide (BAS 752 00 F) behaves in a similar manner to BAS 752 01
F, and therefore the current terrestrial invertebrate risk assessment is considered acceptable.
EPA’s final conclusion
For the aquatic environment, based on the available information it is it is not possible to predict what
the interactions between the components in the mixture with both active ingredients would be. It is not
possible to conclude that mefentrifluconazole alone is driving the toxicity as there might be
interactions between the components impacting the overall toxicity. There is still the potential for the
components of the actual formulation to interact in a manner that deviates from additivity, therefore
the proposed controls may not be conservative enough to account for this uncertainty.
It is important to note here however that the endpoint selected for use in the refined aquatic risk
assessment is a chronic NOEC of 0.0091 mg/L (21-day) for Daphnia magna obtained for the pure
active ingredient mefentrifluconazole (see the aquatic risk assessment below). This value is between
58 to 104 times lower than the most sensitive mefentrifluconazole acute toxicity endpoints for fish,
aquatic invertebrates and algae, and is considered a worst-case scenario. Although there is the
potential that a synergistic effect may occur on a chronic basis as a result of the addition of
fluxapyroxad, this would not affect the aquatic risk assessment, and would not change the buffer zone
calculation.
For the terrestrial environment, although there is still uncertainty in regard to mixture toxicity of
Revystar Fungicide, no strong synergistic reactions between active ingredients are expected for soil,
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bees, non-target arthropods and birds as another two-way mixture formulation containing the same
active ingredients is not toxic to any of these terrestrial organisms. It should be noted that this is not
the actual formulation. This uncertainty is considered acceptable because the formulated product
Revystar Fungicide is likely not toxic, assuming other formulation components are not highly toxic.
The current risk assessment for the terrestrial environment is considered acceptable.
Quantitative environmental risk assessment
The active ingredient fluxapyroxad contained in Revystar® Fungicide, approved in New Zealand in
other formulations for use on cereal grains at a similar application rate (Adexar, application
APP201884, approval HSR100948), has not been reviewed or assessed in the context of this memo.
This environmental risk assessment focusses only on the active ingredient mefentrifluconazole, which
has not previously been approved in New Zealand.
Aquatic risk assessment
The basis for the aquatic risk assessment is a comparison of the Expected Environmental
Concentrations (EEC) with toxicity endpoints to which safety factors have been applied. The EEC is
divided by the toxicity endpoint to calculate a risk quotient (RQ) value. The methodology for the aquatic
risk assessment, including the level of concern (LOC) ascribed to specific RQ values, is described in
detail in the EPA standard risk assessment methodology (EPA 2018).
Calculation of expected environmental concentrations
The parameters used in GENEEC2 modelling are listed in Table 29. As an initial worst-case scenario
the aerobic soil DT50 from the laboratory studies was used as an initial conservative evaluation. It was
noted by the staff that the field DT50 values were lower which could potentially be used to refine the
risk assessment.
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Table 29: Input parameters for GENEEC2 analysis for mefentrifluconazole
Parameters Application method Revystar® Fungicide
Crop(s) Cereals
Application rate (g/ha) 150 g ai/ha
Application rate (lbs/acre) 0.1338
Application frequency 2 (maximum)
Application interval (days) 21
Kd (mL/g) 30.63 (lowest value non-sand soil)
Aerobic soil DT50 (days) 1000 (80th percentile, lab)1
Pesticide wetted in? No
Methods of application Ground spray, high-boom Aerial spray
Droplet size Medium to coarse2 Coarse to very coarse2
‘No spray’ zone 0
Depth of incorporation (in) 0 (ground-spray application), not applicable for aerial application
Water solubility (ppm) 0.81
Aerobic aquatic DT50 whole
system (days) 213 (worst-case)
Aqueous photolysis DT50
(days) 2.3
1 Note that if the 80th percentile field value of 309 days is entered as the DT50 value instead of the laboratory DT50
value (1000 days), this makes no difference to the EEC values
2 Droplet sizes specified and confirmed by the applicant
Output from the GENEEC2 model
Ground-based application
RUN No. 1 FOR mefentrifluconaz ON cereals * INPUT VALUES *
--------------------------------------------------------------------
RATE (#/AC) No.APPS & SOIL SOLUBIL APPL TYPE NO-SPRAY INCORP
ONE(MULT) INTERVAL Kd (PPB ) (%DRIFT) ZONE(FT) (IN)
--------------------------------------------------------------------
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0.134( 0.266) 2 21 30.6 810.0 GRHIME( 1.2) 0.0 0.0
FIELD AND STANDARD POND HALFLIFE VALUES (DAYS)
--------------------------------------------------------------------
METABOLIC DAYS UNTIL HYDROLYSIS PHOTOLYSIS METABOLIC COMBINED
(FIELD) RAIN/RUNOFF (POND) (POND-EFF) (POND) (POND)
--------------------------------------------------------------------
1000.00 2 0.00 2.30- 285.20 213.00 121.93
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
--------------------------------------------------------------------
2.73 2.69 2.48 2.08 1.84
Aerial application
RUN No. 1 FOR mefentriflucaonz ON cereals * INPUT VALUES *
--------------------------------------------------------------------
RATE (#/AC) No.APPS & SOIL SOLUBIL APPL TYPE NO-SPRAY INCORP
ONE(MULT) INTERVAL Kd (PPB ) (%DRIFT) ZONE(FT) (IN)
--------------------------------------------------------------------
0.134( 0.266) 2 21 30.6 810.0 AERL_D( 7.1) 0.0 0.0
FIELD AND STANDARD POND HALFLIFE VALUES (DAYS)
--------------------------------------------------------------------
METABOLIC DAYS UNTIL HYDROLYSIS PHOTOLYSIS METABOLIC COMBINED
(FIELD) RAIN/RUNOFF (POND) (POND-EFF) (POND) (POND)
--------------------------------------------------------------------
1000.00 2 0.00 2.30- 285.20 213.00 121.93
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
--------------------------------------------------------------------
3.18 3.14 2.90 2.45 2.16
The maximum Estimated Environmental Concentrations (EEC) for mefentrifluconazole when applied
as the formulated substance Revystar® Fungicide as estimated by GENEEC2 are 2.73 μg/L and 3.18
µg/L for ground-spray and aerial applications, respectively.
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Calculated risk quotients
The calculated acute risk quotients for each trophic level considering the above EEC and lowest
relevant toxicity figures are presented in Table 30. The calculated chronic risk quotients are presented
in Table 31.
Table 30: Acute risk quotients derived from the GENEEC2 model and toxicity data
Species
Peak EEC
from
GENEEC2
(mg/L)
LC50 or
EC50
(mg/L)
Acute
RQ Conclusion
Ground-based application
Fish, Oncorhynchus
mykiss
0.00273 0.532 0.0051 Below LOC for non-threatened
and threatened species
Crustacea, Daphnia
magna
0.00273 0.944 0.0029 Below LOC for non-threatened
and threatened species
Marine diatom,
Skeletonema costatum1
0.00273 0.679 0.0040 Below LOC for non-threatened
and threatened species
Aquatic plants, Lemna
gibba
0.00273 >1.894 <0.0014 Below LOC for non-threatened
and threatened species
Aerial application
Fish, Oncorhynchus
mykiss
0.00318 0.532 0.0060 Below LOC for non-threatened
and threatened species
Crustacea, Daphnia
magna
0.00318 0.944 0.0034 Below LOC for non-threatened
and threatened species
Marine diatom,
Skeletonema costatum
0.00318 0.679 0.0047 Below LOC for non-threatened
and threatened species
Aquatic plants, Lemna
gibba
0.00318 >1.894 <0.0017 Below LOC for non-threatened
and threatened species
1 Note that the most sensitive algae toxicity endpoint was determined from a marine species Skeletonema
costatum. The environmental risk assessment is typically based on freshwater species. Since no risks are
identified however, this has been left as is for conservatism
Table 31: Chronic risk quotients derived from the GENEEC2 model and toxicity data
Species
Relevant
EEC from
GENEEC2
(mg/L)
NOEC
(mg/L)
Chronic
RQ Conclusion
Ground-based application
Fish, Danio rerio 0.00184
(90-day)1
0.022
(140-day) 0.084
Below LOC for non-threatened and
threatened species
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Species
Relevant
EEC from
GENEEC2
(mg/L)
NOEC
(mg/L)
Chronic
RQ Conclusion
Crustacea, Daphnia
magna
0.00248
(21-day)1
0.0091
(21-day) 0.27
Below LOC for non-threatened
species
Above LOC for threatened
species
Aerial application
Fish, Danio rerio 0.00216
(90-day)1
0.022
(140-day) 0.098
Below LOC for non-threatened and
threatened species
Crustacea, Daphnia
magna
0.00290
(21-day)1
0.0091
(21-day) 0.32
Below LOC for non-threatened
species
Above LOC for threatened
species
1 Relevant Expected Environmental Concentrations from GENEEC2 were selected to be as close as possible to
the chronic toxicity endpoints.
It should be noted that the chronic risk to threatened fish species from aerial application is just below
the trigger level of 0.1. Since the refinement will be based on the most sensitive endpoint however
(chronic toxicity to Daphnia), this is considered to be protective of chronic risks to threatened fish
species.
As a refinement for the risks to threatened species of crustaceans the non-normalised soil DT50 from
the field studies was used (309 days). The expected environmental concentration (EEC) at 21 days
after application was 2.43 µg/L and 2.86 µg/L for ground based and aerial applications, respectively.
This refinement still results in an RQ above the level of concern for threatened crustaceans however.
Refinement of the aquatic risk assessment
Predicted exposures are above the level of concern for chronic risks to threatened species of aquatic
invertebrates (Daphnia magna) for mefentrifluconazole following application of Revystar Fungicide to
cereals by both ground-based and aerial application. The scenario modelled is a worst-case, using
the maximum application rate at the shortest interval and maximum frequency of application. Since
risks were identified further modelling was performed to consider whether buffer zones may be able to
mitigate risks from spray drift and runoff.
Spray drift
The Agdrift model was used to calculate the required downwind buffer zone to protect the aquatic
environment from adverse effects of the substance due to spray drift using application from a high
boom [see Table 32 and relevant spray drift scenarios (APVMA 2010)].
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For aerial application, the AGDisp® model was used to calculate the deposition curves. This used the
EPA’s standard assumptions regarding aerial application of fungicides to agricultural land [see EPA
risk assessment methodology (EPA 2018)] with the following exceptions.
Droplet size: ASABE Coarse droplets
Water volume: 60 L/ha
Active fraction: 0.0025
Non-volatile fraction: 0.00375
Exact buffer zones are impractical and too precise to be applied in the real world. Therefore, the
buffer zone distance is rounded so it can be visualized and remembered by end-users.
Table 32: Input parameters and calculation of spray drift buffer zone for the refined risk
assessment of mefentrifluconazole
Input parameters Ground-based Aerial
Application rate (kg ai/ha) 0.150 0.150
Number of applications 2 2
Application interval 21 days 21 days
Application method High boom, medium droplets ASABE coarse droplets
Koc (mL/g) 2511 2511
DT50 (soil) 1000 days 1000 days
DT50 (whole system) 213 days 213 days
Toxicity endpoint 0.0091 mg/L (NOEC, 21-day,
Daphnia magna)
0.0091 mg/L (NOEC, 21-day,
Daphnia magna)
Assessment factor 10 10
Buffer zone (m) – model 0 m 0 m
Buffer zone (m) – control 0 m 0 m
Runoff
The REXTOX model was used to calculate the required buffer zone to protect the aquatic
environment from adverse effect s of the substance due to runoff (see Table 33).
Table 33: Input parameters and calculation of runoff buffer zone for the refined risk
assessment
Input parameters Mefentrifluconazole
Application rate (kg ai/ha) 0.150
Koc 2511 mL/g
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DT50 soil 1000 days
Toxicity endpoint 0.0091 mg/L (NOEC, 21-day, Daphnia magna)
Assessment factor 10
Buffer zone (m) – model 0
Buffer zone (m) – control 0
No runoff buffer zone is necessary following application of the active ingredient mefentrifluconazole,
following application of the formulated substance Revystar Fungicide.
Uncertainties and data gaps
No uncertainties or data gaps have been identified.
Conclusions of the aquatic risk assessment
Predicted exposures concentrations of mefentrifluconazole, applied as the formulated product
Revystar® Fungicide resulted in calculated RQs above the LOC for the aquatic environment. Chronic
risks to threatened species of aquatic invertebrates were identified for both ground-based (RQ = 0.27,
LOC = 0.1) and aerial applications (RQ = 0.32, LOC = 0.1). A refinement of the soil DT50 did not result
in risk below the level of concern in the screening step. The following controls are proposed to reduce
exposures below the level of concern:
Use restrictions
The maximum application rate is 150 g mefentrifluconazole/ha, maximum two
applications/year, and a minimum interval between applications of 21 days
Apply with ground-based equipment and minimum medium droplets, as defined by the
American Society of Agricultural and Biological Engineers ASABE Standard (S572) or the
British Crop Production Council guideline. This information should be required on the
label so that users are aware of this control.
For aerial application, use minimum coarse droplets, as defined by the American Society
of Agricultural and Biological Engineers ASABE Standard (S572) or the British Crop
Production Council guideline. This information should be required on the label so that
users are aware of this control.
A label statement indicating: “DO NOT apply when wind speeds are less than 3 km/hr or
more than 20 km/hr as measured at the application site”.
Groundwater risk assessment
The predicted concentration of the active ingredient mefentrifluconazole and its relevant metabolite
1,2,4-triazole in groundwater, calculated using the Sci-Grow model, is shown in Table 34. The
concentration is initially compared to the EU limit for the maximum permissible concentration of
pesticide active ingredients and their relevant metabolites of 0.1 µg/L.
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Table 34: Input parameters for Sci-Grow analysis and resulting PEC values
Input parameters Mefentrifluconazole Metabolite M750F001
(1,2,4-triazole)
Application rate (kg ai/ha) 0.150 0.0013551
Application rate (lb ai/acre)2 0.1338 0.001209
Number of applications 2 2
Koc3 2511 mL/g (lowest value
non-sand soil)
43 mL/g (lowest value non-
sand soil, n = 5)4
Aerobic soil DT50 (days) 1000 (80th percentile lab
DT50, n = 7)
92.8
PECgw (µg/L) 0.0192 0.00779
1 Formula to calculate equivalent metabolite application rate: (metabolite molecular weight / parent molecular
weight) * (metabolite maximum percent formed /100) * parent application rate (kg ai/ha) ie.
(69.1/397.8)*(5.2/100)*0.15 = 0.001329 kg ai/ha
2 The application rate is conversion from kg ai/ha to lb/acre (the units required to be entered into the model) by
multiplying it by 0.892
3 Lowest Koc from a non-sandy soil (normalised values for the OC, temp and pH)
4 The Koc and aerobic soil DT50 values for metabolite 1,2,4-triazole were taken from APP203363
For mefentrifluconazole and its metabolite 1,2,4-triazole, the concentration is below the 0.1 µg/L
trigger level set by the European regulators. Therefore, risks to groundwater are considered below the
level of concern.
Conclusions of the groundwater risk assessment
For mefentrifluconazole and its metabolite M750F001 (1,2,4-triazole) the predicted concentration in
groundwater is below the 0.1 µg/L trigger level set by the European regulators. Therefore, risks to
groundwater are considered below the level of concern.
Sediment risk assessment
The sediment risk assessment for the active ingredient mefentrifluconazole was performed following
the method outlined in the EPA standard risk assessment methodology (EPA 2018).
The input parameters used in the risk assessment are summarised in Table 35.
Table 35: Mefentrifluconazole input values and calculations for sediment risk assessment
Input parameters Ground-based application Aerial application
Predicted Environmental
Concentration (PEC) local water1
0.00273 mg/L 0.00318 mg/L
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Toxicity value
≥1.158 mg ai/kg dry sediment
(worst-case NOEC, 28-days,
Chironomus riparius)
≥1.158 mg ai/kg dry sediment
(worst-case NOEC, 28-days,
Chironomus riparius)
Assessment factor2 10 10
Koc 2511 mL/g (lowest value non-sand
soil)
2511 mL/g (lowest value non-sand
soil)
PEC local sediment 0.1512 mg/kg 0.1512 mg/kg
RQ ≤1.31 ≤1.52
1 Peak EEC values from GENEEC2
2 Four sediment toxicity tests are available for four different sediment-dwelling organisms. Although three of these
studies are described as “acute” and only one as “chronic” (long-term), sub-lethal endpoints were derived for two
out of three of the acute studies. As such, an assessment factor of 10 was applied as three tests (one long-term
test plus two acute tests with sub-lethal endpoints derived) were available with species representing different
living and feeding conditions.
Conclusions of the sediment risk assessment
The risk quotients for sediment-dwelling organisms following both ground-based and aerial application
were both identified as potentially being above the level of concern (LOC = 1).
Only one chronic endpoint, which is not an absolute value, was available for sediment-dwelling
organisms, and the risk assessment was performed with this value (28-day NOEC of ≥1.158 mg ai/kg
for Chironomus riparius). The No Observed Effect Concentration (NOEC) determined in this case was
the highest concentration tested, and no significant effects were observed at this concentration. If a
higher concentration had been tested, the NOEC could potentially be higher, thus resulting in a lower
risk.
Using a weight-of-evidence approach, given the uncertainty in the determined NOEC value, the fact
that the active ingredient mefentrifluconazole is a fungicide (and no risks were identified for pollinators
or non-target arthropods), and other regulators (EFSA 2018) concluded that risks to sediment-
dwelling organisms were low, risks to sediment-dwelling organisms are considered to be low.
Terrestrial risk assessment
The terrestrial risk assessment considers the risks to soil organisms, terrestrial plants, birds, bees and
non-target arthropods.
The methodology for the terrestrial risk assessment is described in the EPA standard risk assessment
methodology (EPA 2018)
Soil macro-organisms
The soil organism risk assessment is based on a comparison of the Predicted Environmental
Concentrations (PECs) with toxicity values for the substance. The toxicity value is divided by the PEC
to give a Toxicity Exposure Ratio (TER). The different levels of concern assigned to TER values are
listed in the EPA standard risk assessment methodology (EPA 2018).
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The results of the acute risk assessment for soil organisms are summarised in Table 36.
Table 36: Acute TER values for soil organisms
Species
LC50
(mg/kg
soil)
Drift (%)
PEC
(mg/kg
soil)
TER
acute Conclusion
Scenario – mefentrifluconazole, two applications to cereals at 150 g ai/ha – “in-field”
Earthworm,
Eisenia fetida >500 NA 0.40 >1259
Below LOC for threatened/non-
threatened species
Scenario – mefentrifluconazole, two applications to cereals at 150 g ai/ha – “off-field”
Earthworm,
Eisenia fetida >500 2.38 0.009 >52903
Below LOC for threatened/non-
threatened species
Acute toxicity exposure ratios (TERs) for soil organisms for the active ingredient mefentrifluconazole
following application of Revystar® Fungicide are below the level of concern (LOC) for non-threatened
and threatened species.
