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Competent Authority Report: UK BENDIOCARB April 2008

Directive 98/8/EC concerning the placing of biocidal products on the market

Inclusion of active substances in Annex I or IA to Directive 98/8/EC

Document I

Bendiocarb Product-type (PT) 18

(Insecticides, Acaricides and products to control other arthropods)

Annex I - UK

Doc I – Overall Summary and Assessment of 48


CONTENTS

1. STATEMENT OF SUBJECT MATTER AND PURPOSE .................................. 4

1.1. Introduction ..................................................................................................... 4

2. OVERALL SUMMARY AND CONCLUSIONS ................................................... 5

2.1. Presentation of the Active Substance ............................................................ 5

2.1.1. Identity, Physico-Chemical Properties & Methods of Analysis....... 5

2.1.2. Intended Uses and Efficacy ............................................................... 5

2.1.3. Classification and Labelling .............................................................. 5

2.2. Summary of the Risk Assessment .................................................................. 6

2.2.1. Human Health and Companion Animal Risk Assessment ............... 6

2.2.1.1. Hazard identification ........................................................................... 6

2.2.1.2. Exposure assessment ......................................................................... 12

2.2.2. Environmental Risk Assessment...................................................... 18

2.2.2.1. Fate and distribution in the environment........................................... 18

2.2.2.2. Effects assessment............................................................................. 20

2.2.2.3. PBT assessment................................................................................. 20

2.2.2.4. Exposure assessment ......................................................................... 21

2.2.2.5. Risk characterisation ......................................................................... 25

2.2.3. List of endpoints ............................................................................... 27

3. DECISION ............................................................................................................... 27

3.1. Background to the Decision.......................................................................... 27

3.2. Decision regarding Inclusion in Annex I..................................................... 28

3.3. Elements to be taken into account by Member States when authorising products.......................................................................................................... 29

3.4. Requirement for further information ......................................................... 30

3.5. Updating this Assessment Report ................................................................ 30



APPENDIX I: LIST OF ENDPOINTS ......................................................................... 31

Chapter 1: Identity, Physical and Chemical Properties, Classification and Labelling ........................................................... 31

Chapter 2: Methods of Analysis ........................................................ 34

Chapter 3: Impact on Human Health ............................................... 35

Chapter 4: Fate and Behaviour in the Environment....................... 41

Chapter 5: Effects on Non-target Species......................................... 44

Chapter 6: Other End Points ............................................................. 46

APPENDIX II: LIST OF INTENDED USES ............................................................... 46

APPENDIX III: LIST OF STUDIES............................................................................. 48



1. STATEMENT OF SUBJECT MATTER AND PURPOSE

1.1. Introduction

This report and the supporting Documents II-A, II-B, II-C, III-A and III-B review the use of an existing biocidal active substance, bendiocarb, as an insecticide, according to the procedures of Directive 98/8/EC concerning the placing of biocidal products on the market. The UK Competent Authority (UK CA, the Health & Safety Executive, HSE) proposes the inclusion of bendiocarb as an insecticide on to Annex I of Directive 98/8/EC. This report has not yet been discussed with experts from other Member States and contains only the views of the UK CA.

Bendiocarb is marketed by Bayer Environmental Science and they submitted a dossier to the UK CA, including original test reports and study summaries, and this was accepted as complete for evaluation.

For the use of bendiocarb as an insecticide, the risks to human health and the environment, including any risks from physico-chemical properties and possible unacceptable effects, have been assessed in accordance with the provisions laid down in the Directive.

The report will help Member States to make future decisions on individual biocidal products containing bendiocarb, in accordance with the provisions of that Directive, and in particular the provisions of Article 5(1) and the common principles laid down in Annex VI of that Directive.

The information in this evaluation report is, at least partly, based on information that is protected under the provisions of Directive 98/8/EC. This evaluation report shall not be used to support any registration outside the context of Directive 98/8/EC, e.g. in other countries, unless the applicant has demonstrated legitimate access to the information on which this evaluation report is based.