Table 37: Chronic TER values for soil organisms (Tier I1)
Species
NOEC
(mg/kg
soil)
Drift (%)
PEC
(mg/kg
soil)
TER
chronic Conclusion
Scenario – mefentrifluconazole, two applications to cereals at 150 g ai/ha – “in-field”
Earthworm,
Eisenia fetida 4.0 NA 0.40 10.1
Below LOC for non-threatened
species
Above LOC for threatened
species
Scenario – mefentrifluconazole, two applications to cereals at 150 g ai/ha – “off-field”
Earthworm,
Eisenia fetida 4.0 2.38 0.009 423
Below LOC for threatened/non-
threatened species
1 No crop interception is included in the Tier I calculations. Assumes application to bare soil.
Risks to soil organisms were below the level of concern with the exception of the chronic risks to
threatened soil organisms for the active ingredient mefentrifluconazole following application of
Revystar® Fungicide in-field.
Due to the risk identified for threatened earthworm species in-field, chronic TER values were refined,
taking into account interception by the crop. A crop interception value of 80% was applied
(corresponding to the growth stage BBCH 30-39, which is the earliest growth stage that the substance
will be applied as clarified by the applicant).
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Table 38: Chronic TER values for soil organisms (Tier II1)
Species
NOEC
(mg/kg
soil)
Drift (%)
PEC
(mg/kg
soil)
TER
chronic Conclusion
Scenario – mefentrifluconazole, two applications to cereals at 30 g/ha (150 g ai/ha with 80% crop
interception) – “in-field”
Earthworm,
Eisenia fetida 4.0 NA 0.08 50
Below LOC for threatened/non-
threatened species
1 Crop interception is included in the Tier II calculations, assuming that a proportion of the applied fungicide will
be intercepted by the crop and remain on the foliage rather reach the soil
The chronic TER for threatened species in-field is below the LOC, taking into account a realistic crop
interception value of 80%.
The applicant has provided the argument that there are 179 taxa or earthworms in New Zealand with
only one species reported as “at risk - declining” (Deinodrilus gorgon) and 31 reported as “at risk -
naturally uncommon” (Department Of Conservation (DOC) 2014). Despite a potentially large
distribution area for this earthworm species on the West Coast, the best documented natural habitat is
not threatened by agriculture but rather by on-going and future mining activities on the Stockton and
Denniston Plateaus. Furthermore, Deinodrilus gorgon is reported have a total area of occupancy
≤1000 ha (10 km2) in New Zealand. The other 31 species ranked as “naturally uncommon” are
predominantly endemic to New Zealand. These 32 earthworm species are confined to a specific
forestry areas or occur within naturally small and widely scattered populations, where this distribution
is not the result of human disturbance.
A recent survey (Kim Y. 2017) sampled earthworms on the South Island including several locations in
the Canterbury region, which is a main wheat and barley growing area in New Zealand. Samples
collected from agricultural land found only native earthworm species classified as “not threatened”
and/or earthworm species exotic to New Zealand. The additional lines of scientific evidence provided
by Buckley et al. (Department Of Conservation (DOC) 2014) and Kim et al. (Kim Y. 2017) indicate
threatened species of earthworms in New Zealand are unlikely to be exposed to Revystar®
Fungicide.
The NZ EPA accepts this argument and agrees that threatened species of earthworm identified in
New Zealand are unlikely to be exposed to Revystar Fungicide in-field.
Soil microorganisms
For mefentrifluconazole the data indicate that there are no effects on the nitrogen and carbon
transformation in a field soil test concentration of 2.53 mg ai/kg soil dry weight (highest concentration
tested). The PEC calculated in the earthworm risk assessment is 0.4 kg ai/kg soil which is far below
the NOEC for soil microorganisms. As such, there is no risk to soil microorganisms following use of
Revystar Fungicide.
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Soil accumulation
Mefentrifluconazole was determined to be persistent in soil and therefore the accumulation of the
active ingredient in soil over time was evaluated. The PEC calculator (v. 1.0) developed by the UK
regulator was used and the accumulation according to the Good Agricultural Practises (GAP) for a
period of 20 years was considered. The input parameters and results of the modelling are displayed in
Table 39. Corresponding acute and chronic TER values are shown in Table 40 and Table 41,
respectively.
Table 39: Input parameters for PEC soil accumulation and resulting PAC1 values
Input parameters Mefentrifluconazole
Soil depth 5 cm
Soil density 1.5 g cm3
Application rate (kg ai/ha) 0.150
Number of applications 2
Application interval 21 days
Soil DT50 (lab) ≥1000 days
Crop interception 0% (Tier I) 80% (Tier II)
PAC1 value – steady state (mg/kg) 1.765 0.353
PAC1 value – peak (mg/kg) 1.388 0.278
1 Predicted Accumulation Concentration (PAC)
Table 40: Acute TER values for soil organisms (Tier I1) – soil accumulation
Species LC50
(mg/kg soil)
PAC (mg/kg
soil) TER (acute) Conclusion
Earthworm,
Eisenia fetida >500
1.765
(peak) 360
Below LOC for threatened/non-
threatened species
Earthworm,
Eisenia fetida >500
1.388
(steady state) 283
Below LOC for threatened/non-
threatened species
1 No crop interception is included in the Tier I calculations. Assumes application to bare soil.
Table 41: Chronic TER values for soil organisms – soil accumulation
Species NOEC
(mg/kg soil)
PAC (mg/kg
soil)
TER
(chronic) Conclusion
Tier I (0% crop interception)
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Species NOEC
(mg/kg soil)
PAC (mg/kg
soil)
TER
(chronic) Conclusion
Earthworm,
Eisenia fetida 4.0
1.765
(peak) 2.88
Above LOC for threatened/non-
threatened species
Earthworm,
Eisenia fetida 4.0
1.388
(steady state) 2.27
Above LOC for threatened/non-
threatened species
Tier II (80% crop interception)
Earthworm,
Eisenia fetida 4.0 0.353 (peak) 14.39
Below LOC for non-threatened
species
Above LOC for threatened
species
Earthworm,
Eisenia fetida 4.0
0.278
(steady state) 11.33
Below LOC for non-threatened
species
Above LOC for threatened
species
Both the highest exposure concentration (peak PAC) and steady state PAC values were used to
calculate the TER values for acute and chronic exposure to earthworms. The acute TER values were
below the level of concern for both non-threatened and threatened species. At Tier I (assuming 0%
crop interception), chronic risks to earthworms were above the level of concern for both non-
threatened and threatened species.
At Tier II (assuming 80% crop interception corresponding to growth stage BBCH 30-39 as described
above, is the earliest growth stage that the substance will be applied), chronic risks were identified
only for threatened species, which as described above are unlikely to be exposed to Revystar®
Fungicide in-field.
Conclusions of the soil organism risk assessment
Acute TERs for soil organisms for the active ingredient mefentrifluconazole following application of
Revystar® Fungicide are below the LOC for non-threatened and threatened species, both in-field and
off-field.
Chronic TERs for soil organisms for the active ingredient mefentrifluconazole following application of
Revystar® Fungicide are above the LOC for threatened species in-field. TERs were below the LOC
for non-threatened species in-field, as well as for off-field for both non-threatened and threatened
species. Due to the risk identified for threatened earthworm species in-field, chronic TER values were
refined, taking into account interception by the crop (80%). The chronic TER for threatened species
in-field is still above the LOC however. Further evaluation indicated that threatened species are
unlikely present in the application areas of Revystar® Fungicide as a result the risk is considered to
be below the LOC.
In regard to soil accumulation, the acute TER values were below the level of concern for both non-
threatened and threatened species. At Tier I (assuming 0% crop interception), chronic risks to
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earthworms were above the LOC for both non-threatened and threatened species.
At Tier II (assuming 80% crop interception corresponding to growth stage BBCH 30-39 as described
above, is the earliest growth stage that the substance will be applied), chronic risks were identified
only for threatened species, which are considered unlikely to be exposed to Revystar® Fungicide in-
field.
Non-target plant risk assessment
The non-target plant risk assessment is based on a comparison of the PEC with toxicity values for the
substance. Depending on the type of data provided, for non-threatened plants a TER or an RQ is
calculated (a TER is used when an EC50 is available, an RQ is used when an EC25 is available). For
threatened non-target plants an RQ is calculated by comparing the PEC with a NOEC. The different
levels of concern assigned to specific TER/RQ values are listed in the EPA standard risk assessment
methodology (EPA 2018).
RQ values for non-threatened non-target plants are shown in Table 43. TER values for threatened
non-target plants are shown in Table 42. No crop interception was incorporated in the risk
assessment.
Table 42: RQ value for non-target plant – edge of field
Scenarios
Exposure
(g ai/ha) *
drift factor
* MAF1
EC25
(g ai/ha) RQ Conclusion
Revystar® Fungicide – 150 g ai/ha, two applications
Cereals 6.78 >1502 0.045 Below LOC for non-threatened
species
1 Drift factor is 2.38%, a worst-case MAF of 1.9 was used
2 Toxicity endpoint is the same for vegetative vigour and seedling emergence
Table 43: RQ value for threatened non-target plants
Scenarios
Exposure
(g ai/ha) *
drift factor*
MAF11
NOEC
(g ai/ha) RQ Conclusion
Revystar® Fungicide – 150 g ai/ha, two applications
Cereals 6.78 752 0.090 Below LOC for threatened species
1 Drift factor is 2.38%, a worst-case MAF of 1.9 was used
2 Lowest toxicity endpoint used as worst-case (seedling emergence). This endpoint should be treated with caution however since there is some uncertainty in derivation of this endpoint.
Conclusion for non-target plant risk assessment
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Risk Quotients (RQs) to non-target plants calculated for mefentrifluconazole when applied to cereals
as the formulated product Revystar® Fungicide are below the level of concern.
Bird risk assessment
The bird risk assessment is based on a comparison of the PEC with toxicity values for the substance.
The toxicity value is divided by the PEC to give a Toxicity Exposure Ratio (TER). The different levels
of concern assigned to specific TER values are listed in the EPA standard risk assessment
methodology (EPA 2018).
Screening assessment
Predicted exposure to mefentrifluconazole under the bird acute dietary and reproduction screening
assessments is shown in Table 44.
Table 44: Exposure of birds for acute and reproduction screening assessments
Screening
type1
Indicator
species2
Application
rate
(kg/ha)
Short-
cut
value
(90th%)3
TWA4
MAF
(90th
%)5
No of
applications DDD
Cereals, two applications, 21-day spray interval
Acute
Small
omnivorous
bird
0.15 158.8 NA 1.1 2 26.20
Reproduction
Small
omnivorous
bird
0.15 64.8 0.53 1.2 2 6.18
1 EFSA (EFSA 2009), Table 5 p27 2 EFSA, (EFSA 2009), Table 6 p28 3 90th %ile short-cut value used for the acute assessment, mean value used for the reproduction assessment. EFSA,
(EFSA 2009), Table 6 p28 4 The exposure assessment of the reproduction assessment uses time-weighted average (TWA) exposure estimates
over 1, 2, 3 or 21 days for different phases of the assessment. 1 day = 1.0; 2 days = 0.93; 3 days = 0.9; 21 days = 0.53. EFSA, (EFSA 2009), Table 11 p34.
5 90th %ile MAF value used for the acute assessment, mean value used for the reproduction assessment. EFSA, (EFSA 2009), Table 7 p29
Calculation of TERs
TER calculations for the acute dietary and reproductive risk assessment are detailed in Table 45.
Table 45: TER values for acute dietary risk assessment (TWA = 0.53)
Crops &
BBCH class
Generic
focal
species1
Daily
dietary
dose
(DDD)
Toxicity
endpoint
value (mg/kg
bw/d)*
TER ratio Conclusion
Application rate (kg/ha) – Number of applications
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Crops &
BBCH class
Generic
focal
species1
Daily
dietary
dose
(DDD)
Toxicity
endpoint
value (mg/kg
bw/d)*
TER ratio Conclusion
Acute Small
omnivorous
bird
26.20 816 31.1 Risks below LOC for
threatened and non-
threatened species
Reproduction Small
omnivorous
bird
6.18 25.3 4.1 Risks above LOC
for non-threatened
and threatened
species
Conclusions of the bird screening risk assessment
The acute screening risk assessment indicates an acute risk below the level of concern to birds from
mefentrifluconazole from the use of Revystar® Fungicide. In the reproductive screening assessment
the TER values indicate a chronic risk above the level of concern to birds. As risks were above the
level of concern a Tier 1 risk assessment for chronic toxicity was performed.
Tier 1 assessment
Tier 1 uses the same general approach as the screening assessment but requires more specific
exposure scenarios. More details are provided in the EPA standard risk assessment methodology
(EPA 2018).
For each generic focal species the daily dietary dose (DDD) is presented in Table 44 (acute and
chronic).
The toxicity figures are the same than those considered in the screening assessment.
The indicator species mentioned in Table 46 (chronic) are not real species but have to be considered
as representative of groups of birds of the same size and same feeding behaviour.
Table 46: TER values for chronic risk assessment – Tier 1 assessment
Crops &
BBCH
class
Focal species
Short-
cut
value2
(90th %)
Toxicity
endpoint
(mg/kg
bw)
TER ratio Conclusion
Mefentrifluconazole – Cereals, 150 g ai/ha, two applications, 21-day spray interval
BBCH 10 -
29
Small omnivorous bird “lark”.
Combination (invertebrates
with interception (25% crop
leaves, 25% weed seeds,
50% ground arthropods
10.9
25.3
24.3
Below the LOC for
non-threatened and
threatened species
BBCH 30 -
39
Small omnivorous bird “lark”.
Combination (invertebrates
5.4 49.1
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with interception (25% crop
leaves, 25% weed seeds,
50% ground arthropods
BBCH ≥ 40 Small omnivorous bird “lark”.
Combination (invertebrates
with interception (25% crop
leaves, 25% weed seeds,
50% ground arthropods
3.3 80.4
Early
(shoots)
autumn-
winter
BBCH 10-29
Large herbivorous bird
"goose" Grass + cereals
100% cereal shoots
16.2 16.4
Late post-
emergence
(May-
June)BBCH
71-89
Small insectivorous bird
"passerine". Foliar insects,
100% foliar insects
22.4 11.8
Late
season-
Seed heads
Small
granivorous/insectivorous
bird “bunting” Grains/ear
100% cereal seeds
12.5 21.2
Conclusion for bird risk assessment (Tier 1)
The chronic Tier 1 risk assessment indicates risks below the level of concern to both threatened and
non-threatened birds from the use of Revystar® Fungicide.
Secondary poisoning
Given the criteria under the HSNO Act the active ingredient mefentrifluconazole is not considered to
be bioaccumulative (BCF <500). Therefore, no risk assessment via secondary poisoning is
performed.
Conclusions for bird risk assessment
TER values for birds calculated for the active ingredient mefentrifluconazole when applied to cereals
as the formulated product Revystar® Fungicide are below the LOC for acute risks, and any risks are
negligible. In the reproductive screening assessment, the TER values indicate a chronic risk above
the LOC to non-threatened and threatened bird species. After the Tier I risk assessment, risks to non-
threatened and threatened species of birds are considered below the LOC. The risks from secondary
poisoning is considered to be low.
Pollinator risk assessment
The basis for the pollinator risk assessment is a comparison of the environmental exposure
concentration (EEC) with toxicity endpoints to which safety factors have been applied. The EEC is
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divided by the toxicity endpoint to calculate a risk quotient (RQ) value. The methodology for the
pollinator risk assessment, including the level of concern (LOC) ascribed to specific RQ values, is
described in detail in the EPA standard risk assessment methodology (EPA 2018). The results of the
bee risk assessment are shown in Table 47.
Table 47: Bee exposure estimates and RQ values
Use scenario Application
rate (kg ai/ha)
EEC (µg
ai/bee)
Toxicity
endpoint
value (µg
ai/bee)
RQ Conclusion
Acute / Adult bees – contact
Cereals 0.15 0.36 >100 <0.0036 Below the LOC
Acute / Adult bees – oral
Cereals 0.15 4.29 >100 <0.04 Below the LOC
Chronic / Adult bees – oral
Cereals 0.15 4.29 110.5 0.04 Below the LOC
Acute / Larvae bees – oral
Cereals 0.15 1.96 43.9 0.04 Below the LOC
Conclusions of the pollinator risk assessment
The risks to pollinators are below the LOC and any risks are negligible.
Non-target arthropod risk assessment
The non-target arthropod risk assessment is a comparison of the predicted environmental
concentration (PEC) with toxicity endpoints to which safety factors have been applied. The PEC is
divided by the toxicity endpoint to calculate a hazard quotient (HQ) value. The methodology for the
pollinator risk assessment, including the level of concern (LOC) ascribed to specific HQ values, is
described in detail in the EPA standard risk assessment methodology (EPA 2018).
Results of the Tier I in-field and off-field non-target arthropod risk assessment are shown in Table 48
and Table 49, respectively.
Table 48: In-field HQ values for non-target arthropods (Tier I)
Species LR50
(g ai/ha)
Application rate
(g ai/ha) MAF
Hazard
Quotient Conclusion
Parasitic wasp, Aphidius
rhopalosiphi 0.954 150 1.7 267 Above the LOC
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Species LR50
(g ai/ha)
Application rate
(g ai/ha) MAF
Hazard
Quotient Conclusion
Predatory mite,
Typhlodromus pyri 7.691 150 1.7 33 Above the LOC
Table 49: Off-field HQ values for non-target arthropods (Tier I) [drift factor = 2.77%1]
Species LR50
(g ai/ha)
Application rate
(g ai/ha) MAF
Hazard
Quotient Conclusion
Parasitic wasp, Aphidius
rhopalosiphi 0.954 150 1.7 6.36 Above the LOC
Predatory mite,
Typhlodromus pyri 7.691 150 1.7 0.79 Below the LOC
1 BBA drift value for two applications to field crops (1 m)
At Tier I all hazard quotients were above the level of concern (LOC) with the exception of the off-field
hazard quotient for the predatory mite (Typhlodromus pyri). As such, a Tier II non-target arthropod
risk assessment was performed. Results of the Tier II in-field and off-field non-target arthropod risk
assessment are shown in Table 50 and Table 51, respectively.
Table 50: In-field HQ values for non-target arthropods (Tier II)
Species LR50
(g ai/ha)
Application rate
(g ai/ha) MAF
Hazard
Quotient Conclusion
Parasitic wasp, Aphidius
rhopalosiphi >300 150 1.7 <0.85 Below the LOC
Predatory mite,
Typhlodromus pyri >300 150 1.7 <0.85 Below the LOC
Table 51: Off-field HQ values for non-target arthropods (Tier II) [drift factor = 2.77%1]
Species LR50
(g ai/ha)
Application rate
(g ai/ha) MAF
Hazard
Quotient Conclusion
Parasitic wasp, Aphidius
rhopalosiphi >300 150 1.7 <0.020 Below the LOC
Predatory mite,
Typhlodromus pyri >300 150 1.7 <0.020 Below the LOC
1 BBA drift value for two applications to field crops (1 m)
Conclusion for non-target arthropod risk assessments
Risks to non-target arthropods are below the LOC for both off-field and in-field at Tier II.
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Conclusions of the ecological risk assessment
The EPA staff assessed the potential risk to be triggered by the use of Revystar® Fungicide following
the instructions captured in the proposed label and GAP table.
Aquatic risk assessment
Predicted exposures concentrations of mefentrifluconazole, applied as the formulated product
Revystar® Fungicide resulted in calculated RQs above the LOC for the aquatic environment. Chronic
risks to threatened species of aquatic invertebrates were identified for both ground-based (RQ = 0.27,
LOC = 0.1) and aerial applications (RQ = 0.32, LOC = 0.1). A refinement of the soil DT50 did not result
in risk below the level of concern in the screening step. The following controls are proposed to reduce
exposures below the level of concern:
Use restrictions
The maximum application rate is 150 g mefentrifluconazole/ha, maximum two
applications/year, and a minimum interval between applications of 21 days
Apply with ground-based equipment and minimum medium droplets, as defined by the
American Society of Agricultural and Biological Engineers ASABE Standard (S572) or the
British Crop Production Council guideline. This information should be required on the
label so that users are aware of this control.
For aerial application, use minimum coarse droplets, as defined by the American Society
of Agricultural and Biological Engineers ASABE Standard (S572) or the British Crop
Production Council guideline. This information should be required on the label so that
users are aware of this control.
A label statement indicating: “DO NOT apply when wind speeds are less than 3 km/hr or
more than 20 km/hr as measured at the application site”.
Groundwater risk assessment
For mefentrifluconazole and its metabolite M750F001 (1,2,4-triazole) the predicted concentration in
groundwater is below the 0.1 µg/L trigger level set by the European regulators. Therefore, risks to
groundwater are considered below the level of concern.
Sediment risk assessment
The risk quotients for sediment-dwelling organisms following both ground-based and aerial application
were both identified as potentially being above the level of concern (LOC = 1).
Only one chronic endpoint, which is not an absolute value, was available for sediment-dwelling
organisms, and the risk assessment was performed with this value (28-day NOEC of ≥1.158 mg ai/kg
for Chironomus riparius). The NOEC determined in this case was the highest concentration tested,
and no significant effects were observed at this concentration. If a higher concentration had been
tested, the NOEC could potentially be higher, thus resulting in a lower risk.
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Using a weight-of-evidence approach, given the uncertainty in the determined NOEC value, the fact
that the active ingredient mefentrifluconazole is a fungicide (and no risks were identified for pollinators
or non-target arthropods), and other regulators (EFSA) concluded that risks to sediment-dwelling
organisms were low, risks to sediment-dwelling organisms are considered to be low.
Soil organism risk assessment
Acute TERs for soil organisms for the active ingredient mefentrifluconazole following application of
Revystar® Fungicide are below the LOC for non-threatened and threatened species, both in-field and
off-field.
Chronic TERs for soil organisms for the active ingredient mefentrifluconazole following application of
Revystar® Fungicide are above the LOC for threatened species in-field. TERs were below the LOC
for non-threatened species in-field, as well as for off-field for both non-threatened and threatened
species. Due to the risk identified for threatened earthworm species in-field, chronic TER values were
refined, taking into account interception by the crop (80%). The chronic TER for threatened species
in-field is still above the LOC however. Further evaluation indicated that threatened species are
unlikely present in the application areas of Revystar® Fungicide as a result the risk is considered to
be below the LOC.
In regard to soil accumulation, the acute TER values were below the level of concern for both non-
threatened and threatened species. At Tier I (assuming 0% crop interception), chronic risks to
earthworms were above the LOC for both non-threatened and threatened species.
At Tier II (assuming 80% crop interception corresponding to growth stage BBCH 30-39 as described
above, is the earliest growth stage that the substance will be applied), chronic risks were identified
only for threatened species, which are considered unlikely to be exposed to Revystar® Fungicide in-
field.
Non-target plant risk assessment
Risk Quotients (RQs) to non-target plants calculated for mefentrifluconazole when applied to cereals
as the formulated product Revystar® Fungicide are below the level of concern.
Bird risk assessment
TER values for birds calculated for the active ingredient mefentrifluconazole when applied to cereals
as the formulated product Revystar® Fungicide are below the LOC for acute risks, and any risks are
negligible. In the reproductive screening assessment, the TER values indicate a chronic risk above
the LOC to non-threatened and threatened bird species. After the Tier I risk assessment, risks to non-
threatened and threatened species of birds are considered below the LOC. The risks from secondary
poisoning is considered to be low.
Pollinator risk assessment
The risks to pollinators are below the LOC and any risks are negligible.
Non-target arthropod risk assessments
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Risks to non-target arthropods are below the LOC for both off-field and in-field.
It is considered that the risks to the environment from the proposed use of Revystar® Fungicide are
acceptable with the proposed controls.
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Appendix I: Proposed controls
Prescribed controls
The hazard classifications of Revystar determine a set of prescribed controls specified by the EPA
Notices. There are also requirements in the Health and Safety at Work (HSW) (Hazardous
Substance) Regulations.
The Hazardous Substances Labelling, Safety Data Sheet (SDS), Packaging, Disposal and Hazardous
Property Controls (HPC) Notices 2017 apply to Revystar.
Exposure thresholds
Exposure thresholds proposed for mefetrifluconazole are shown in Table 52. Acceptable Daily
Exposure (ADE) and Potential Daily Exposure (PDE) values are not controls as such, but are health
based exposure guidance values which can be used to inform risk assessments as well as the setting
of controls, such as Maximum Residue Levels under the ACVM Act.
The EPA has reviewed health based exposure guidance values established by overseas regulators
(shown in Table 53) to inform the selection of ADE and PDE values for mefetrifluconazole
Table 52: Derivation of appropriate health-based exposure guidance value for
mefetrifluconazole
Available
international
toxicological
thresholds
Key Systemic
effect
NOAEL
(mg/kg
bw/day)
Uncertainty
factors
Value
(mg/kg
bw/day)
Modifications Remarks
EFSA (EFSA
2018) -ADI
No treatment
related changes
were observed
at the NOAEL
Not carcinogenic
in mice
3.5 100 0.035 None
18-month
dietary chronic
toxicity/carcinog
enicity study:
mice
Based on the assessment of the available data, the following Acceptable Daily Exposure (ADE),
Potential Daily Exposure (PDE) and Acute reference dose (ARfD) values have been provided (see
Table 27).
No Tolerable Exposure Limit (TEL) value has been set for this substance. This is because it is not
considered that exposure is likely to result in an appreciable toxic effect based on the quantitative risk
assessment done here.
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Table 53: exposure thresholds for mefentrifluconazole
Active Ingredient ADE PDE ARfD TEL
mefentrifluconazole, 0.035 mg/kg
bw/d (EFSA)
PDE (Food) =
0.025 mg/kg
bw/d
PDE (Drinking water)
= 0.007 mg/kg
bw/d
PDE (Other) =
0.0035 mg/kg
bw/d
0.15 mg/kg bw/d Not set at this
time
Impurity limits
The following limits as shown in Table 54 are set for toxicologically relevant impurities in
mefentrifluconazole based on the European Commission specification (EC 2019).
Table 54: Impurities limits proposed for Revystar
Active ingredient Impurity and maximum limits (mg/kg) Source/ specification
(FAO/APVMA/NZ EPA)
mefentrifluconazole
N,N-dimethylformamide (DMF; 68-12-2) : 0.5 g/kg
toluene (108-88-3) : 1 g/kg
1,2,4-(1H)-triazole (288-88-0): 1 g/kg
European Commission
(EC 2019)
Ecotoxicity controls
Application restrictions
A maximum application rate is proposed to be set for Revystar, as shown in Table 55.
Table 55: Maximum application rates for Revystar
Active component Maximum application rate
Mefentrifluconazole 150 g ai/ha, maximum 2 application/year, interval between application 21 days
Fluxapyroxad 75 g ai/ha, maximum 2 application/year, interval between application 21 days
Application method
Revystar must not be applied when wind speeds are less than 3 km/hr or more than 20 km/hr as
measured at the application site.
Apply with ground-based equipment and minimum medium droplets, as defined by the American
Society of Agricultural and Biological Engineers ASABE Standard (S572) or the British Crop
Production Council guideline. This information should be required on the label so that users are aware
of this control
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For aerial application, use minimum coarse droplets, as defined by the American Society of
Agricultural and Biological Engineers ASABE Standard (S572) or the British Crop Production Council
guideline. This information should be required on the label so that users are aware of this control
Buffer zones
None identified
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Appendix J: Study summaries
Manufacturer code name for mefentrifluconazole is BAS 750 F.
Manufacturer code name for Revystar® Fungicide is BAS 752 00 F.
Toxicity study summaries
Mammalian toxicity studies on mefentrifluconazole and Revystar® Fungicide have been reviewed.
These studies are used to describe potential risks to human health. The effects on mammals in these
studies are used as proxies for the impact on humans. Data from the studies have been used for
classifying the active ingredient and the formulated substance and for derivation of appropriate health-
based criteria which are used in risk assessment. Data summaries for mefentrifluconazole can be
found in the European Commission Draft Assessment Report (EC 2017) Volume 3 – B.6 (AS). Data
summaries for Revystar® are provided in Table 56 to Table 62.
Mammalian toxicology - Robust study summaries for Revystar®
Acute toxicity [6.1]
Table 56: Acute Oral Toxicity [6.1 (oral)]
Type of study Acute oral lethality
Flag Key study
Test Substance BAS 752 00 F ; Batch: FD-140205-0020; BAS 750 F: 100.5 g/L; BAS
700 F: 52.5 g/L
Endpoint LD50
Value >300 mg/kg LD50 <2000 mg/kg
Reference
2014). BAS 752 00 F - Acute oral toxicity study in rats.
:
Klimisch Score 1
Amendments/Deviations None of significance
GLP Yes
Test Guideline/s OECD 423; Commission Regulation (EC) No 440/2008; US EPA
OPPTS 870.1100
Species Rat
Strain Wistar, Crl:WI (Han) SPF
No/Sex/Group 2000 mg/kg bw in 3 F, 300 mg/kg bw in 6 F (2 groups of 3)
Dose Levels 300 and 2000 mg/kg
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Exposure Type Oral gavage
Study Summary
2000 mg/kg (single test group):
Two animals were sacrificed in a moribund state after 5 hours. Clinical
signs consisted of: impaired general state (3/3), poor general state (2/3),
dyspnoea (3/3), gasping (2/3), flat respiration (2/3), piloerection (3/3),
cowering (1/3), abdominal position (2/3), and staggering (2/3) in two
animals.
Macroscopic pathological findings in the two animals that were
sacrificed moribund consisted of a red discoloration and thickening of
the glandular stomach.
300 mg/kg (first test group):
No mortality occurred. An Impaired general state and pilo-erection was
observed in all animals
300 mg/kg (second test group):
No mortality or clinical signs were observed.
There were no macroscopic pathological findings in the surviving
animals sacrificed at the end of the observation period (all doses).
The mean body weight of the surviving animal in the 2000mg/kg bw test
group increased within the normal range throughout the study period.
The body weight of one animal each in both 300 mg/kg bw test groups
increased within the normal range throughout the study period, while the
two other animals in each test group showed stagnation of body weight
during the second observation week.
Additional Comments No additional comments
Conclusion The LD50 was greater than 300 mg/kg bw but less than 2000 mg/kg bw.
Accordingly, the substance is classified as 6.1D.
Table 57: Acute Dermal Toxicity [6.1 (dermal)]
Type of study Acute dermal lethality
Flag Key study
Test Substance BAS 752 00 F ; Batch: FD-140205-0020; BAS 750 F: 100.5 g/L; BAS
700 F: 52.5 g/L
Endpoint LD50
Value >5000 mg/kg
Reference
(2014). “BAS 752 00 F - Acute dermal
toxicity study in rats.”
Klimisch Score 1
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Amendments/Deviations None of significance
GLP Yes
Test Guideline/s OECD 402; Commission Regulation (EC) No 440/2008; US EPA
OPPTS 870.1200
Species Rat
Strain Wistar, Crl:WI (Han) SPF
No/Sex/Group 5/sex/group
Dose Levels 5000 mg/kg
Exposure Type Dermal under a semi-occlusive wrap
Study Summary
No mortality, signs of systemic toxicity, or local skin effects were
observed.
The mean body weight of the male animals increased within the normal
range throughout the study period.
The body weight of the female animals increased within the normal
range throughout the study period with two exceptions in which a
stagnation of body weight occurred during the first week. Body weights
were within the normal range during the second week.
No macroscopic pathologic abnormalities were noted in any animal at
study termination.
Additional Comments No additional comments
Conclusion The LD50 was greater than 5000 mg/kg. Accordingly, the substance is
not classified.
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Table 58: Acute Inhalation Toxicity [6.1 (inhalation)]
Type of study Acute inhalation lethality
Flag Key study
Test Substance BAS 752 00 F ; Batch: FD-140205-0020; BAS 750 F: 100.5 g/L; BAS
700 F: 52.5 g/L
Endpoint LC50
Value >1.9 mg/L LC50 <5.1 mg/L
Reference
2014). “BAS 752 00 F: 4-Hour Acute Inhalation Toxicity
Study in the Rat.”
Klimisch Score 1
Amendments/Deviations None of significance
GLP Yes
Test Guideline/s OECD 403; Commission Regulation (EC) No 1907/2006 and 440/2008;
US EPA OPPTS 870.1300
Species Rat
Strain RccHan: WIST(SPF)
No/Sex/Group 5/sex/group
Dose Levels
0.9 mg/L; MMAD / GSD (mean): 2.76 μm / 3.29
1.9 mg/L; MMAD / GSD (mean): 2.38 μm / 2.97
5.1 mg/L; MMAD / GSD (mean): 1.91 μm / 2.59
Exposure Type Nose only
Study summary
All animals exposed to 5.1 mg/L air spontaneously died or were
sacrificed in extremis on the day of exposure. All animals exposed to 0.9
or 1.9 mg/L air survived the scheduled observation period.
Clinical signs observed prior to death consisted of swaying gait, apathy,
prostration, ruffled fur, laboured breathing, breathing noises and
salivation.
Principal signs of toxicity observed after exposure to 1.9 or 0.9 mg/L air
consisted of decreased activity, hunched posture, ruffled fur, and
salivation. These generally receded within the first week after exposure.
Laboured breathing and breathing noises were observed during the first
and second week after exposure and persisted until the end of the
observation period.
Body weight loss or stagnation of body weight gain was observed
between test days 1 and 4 in all animals exposed to 1.9 mg/L air. Two
males additionally showed body weight loss or stagnation of body weight
gain at isolated measurement intervals after test day 4.
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Body weight loss was observed between test days 1 and 2 in all animals
exposed to 0.9 mg/L air and body weight loss or stagnation of body
weight gain continued until test day 4 in 4/5 males and 3/5 females.
Thereafter, normal body weight gain was observed in all animals
exposed to 0.9 mg/L air.
At necropsy, all animals exposed to 5.1 mg/L air showed reddish or
dark-brown discoloration of the lungs. No macroscopic findings were
present at necropsy in the animals exposed to 0.9 or 1.9 mg/L.
Additional Comments No additional comments
Conclusion The LC50 is greater than 1.9 mg/L but less than 5.1 mg/L. Accordingly,
the substance is classified as 6.1D.
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Table 59: Skin Irritation [6.3/8.2]
Type of study Primary skin irritation/corrosion
Flag Key study
Test Substance BAS 752 00 F ; Batch: FD-140205-0020; BAS 750 F: 100.5 g/L; BAS
700 F: 52.5 g/L
Endpoint Mean Draize score for erythema and oedema
Value Mean score - Erythema: 3.0, Oedema: 1.6
Reference
(2014). “BAS 752 00 F - Acute dermal
irritation / corrosion in rabbits.”
Klimisch Score 1
Amendments/Deviations None of significance
GLP Yes
Test Guideline/s OECD 404; Commission Regulation (EC) No 440/2008; US EPA
OPPTS 870.2500
Species Rabbit
Strain New Zealand White: Hsdlf; NZW (SPF)
No/Sex/Group 3 F
Dose Levels 0.5 mL
Exposure Type Dermal under semi-occlusive dressing
Study Summary
The following test item-related clinical observations were recorded
during the course of the study: very slight to moderate erythema (grade
1 to 3); very slight to slight oedema (grade 1 to 2), and scaling.
The cutaneous reactions eventually decreased in severity but were not
fully reversible in all animals within the 14-day observation period after
removal of the patch (study termination). In two animals, well-defined
erythema (grade 2), very slight oedema (grade 1) and scaling were still
noted; while the third animal showed very slight erythema (grade 1) and
scaling on day 14.
Mean scores over 24, 48 and 72 hours for all three animals were 3.0 for
erythema and 1.6 for oedema.
Additional Comments No additional comments
Conclusion
The mean scores over 24, 48 and 72 hours for all three animals were
3.0 for erythema and 1.6 for oedema. Accordingly, the substance is
classified as 6.3A for skin irritation.
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Table 60: Eye Irritation [6.4/8.3]
Type of study Eye irritation/corrosion
Flag Key study
Test Substance BAS 752 00 F ; Batch: FD-140205-0020; BAS 750 F: 100.5 g/L; BAS
700 F: 52.5 g/L
Endpoint
Mean Draize score for cornea, conjunctiva (redness and chemosis), and
iris
Value
Mean Draize Score -
Cornea
-Opacity: 1.0
Conjunctiva
-Redness: 1.6
-Chemosis: 1.1
Iris: 0.6
Reference
(2014). “BAS 752 00 F - Acute eye
irritation in rabbits.”
2015. “BAS 752 00 F - Acute eye irritation in rabbits.”
,
Klimisch Score 1
Amendments/Deviations None of significance
GLP Yes
Test Guideline/s OECD 405; Commission Regulation (EC) No 440/2008; US EPA
OPPTS 870.2400
Species Rabbit
Strain New Zealand White: Hsdlf; NZW (SPF)
No/Sex/Group 3 F
Dose Levels 0.1 mL
Exposure Type Direct ocular instillation
Study Summary
Ocular reactions were assessed approximately 1, 24, 48 and 72 hours
after application and on study Day 7. Additional eye examinations were
performed from hour 24 until study day 7 after application with the
instillation of a fluorescein solution. Due to a negative finding on study
day 7 (no corneal lesions detectable with fluorescein) and the observed
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reversibility of ocular reactions in all animals the study was terminated
on study day 7.
The following observations were recorded during the course of the
study: slight to moderate corneal opacity (grade 1-2); moderate iritis
(grade 1); slight to severe conjunctival redness (grade 1-3); slight to
moderate conjunctival chemosis (grade 1-2); slight to obvious discharge
(grade 1-2); desquamation of corneal epithelium and contracted pupil
was noticed from hour 48 until hour 72 after application. Injected scleral
vessels in a circumscribed or circular area were observed from hour 1
until study day 7 at the latest. Corneal lesions detectable with the aid of
fluorescein grade 1- 4 (i.e. affected area) were seen from hour 24 until
hour 72.
The ocular reactions were reversible in all animals within 7 days after
application.