2. OVERALL SUMMARY AND CONCLUSIONS

2.1. Presentation of the Active Substance

2.1.1. Identity, Physico-Chemical Properties & Methods of Analysis

The main identification characteristics and the physico-chemical properties of bendiocarb are given in Appendix I to this document. The active substance must be technically equivalent to the specification given.

The methods of analysis for the active substance as manufactured and for the determination of impurities have been validated. The methods of analysis in environmental matrices, as appropriate for the areas of use assessed, have been validated and shown to be sufficiently sensitive with respect to the levels of concern.

2.1.2. Intended Uses and Efficacy

The assessment of the biocidal activity of the active substance demonstrates that it has a sufficient level of efficacy against the target organisms and the evaluation of the data provided in support of the efficacy of the accompanying product, establishes that the product may be expected to be efficacious.

In addition, in order to facilitate the work of Member States in granting or reviewing authorisations, and to apply adequately the provisions of Article 5(1) of Directive 98/8/EC and the common principles laid down in Annex VI of that Directive, the intended uses of the substance, as identified during the evaluation process, are listed in Appendix II.

2.1.3. Classification and Labelling

Active Substance (Bendiocarb)

The classification of bendiocarb is currently assigned according to Annex I of Council Directive 67/548/EEC and is presented in Table 1.1.

Table 1.1 Current classification of bendiocarb

Classification T: Toxic Xn: Harmful N: Dangerous for the environment

R-phrases

R23: Toxic by inhalation. R25: Toxic if swallowed. R21: Harmful in contact with skin. R50/53: Very toxic to aquatic organisms. May cause long-term adverse effects in the aquatic environment.

On the basis of a review of the data submitted, it is considered that the current classification (as detailed in Table 1.1) is appropriate.



Biocidal Product (Ficam W) The current classification of ‘Ficam W’ is presented in Table 1.2.

Table 1.2 Current classification of ‘Ficam W’ guide recipe

Classification T: Toxic Xn: Harmful N: Dangerous for the environment

R-phrases

R23: Toxic by inhalation. R25: Toxic if swallowed. R21: Harmful in contact with skin. R50/53: Very toxic to aquatic organisms. May cause long-term adverse effects in the aquatic environment.

Based on the review of product data submitted for Ficam W, the UK CA disagrees with the current classification, as detailed in Table 1.2. Studies with Ficam W demonstrated acute toxicity by the oral and inhalation routes that met the EU criteria for classification as Toxic (T; R25, R23), whereas the available information did not support classification for acute toxicity by the dermal route. As such, the UK CA’s proposed classification of Ficam W is presented within Table 1.3.

Table 1.3 Proposed classification of ‘Ficam W’ guide recipe

Classification T: Toxic N: Dangerous for the environment

R-phrases

R23: Toxic by inhalation. R25: Toxic if swallowed. R50/53: Very toxic to aquatic organisms. May cause long-term adverse effects in the aquatic environment.

In addition, the product can be diluted with water and applied at an in-use concentration of 0.3 % w/w technical bendiocarb. The diluted product is Not Classified.

2.2. Summary of the Risk Assessment

2.2.1. Human Health and Companion Animal Risk Assessment

2.2.1.1. Hazard identification

2.2.1.1.1. Toxicology Hazard summary

The potential for bendiocarb and Ficam W (containing 82.47 % w/w technical bendiocarb) to cause adverse health effects has been investigated in studies in laboratory animals. For repeated oral, inhalation and dermal administration, genotoxicity, carcinogenicity, reproductive toxicity and neurotoxicity, information on bendiocarb has been used to predict the likely health hazards of Ficam W.

Several studies in a number of laboratory animal species have indicated that bendiocarb is acutely toxic by the oral route and meets the EU criteria for classification as Toxic (T; R25).



Two acute dermal studies in rats indicate that for this endpoint, bendiocarb meets the EU criteria for classification as Harmful (Xn; R21). One acute inhalation study with bendiocarb in rats indicates that a classification as Toxic by inhalation is appropriate (T; R23). Studies with Ficam W demonstrated acute toxicity by the oral and inhalation routes that met the EU criteria for classification as Toxic (T; R25, R23), whereas the available information did not support classification for acute toxicity by the dermal route.