Mean scores calculated for each animal over 24, 48 and 72 hours were
1.3, 0.7 and 1.0 for corneal opacity, 1.0, 0.7 and 0.0 for iris lesions, 2.7,
1.0 and 1.0 for redness of the conjunctiva and 2.0, 0.7 and 0.7 for
chemosis.
Additional Comments No additional comments
Conclusion
The mean scores over 24, 48 and 72 hours for all three animals were
1.0 for corneal opacity, 1.6 and 1.1 for conjunctival redness and
chemosis respectively, and 1.1 for iritis. Accordingly, the substance is
classified as 6.4A for eye irritation.
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Table 61: Contact Sensitisation [6.5]
Type of study Primary skin sensitisation – local lymph node assay
Flag Key study
Test Substance BAS 752 00 F ; Batch: FD-140205-0020; BAS 750 F: 100.5 g/L; BAS
700 F: 52.5 g/L
Endpoint Stimulation index (SI)
Value SI: 4.06 with 25% w/w; EC3 = 19.6%
Reference
(2014). “BAS 752 00 F – Skin Sensitisation: Local Lymph
Node Assay.”
.:
Klimisch Score 1
Amendments/Deviations None of significance
GLP Yes
Test Guideline/s OECD 429; Commission Regulation (EC) No. 440/2008, B.42
Species Mouse
Strain CBA/CaOlaHsd
No/Sex/Group 5 F / 4 groups
Dose Levels Vehicle control, 5, 10, and 25% (w/w)
Exposure Type Topical application (25 µL) on the ear dorsum
Study Summary
The animals did not show any signs of systemic toxicity during the
course of the study and no cases of mortality were observed. The
animals treated with a test item concentration of 10 and 25% showed an
erythema of the ear skin (score 1 and 2). Animals treated with 5% test
item concentration did not show any signs of local skin irritation. In the
group treated with a test item concentration of 25%, a statistically
significant increase in ear weights was observed in comparison to the
values of the vehicle control group. For BALB/c mice, a cut-off value of
1.1 for the ear weight index was reported for a positive response
regarding ear skin irritation. The index determined for the high dose
group just reached this threshold (index of 1.10), thus indicating a slight
irritant property of the test item. Nevertheless, the threshold value of
25% increase in ear weights for excessive local skin irritation mentioned
in OECD guideline 429 was not exceeded in any group.
Stimulation Indices (SI) of 0.89, 1.10, and 4.06 were determined with the
test item at concentrations of 5, 10, and 25% in acetone/olive oil (4+1,
v/v), respectively. A dose response was observed and an EC3 value of
19.6 % was derived.
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Additional Comments
A score of 4.06 is just above the cut-off value of 3 and the fact there was
evidence of irritation which could also add to the SI value indicates the
material is likely a very weak sensitiser.
Conclusion The test substance was determined to have contact sensitisation
potential based on a SI >3 at 25% w/w and is accordingly labelled 6.5B
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Dermal Absorption of Mefentrifluconazole (BAS 750 F) in Revystar® (BAS 752 00 F)
Table 62: Dermal Absorption – In Vitro
Study type In vitro dermal absorption through human skin
Flag Key study
Test Substance
Carbon-14 labelled BAS 750 F (mefentrifluconazole), Batch: 1062-2001;
Specific activity: 5.46 MBq/mg; Radiochemical purity: >98%; Non-
radiolabelled material test item Name: BAS 750 F; Batch: COD-001880;
Purity: 98.6%, and BAS 752 00 F; Batch: FD-140205-0020; BAS 750 F:
100.5 g/L; BAS 700 F: 52.5 g/L; Vehicle: Diluted with water
Endpoint Absorption kinetics
Value
Concentration Absorption %
1000 µg/cm2 / 100 mg/ml (concentrate) 0.36 ± 0.26
5.0 µg/cm2 / 0.50 mg/ml (1:200 dilution) 2.82 ± 0.98
Reference
(2014). “14C-BAS 750 F in BAS 752 00 F
Study of penetration through human skin in vitro.”
Klimisch Score 1
Amendments/Deviations None of significance
GLP Yes
Test Guideline OECD 428 and OECD Guidance Document No. 28 for the Conduct of Skin
Absorption Studies.
Species Human
Strain NA
No/Sex/Group 8 (abdominal)
Dose Levels Concentrated active: 1000 µg/cm2 / 100 mg/ml
1:200 dilution: 5.0 µg/cm2 / 0.5 mg/ml
Exposure Type In vitro using flow-through diffusion chambers in static mode
Study Summary
Split-thickness human skin membranes were mounted into Franz-type flow
through diffusion cells operated in static mode. The skin surface
temperature was maintained at 32°C ± 1°C throughout the experiment.
The integrity of the skin preparation was determined by measuring its trans
epidermal electrical resistance (TEER).
Absorption of [14C]-750 F was assessed by collecting receptor fluid at 1, 2,
4, 6, 8, 12, and 24 hours post dose. At 24 h post dose, the underside of
the skin was rinsed with receptor fluid (receptor rinse). The skin was
removed from the cells and dried with a tissue swab. The cell was
dismantled and the donor chamber and receptor chamber were retained
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separately for analysis. The stratum corneum was removed by tape
stripping and the skin divided into exposed and unexposed skin.
100 mg/mL: At 24 h post dose, the total recovery was 96.64% of the
applied dose. The stratum corneum retained 0.24% of the applied dose
and the total unabsorbed dose was 96.04% of the applied dose. The total
absorbed dose was 0.36 ± 0.26%.
0.5 mg/mL: At 24 h post dose, the total recovery was 98.45% of the
applied dose. The stratum corneum retained 1.21% of the applied dose
and the total unabsorbed dose was 94.41% of the applied dose. The total
absorbed dose was 2.82 ± 0.98%.
Additional Comments Values used in the risk assessment were the same as those suggested by
the applicant.
Conclusion
The results of this study indicate mefentrifluconazole in Revystar® is
poorly absorbed (0.36 ± 0.26%) through the skin as a concentrate (100
mg/mL) and when diluted 1:200 with water (0.5 mg/ml) into an in-use spray
dilution (2.82 ± 0.98%). Due to variation in the data the values used in the
risk assessment were the average plus one SD and rounded up to 1% for
the concentrate and 4% for the dilution.
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Environmental fate studies
Unless otherwise noted, all studies were conducted according to GLP and were fully compliant with all
requirements of the standard international test methods used. All data for mefentrifluconazole and its
metabolites were sourced from the mefentrifluconazole DAR unless otherwise stated. Study
summaries have only been included in Appendix J where there are comments in regard to individual
studies, and are provided in Table 63 to Table 70
Abiotic degradation
Table 63: Photodegradation in soil (photolysis): active ingredient (key study)
Study type Soil photolysis
Flag Key study
Test Substance BAS 750 F (mefentrifluconazole)
Endpoint DT50
Value 93 days (chlorophenyl-label) and 170 days (triazole-label)
Reference (3.6.5) Hassink and Delgado (2014a). Soil photolysis of BAS 750 F. BASF Study
Identification Number: 433829. BASF Registration Document Number (Doc
ID): 2014/1181666.
Study Summary The summary in the Draft Assessment Report (DAR) – BAS 750F – Volume 3
– Annex B.8 (AS) Environmental fate and behaviour (2017) is fully accepted
by the EPA Staff.
Comments The determined DT50 values indicate that the degradation rate of BAS 750 F
under irradiated conditions is faster than in the dark control, thus BAS 750 F
may undergo photolysis in soil although at a very slow rate. It should be noted
that in all treatments the DT50 values have been extrapolated more than twice
the study period and should be interpreted with care.
Conclusion Estimated soil photolysis DT50 values for BAS 750 F are 93 and 170 days for
the chlorophenyl- and triazole-labels, respectively. As such, a photolysis in soil
is expected to be of limited influence on degradation behaviour and metabolite
formation in soil.
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Biological degradation – biodegradation in soil
Table 64: Terrestrial field dissipation: other formulation (key study)
Study type Terrestrial field dissipation
Flag Key study
Test Substance BAS 750 F (mefentrifluconazole) applied in formulation BAS 750 01 F (EC) or
BAS 750 UA F (SC)
Endpoint DisT50 (non-normalised)
Value Range from 101 to 292 days (New York site = 281 days; North Dakota site =
286 days; Washington site = 286 days; California site = 266 days; Oklahoma
site = 292 days and Illinois site = 101 days)
[Note: DisT50field values were expressed as active ingredient
(mefentrifluconazole) but applied as formulation BAS 750 01 F (EC),
containing a nominal concentration of 100 g ai/L or BAS 750 UA F (SC),
containing a nominal concentration of 400 g ai/L. The target application rate
was 150 g ai/ha]
Reference (3.6.11) Jacobson et al. (2016a). Terrestrial field dissipation of the fungicide BAS 750 F
following broadcast applications of BAS 750 01 F (EC) or BAS 750 UA F (SC).
BASF Study Identification Number: 433578. BASF Registration Document
Number (Doc ID): 2015/7006396.
Study Summary The summary in the Draft Assessment Report (DAR) – BAS 750F – Volume 3
– Annex B.8 (AS) Environmental fate and behaviour (2017) is fully accepted
by the EPA Staff.
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Comments It should be noted that neither of the formulations tested are Revystar®
Fungicide, which may limit applicability of results. The application rate of the
active ingredient BAS 750 F is the maximum rate that will be applied as
Revystar® Fungicide however (150 g ai/ha, with the exception of the
Oklahoma soil where the target rate was 200 g ai/ha). Three applications were
made at each site (with the exception of the Illinois site where two applications
were made), which is also more than listed on the GAP and is therefore
considered a conservative estimate of the DT50 values.
The dissipation of BAS 750 F in soil under field conditions was investigated at
six sites in the U.S. As sampling and analysis are still ongoing, interim results
were reported. Based upon climatic information and characteristics of the soil
presented it is considered that the conditions in the study at US test sites can
be deemed comparable to those in the EU agricultural conditions to enable
them to be considered in support of the proposed EU use of BAS 750F, once
the final report is made available. Whether the conditions at the US test sites
are comparable to NZ conditions is unclear however.
BAS 750 F dissipated slowly with preliminary DisT50 values from 101 to 292
days. The 101 day result is unusually short as compared to the other 5 sites
with preliminary DT50 values ranging from 266-292 days.
The interim data presented are acceptable as presented thus far to give an
indication of the likely rate of dissipation of BAS 750 F in field conditions and
further supports the EU data in the consideration of the lack of significance of
the M750F003 metabolite in field conditions at the proposed GAP of 2 x 150 g
ai/ha. However, it should be noted that if interpretation of metabolite data and
the calculation of any kinetic parameters is required for M750F003 this could
prove difficult due to the multiple applications used within the field trials. Due
to the interim nature of the data study and areas that require clarification and
further investigation no further consideration of these data has been made in
this evaluation.
Conclusion The U.S. field DisT50 values (non-normalised) ranged from 101-292 days.
The metabolites 1,2,4-triazole and M750F003 were detected at all trial sites.
1,2,4-triazole was observed in some sites prior to or at application and at NY
(R140591), ND (R140592) these initial values were at quantifiable levels. The
metabolite M750F003 was detected at quantifiable amounts (>0.002 mg/kg) at
four of the six trial sites.
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Table 65: Terrestrial field dissipation: other formulation (key study)
Study type Terrestrial field dissipation study
Flag Key study
Test Substance BAS 750 F (mefentrifluconazole) applied in formulation EXP 5834378 F-AV
Endpoint DegT50
Value NA (see comments)
Reference (3.6.9) Schäufele (2015d). Field soil dissipation study of Reg. No. 5834378 in the
formulation EXP 5834278 F-AV on bare soil at six sites in Europe, 2013.
BASF Study Identification Number: 430699. BASF Registration Document
Number (Doc ID): 2015/1046920.
Study Summary The summary in the Draft Assessment Report (DAR) – BAS 750F – Volume 3
– Annex B.8 (AS) Environmental fate and behaviour (2017) is fully accepted
by the EPA Staff.
Comments Quantifiable residues of BAS 750 F residues were detected only in the first 20
cm of the soils. No residues above the LOQ were detected below 20 cm in any
sample at any site. Altogether, it can be concluded that BAS 750 F does not
show any significant tendency to move into deeper soil layers indicating low
potential to leach to groundwater.
See also final report amendment (Schäufele, 2015e) and EC DAR (EC 2017)
Doc ID 2015/1249176.
Conclusion NA (see kinetic evaluation in EC DAR (EC 2017) Doc ID 2015/1249176 for
DT50 endpoints)
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Table 66: Terrestrial field dissipation: other formulation (supporting study)
Study type Amendment to terrestrial field dissipation
Flag Supporting study
Test Substance BAS 750 F (mefentrifluconazole) applied in formulation EXP 5834378 F-AV
Endpoint NA (see comments)
Value NA (see comments)
Reference (3.6.10) Schäufele (2015e). Final report amendment No. 1: Field soil dissipation study
of Reg. No. 5834378 in the formulation EXP 5834278 F-AV on bare soil at six
sites in Europe, 2013. BASF Study Identification Number: 430699. BASF
Registration Document Number (Doc ID): 2015/1242234.
Study Summary The summary in the Draft Assessment Report (DAR) – BAS 750F – Volume 3
– Annex B.8 (AS) Environmental fate and behaviour (2017) is fully accepted
by the EPA Staff.
Comments Initial report (Schäufele (2015d) reported the sum of daily solar radiation but
the mean of daily solar radiation should have been reported instead. This
amendment does not impact the integrity of the study.
Conclusion NA (see comments)
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Table 67: Accumulation behaviour in soil under field conditions: other formulation (key study)
Study type Accumulation behaviour in soil under field conditions following repeated
application onto winter wheat over several years
Flag Key study
Test Substance BAS 750 F (mefentrifluconazole) applied in formulation BAS 750 01 F
Endpoint NA (see comments)
Value NA (see comments)
Reference (3.6.18) Schäufele (2015b). Accumulation behaviour of BAS 750 F in soil under field
conditions in the United Kingdom following repeated application onto winter
wheat over several years. BASF Study Identification Number: 433573. BASF
Registration Document Number (Doc ID): 2015/1076325.
Study Summary The summary in the Draft Assessment Report (DAR) – BAS 750F – Volume 3
– Annex B.8 (AS) Environmental fate and behaviour (2017) is fully accepted
by the EPA Staff.
Comments The study is ongoing; no residue data is presented within the interim report.
While this interim reports presents the study design no assessment of the
accumulation of BAS 750 F can be made.
Note that the test item applied in this study was not Revystar Fungicide but
formulation BAS 750 01 F. Whilst this also an emulsifiable concentrate
formulation containing the same concentration of mefentrifluconazole as
Revystar Fungicide (100 g/L), formulation BAS 750 01 F does not contain
fluxapyroxad.
Conclusion NA (see comments)
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Table 68: Accumulation behaviour in soil under field conditions: other formulation (key study)
Study type Accumulation behaviour in soil under field conditions following repeated
application onto winter barley over several years
Flag Key study
Test Substance BAS 750 F (mefentrifluconazole) applied in formulation BAS 750 01 F
Endpoint NA (see comments)
Value NA (see comments)
Reference (3.6.19) Schäufele (2015c). Accumulation behaviour of BAS 750 F in soil under field
conditions in Germany following repeated application onto winter barley over
several years. BASF Study Identification Number: 711494. BASF Registration
Document Number (Doc ID): 2015/1076326.
Study Summary The summary in the Draft Assessment Report (DAR) – BAS 750F – Volume 3
– Annex B.8 (AS) Environmental fate and behaviour (2017) is fully accepted
by the EPA Staff.
Comments The study is ongoing; no residue data is presented within the interim report.
While this interim reports presents the study design no assessment of the
accumulation of BAS 750 F can be made.
Note that the test item applied in this study was not Revystar Fungicide but
formulation BAS 750 01 F. Whilst this also an emulsifiable concentrate
formulation containing the same concentration of mefentrifluconazole as
Revystar Fungicide (100 g/L), formulation BAS 750 01 F does not contain
fluxapyroxad.
Conclusion NA (see comments)
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Mobility in soil
Table 69: Adsorption/desorption in soil: active ingredient (key study)
Study type Soil adsorption/desorption
Flag Key study
Test Substance BAS 750 F (mefentrifluconazole)
Endpoint Kd/Koc
Value Kd values range from 29.75 to 121.5 mL/g
Koc values ranged from 2511 to 4958 mL/g
Lowest Kd from non-sand soil = 30.63 mL/g (La Gironda soil)
Lowest Koc from non-sand soil = 2511 mL/g (La Gironda soil)
[Note: Kd/Koc values were calculated from raw data presented in the study
report for use in EPA’s risk assessment as Freundlich sorption parameters
reported only]
Reference (3.6.21) Sacchi (2016). Adsorption / desorption behaviour of 14C-BAS 750 F on
different US, Japanese and European soil. BASF Study Identification Number:
433570. BASF Registration Document Number (Doc ID): 2016/3003661.
Study Summary The summary in the Draft Assessment Report (DAR) – BAS 750F – Volume 3
– Annex B.8 (AS) Environmental fate and behaviour (2017) is fully accepted by
the EPA Staff.
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Comments The following Kd and Koc values were measured for the test item in each soil:
Soil Soil Type Kd (mL/g) Koc (mL/g)
IN Loam 60.15 4930
New Jersey Loam 42.25 4225
Obhiro Loam 121.5 3575
Fiorentiono Poggio
Renactico 1 Loam 44.05 4405
La Gironda Sandy clay
loam 30.631 25111
Li10 Loamy sand 34.48 3629
Lufa 5M Sandy loam 36.18 3289
Lufa 2.12 Sand 29.75 4958
1 Values in bold are lowest values from a non-sand soil
2 Results for Lufa 2.1 soil not considered as soil type classified as a sand and
the EPA uses the lowest value, non-sand soil for the risk assessment
It should be noted that the adsorption/desorption results presented in the study
report were expressed as the Freundlich sorption parameters Kf, Kfoc and 1/n.
For use in the risk assessment the EPA has calculated the sorption
parameters Kd and Koc from the raw data included in the study report.
Conclusion For BAS 750 F the Kd values ranged from 29.75 to 121.5 mL/g and Koc
values ranged from 2511 to 4958 mL/g. According to the McCall scale (McCall
et al. 1981) of pesticide mobility, BAS 750 F would be classified as slightly
mobile.
The EPA uses the lowest value non-sand soil in the risk assessment, as such
the lowest Kd and Koc values were obtained for the La Gironda soil, with
values of 30.63 mL/g and 2511 mL/g, respectively.
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Bioconcentration/bioaccumulation studies
Table 70: Bioconcentration study: active ingredient (key study)
Study type Bioconcentration, flow-through, uptake period of 14 days
Flag Key study
Test Substance BAS 750 F (mefentrifluconazole)
Endpoint BCFKLg (whole fish)
Value 385
Reference (3.6.32) 14C-BAS 750 F (label: triazole-3(5)-C14):
Bioconcentration Study in the Rainbow Trout (Oncorhynchus mykiss).