Bendiocarb was only mildly irritating to the skin and eyes; Ficam W did not demonstrate any skin or eye irritancy. Although no specific information was available on the ability of bendiocarb or Ficam W to irritate the respiratory tract, there was no information from other studies to indicate that they had this property. Neither bendiocarb nor Ficam W met the EU classification criteria for skin, eye or respiratory tract irritation and, hence, no further consideration will be given to the irritation end-point in the risk characterisation.

Bendiocarb and Ficam W were negative in guinea pig tests for skin sensitisation; these findings were supported by the absence of sensitisation responses in repeat-dose dermal studies and in medical surveillance data on manufacturing plant personnel, and by the general lack of sensitising activity in carbamate insecticides (Baron, 1991). There is no specific information to determine the potential of bendiocarb or Ficam W to induce respiratory sensitisation; however, there are no structural alerts for bendiocarb, there have been no reports of respiratory sensitisation in medical surveillance data on manufacturing personnel, and the co-formulants of Ficam W are not classified for respiratory sensitisation. Therefore, no classification for skin or respiratory sensitisation is proposed, and these end-points will not be considered further in the risk characterisation.

The most sensitive markers for identifying NOAELs for use in the risk characterisation were considered to be inhibitions in brain and erythrocyte cholinesterase activities: inhibitions of 20 % or greater were considered to be toxicologically significant. Therefore, only repeated-dose studies that provided such measurements were used to derive NOAELs for use in the risk characterisation. The repeated-dose toxicity of bendiocarb has been investigated by the oral route in rats (dietary studies of 90 days and 104 weeks duration) and dogs (dietary studies of 112 days and 104 weeks duration). There were no treatment-related mortalities or overt clinical signs of toxicity in any of the studies. In both the sub-chronic and chronic studies, the dog was more sensitive than the rat; therefore, these studies were chosen to take forward in the risk characterisation. Although a two-year exposure does not constitute a life-time study in dogs, this study provided a lower NOAEL than that which used the rat. Following oral exposure a NOAEL of 1 mg kg-1 d-1 was identified from the 112 day dog study for use in short-term oral exposure scenarios; and a NOAEL of 0.65 mg kg-1 d-1 from the two year dog dietary study for use in long-term oral exposure scenarios.

The repeated-dose toxicity of bendiocarb has been investigated by the dermal route in rats (a 21-day study) and rabbits (a 21-day study). In the rat study, bendiocarb was applied as Ficam W. No mortalities occurred at any dose level. Toxic effects, which were consistent with exposure to this class of chemical, were observed from 200 mg kg-1 d-1 in a dose-response relationship and were severe in the highest-dose group (800 mg kg-1 d-1). The effects appeared 30-45 minutes after each dosing but were rapidly reversible, having resolved within 24 hours of treatment initiation. As erythrocyte and brain cholinesterase activities were not measured, this



study will not be considered further in the risk characterisation. In the rabbit study, bendiocarb was applied as Ficam Plus (31 % active substance). No mortalities occurred, and the only overt sign of toxicity was a slight, transient erythema in some animals. At necropsy, diffuse, minimal epidermal thickening was seen in the treated skin of all male and three female rabbits in the high-dose group. A NOAEL of 1.67 mg kg-1 d-1 was determined, based on inhibitions in erythrocyte cholinesterase activity.

The repeated-dose toxicity of bendiocarb has been investigated by the inhalation route in rats (studies of 14 days and 13 weeks duration). No treatment-related deaths occurred in either study. In the 14-day study, clinical signs (rigid tails, unsteady gait, slight tremors) were observed immediately after exposure in the 50 and 100 mg m-3 groups but had resolved by one hour after dosing. Statistically significant reductions in body-weight gain occurred in male rats in the 50 and 100 mg m-3 groups (54 and 71 % decrease over days 0-14), and the terminal body weights were lower than the controls (11 % and 13 %, respectively). The body weights and body-weight gains of females were less affected than those of males. As erythrocyte and brain cholinesterase activities were not accurately measured, this study will not be considered further in the risk characterisation. In the 13-week study, no treatment-related clinical signs were observed, and body-weight gain and food consumption were unaffected by treatment. Exposure to bendiocarb had no effect on ophthalmoscopic examination, haematology, organ weights, macroscopic abnormalities or clinical chemistry other than acetylcholinesterase activity. Brain cholinesterase activity was reduced at 13 weeks in the 20 mg m-3 group (by 26 % in males and 22 % in females). A treatment-related effect was noted on the incidence of aggregations of alveolar macrophages in the lungs of males in the high-dose group. The NOAEC was determined to be 2.0 mg m-3 based on the inhibitions in brain cholinesterase activity, which converts to a systemic dose equivalent of 0.6 mg kg-1 d-1. Bendiocarb did not meet the EU criteria for classification for repeated-dose toxicity by the oral, dermal or inhalation routes. Similarly, as none of its co-formulants are classified for repeated-dose toxicity, no classification for Ficam W is appropriate.

Bendiocarb was negative in five in vitro Ames and gene mutation assays. A positive result was obtained in an in vitro cytogenetics assay in cultured human lymphocytes; however, it was negative in an in vivo bone marrow cytogenetics assay and two additional in vivo assays (a mouse micronucleus test and a rodent dominant lethal test). The data do not support classification for mutagenicity. Likewise, as none of the co-formulants are classified for mutagenicity, no classification for Ficam W is appropriate.

The carcinogenic potential of bendiocarb has been investigated in life-time dietary studies in rats and mice. No carcinogenicity or neoplastic changes were observed in either species at concentrations that significantly reduced survival in mice and resulted in brain cholinesterase inhibition in rats. Although the survival rate in the rat study was low at two years, this study combined with the mouse study and the absence of genotoxicity indicate that bendiocarb is not carcinogenic. The available data do not support classification for carcinogenicity. Additionally, as none of the co-formulants are classified for carcinogenicity, no classification for Ficam W is appropriate.

The developmental toxicity of bendiocarb has been investigated in standard rat and rabbit oral (gavage) studies. There was no indication that bendiocarb is a developmental toxicant. The



available data do not support classification for developmental effects. Additionally, as none of the co-formulants are classified for developmental toxicity, no classification for Ficam W is appropriate.

The effects of bendiocarb on fertility have been investigated in a three-generation oral (dietary) reproduction study in rats. There were no indications that bendiocarb affected fertility. The available data do not support classification for fertility effects. Additionally, as none of the co-formulants are classified for fertility effects, no classification for Ficam W is appropriate.

The potential for bendiocarb to cause delayed neurotoxicity has been investigated in an oral (gavage) neurotoxicity study in hens. No signs of neurotoxicity were reported in hens following a single dose that resulted in mortalities. Additionally, as none of the co-formulants are known to cause neurotoxicity, Ficam W would not be expected to have this effect.

2.2.1.1.2. Critical endpoints

For risk characterisation for repeated exposure, one critical effect, inhibition of brain and/or erythrocyte cholinesterase activity, was identified from studies in dogs, rats and rabbits. This effect may arise from short-term and long-term oral, dermal or inhalation exposure scenarios.

The inhibitions in cholinesterase activity observed after bendiocarb administration are directly attributable to its insecticidal mode of action, which is to reversibly inhibit acetylcholinesterase. The inhibitions in cholinesterase activity and the clinical signs associated with them are rapidly reversible on cessation of exposure, with no long-term effects.

There are slight species differences in susceptibility to the toxic effects of bendiocarb, although all species tested responded to exposure with clinical signs that were typical of a reversible carbamate cholinesterase inhibitor (including muscular fibrillation, urinary incontinence, salivation, tremors, lacrimation and reduced activity). In acute oral studies, the cat was the most sensitive of the tested species. In repeated-dose studies, dogs were more sensitive to the inhibition of cholinesterase than were rats. In the absence of any information on human susceptibility to the anti-cholinesterase effects of bendiocarb, the toxicity observed in dogs, rabbits and rats repeatedly exposed to bendiocarb by the oral, dermal and inhalation routes, respectively, will be considered to be potentially relevant to human health.