Study Summary The summary in the Draft Assessment Report (DAR) – BAS 750F – Volume 3
– Annex B.9 (AS) Ecotoxicology (2017) is fully accepted by the EPA Staff.
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Comments It is noted in the DAR that the usual uptake phase for this test has a duration
of 28 days instead of 14 days in this study.
The steady state was reached before 3 days and thus there was sufficient
time to ensure the steady state was reached. The depuration phase was 7
days, 7 days only 3% of the accumulated active remained. Therefore the
reduced duration of the experiment is not expected to have adversely affected
the results. While only one test concentration has been studied, this is
acceptable according to OECD 305 (2012) this is under the proviso that a
justification has been submitted by the applicant. The justification submitted by
the applicant is presented below:
“The OECD guideline 305 on “Bioaccumulation in Fish” (adopted 2012) states
that “the testing of only one test concentration can be considered sufficient,
when it is likely that the bioconcentration factor (BCF) is independent of the
test concentration”. The guidance further mentions that for non-polar organic
substances the exposure of fish to a single concentration is expected to be
sufficient as no concentration effects are expected.
An extensive data review of Creton et al. (2013) supports the use of only one
test concentration in BCF studies specifically for plant protection products. The
researchers reviewed 55 active substances with a wide log KOW range (-0.81
to 6.9) and various modes of action. They compared BCF values from low and
high test concentrations (generally a factor of 10 apart) and found a linear
relationship for all examined dimensions (whole body, edible and non-edible
tissue). Among the 55 reviewed active substances also triazoles were present,
e.g. prothioconazole, triticonazole, metconazole and epoxiconazole. The ratio
between the ‘low-concentration BCF’ and ‘high-concentration BCF’ for
triazoles differed only between 0.85 and 1.19. Paragraph 78 from the OECD
305 guidelines defines that a concentration dependence is not indicated if
uptake and depuration rate (and therefore also the kinetic BCF as a function of
these rate constants) vary by less than 20% from two test concentrations. This
is the case for plant protection products and specifically for triazole fungicides.
The review by Creton et al. (2013) demonstrates clearly that no significant
difference between the BCF in low and high concentrations can be found for
plant protection products, although the data set considered substances with
highly differing physico-chemical properties and even different fish species in
the tests.
In order to minimize vertebrate testing and since no concentration effect is
expected for the triazole fungicide BAS 750 F, only one test concentration was
chosen to be sufficient for the respective bioconcentration study in fish.”
References:
OECD (2012): Test No. 305: Bioaccumulation in Fish: Aqueous and Dietary
Exposure, OECD Guidelines for the Testing of Chemicals, Section 2, OECD
Publishing
Creton S., Weltje L., Hobson H., Wheeler J.R. (2013): Reducing the number of
fish in bioconcentration studies for plant protection products by reducing the
number of test concentrations. Chemosphere 90 (2013), 1300–1304.
The Creton et al. (2013) paper demonstrated that there were no statistically
significant differences between BCF values determined using high or low test
concentrations. The RMS has noted that only some of the triazole data
presented in the paper has been included in the above consideration by the
Applicant. Additional triazole data for tetraconaole and tebuconzole is present
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– these indicate ratios of 1.04 and 1.69, respectively. It is noted that the ratio
for tebuconazole is the second highest ratio reported for all active substances
included in the study – and appears to be somewhat higher than that reported
for the other 5 triazole fungicides (prothioconazole, triticonazole, metconazole,
tetraconazole and epoxiconazole). Therefore, the range in values for triazole
fungicides (0.85-1.69) is somewhat wider than stated above. The maximum
difference observed for all pesticides is 2.4m this relatively high value is
observed for a substance with a very low BCF and differences might be due to
small experimental errors.
Given that is unknown whether a high or low concentration was tested for BAS
750 F – the range in ratios indicates that the BCF value could potentially be
15% lower or 70% higher if a further concentration had been tested. It is noted
that the whole fish BCFKLg value for BAS 750 F is 385. Therefore, assuming a
worst case ratio of 1.7 for triazoles – the BCF value would potentially increase
to 654.5. This value would be above the EPA’s bioaccumulation trigger value
of >500. As a consequence, it is considered possible that testing a further
concentration could have an impact on this evaluation.
In addition, it is noted that the Creton et al. (2013) study states that “data were
available from 166 studies of which 108 used only one test concentration”.
Therefore, the use of single test concentrations appears to be relatively
common.
In conclusion the presented BCFKLg should be considered with care
considering the potential for bioaccumulation.
Conclusion BCFKLg (whole fish) = 385 [Note this value should be treated with care given
the comments above]
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Ecotoxicity study summaries
Unless otherwise noted, all studies were conducted according to GLP and were fully compliant with all
requirements of the standard international test methods used. All data for mefentrifluconazole and its
metabolites were sourced from the mefentrifluconazole DAR unless otherwise stated. Study
summaries have only been included in Appendix J where there are comments in regard to individual
studies, and are provided in Table 71 to Table 109.
Aquatic ecotoxicity of the active ingredient
Short-term aquatic toxicity studies
Table 71: Acute toxicity to fish (rainbow trout): active ingredient (key study) [9.1]
Study type Acute toxicity to fish
Species Rainbow trout, Oncorhynchus mykiss
Flag Key study
Test Substance BAS 750 F (mefentrifluconazole)
Endpoint LC50 and NOEC
Value LC50 (96-hrs) = 0.532 mg/L (mean measured)
NOEC (96-hrs) = 0.142 mg/L
Reference (4.6.10) (2014a). BAS 750 F: Acute Toxicity Study in the Rainbow Trout
(Oncorhynchus mykiss).
Study Summary The summary in the Draft Assessment Report (DAR) – BAS 750F – Volume
3 – Annex B.9 (AS) Ecotoxicology (2017) is fully accepted by the EPA Staff.
Comments It was noted in the DAR that the body length of the test subjects was 5.5-6.6
cm, exceeding the recommended body length for this species (5.0 ± 1.0 cm).
This might have decreased the sensitivity of the test organisms. However, as
this was the only deviation, all the validity criteria were met and no adverse
effects were observed, the study is still considered acceptable.
Conclusion LC50 (96-hrs) = 0.532 mg/L (mean measured)
NOEC (96-hrs) = 0.142 mg/L
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Table 72: Acute toxicity to fish (zebrafish): active ingredient (key study) [9.1]
Study type Acute toxicity to fish
Species Zebrafish, Danio rerio
Flag Key study
Test Substance BAS 750 F (mefentrifluconazole)
Endpoint LC50 and NOEC
Value LC50 (96-hrs) = 0.906 mg/L (mean measured)
NOEC for mortality (96-hrs) = 0.735 mg/L
Reference (4.6.13) (2015a). BAS 750 F (Reg. No. 5834378): Zebrafish Acute toxicity
test.
Study Summary The summary in the Draft Assessment Report (DAR) – BAS 750F – Volume
3 – Annex B.9 (AS) Ecotoxicology (2017) is fully accepted by the EPA Staff.
Comments It is noted in the DAR that the hardness and the conductivity exceeded the
recommended limit of 250 mg CaCO3/L and 10 μS cm-1 respectively,
although as all the validity criteria were met and no negative effects were
observed in the controls, this deviation is not expected to have adversely
affected the experiment.
Conclusion LC50 (96-hrs) = 0.906 mg/L (mean measured)
NOEC for mortality (96-hrs) = 0.735 mg/L
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Table 73: Acute toxicity to Daphnia magna: active ingredient (key study) [9.1]
Study type Acute toxicity to aquatic invertebrates
Species Aquatic invertebrate, Daphnia magna
Flag Key study
Test Substance BAS 750 F (mefentrifluconazole)
Endpoint EC50 and NOEC
Value EC50 (48-hrs) = 0.944 mg/L (geometric mean measured)
NOEC (48-hrs) = 0.254 mg/L
Reference (4.6.23) Brzozowska (2014a). BAS 750 F: Daphnia magna, Acute Immobilisation
Test. BASF Study Identification Number: 433171. BASF Registration
Document Number (Doc ID): 2013/1250866.
Study Summary The summary in the Draft Assessment Report (DAR) – BAS 750F – Volume
3 – Annex B.9 (AS) Ecotoxicology (2017) is fully accepted by the EPA Staff.
Comments It was noted in the DAR that the temperature differed outside ±1°C (OECD
202 (2004)) and the hardness of the test medium is not reported. However as
all the validity criteria were met and no negative effects were observed in the
control organisms, these deviations are not expected to have adversely
affected the experiment.
Conclusion EC50 (48-hrs) = 0.944 mg/L (geometric mean measured)
NOEC (48-hrs) = 0.254 mg/L
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Table 74: Acute toxicity to saltwater mysid shrimp: active ingredient (key study) [9.1]
Study type Acute toxicity to aquatic invertebrates
Species Mysid shrimp, Americamysis bahia
Flag Key study
Test Substance BAS 750 F (mefentrifluconazole)
Endpoint LC50 and NOEC
Value LC50 (96-hrs) = 1.30 mg/L (mean measured)
NOEC (96-hrs) = 0.415 mg/L
Reference (4.6.29) VanHooser (2014a). BAS 750 F: Acute Toxicity Test With the Saltwater
Mysid, Americamysis bahia, Determined Under Flow-Through Test
Conditions. BASF Study Identification Number: 433266. BASF Registration
Document Number (Doc ID): 2014/7002845.
Study Summary The summary in the Draft Assessment Report (DAR) – BAS 750F – Volume
3 – Annex B.9 (AS) Ecotoxicology (2017) is fully accepted by the EPA Staff.
Comments It is noted in the study that a white precipitate was observed in some test
solutions, and consequently the results may underestimate the toxicity of the
active. Given that the sample solutions were centrifuged before analysis, it
can be expected that the mean measured samples are representative of the
dissolved concentrations the test organisms were exposed to, so no further
consideration is required.
Conclusion LC50 (96-hrs) = 1.30 mg/L (mean measured)
NOEC (96-hrs) = 0.415 mg/L
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Table 75: Acute toxicity to algae: active ingredient (key study) [9.1]
Study type Acute toxicity growth inhibition test
Species Algae, Pseudokirchneriella subcapitata
Flag Key study
Test Substance BAS 750 F (mefentrifluconazole)
Endpoint ErC50 (72-hrs, geometric mean measured)
Value 1.352 mg/L
Reference (4.6.41) Brzozowska (2014b). BAS 750 F (Reg. No. 5834378) Pseudokirchneriella
subcapitata SAG 61.81 Growth Inhibition Test, Determined Under Flow-
Through Test Conditions. BASF Study Identification Number: 433170. BASF
Registration Document Number (Doc ID): 2013/1250865.
Study Summary The summary in the Draft Assessment Report (DAR) – BAS 750F – Volume
3 – Annex B.9 (AS) Ecotoxicology (2017) is fully accepted by the EPA Staff.
Comments In the DAR it is noted that the temperature should be maintained within the
range of 21-24°C (OECD 201 (2011)) rather than 24.1-24.4°C. Given that the
deviation was only marginally above the limit, all the validity criteria were met
and no negative effects were observed in the controls, this deviation is not
expected to have adversely affected the study.
Conclusion ErC50 (72-hrs) = 1.352 mg/L (geometric mean measured)
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Table 76: Acute toxicity to algae: active ingredient (key study) [9.1]
Study type Acute toxicity growth inhibition test
Species Marine diatom, Skeletonema costatum
Flag Key study
Test Substance BAS 750 F (mefentrifluconazole)
Endpoint IrC50 and NOEC
Value IrC50 (72-hrs) = 0.723 mg/L (initial measured concentration)
NOEC (72-hrs) = 0.111 mg/L (initial measured concentration)
IrC50 (96-hrs) = 0.704 mg/L (initial measured concentration)
NOEC (96-hrs) = 0.217 mg/L (initial measured concentration)
(in regard to endpoints see comments section below)
Reference (4.6.47) Bergfield (2015a). BAS 750 F: Growth Inhibition Test with the Marine Diatom,
Skeletonema costatum. BASF Study Identification Number: 433265. BASF
Registration Document Number (Doc ID): 2015/7000620.
Study Summary The summary in the Draft Assessment Report (DAR) – BAS 750F – Volume
3 – Annex B.9 (AS) Ecotoxicology (2017) is fully accepted by the EPA Staff.
Comments It should be noted that these endpoints have been recalculated and this has
been summarised in the next table
During the test concentration did not remain stable (<80% of the initial
concentration), the mean of geometric mean concentration should have been
calculated.
Conclusion Not considered appropriate
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Table 77: Acute toxicity to algae: active ingredient (key study) [9.1]
Study type Recalculation of endpoints from Bergfield (2015a) “BAS 750 F: Growth
Inhibition Test with the Marine Diatom, Skeletonema costatum” (as
summarised in the previous table)
Flag Key study
Test Substance BAS 750 F (mefentrifluconazole)
Endpoint ErC50
Value ErC50 (72-hrs) = 0.679 mg/L (geometric mean measured)
ErC50 (96-hrs) = 0.676 mg/L (geometric mean measured)
Reference (4.6.48) Horn (2016a). Recalculation of endpoints for the study by Bergfield A., 2015a
(BASF DocID 2015/7000620): “BAS 750 F: Growth Inhibition Test with the
Marine Diatom, Skeletonema costatum”. BASF Registration Document
Number (Doc ID): 2016/1292092.
Klimisch Score 1
Study Summary The summary in the Draft Assessment Report (DAR) – BAS 750F – Volume
3 – Annex B.9 (AS) Ecotoxicology (2017) is fully accepted by the EPA Staff.
Comments It is noted in the DAR that changes to the morphology of the cells should be
observed and some conditions of the test medium such as hardness and
conductivity were not reported.
Conclusion ErC50 (72-hrs) = 0.679 mg/L (geometric mean measured)
ErC50 (96-hrs) = 0.676 mg/L (geometric mean measured)
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Table 78: Acute toxicity to algae: active ingredient (key study) [9.1]
Study type Acute toxicity growth inhibition test
Species Freshwater diatom, Navicula pelliculosa
Flag Key study
Test Substance BAS 750 F (mefentrifluconazole)
Endpoint IrC50 and NOEC
Value IrC50 (72-hrs) = 1.57 mg/L
NOEC (72-hrs) = 0.358 mg/L
IrC50 (96-hrs) = 1.89 mg/L
NOEC (96-hrs) = 0.358 mg/L
(in regard to endpoints see also comments section below)
Reference (4.6.49) Bergfield (2015b). BAS 750 F: Growth Inhibition Test with the Freshwater
Diatom, Navicula pelliculosa. BASF Study Identification Number: 433178.
BASF Registration Document Number (Doc ID): 2015/7000618.
Study Summary The summary in the Draft Assessment Report (DAR) – BAS 750F – Volume
3 – Annex B.9 (AS) Ecotoxicology (2017) is fully accepted by the EPA Staff.
Comments It should be noted that these endpoints have been recalculated and this has
been summarised in the next table
Conclusion IrC50 (72-hrs) = 1.57 mg/L
NOEC (72-hrs) = 0.358 mg/L
IrC50 (96-hrs) = 1.89 mg/L
NOEC (96-hrs) = 0.358 mg/L
(in regard to endpoints see also comments section below)
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Table 79: Acute toxicity to algae: active ingredient (key study) [9.1]
Study type Recalculation of endpoints from Bergfield (2015b) “BAS 750 F: Growth
Inhibition Test with the Freshwater Diatom, Navicula pelliculosa” (as
summarised in the previous table)
Flag Key study
Test Substance BAS 750 F (mefentrifluconazole)
Endpoint ErC50
Value ErC50 (72-hrs) = 1.347 mg/L (geometric mean measured)
ErC50 (96-hrs) = 1.577 mg/L
Reference (4.6.50) Horn (2016b). Recalculation of endpoints for the study by Bergfield A., 2015b
(BASF DocID 2015/7000618): “BAS 750 F: Growth Inhibition Test with the
Freshwater Diatom, Navicula pelliculosa”. BASF Registration Document
Number (Doc ID): 2016/1292093.
Study Summary The summary in the Draft Assessment Report (DAR) – BAS 750F – Volume
3 – Annex B.9 (AS) Ecotoxicology (2017) is fully accepted by the EPA Staff.
Comments It is noted in the DAR that changes to the morphology of the cells should be
observed and some conditions of the test medium such as hardness and
conductivity were not reported. Due to poor initial recovery and undissolved
test material in the solution, the nominal 7.0 mg ai/L treatment level was not
used for statistical analysis. However, basing the ECx values off the other
five test concentrations is acceptable.
Conclusion ErC50 (72-hrs) = 1.347 mg/L (geometric mean measured)
ErC50 (96-hrs) = 1.577 mg/L
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Table 80: Acute toxicity to algae: active ingredient (key study) [9.1]
Study type Acute toxicity growth inhibition test
Species Cyanobacterium, Anabaena flos-aquae
Flag Key study
Test Substance BAS 750 F (mefentrifluconazole)
Endpoint ErC50 and NOEC
Value ErC50 (72-hrs) = >3.08 mg/L (geometric mean measured)
NOEC (72-hrs) = 3.08 mg/L
ErC50 (96-hrs) = >3.08 mg/L (geometric mean measured)
NOEC (96-hrs) = 3.08 mg/L
Reference (4.6.51) Bergfield (2015c). BAS 750 F: Growth Inhibition Test with the
Cyanobacterium, Anabaena flos-aquae. BASF Study Identification Number:
433179. BASF Registration Document Number (Doc ID): 2015/7000617.
Study Summary The summary in the Draft Assessment Report (DAR) – BAS 750F – Volume
3 – Annex B.9 (AS) Ecotoxicology (2017) is fully accepted by the EPA Staff.
Comments It is noted in the DAR that changes to the morphology of the cells should be
observed and some conditions of the test medium such as hardness and
conductivity were not reported.
Conclusion ErC50 (72-hrs) = >3.08 mg/L (geometric mean measured)
NOEC (72-hrs) = 3.08 mg/L
ErC50 (96-hrs) = >3.08 mg/L (geometric mean measured)
NOEC (96-hrs) = 3.08 mg/L
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Long-term aquatic toxicity studies
Table 81: Chronic toxicity to fish: active ingredient (key study)
Study type Early life-stage toxicity test
Species Zebrafish, Danio rerio
Flag Key study
Test Substance BAS 750 F (mefentrifluconazole)
Endpoint NOEC (36 days)
Value NOEC = 0.027 mg/L (mean measured), total length was most sensitive
toxicological endpoint
Reference (4.6.17)
2015a). BAS 750 F - Early Life-Stage Toxicity Test on the
Zebrafish (Danio rerio) in a flow through system.
Study Summary The summary in the Draft Assessment Report (DAR) – BAS 750F – Volume
3 – Annex B.9 (AS) Ecotoxicology (2017) is fully accepted by the EPA Staff.
Comments
It is noted in the DAR that the validity criterion of temperature difference
remaining within ±1.5°C was not met. However, the temperature minimum
was according to a continuous temperature measurement rather than
instantaneous which did not record any deviation. This would mean that the
marginal passing was temporary (45-hr) and probably did not affect the test.
This is supported by no negative effects being observed in the control
organisms. Additionally the analytical results pass outside ±20% of the
nominal, but the results were >100% of the nominal and the endpoint is
based on mean measured concentration and results are therefore corrected
for this deviation. Consequently, this failing of the validity criteria is not
expected to have adversely affected the test and is therefore considered
acceptable. The recommended duration of the test is 30 days post-hatch,
although the study duration of 32 days post-hatch is not expected to have
adversely affected the test.
Conclusion NOEC = 0.027 mg/L (mean measured), total length was most sensitive
toxicological endpoint
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Table 82: Chronic toxicity to fish: active ingredient (key study)
Study type Life cycle test
Species Zebrafish, Danio rerio
Flag Key study
Test Substance BAS 750 F (mefentrifluconazole)
Endpoint NOEC (140 days)
Value 0.022 mg/L (mean measured)
Reference (4.6.67) ). BAS 750 F: Life Cycle Toxicity Test on the Zebrafish (Danio
rerio) in a Flow Through System.
Klimisch Score 1
Amendments/Deviations None
GLP Yes
Test Guideline/s OPPTS 850.1500 (Fish life cycle toxicity)
Nominal test
concentrations
0 (Control), 3.40, 6.40, 12.0, 23.0 and 44.0 μg/L
Mean-measured test
concentrations
F0 generation <LOD, 3.16 μg ai/L ±0.19 (93%); 6.95 μg ai/L ±0.43 (109%);
12.9 μg ai/L ±0.86 (107%); 22.2 μg ai/L ±2.92 (97%); 45.5 μg ai/L ±3.51
(104%)
F1 generation <LOD; 3.72 μg ai/L ±0.30 (109%); 7.36 μg ai/L ±0.36 (115%);
13.3 μg ai/L ±0.98 (111%); 24.5 μg ai/L ±1.31 (107%); 46.8 μg ai/L ±2.53
(106%) [μg ai/L ±SD (% of nominal)]
Analytical measurements Yes, LC-MS-MS
Validity criteria met Yes
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Study Summary A fish full life cycle test using zebrafish (Danio rerio) was conducted to
assess the effects of BAS 750 F on population-relevant endpoints over two
generations and to determine a no observed effect concentration (NOEC).
The exposure period was 140 days. The experiment was conducted under
flow-through conditions with continuous exposure to five concentrations of
the test substance and a dilution water control: 0 (Control), 3.40, 6.40, 12.0,
23.0 and 44.0 μg/L as nominal concentrations based on active ingredient.
To initiate the F0-generation exposure, freshly fertilized zebrafish eggs (<5
hours old) were obtained by proportionally pooling eight clutches obtained
from non-exposed brood stock fish. Each test group initially consisted of 150
embryos evenly and randomly distributed among five replicates. After
hatching the zebrafish were allowed to grow to maturity. Starting on test day
71 spawning trays were inserted once weekly in each replicate aquarium to
monitor the onset of sexual maturity by qualitatively estimating the egg
production. On test days 104-106, fish of the F0-generation test groups were
reduced to form spawning groups consisting of five males plus five females
per replicate. Starting on test day 107, egg production and fertility were
enumerated on 22 days. After the reproduction evaluation period, the F0
spawning groups were terminated on test day 140. Upon sacrifice the
phenotypic sex of each F0 generation individual was confirmed with a direct
macroscopic evaluation of the gonads.
Fertilized eggs from the F0-test groups were used to start a first filial
generation (F1-generation) on test day 98. The F1-generation test groups
consisted of 100 embryos from the corresponding F0-test group evenly
distributed among 4 replicates. The F1-generation fish were exposed for a
total of 36 days, equivalent to an early life stage test, at nominal
concentrations identical to the parental exposure. Over the two generations,
effects on hatching success, time to hatch, survival, growth (body length and
weight) and signs of toxicity (appearance/behaviour) were recorded.
Additionally the reproduction of the F0-generation was quantitatively
evaluated by assessing fecundity (eggs per female reproductive day) and
fertility.
Samples for concentration control analyses were collected generally weekly
from all test groups during the exposure period. The concentration of the test
substance in the control group was below the limit of quantification
throughout the exposure period. The mean measured concentrations were in
the range of 93-109% of the corresponding nominal concentrations in the F0-
generation and in the range of 106-115% of the corresponding nominal
concentration in the F1-generation. The individually measured concentrations
during the exposure period were generally within the range ±20% of the
nominal concentrations with very few exceptions.
All individually measured values were within a range of ± 20% of the mean
measured. Both, the nominal and mean measured concentrations are
considered an accurate representation of the actual exposure concentrations
over the course of the test.
Environmental and water quality parameters were monitored regularly
throughout the test and remained within acceptable ranges. Water
temperature measurements were generally within the range of 27±1.5°C. The
pH was stable during the whole exposure period and was in the range 7.8-
8.2. The dissolved oxygen concentrations were maintained between 5.9 and
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8.5 mg/L, corresponding to approximately 73–105% of the maximum air
saturation value at test temperature.
There was no adverse treatment-related effect on hatching success, time to
hatch, survival, or any apparent signs of toxicity and abnormalities in the F0-
generation fish. However among the F0-generation fish sacrificed at
reduction (test days 104-106) and at the termination of the spawning groups
(test day 140), the body weight and length of the female fish from treatment
group 5 (44.0 μg ai/L) were significantly reduced in comparison to the control
group (2-3% for body length and 12-13% for body weight compared to the
control group). The body weight and length of male fish on both occasions
was not affected in any of the treatment groups.
Moreover there was a statistically significant reduction in fecundity
(approximately 10% in comparison to the control group), but not fertility in F0-
generation fish of treatment group 5 (44.0 μg ai/L). This finding is consistent
with the reduced body weight of adult female fish in this treatment group. In
the F1-generation the survival from swim-up until termination was statistically
significantly reduced in comparison to the control group in test group 5 (44.0
μg ai/L). There was no adverse treatment related effect on hatching success,
time to hatch, or juvenile fish growth. Overall the pattern of effects are
consistent and indicate a systemic toxic effect observed only in the highest
treatment group.
In conclusion the overall NOEC identified in this test was 23.0 μg ai/L
(nominal concentration) 22.2 μg ai/L (mean measured concentration in the
F0-generation). The LOEC was 44.0 μg ai/L (nominal concentration) and 45.5
μg ai/L (mean measured concentration in the F0-generation).
Comments None
Conclusion NOEC (140-day) = 0.022 mg/L (mean measured)
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Table 83: Endocrine disruption in fish: active ingredient (key study)
Study type Fish sexual development test
Species Zebrafish, Danio rerio
Flag Key study
Test Substance BAS 750 F (mefentrifluconazole)
Endpoint NOEC (69 days, mean measured)
Value ≥0.045 mg ai/L
Reference (4.6.18) BAS 750 F Fish sexual development test on the zebrafish
(Danio rerio).
Study Summary The summary in the Draft Assessment Report (DAR) – BAS 750F – Volume
3 – Annex B.9 (AS) Ecotoxicology (2017) is fully accepted by the EPA Staff.
Comments It is noted in the DAR that the high percentage coefficients of variation for
male vitellogenin (VTG) measurements. This was caused by some males
having abnormally high VTG values. Although the reason is unknown,
contamination with female blood has been excluded by only using scalpels
once. High VTG individuals were found in the control and all treatment
groups independent of concentration. The RMS equally notes that the
percentage coefficients of variations were present in the females that also
appeared in the control and all treatment groups independent of
concentration. No significant differences in VTG concentrations were
observed between any concentration and the control for both male and
female fish, although no conclusions on endocrine disruption can be drawn
based upon this. While the high coefficient of variations may increase the
difficulty of detecting statistically significant differences, no clear dose
dependent effects on VTG appear to be present for either gender.
Conclusion NOEC (69 days) ≥0.045 mg ai/L (mean measured)
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Table 84: Chronic toxicity to Daphnia magna: active ingredient (key study)
Study type Chronic toxicity semi-static test
Species Aquatic invertebrate, Daphnia magna
Flag Key study
Test Substance BAS 750 F (mefentrifluconazole)
Endpoint NOEC (21 days)
Value 0.0091 mg/L (time-weighted mean)
Reference (4.6.31) Janson (2014a). Chronic toxicity of BAS 750 F (Reg.No.5834378) to Daphnia
magna Straus in a 21-day semi-static test. BASF Study Identification
Number: 433175. BASF Registration Document Number (Doc ID):
2014/1098028.
Study Summary The summary in the Draft Assessment Report (DAR) – BAS 750F – Volume
3 – Annex B.9 (AS) Ecotoxicology (2017) is fully accepted by the EPA Staff.
Comments It is noted in the DAR that any tests for significance between the control and
solvent control was not reported, although there does not appear to be any
discrepancies between the solvent control and the water control that would
be deemed significant and a pooled control was used for comparison with the
test concentrations. Therefore, this is considered not to impact the results.
Conclusion NOEC (21 days) = 0.0091 mg/L (time-weighted mean)
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Table 85: Chronic toxicity to Daphnia longispina: active ingredient (key study)
Study type Chronic toxicity (semi-static test) to Daphnia longispina
Species Daphnia longispina
Flag Key study
Test Substance BAS 750 F (mefentrifluconazole)
Endpoint NOEC (21 days, time-weighted mean)
Value 0.0342 mg/L
Reference (4.6.32) Janson (2015b). Chronic toxicity of BAS 750 F (Reg.No.5834378) to Daphnia
longispina in a 21-day semi-static test. BASF Study Identification Number:
733331_1. BASF Registration Document Number (Doc ID): 2015/1003912
and 2015/1251197(report amendment)
Study Summary The summary in the Draft Assessment Report (DAR) – BAS 750F – Volume
3 – Annex B.9 (AS) Ecotoxicology (2017) is fully accepted by the EPA Staff.
Comments It is noted in the DAR that any tests for significance between the controls was
not reported, although there does not appear to be any discrepancies
between the solvent control and the water control that would be deemed
significant. Therefore, this is considered not to impact the results.
Conclusion NOEC (21 days) = 0.0342 mg/L (time-weighted mean)
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Table 86: Chronic toxicity to Daphnia pulex: active ingredient (key study)
Study type Chronic toxicity semi-static test
Species Daphnia pulex
Flag Key study
Test Substance BAS 750 F (mefentrifluconazole)
Endpoint NOEC (21 days, time-weighted mean)
Value 0.0276 mg/L
Reference (4.6.34) Janson (2015a). Chronic toxicity of BAS 750 F (Reg.No.5834378) to Daphnia
pulex in a 21-day semi-static test. BASF Study Identification Number:
733331. BASF Registration Document Number (Doc ID): 2015/1003913.
Study Summary The summary in the Draft Assessment Report (DAR) – BAS 750F – Volume
3 – Annex B.9 (AS) Ecotoxicology (2017) is fully accepted by the EPA Staff.
Comments It is noted in the DAR that tests for significance between the controls was not
reported, although there does not appear to be any discrepancies between
the solvent control and the water control that would be deemed significant.
Therefore, this is considered not to impact the results.
Conclusion NOEC (21 days) = 0.0276 mg/L (time-weighted mean)
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Acute/sub-chronic toxicity to sediment-dwelling organisms
Table 87: Acute and sub-chronic toxicity to sediment-dwelling organisms: active ingredient
(key study)
Study type Toxicity test under static-renewal conditions, spiked sediment
Species Midge, Chironomus dilutus
Flag Key study
Test Substance BAS 750 F (mefentrifluconazole)
Endpoint NOEC (10 days)
Value NOEC (10 days) = 7.08 mg/kg dry sediment (midge growth, geometric mean
measured)
Reference (4.6.36) Clark (2015a). BAS 750 F – 10-day toxicity test exposing midge (Chironomus
dilutus) to a test substance applied to sediment under static-renewal
conditions. BASF Study Identification Number: 766634. BASF Registration
Document Number (Doc ID): 2015/7000621.
Study Summary The summary in the Draft Assessment Report (DAR) – BAS 750F – Volume
3 – Annex B.9 (AS) Ecotoxicology (2017) is fully accepted by the EPA Staff.
Comments The RMS notes that the test guidelines EPA 850.1735 (1996) is intended for
testing saltwater mysids rather than Chironomus species. Additionally,
dissolved oxygen levels nearly fell below (3.5 mg/L) the acceptable levels
according to EPA 850.1735, although increasing the flow rate appears to
have mediated this. The minimum light intensity was 280 lux rather than the
minimum of 500 lux recommended in EPA 850.1735 (1996), given there were
no observed adverse effects on the controls, this deviation is not expected to
have adversely affected the study. The EPA considers that the study is
robust and the information can be used for the assessment of the chemical.
It is noted in the DAR that arithmetic mean measured concentrations rather
than geometric mean measured concentrations have been used to calculate
the endpoints, resulting in the endpoints slightly underestimating toxicity.
Consequently the endpoints have been recalculated using geometric mean
measured concentration so that the EC50 is >96 mg ai/kg dry sediment, the
NOEC for midge survival is 22 mg ai/kg dry sediment and the NOEC for
midge growth is 7.08 mg ai/kg dry sediment. The study is considered
acceptable and suitable for risk assessment purposes and the proposed
endpoint is an EC50 of >96 mg ai/L and a NOEC of 7.08 mg ai/L.
Conclusion NOEC (10 days) = 7.08 mg/kg dry sediment (midge growth, geometric mean
measured)
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Table 88: Acute and sub-chronic toxicity to sediment-dwelling organisms: active ingredient
(key study)
Study type Acute and sub-chronic toxicity test under static-renewal conditions, spiked
sediment
Species Freshwater amphipod, Hyalella azteca
Flag Key study
Test Substance BAS 750 F (mefentrifluconazole)
Endpoint NOEC (10 days, mean measured)
Value NOEC (10 days) = 100 mg/kg dry sediment (amphipod growth)
Reference (4.6.39) Clark (2015b). BAS 750 F – 10-day toxicity test exposing freshwater
amphipods (Hyalella azteca) to a test substance applied to sediment under
static-renewal conditions. BASF Study Identification Number: 733145. BASF
Registration Document Number (Doc ID): 2015/7000622.
Study Summary The summary in the Draft Assessment Report (DAR) – BAS 750F – Volume
3 – Annex B.9 (AS) Ecotoxicology (2017) is fully accepted by the EPA Staff.
Comments It is noted in the DAR that the conditions of the overlying water varied and
were not equal to the ranges expected for reconstituted water. In particular,
conductivity was 380-480 μS/cm although it should range over 330-360
μS/cm according to 850.1735. Given that no negative effects were observed
in the controls, the overlying water is not expected to have adversely affected
the test. Additionally, the length of the test organisms should be measured
and considered with growth, there is no indication effects to length in the
report, although as there has been no effect on weight, it is not expected that
length would have been significantly affected.
Conclusion NOEC (10 days) = 100 mg/kg dry sediment (amphipod growth)
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Table 89: Acute and sub-chronic toxicity to sediment-dwelling organisms: active ingredient
(key study)
Study type Acute and sub-chronic toxicity test under static-renewal conditions, spiked
sediment
Species Estuarine amphipod, Leptocheirus plumulosus
Flag Key study
Test Substance BAS 750 F (mefentrifluconazole)
Endpoint NOEC and LC50 (10 days, mean measured)
Value NOEC (10 days) = 95 mg/kg dry sediment (amphipod survival)
LC50 (10 days) > 95 mg/kg dry sediment
Reference (4.6.40) Clark (2015c). BAS 750 F – 10-day toxicity test exposing estuarine
amphipods (Leptocheirus plumulosus) to a test substance applied to
sediment under static conditions. BASF Study Identification Number: 433271.
BASF Registration Document Number (Doc ID): 2015/7000623.
Study Summary The summary in the Draft Assessment Report (DAR) – BAS 750F – Volume
3 – Annex B.9 (AS) Ecotoxicology (2017) is fully accepted by the EPA Staff.
Comments It’s noted in the DAR that 800 mL of overlying water (EPA 850.1740(1996))
should be used rather than 725 mL, given all the validity criteria were met
and no negative effects were observed in the controls, this deviation is not
expected to have adversely affected the study.
Conclusion NOEC (10 days) = 95 mg/kg dry sediment (amphipod survival mean
measured)
LC50 (10 days) > 95 mg/kg dry sediment (mean measured)
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Chronic toxicity to sediment-dwelling organisms
Table 90: Chronic toxicity to sediment-dwelling organisms: active ingredient (key study)
Study type Chronic toxicity test, static, spiked sediment
Species Midge, Chironomus riparius
Flag Key study
Test Substance BAS 750 F (mefentrifluconazole)
Endpoint NOEC (28 days, initial measured based on emergence rate and development
rate)
Value ≥1.158 mg/kg dry sediment (emergence rate and development rate, based on
initial measured concentrations)
Reference (4.6.38) Backfisch and Weltje (2015a). Chronic toxicity of Reg. No. 5834378 to the
non-biting midge Chironomus riparius. BASF Study Identification Number:
433176. BASF Registration Document Number (Doc ID): 2014/1243181.
Study Summary The summary in the Draft Assessment Report (DAR) – BAS 750F – Volume
3 – Annex B.9 (AS) Ecotoxicology (2017) is fully accepted by the EPA Staff.
Comments It is noted in the DAR that egg masses should be collected four or five days
before test initiation according to OECD 218 (2004) rather than three days
prior in this study, although no adverse effects were observed in the control,
so this deviation is not expected to have adversely affected the study.
Conclusion NOEC (28 days) ≥1.158 mg/kg dry sediment (emergence rate and
development rate, based on initial measured concentrations)
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Aquatic ecotoxicity of metabolites of mefentrifluconazole
Table 91: Chronic toxicity to fish: metabolite M750F001, 1,2,4-triazole (key study)
Study type Early life-stage toxicity test
Species Rainbow trout, Oncorhynchus mykiss
Flag Key study
Test Substance Metabolite M750F001 (1,2,4-triazole)
Endpoint NOEC
Value 3.20 mg/L (nominal)
Reference (4.6.73) 2002). 1,2,4-triazole – juvenile growth test, fish
(Onchorhynchus mykiss).
Study Summary The summary in the Draft Assessment Report (DAR) – Epoxiconazole –
Volume 3, Annex B, B.9, Ecotoxicology (2006) is fully accepted by the EPA
Staff.
Comments Note that the NOErC endpoint determined in the study was ≥100 mg test
item/L. Since 3.20 mg/L was the endpoint selected in the DAR (2006), the
EPA aligned with this decision.
Conclusion NOEC = 3.20 mg/L (nominal)
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Table 92: Acute toxicity to algae: metabolite M750F005 (key study)
Study type Acute toxicity growth inhibition test
Species Algae, Pseudokirchneriella subcapitata
Flag Key study
Test Substance Metabolite M750F005
Endpoint ErC50 (72-hrs)
Value ≥8.572 mg/L (geometric mean)
Reference (4.6.45) Rzodeczko (2016b). Reg. No. 6003433 (metabolite of BAS 750 F,
M750F005) Pseudokirchneriella subcapitata SAG 61.81 Growth Inhibition
Test. BASF Study Identification Number: 433192. BASF Registration
Document Number (Doc ID): 2015/1184816.