In a 112-day oral dog study, a NOAEL of 1.0 mg kg-1 d-1 was identified based on toxicologically significant inhibitions in brain cholinesterase activity. This value is proposed for use in the risk characterisation of anti-cholinesterase activity in acute/medium-term oral and dermal exposure scenarios.

In a 13-week rat inhalation study, a NOAEC of 2 mg m-3 was identified, based on toxicologically significant reductions in brain cholinesterase activity. This value is proposed for use in the risk characterisation of anti-cholinesterase activity in acute/medium-term inhalation exposure scenarios.

For long term exposure scenarios, a two-year dietary study in dogs is used. A NOAEL of 0.65 mg kg-1 d-1 was identified, based on toxicologically significant inhibitions in brain cholinesterase activity.



Data are also available in cats exposed to bendiocarb, with an acute oral LD50 value of 11 mg kg-1 reported; no adverse effects being reported at 0.5 mg kg-1 (the lowest dose tested). In addition, no adverse effects were reported in cats exposed for 15 days in a room to a dust containing bendiocarb at a coverage rate of 20 g m-2 (equivalent to 0.2 g m-2 bendiocarb).

2.2.1.1.3. Uncertainties

Dermal Absorption Values Used in the Risk Assessment

A dermal absorption study has been conducted with Ficam W on dermatomed human skin. Ficam W, formulated in water, was applied for eight hours, and the receptor fluid was sampled for 24 hours. Recovery of radiolabel in the study was 91 % (range: 86 – 95 %). At the end of the study, 3.3 % (range: 1.8 – 6 %) of the applied dose had reached the receptor fluid, 1.1 % (range: 0.2 – 2.9 %) was found in the skin below the stratum corneum, while 0.5 % (range: 0.2 – 1.0 %) was retained within the stratum corneum. Peak flux across the skin occurred approximately 4 - 5 h following administration (equivalent to 0.45 % of the administered dose), and decreased significantly from this point to the end of the study (0.02 % of the administered dose reached the receptor fluid between 23 – 24 h post-administration). Thus, the residues remaining in the stratum corneum are considered not to contribute to the overall systemic body burden. The stratum corneum was removed using 10 tape strips, however, the results report “no sample” for the bottom 5 strips of each of the 6 skin samples used in the study. The Applicant has clarified that “no sample” in the study report refers to the fact that the entire stratum corneum is considered to have been removed within the first 5 strips taken and so, no additional strips were removed. When the dose remaining in the skin after tape stripping was considered, the dermal absorption of bendiocarb in an aqueous formulation ranged from 2.6 to 8.9 % of the applied dose, with a mean value of 4.4 %. It is noted that the individual value of 8.9 % absorption could be considered to be an outlier, given that the next highest individual absorption value is 4.8 %. A mean dermal absorption value of 4.4 % (range 2.6 – 8.9 %) can be derived from this study.

An additional study to investigate the dermal absorption of bendiocarb has been conducted with Ficam D (1.25 % bendiocarb in a dustable powder). The substance was applied without wetting to dermatomed human skin for eight hours and the receptor fluid was sampled for 24 hours. The total amount of radioactivity not absorbed through the skin accounted for 95 % of the applied dose, whilst the amount that was considered to have been absorbed accounted for 0.2 % of the applied dose. When the dose remaining in the skin after tape stripping was considered, the dermal absorption of bendiocarb applied as a dust ranged from 0.1 to 0.4 % of the applied dose, with a mean value of 0.26 %.

For the risk characterisation of Ficam W applied as an aqueous formulation, it is proposed to use a worst-case dermal absorption value of 9 % bendiocarb, although this will represent a very conservative approach. However, where refinement of the risk characterisation is necessary, the less conservative dermal absorption value of 4.4 % will be applied. Additionally, a worst-case dermal absorption value of 0.4 % for bendiocarb applied as a dust is proposed for use, as appropriate in the risk characterisation. Again, where refinement of the risk characterisation is necessary, the less conservative dermal absorption value of 0.26 % will be applied.