Study Summary The summary in the Draft Assessment Report (DAR) – BAS 750F – Volume
3 – Annex B.9 (AS) Ecotoxicology (2017) is fully accepted by the EPA Staff.
Comments It is noted in the DAR that the pH should increase by no more than 1.5 over
the course of the test, and the pH increased from 7.24-8.82 in the solvent
control, and from 7.06-8.62 in the 4-fold dilution. This is only marginally over
the 1.5. This deviation is not expected to have adversely affected the
experiment.
Conclusion ErC50 (72-hrs) ≥8.572 mg/L (geometric mean)
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Table 93: Acute toxicity to fish: metabolite M750F006 (key study)
Study type Acute toxicity to fish
Species Rainbow trout, Oncorhynchus mykiss
Flag Key study
Test Substance Metabolite M750F006
Endpoint LC50 (96-hrs)
Value 6.20 mg/L (geometric mean)
Reference (4.6.12) (2016c). Reg. No. 5863469 (Metabolite of BAS 750 F,
M750F006) Rainbow trout, Acute toxicity test.
Study Summary The summary in the Draft Assessment Report (DAR) – BAS 750F – Volume
3 – Annex B.9 (AS) Ecotoxicology (2017) is fully accepted by the EPA Staff.
Comments It is noted in the DAR that given that signs of treatment related intoxication
were observed at 2.696 mg/L the LOEC and NOEC should be 2.696 and
1.478 mg/L respectively. It is also noted that the conductivity of 580-590
μS/cm exceeds the recommended conductivity of ≤10 μS/cm in OECD 203
(1992). Given all the validity criteria were met and no adverse effects were
observed in the controls, this deviation is not expected to have negatively
affected the experiment.
Conclusion LC50 (96-hrs) = 6.20 mg/L (geometric mean)
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Table 94: Acute toxicity to Daphnia magna: metabolite M750F006 (key study)
Study type Acute toxicity to aquatic invertebrates
Species Aquatic invertebrate, Daphnia magna
Flag Key study
Test Substance Metabolite M750F006
Endpoint EC50 (48-hrs)
Value 4.42 mg/L (48-hrs) geometric mean
Reference (4.6.26) Rzodeczko (2015c). Reg. No. 5863469 (Metabolite of BAS 750 F,
M750F006) Daphnia magna, Acute immobilisation test. BASF Study
Identification Number: 433190. BASF Registration Document Number (Doc
ID): 2015/1001492.
Study Summary The summary in the Draft Assessment Report (DAR) – BAS 750F – Volume
3 – Annex B.9 (AS) Ecotoxicology (2017) is fully accepted by the EPA Staff.
Comments It is noted in the DAR that there were mortalities observed in line with the
probit curve at 0.84 and 1.83 mg/L, even though they were not significant,
treatment related mortality appears to be present at these test
concentrations. Therefore the NOEC has been adjusted to reflect this.
Conclusion EC50 = 4.42 mg/L (48-hours geometric mean)
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Table 95: Acute toxicity to algae: metabolite M750F006 (key study)
Study type Acute toxicity growth inhibition test
Species Algae, Pseudokirchneriella subcapitata
Flag Key study
Test Substance Metabolite M750F006
Endpoint ErC50 (72-hrs)
Value 1.424 mg/L (geometric mean)
Reference (4.6.44) Rzodeczko (2016c). Reg. No. 5863469 (Metabolite of BAS 750 F,
M750F006) Pseudokirchneriella subcapitata SAG 61.81 Growth Inhibition
Test. BASF Study Identification Number: 789142. BASF Registration
Document Number (Doc ID): 2015/1184815.
Study Summary The summary in the Draft Assessment Report (DAR) – BAS 750F – Volume
3 – Annex B.9 (AS) Ecotoxicology (2017) is fully accepted by the EPA Staff.
Comments It is noted in the DAR that the pH should increase by no more than 1.5 over
the course of the test, and the pH increased from 7.24-8.82 in the solvent
control. As this only occurred in the solvent control, all the validity criteria
were met and no negative effects were observed in the controls, this
deviation is not expected to have adversely affected the experiment.
Conclusion ErC50 (72-hrs) = 1.424 mg/L (geometric mean)
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Table 96: Acute toxicity to Daphnia magna: metabolite M750F007 (key study)
Study type Acute toxicity to aquatic invertebrates
Species Aquatic invertebrate, Daphnia magna
Flag Key study
Test Substance Metabolite M750F007
Endpoint EC50 (48-hrs)
Value >10 mg/L (analytically confirmed nominal)
Reference (4.6.24) Backfisch and Härthe (2015a). Acute toxicity of Reg. No. 6003432
(M750F007; metabolite of BAS 750 F) to Daphnia magna Straus in a 48 hour
static test. BASF Study Identification Number: 433184. BASF Registration
Document Number (Doc ID): 2015/1003915.
Study Summary The summary in the Draft Assessment Report (DAR) – BAS 750F – Volume
3 – Annex B.9 (AS) Ecotoxicology (2017) is fully accepted by the EPA Staff.
Comments It is noted in the DAR that the although mean measured concentrations were
not maintained within ±20% of the nominal, for 10 mg/L the recovery was
100% at initiation and 98.2% at 48h. As the endpoints are >10 mg/L, basing
the endpoint off nominal concentrations is acceptable.
Conclusion EC50 (48-hrs) >10 mg/L (analytically confirmed nominal)
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Soil toxicity of the active ingredient
Toxicity to terrestrial plants
Table 97: Effects on non-target plants (seedling emergence): formulation BAS 750 01 F
(supporting study)
Study type Effects on non-target plants (seedling emergence)
Species Ten species: oilseed rape (Brassica napus), lettuce (Lactuca sativa), tomato
(Solanum lycopersicum), green cabbage (Brassica oleracea var. sabellica),
soya bean (Glycine max), carrot (Daucus carota), onion (Allium cepa), rye
grass (Lolium multiflorum), wheat (Triticum aestivum) and corn (Zea mays).
Flag Supporting study (see comments)
Test Substance BAS 750 01 F (emulsifiable concentrate formulation containing 100 g/L
mefentrifluconazole)
Endpoint NOER, ER25 and ER50 (21 days, seedling emergence)
Value NOER (21 days, plant dry weight) = 750 g Tl/ha [equivalent to 75 g ai/ha
based on a mefentrifluconazole concentration of 100 g/L]
ER25 (21 days, seedling emergence) >1500 mL TI/ha [equivalent to >150 g
ai/ha based on a mefentrifluconazole concentration of 100 g/L]
ER50 (21 days, seedling emergence) >1500 mL TI/ha [equivalent to >150 g
ai/ha based on a mefentrifluconazole concentration of 100 g/L]
All species showed equal sensitivity to the test item.
Reference (4.6.70) Marquardt (2015a). BAS 750 01 F: A test to determine the effects on non-
target plants. BASF Study Identification Number: 730827. BASF Registration
Document Number (Doc ID): 2014/1242738.
Study Summary The summary in the Draft Assessment Report (DAR) – BAS 750F – Volume
3 – Annex B.9 (PPP) Ecotoxicology (2017) is fully accepted by the EPA Staff.
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Comments Note that the test item applied in this study was not Revystar Fungicide but
formulation BAS 750 01 F. Whilst this also an emulsifiable concentrate
formulation containing the same concentration of mefentrifluconazole as
Revystar Fungicide (100 g/L), formulation BAS 750 01 F does not contain
fluxapyroxad however.
The following comments were noted in the DAR:
Pre-emergence application of BAS 750 01 F under worst-case greenhouse
conditions did not result in treatment-related symptoms of phytotoxicity for
any of the tested plant species. No adverse effects on seedling emergence
and plant height were observed for all plant species tested up to and
including 1500.0 mL BAS 750 01 F/ha. Statistically significant effects on dry
weight were observed for wheat at an application rate of 1500.0 mL BAS 750
01 F/ha.
The ER50 value based on seedling emergence, plant height and dry weight
was >1500.0 mL BAS 750 01 F/ha for all tested plant species (the highest
rate tested). The NOER for phytotoxicity, seedling emergence and plant
height was ≥1500.0 mL BAS 750 01 F/ha, and the NOER for plant dry weight
was 750.0 mL BAS 750 01 F/ha.
The study was carried out according to GLP and follows the guideline OECD
208 with no significant deviations. The study report notes that there were a
number of deviations from guidance with regards to relative humidity, with
levels less than the recommended minimum of 45% (mean minimum 40% for
seven days after application for onion, mean minimum 40.34% for two days
for all other species). This is not considered to have had a significant effect
on the results as the study validity criteria were met.
The apparent large deviations from the control that do not result in
statistically significant results indicate that the study design lacks sensitivity.
However as no effects greater than 50% were observed, and as there
appears to be no dose-response relationship for any of the tested species,
the ER50 value derived from this study is considered appropriate for risk
assessment. That said there is uncertainty regarding the NOER values
derived.
Conclusion NOER (21 days, plant dry weight) = 750 g Tl/ha [equivalent to 75 g ai/ha
based on a mefentrifluconazole concentration of 100 g/L]
ER25 (21 days, seedling emergence) >1500 mL TI/ha [equivalent to >150 g
ai/ha based on a mefentrifluconazole concentration of 100 g/L]
ER50 (21 days, seedling emergence) >1500 mL TI/ha [equivalent to >150 g
ai/ha based on a mefentrifluconazole concentration of 100 g/L]
All species showed equal sensitivity to the test item.
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Table 98: Effects on non-target plants (vegetative vigour): formulation BAS 750 01 F
(supporting study)
Study type Effects on non-target plants (vegetative vigour)
Species Ten species: oilseed rape (Brassica napus), lettuce (Lactuca sativa), tomato
(Solanum lycopersicum), green cabbage (Brassica oleracea var. sabellica),
soya bean (Glycine max), carrot (Daucus carota), onion (Allium cepa), rye
grass (Lolium multiflorum), wheat (Triticum aestivum) and corn (Zea mays).
Flag Supporting study (see comments)
Test Substance BAS 750 01 F (emulsifiable concentrate formulation containing 100 g/L
mefentrifluconazole)
Endpoint NOER, ER25 and ER50 (21 days, plant dry weight)
Value NOER (21 days, plant dry weight) = 1500 mL TI/ha [equivalent to 150 g ai/ha
based on a mefentrifluconazole concentration of 100 g/L]
ER25 (21 days, plant dry weight) >1500 mL TI/ha [equivalent to >150 g ai/ha
based on a mefentrifluconazole concentration of 100 g/L]
ER50 (21 days, plant dry weight) >1500 mL TI/ha [equivalent to >150 g ai/ha
based on a mefentrifluconazole concentration of 100 g/L]
All species showed equal sensitivity.
Reference (4.6.71) Marquardt (2015a). BAS 750 01 F: A test to determine the effects on non-
target plants. BASF Study Identification Number: 730828. BASF Registration
Document Number (Doc ID): 2016/7010990
Study Summary The summary in the Draft Assessment Report (DAR) – BAS 750F – Volume
3 – Annex B.9 (AS) Ecotoxicology (2017) is fully accepted by the EPA Staff.
Comments Note that the test item applied in this study was not Revystar Fungicide but
formulation BAS 750 01 F. Whilst this also an emulsifiable concentrate
formulation containing the same concentration of mefentrifluconazole as
Revystar Fungicide (100 g/L), formulation BAS 750 01 F does not contain
fluxapyroxad however.
The following comments were noted in the DAR:
Post-emergence application of BAS 750 01 F under worst-case greenhouse
conditions resulted in no treatment-related symptoms of phytotoxicity for all
tested plant species. Thus, the NOER was ≥1500.0 mL BAS 750 01 F/ha for
all tested plant species.
The ER50 value based on plant dry weight and height was >1500.0 mL BAS
750 01 F/ha for all tested plant species (the highest rate tested).
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The study was carried out according to GLP and follows the guideline OECD
227 with no significant deviations. The apparent large deviations from the
control that do not result in statistically significant results indicate that the
study design lacks sensitivity. However as no effects greater than 25% were
observed, this is not thought to have had an adverse impact on the study. As
there appears to be no dose-response relationship for any of the tested
species, the ER50 value derived from this study is considered appropriate for
risk assessment.
Conclusion NOER (21 days, plant dry weight) = 1500 mL TI/ha [equivalent to 150 g ai/ha
based on a mefentrifluconazole concentration of 100 g/L]
ER25 (21 days, plant dry weight) >1500 mL TI/ha [equivalent to >150 g ai/ha
based on a mefentrifluconazole concentration of 100 g/L]
ER50 (21 days, plant dry weight) >1500 mL TI/ha [equivalent to >150 g ai/ha
based on a mefentrifluconazole concentration of 100 g/L]
All species showed equal sensitivity.
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Terrestrial vertebrate toxicity of the active ingredient
Acute toxicity to birds (oral)
Table 99: Acute toxicity to birds (oral): active ingredient (key study) [9.3]
Study type Acute toxicity to birds (single dose)
Species Bobwhite quail, Colinus virginianus
Flag Key study
Test Substance BAS 750 F (mefentrifluconazole)
Endpoint LD50 and NOEL (acute oral)
Value LD50 = 816 mg ai/kg bw
NOEL = 300 mg/kg bw
Reference (4.6.2) (2014a). BAS 750 F - Acute toxicity in the bobwhite quail (Colinus
virginianus) after single administration (LD50).
Study Summary The summary in the Draft Assessment Report (DAR) – BAS 750F – Volume
3 – Annex B.9 (AS) Ecotoxicology (2017) is fully accepted by the EPA Staff.
Comments The following comments were included in the DAR:
The study is considered acceptable and suitable for risk assessment
purposes. The RMS agrees that the test conditions being outside the
guideline levels did not have a negative impact on the test.
Conclusion LD50 (acute oral) = 816 mg ai/kg bw
NOEL (acute oral) = 300 mg/kg bw
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Table 100: Acute toxicity to birds (oral): active ingredient (key study) [9.3]
Study type Acute toxicity to birds (single dose)
Species Mallard duck, Anas platyrhychos
Flag Key study
Test Substance BAS 750 F (mefentrifluconazole)
Endpoint LD50 and NOEL (acute oral)
Value LD50 >2000 mg/kg bw
[Note that based on the EFSA guidance in cases where there is no mortality
the LD50 can be extrapolated using a factor of 1.614 (5 birds tested at limit
dose) by multiplying the limit dose by the extrapolation factor (ie. 2000 x
1.614 = 3228 mg ai/kg]
NOEL (mortality) = >2000 mg/kg bw
Reference (4.6.3) 2014b). BAS 750 F - Acute toxicity in the mallard duck (Anas
platyrhynchos) after single oral administration (LD50).
.
Study Summary The summary in the Draft Assessment Report (DAR) – BAS 750F – Volume
3 – Annex B.9 (AS) Ecotoxicology (2017) is fully accepted by the EPA Staff.
Comments The following comments were included in the DAR:
The study is considered acceptable and suitable for risk assessment
purposes. The RMS agrees that the environmental test conditions being
outside the guideline levels did not have a negative impact on the test, and
that the temperature exceeded self-imposed rather than the guideline limits,
whereas maximum humidity of 100% exceeded the guideline maximum of
70%. Additionally it is noted that the variation in the test organisms’ body
weight of 16.8% exceeds the recommended ±10% in EPA 850.2100 (1996),
although as no negative effects were observed in the controls and consistent
responses were observed across test organisms, this deviation is not
considered to have adversely affected the test.
Conclusion LD50 (acute oral) >2000 mg/kg bw
[Note that based on the EFSA guidance in cases where there is no mortality
the LD50 can be extrapolated using a factor of 1.614 (5 birds tested at limit
dose) by multiplying the limit dose by the extrapolation factor (ie. 2000 x
1.614 = 3228 mg ai/kg]
NOEL (mortality) = >2000 mg/kg bw
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Table 101: Acute toxicity to birds (oral): active ingredient (key study) [9.3]
Study type Acute toxicity to birds (single dose)
Species Canary, Serinus canaria
Flag Key study
Test Substance BAS 750 F (mefentrifluconazole)
Endpoint LD50 (acute oral)
Value LD50 (acute oral) >2860 mg ai/kg bw
[Note that based on the EFSA guidance in cases where there is a single
mortality the LD50 can be extrapolated using a factor of 1.228 (5 birds tested
at limit dose) by multiplying the limit dose by the extrapolation factor (ie. 2860
x 1.228 = 3512 mg ai/kg]
Reference (4.6.4) (2015a). BAS 750 F - Acute toxicity in the canary (Serinus canaria)
after single oral administration (LD50).
Study Summary The summary in the Draft Assessment Report (DAR) – BAS 750F – Volume
3 – Annex B.9 (AS) Ecotoxicology (2017) is fully accepted by the EPA Staff.
Comments The following comments were included in the DAR:
The study is considered acceptable and suitable for risk assessment
purposes and the proposed endpoints are an LD50 of >2860 mg ai/kg bw and
a NOEL for mortality of ≥2860 mg ai/kg bw. The RMS agrees that humidity
exceeding the guideline levels did not have a negative impact on the test,
and that the temperature passed outside self-imposed rather than guideline
limits. It is additionally noted that food should be withheld for a minimum of
15-hrs (EPA 850.2100 (1996) prior to dosing rather than 2-3 hrs, and the
variation in body weight was 12.3%, only marginally exceeding the
recommended maximum of 10%. Given that the capsules were ingested and
no regurgitation was observed, these deviations are not expected to have
adversely affected the experiment.
Conclusion LD50 (acute oral) = >2860 mg/kg bw
[Note that based on the EFSA guidance in cases where there is a single
mortality the LD50 can be extrapolated using a factor of 1.228 (5 birds tested
at limit dose) by multiplying the limit dose by the extrapolation factor (ie. 2860
x 1.228 = 3512 mg ai/kg]
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Acute toxicity to birds (dietary)
Table 102: Acute toxicity to birds (dietary): active ingredient (disregarded study)
Study type Acute toxicity to birds (dietary)
Species Bobwhite quail, Colinus virginianus
Flag Disregarded (see comments)
Test Substance BAS 750 F (mefentrifluconazole)
Endpoint Study deemed unreliable
Value 858 mg/kg bw/d
Reference (4.6.5) (2014c). BAS 750 F - Avian dietary toxicity test in chicks of the bobwhite
quail (Colinus virginianus).
Study Summary The summary in the Draft Assessment Report (DAR) – BAS 750F – Volume
3 – Annex B.9 (AS) Ecotoxicology (2017) is fully accepted by the EPA Staff.
Comments In the DAR it is stated that food avoidance and the toxic effect of the item has
impacted food consumption and body weight data. Consequently, higher
concentration dose groups resulted in reduced daily doses. Therefore,
despite some clear effects on mortality, the effects cannot be separated from
the issue of food avoidance meaning doses cannot reliably attributed to
effects. Additionally, the effect of food avoidance may be causing starvation
and contributing to the mortalities. These issues will result in endpoints that
underestimate the toxicity to birds.
Note this study was also amended by Keller (2015a, BASF Registration
Document Number (Doc ID): 215/1223324), but does not affect the endpoint.