Inter- and Intra-species Variability

Oral exposure to bendiocarb results in acute, fatal toxicity to a number of laboratory animal species and, on repeated exposure, inhibitions in brain and erythrocyte cholinesterase activity in dogs and rats. Dermal exposure to bendiocarb results in acute, fatal toxicity to rats and, on short-term repeated exposure, inhibitions in erythrocyte cholinesterase and alkaline phosphatase activity in rabbits. Inhalation exposure to bendiocarb results in acute, fatal toxicity to rats and, on short-term repeated exposure, inhibitions in brain cholinesterase activity and an increased incidence of aggregation of alveolar macrophages in rats. There is no definitive information available to identify the relative sensitivities of humans compared with experimental animals in relation to the ability of bendiocarb to cause these effects. Similarly, there are no data to reliably inform on the potential for inter-individual variability in susceptibility to the effects. Given these uncertainties, standard default factors of 10 to account for potential inter-species and of 10 to account for intra-species variability will be included in the risk characterisation. Therefore, assessment factors of 100 will be applied to both occupational and consumer exposure scenarios.

Route to Route Extrapolation

There are no long-term dermal or inhalation studies available for systemic toxicity. However, the toxicokinetics studies indicate that there does not appear to be significant first-pass metabolism, so that similar toxicokinetic and toxicodynamic profiles for bendiocarb would be expected after oral, dermal and inhalation exposures. Hence, oral to dermal and oral to inhalation extrapolation for systemic effects is considered to be valid for the risk characterisation of long-term repeated dermal and repeated inhalation exposure scenarios.

For short and medium term inhalation exposure scenarios, a NOAEL from a 13 week rat inhalation study is used. Although, a 21 day dermal study is available in rats, there is no information regarding the dermal absorption of bendiocarb through rabbit skin and so a systemic dose level following dermal exposure cannot be established for use in the risk characterisation. Therefore, oral to dermal extrapolation for systemic effects is considered to be valid for the risk characterisation of short and medium term dermal exposure scenarios.

Dose-response/severity of key health effect

There are 3 key repeat-dose studies that will be used in the risk characterisation. These comprise a 13-week rat study for acute and medium term inhalation scenarios, a 112-day dog study for acute and medium term oral and dermal exposure scenarios and a two-year dog study for long-term exposure scenarios (by all routes).

In the 112-day oral dog study, the NOAEL of 1 mg kg-1 d-1 was based on inhibitions in brain cholinesterase activity that were observed at 112 days. The inhibitions in brain cholinesterase activity were dose-related, with no treatment-related effects occurring at 0.2 mg kg-1 d-1, a 10 % reduction (considered to be within normal limits) at 1 mg kg-1 d-1, and reductions of 28 % to 42 % in females and males, respectively, at 6.25 mg kg-1 d-1. These toxic effects were reversible within two to three days.



In the two-year oral dog study, an inhibition in brain cholinesterase activity was the key health effect and was used to set a NOAEL of 0.65 mg kg-1 d-1. At 0.65 mg kg-1 d-1 no adverse effects occurred; at 3.12 mg kg-1 d-1 (the LOAEL) there was a 20 % decrease in brain cholinesterase activity at 104 weeks; and at 16.24 mg kg-1 d-1 there were 26 % and 34 % reductions in brain cholinesterase activity at 52 and 104 weeks, respectively. No treatment-related clinical signs or mortalities were associated with these changes.

The key health effect in the 13-week inhalation rat study was a reduction in brain cholinesterase activity at 13 weeks, which resulted in the determination of a NOAEC of 2.0 mg m-3. Signs of toxicity were only detected in the high-dose group (20 mg m-3), with reductions of 22 % to 26 % in brain cholinesterase activity in females and males, respectively. An additional observation in this group was an increased incidence in the aggregations of alveolar macrophages in the lungs of males (6/10 for subpleural aggregations, 4/10 for lung parenchymal aggregations).

In addition to the inhibitions of brain and erythrocyte cholinesterase that were observed in the repeat-dose studies, bendiocarb caused acute toxicity by the oral (several laboratory animal species), dermal (rat) and inhalation (rat) routes. In rats that received a single oral dose of bendiocarb, clinical signs were observed from 1.5 mg kg-1 and deaths from 17.7 mg kg-1 (LD50 values of 25-156 mg kg-1 in males and 27-40 mg kg-1 in females were obtained). In dermal studies on rats, toxic effects occurred at 400 mg kg-1 and 800 mg kg-1 and deaths at 800 mg kg-1 (LD50 values of 566-800 mg kg-1 d-1). In a single acute inhalation study, clinical signs of toxicity occurred from 0.248 mg l-1 and deaths from 0.377 mg l-1 (LC50 of 0.55 mg l-1, equivalent to 550 mg m-3).

2.2.1.2. Exposure assessment

The active substance is manufactured outside the EU. As there is no direct contact with technical bendiocarb within the EU during its manufacture the exposure from its manufacture has not been addressed.

In the EU, potential exposure to the substance will occur through manufacture and repackaging of the product and during its use. Exposure assessments for manufacturing, repackaging and use of Ficam W are outlined below:

a) Manufacture and repackaging of Ficam W (containing bendiocarb)

The product, Ficam W, is formulated infrequently within the EU and repackaged at a second site within the EU. Due to the automated and closed system employed plus the effective personal protective equipment worn by production workers neither inhalation nor dermal exposures are expected for both manufacture and repackaging of Ficam W. Oral exposures are also not expected as both processes should follow the principles of good occupational hygiene practice.

An occupational medical surveillance report for Ficam W production did not reveal any unwanted effects in the workers, apart from skin itches. Between 2000 and 2005, there was one case of intoxication with the worker feeling unwell for a few hours. The worker’s



cholinesterase rate (plasma and red blood cell cholinesterase activity) had decreased but was normal again after one day.

b) Use of Ficam W (containing bendiocarb)

Exposure assessments have been carried out on 1 representative product, Ficam W. Ficam W is a concentrate product (supplied as a powder either within 500g HDPE containers or water soluble sachets) that is diluted in water by the professional operator. The diluted product is applied by professional operators only. The primary and secondary exposure scenarios considered in the risk assessment from the use of Ficam W are:

1. Primary exposure a. long-term exposure for a professional operator mixing and loading of Ficam W

from a 500 g HDPE container into a 5 l knapsack sprayer and then applying the diluted product.

b. long-term exposure for a professional operator spraying diluted Ficam W from a 5 l knapsack sprayer. Exposure from mixing and loading is considered in this scenario to be minimal as the product is supplied in water soluble sachets.

The primary exposure assessments (Tier 2c) for use in the risk assessment are summarised in Table 2.1 and have been compared with a NOAEL of 0.65 mg kg-1 d-1 from a two-year dietary study in dogs is used, based on toxicologically significant inhibitions in brain cholinesterase activity.

Table 2.1 Summary of the exposure scenario for use in the risk assessment

Ficam W (containing bendiocarb)

Tier Default values Systemic exposure

(mg kg-1 d-1) HDPE Container – mixing and loading then spraying

2c 0.0079

Sachets – mixing and loading then spraying

2c

60 kg adult; 2 hours a day; 9 % dermal penetration; 100 fold assessment factor; PPE: impermeable coveralls, gloves, eye/face protection, RPE (10-fold protection factor).

0.0037

2. Secondary exposure

1. acute/medium-term and long-term dermal exposure – following application, infant, child or adult comes into contact with bendiocarb dislodged from smooth, hard, treated surfaces;

2. acute/medium-term and long-term dermal exposure – infant contacts treated soft furnishings (e.g. a carpet), before and after vacuuming;

3. acute/medium-term and long-term dermal exposure – infant, child or adult comes into contact with bendiocarb while sleeping on a mattress that has been treated for bedbugs;

4. acute/medium-term and long-term dermal exposure – adult launders contaminated work clothing at home;



5. acute/medium-term and long-term oral exposure - infant comes into contact with bendiocarb residue dislodged from smooth, hard, treated surfaces and ingests the residue;

6. acute/medium-term oral exposure – kitten ingests residue from treated carpet or other surface, either directly from licking the carpet/surface or through grooming, i.e. by removing from the fur residue that has been dislodged from the carpet, and

7. acute/medium-term and long-term inhalation exposure – infant, child or adult exposed to bendiocarb dislodged from treated carpet during and immediately after vacuuming.