Conclusion Study deemed unreliable
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Table 103: Acute toxicity to birds (dietary): active ingredient (disregarded study)
Study type Acute toxicity to birds (dietary)
Species Mallard duck, Anas platyrhychos
Flag Disregarded study
Test Substance BAS 750 F (mefentrifluconazole)
Endpoint LD50 (8-day dietary)
Value Study deemed unreliable
Reference (4.6.7) (2014d). BAS 750 F - Avian dietary toxicity test in ducklings of the
mallard duck (Anas platyrhynchos).
Study Summary The summary in the Draft Assessment Report (DAR) – BAS 750F – Volume
3 – Annex B.9 (AS) Ecotoxicology (2017) is fully accepted by the EPA Staff.
Comments It is concluded in the DAR that under the conditions of this study, the LD50 for
mallard ducklings (Anas platyrhynchos) was 8347 mg ai/kg diet (extrapolated
value). The LD50 exceeded the highest tested dietary concentration group of
7500 mg ai/kg diet. Calculated on the basis of daily doses, the LD50 was
1213 mg ai/kg bw/day. The "No Observed Effect Level" (NOEL) was <1480
mg ai/kg diet. The NOEL calculated on the basis of daily dose was <244 mg
ai/kg bw/day.
The RMS notes that food avoidance and the toxic effect of the item has
impacted food consumption and bodyweight data. Consequently, higher
concentration dose groups resulted in reduced daily doses. Therefore,
despite some clear effects on mortality, the effects cannot be separated from
the issue of food avoidance meaning doses cannot reliably be attributed to
effects of the active substance. Additionally, the effect of food avoidance may
be causing starvation and contributing to the mortalities. These issues will
result in endpoints that underestimate the toxicity to birds. The study has
proposed an extrapolated value for the LC50, however as there is no clear
dose-response relationship and the confidence limits for the value range over
a factor of 10, the proposed value cannot be accepted.
The RMS agrees that the temperature gradient should be between 22-38°C,
although the minimum temperature reached 17.1°C. Given the temperature
gradient with the ceramic heater and no negative effects observed in the
controls, the test conditions exceeding the recommended values are not
expected to have adversely affected the test. Additionally the mean body
weight for the 1480 mg ai/kg diet group had significantly reduced mean body
weight at day 0, which would make any significant decline in body weight for
this group over the course of the test more difficult to define from the initial
reduced weight.
Conclusion Study deemed unreliable
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Chronic toxicity to birds (reproduction)
Table 104: Chronic toxicity to birds (reproduction): active ingredient (key study)
Study type Chronic toxicity to birds (reproduction)
Species Bobwhite quail, Colinus virginianus
Flag Key study
Test Substance BAS 750 F (mefentrifluconazole)
Endpoint NOEC (22 weeks)
Value 285 mg ai/kg diet (25.3 mg ai/kg bw/day)
Reference (4.6.8) 2014a). BAS 750 F: A reproduction study with the Northern
bobwhite.
Study Summary The summary in the Draft Assessment Report (DAR) – BAS 750F – Volume
3 – Annex B.9 (AS) Ecotoxicology (2017) is fully accepted by the EPA Staff.
Comments In the DAR the following comments are noted:
The study is considered acceptable and suitable for risk assessment
purposes. The relative humidity of the adult study room and the brooding
pens were below the recommended levels of 45-70%. Ideally the water
should be changed every day rather than every 2-3 days as it is in a trough.
Given that all the validity criteria were met and no other negative effects were
observed in the controls, these deviations are not thought to have adversely
affected the experiment. Although there is an apparent dose-response in the
number of eggs laid per hen per day, this does not follow through to other
reproductive parameters such as hatchlings/hen. Therefore no changes to
the NOEC are proposed.
Conclusion NOEC (22 weeks) = 285 mg ai/kg diet (25.3 mg ai/kg bw/day)
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Table 105: Chronic toxicity to birds (reproduction): active ingredient (key study)
Study type Chronic toxicity to birds (reproduction)
Species Mallard duck, Anas platyrhychos
Flag Key study
Test Substance BAS 750 F (mefentrifluconazole)
Endpoint NOEC (21 weeks)
Value 600 mg ai/kg diet (80.5 mg ai/kg bw/day)
Reference (4.6.9) 2015a). BAS 750 F: A reproduction study with the Northern
bobwhite.
Study Summary The summary in the Draft Assessment Report (DAR) – BAS 750F – Volume
3 – Annex B.9 (AS) Ecotoxicology (2017) is fully accepted by the EPA Staff.
Comments The following comments are stated in the DAR:
The study is considered acceptable and suitable for risk assessment
purposes and the proposed endpoints are a NOEC of 600 mg ai/kg diet (80.5
mg ai/kg bw/day). Although statistically significant in reduction in body mass
and gain of adult body weight was observed at 600ppm, this was not
considered test substance related as is due to the reduction in the body
weight of two female birds. Similar body reductions were not observed in the
15 surviving female birds at this concentration and in any of the surviving
male birds, and no dose response relationship was present for the other
concentration. Furthermore the range and standard deviations for these data
indicate both that the recorded weights were highly variable, and that these
two birds are considered to be outliers. Therefore the significant reduction is
not considered to be sufficient for reducing the NOEC to 300 mg ai/kg diet.
The environmental conditions in several areas exceeded the recommended
levels. The light intensity of the adult pens should be around 65 lux. Eggs
should be stored in a cold room of 13-16°C with a relative humidity of 55-
80%, and the relative humidity of the incubator should be around 70%. Given
that no negative effects were observed in the control, these deviations are
not expected to have had an adverse effect on the study.
Conclusion NOEC (21 weeks) = 600 mg ai/kg diet (80.5 mg ai/kg bw/day)
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Toxicity of the active ingredient to terrestrial invertebrates
Acute toxicity to pollinators
Table 106: Acute toxicity to honey bees: active ingredient (key study) [9.4]
Study type Acute toxicity to honey bees (oral and contact)
Species Honey bee, Apis mellifera L.
Flag Key study
Test Substance BAS 750 F (mefentrifluconazole)
Endpoint Acute oral and contact LD50 (48-hrs)
Value Acute oral LD50 (48-hrs) >100 µg ai/bee
Acute contact LD50 (48-hrs) >100 µg ai/bee
Reference (4.6.53) Franke (2015a). Acute toxicity of BAS 750 F to the honeybee Apis mellifera
L. under laboratory conditions. BASF Registration Document Number (Doc
ID): 2015/1128674.
Study Summary The summary in the Draft Assessment Report (DAR) – BAS 750F – Volume
3 – Annex B.9 (AS) Ecotoxicology (2017) is fully accepted by the EPA Staff.
Comments The following comments were included in the DAR:
The study was carried out according to GLP and follows the guideline OECD
213 with no significant deviations. It was noted that the reported relative
humidity (45-67%) fell below guideline recommendations (50-70%), though
as the study validity criteria were met this is not considered to have had a
significant effect on the outcome of the study. It was also noted that the
control treatments included a 50% w/v sucrose solution only and a 50% w/v
sucrose solution with 1% v/v Tween®80 and 1% v/v acetone. For
completeness it would have been appropriate to include controls consisting of
the sucrose solution with separate solvents. However, as there was zero
mortality in the two controls and the treated groups, this is not considered to
be important.
Conclusion Acute oral LD50 (48-hrs) >100 µg ai/bee
Acute contact LD50 (48-hrs) >100 µg ai/bee
Table 107: Acute toxicity to bumble bees: active ingredient (supporting study)
Study type Acute toxicity to bumble bees (oral and contact)
Species Bumble bee, Bombus terrestris L.
Flag Supporting study (see comments)
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Test Substance BAS 750 F (mefentrifluconazole)
Endpoint Acute oral and contact LD50 (96-hrs)
Value Acute oral LD50 (96-hrs) >195.4 µg ai/bee
Acute contact LD50 (96-hrs) >200 µg ai/bee
Reference (4.6.54) Amsel (2015a). Acute toxicity of BAS 750 F to the bumblebee Bombus
terrestris L. under laboratory conditions. BASF Study Identification Number:
767364. BASF Registration Document Number (Doc ID): 2014/1275250.
Study Summary The summary in the Draft Assessment Report (DAR) – BAS 750F – Volume
3 – Annex B.9 (AS) Ecotoxicology (2017) is fully accepted by the EPA Staff.
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Comments The following comments were stated in the DAR:
Oral toxicity
The study was carried out according to GLP. Currently no official guideline for
acute toxicity of an active substance/formulation to bumblebees is in
circulation, therefore the HSE evaluator has made reference to the (yet to be
noted) EFSA guidance, as well as the supplemental papers referred to by the
applicant, in assessing the study. With reference to available guidance, no
significant deviations were noted. No guidance was available regarding the
appropriate sensitivity range for the reference item Dimethoate, although
research by Hanewald et al. (2014) indicates oral 96-hr LD50 of approximately
0.2-2.4 μg/bee (mean 1.2 μg/bee). The study report states an appropriate
range for the oral test as between 0.25 and 1.50 μg ai/bee (not referenced,
lending a degree of uncertainty to this range) and the 48-hr and 96-hr LD50
both fall within this range (being 0.56 and 0.53 μg ai/bee, respectively).
Altogether this suggests that this batch of bees could be quite sensitive, but
this sensitivity falls within available ranges. No mortality occurred in the
controls, which meets the validity criteria in OECD 213 and EFSA guidance
(<10% average control mortality). On balance, the study is considered to be
reliable.
Contact toxicity
The study was carried out according to GLP. Currently no official guideline for
acute toxicity of an active substance/formulation to bumblebees is in
circulation, therefore the HSE evaluator has made reference to (yet to be
noted) EFSA guidance, as well as the supplemental papers referred to by the
applicant, in assessing the study. With reference to available guidance, no
significant deviations were noted. No guidance was available regarding the
appropriate sensitivity range for the reference item Dimethoate, although
research by Hanewald et al. (2014) indicate an acute contact LD50 (96-hrs) of
approximately 1.2-7.5 μg/bee (mean 5 μg/bee). The study report states an
appropriate range for the contact test as between 10.0 and 2.50 μg ai/bee,
however as this range is not referenced there is a degree of uncertainty with
it. The 96-hr LD50 falls within this range (being 4.8 μg ai/bee), and is close to
the mean contact LD50 derived from the Hanewald et al. (2014) paper. This
suggests that this batch of bumblebees displays average sensitivity. No
mortality occurred in the controls, which meets the validity criteria in OECD
214 (<10% average control mortality). On balance, the study is considered to
be reliable.
It is also noted in the DAR that these two studies are provided as additional
information but not used in risk assessment.
Conclusion Acute oral LD50 (96-hrs) >195.4 µg ai/bee
Acute contact LD50 (96-hrs) >200 µg ai/bee
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Table 108: Acute toxicity to honey bee larvae: active ingredient (key study)
Study type Acute toxicity to honey bee larvae
Species Honey bee, Apis mellifera L.
Flag Key study
Test Substance BAS 750 F (mefentrifluconazole)
Endpoint LD50, LC50, NOED and NOEC (96-hrs)
Value LD50 (96-hrs, acute) = 43.9 µg ai/larva
LC50 (96-hrs, acute) = 1.295 g ai/kg food
NOED (96-hrs, acute) = 29.7 µg ai/larva
NOEC (96-hrs, acute) = 0.875 g ai/kg food
Reference (4.6.58) Kleebaum (2015b). Acute toxicity of BAS 750 F to honeybee larvae (Apis
mellifera L.) under laboratory conditions (in vitro). BASF Study Identification
Number: 433204. BASF Registration Document Number (Doc ID):
2013/1235087.
Study Summary The summary in the Draft Assessment Report (DAR) – BAS 750F – Volume
3 – Annex B.9 (AS) Ecotoxicology (2017) is fully accepted by the EPA Staff.
Comments It was noted in the DAR that the mortality in two of the solvent control
replicates was greater than 15% (being 16.7%) after 72 hours; the non-
solvent control mortality mirrored this after 96 hours. The RMS evaluator
considered this to be an acceptable deviation as a) the exceedance of the
limit was only by 1.7%, b) the mean mortality was ≤15%, and c) the larval
grafting procedure integral to the assay is thought to make reliably
maintaining low levels of mortality in the controls a difficult task. The study is
considered to be valid therefore.
Conclusion LD50 (96-hrs, acute) = 43.9 µg ai/larva
LC50 (96-hrs, acute) = 1.295 g ai/kg food
NOED (96-hrs, acute) = 29.7 µg ai/larva
NOEC (96-hrs, acute) = 0.875 g ai/kg food
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Chronic toxicity to pollinators
Table 109: Chronic toxicity to honey bee larvae: active ingredient (disregarded study)
Study type Chronic toxicity to honey bee larvae
Species Honey bee, Apis mellifera L.
Flag Disregarded (see comments)
Test Substance BAS 750 F (mefentrifluconazole)
Endpoint EC50, ED50, NOEC and NOED (21 days)
Value Study deemed not reliable
Reference (4.6.59) Royer (2015a). BAS 750 F (Reg. No. 5834378) - Honey bee larvae test
(repeated exposure, observation 21 days) under laboratory conditions (in
vitro) - Non-GLP. BASF Registration Document Number (Doc ID):
2014/1327676.
Study Summary The summary in the Draft Assessment Report (DAR) – BAS 750F – Volume
3 – Annex B.9 (AS) Ecotoxicology (2017) is fully accepted by the EPA Staff.
Comments This study was not considered suitable for use in the risk assessment as
stated in the DAR. This was due to the following reasons:
The study was not carried out according to GLP, and according to Regulation
EC 283/2013 GLP is a requirement for all studies to be used in risk
assessments. The study follows the OECD ‘Draft Guidance document for
Honey Bee larval toxicity test, repeated exposure’, with a number of
deviations that add an element of uncertainty to the results derived.
Firstly it was noted that no reference item was tested alongside the test
substance. This means that the sensitivity of the test system cannot be
confirmed, and also that the study does not meet the drafted validity criteria.
Secondly, it was noted that fewer than 12 larvae were selected from two of
the colonies (8 each), whilst 32 larvae were selected from the other colony.
Guidance states that a minimum of 12 larvae from each colony should be
selected. That this condition has not been met reduces the statistical power
of the findings.
The apparently repellent effect of the test substance at the concentration of
325 mg ai/kg diet is noted.
Overall given the lack of GLP certification, and the failure to meet the study
validity criteria in draft guidance, the study is not considered suitable for risk
assessment.
The EPA agrees with this reasoning.
Conclusion Study deemed not reliable
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Appendix K: Standard terms and abbreviations
Abbreviation Definition
ai active ingredient
ADE Acceptable Daily Exposure
ADI Acceptable Daily Intake
AOEL Acceptable Operator Exposure Level
BBCH Biologische Bundesanstalt, Bundessortenamt und CHemische Industrie
BCF BioConcentration Factor
Bw body weight
CAS # Chemical Abstract Service Registry Number
cm centimetres
CoA Certificate of Analysis
CRfD Chronic Reference Dose
DDD Daily Dietary Dose
DT50 Dissipation Time (days) for 50% of the initial residue to be lost
dw dry weight
EbC50 EC50 with respect to a reduction of biomass
EC European Commission
EC25 Effective Concentration at which an observable adverse effect is caused in 25 %
of the test organisms
EC50 Effective Concentration at which an observable adverse effect is caused in 50 %
of the test organisms
EEC Estimated Environmental Concentration
EEL Environmental Exposure Limit
EFSA European Food Safety Authority
ErC50 EC50 with respect to a reduction of growth rate (r)
ER50 Effective Residue concentration to 50% of test organisms
FAO Food and Agriculture Organization
g grams
GAP Good Agricultural Practice
GENEEC Generic Estimated Environmental Concentration
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ha hectare
HQ Hazard Quotient
Kd partition (distribution) coefficient
Koc organic carbon adsorption coefficient
Kow octanol water partition coefficient
Kg Kilogram
L litres
Lb pounds
LC50 Lethal Concentration that causes 50% mortality
LD50 Lethal Dose that causes 50% mortality
LOAEC Lowest Observable Adverse Effect Concentration
LOAEL Lowest Observable Adverse Effect Level
LOC Level Of Concern
LOD Limit Of Detection
LOEC Lowest Observable Effect Concentration
LOEL Lowest Observable Effect Level
LR50 Lethal Rate that causes 50% mortality
M Molar
m3 cubic metre
MAF Multiple Application Factor
μm micrometre (micron)
mg milligram
μg microgram
mol mole(s)
MSDS Material Safety Data Sheet
NAEL No Adverse Effect Level
ng nanogram
NOAEC No Observed Adverse Effect Concentration
NOAEL No Observed Adverse Effect Level
NOEC No Observed Effect Concentration
NOEL No Observed Effect Level
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OECD Organisation for Economic Cooperation and Development
PDE Potential Daily Exposure
PEC Predicted Environmental Concentration
PHI Pre-Harvest Interval
pKa Acid dissociation constant (base 10 logarithmic scale)
PNEC Predicted No Effect Concentration
POW Partition coefficient between n-octanol and water
ppb parts per billion (10-9)
PPE Personal Protective Equipment
ppm parts per million (10-6)
REI Restricted Entry Interval
RPE Respiratory Protective Equipment
RQ Risk Quotient
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Appendix L: References
APVMA (2010). "Standard spray drift risk assessment scenarios."
Department Of Conservation (DOC) (2014). Conservation status of New Zealand earthworms, 2014.
EC (2017). Draft Assessment Report prepared according to the Commission Regulation (EU) N
1107/2009 - BAS 750F (Mefentrifluconazole)
EC (2019). FINAL Review report for the active substance mefentrifluconazole. Brussels, European
Commission, Directorate General for health and food safety.
EFSA (2009). "Risk Assessment for Birds and Mammals." EFSA Journal 7(12): 1438.
EFSA (2013). "Guidance on tiered risk assessment for plant protection products for aquatic organisms
in edge-of-field surface waters." EFSA Journal 11(7): 3290.
EFSA (2015). "Outcome of the pesticides peer review meeting on general recurring issues in
ecotoxicology." EFSA Supporting Publications 12(12): 924E.
EFSA (2018). "Peer review of the pesticide risk assessment of the active substance BAS 750 F
(mefentrifluconazole)." EFSA Journal 16(7): e05379.
EPA (2018). Risk Assessment Methodology for Hazardous Substances ; Draft for Consultation.
HSNO
Kim Y., D. N., Nowie M., Robinson B., Boyer S. (2017). "Molecular identification and distribution of
native and exotic earthworms in
New Zealand human-modified soils." New Zealand Ecological Society(41(2)).
PMRA (2019). Proposed Registration Decision - Mefentrifluconazole and related end-use products.
Ottawa, Pest Management Regulatory Agency: 208.
US EPA (2019). Mefentrifluconazole: Section 3 Environmetal Fate and Ecological Risk Assessment.
EPA–HQ–OPP–2018–0002-0032: 194
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Appendix M: Confidential Composition
The composition of Revystar® Fungicide is listed in Table 69.
Table 69: Detailed composition of Revystar® Fungicide
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