The secondary exposure assessments (Tier 1 and 2) for use in the risk assessment are summarised in Table 2.2 and have been compared with a NOAEL of 0.65 mg kg-1 d-1 from a two-year dietary study in dogs for long-term exposure, a NOAEL of 1.0 mg kg-1 d-1 from a 112-day oral dog study for acute/medium-term oral and dermal exposure scenarios and a NOAEC of 2 mg m-3 (equivalent to a systemic dose of 0.6 mg kg-1 d-1) for acute/medium-term inhalation exposure scenarios. A NOAEL of 0.5 mg pure bendiocarb kg/bw from a single oral administration study in cats has been used in the assessment for companion animals.



Table 2.2 Summary of the exposure scenarios for use in the risk assessment

Exposure route

Scenario Tier Default values Systemic exposure

(mg kg-1 d-1) Adult, child and infant come into contact with smooth, treated surfaces

1 60 kg adult, 34.4 kg child and 10 kg infant; 2 % dislodgeable residues to 40 % palm; 0.4 % dermal penetration; 100 fold assessment factor

0.0000032 (I) 0.0000029 (C) 0.0000022 (A)

Infant exposed to soft furnishings before and after vacuuming.

2 10 kg infant; 0.4 % dermal penetration; 100 % skin contact; 100 fold assessment factor.

0.00067 (BV) 0.00006 (AV)

Infant, child or adult sleeps on treated mattress

1 60 kg adult, 34.4 kg child and 10 kg infant; 9 % transfer from mattress to skin; 0.4 % dermal penetration; 100 fold assessment factor

0.0023 (I) 0.0013 (C) 0.0012 (A)

Dermal

Adult launders contaminated clothing

2 60 kg adult; 30 % material contaminates hand; 0.4 % dermal penetration; 2 hours per day 5 days a week; 100 fold assessment factor.

0.0001

Infant contaminates hands and there is hand to mouth transfer

2 10 kg infant; 100 % transfer and 100 % oral absorption; 100 fold assessment factor.

0.00002 (BV) 0.000002

(AV)

Oral

Kitten ingests bendiocarb from treated carpet.

2 Reverse reference scenario to determine how much pure bendiocarb would need to be ingested from a treated carpet by a 0.5 kg kitten to achieve the NOAEL.

961.5 cm2 (BV)

11363.6 cm2 (AV)

Inhalation Infant, child and adult exposed to bendiocarb following vacuuming.

1 60 kg adult, 34.4 kg child and 10 kg infant; 100 fold assessment factor

0.0065 (I) 0.0059 (C) 0.0037 (A)

I = infant C = Child A = adult BV = before vacuuming AV = after vacuuming

3. Combined exposures

a. long term exposure – adult and child exposed to bendiocarb from dislodgeable residues via the inhalation and dermal routes and through laundering of clothing (adult only);

b. infrequent exposure – adult exposed to bendiocarb from dislodgeable residues



via the inhalation and dermal routes, through laundering of clothing, mixing/loading from HDPE containers and spraying the in-use product;

c. infrequent exposures – adult exposed to bendiocarb from dislodgeable residues via the inhalation and dermal routes, through laundering of clothing, mixing/loading from sachets and spraying the in-use product;

d. long term exposure – infant could come into contact with doslodgeable residues from the dermal and inhalation routes.

The combined exposure assessments (Tier 1 and 2) for use in the risk assessment are summarised in Table 2.3 and have been compared with a NOAEL of 0.65 mg kg-1 d-1 from a two-year dietary study in dogs for long-term exposure. For those infrequent events a NOAEL of 1.0 mg kg-1 d-1 from a 112-day oral dog study has been used.

Table 2.3 Summary of exposure scenarios for use in the risk assessment

Systemic exposure (mg kg-1 d-1) Scenario Infant Child Adult

Adult and child exposed to dislodgeable residues. Adult

laundering of clothing.

N/A 0.0059 0.0038

Adult exposed following mixing/loading from HDPE

containers, spraying and dislodgeable residues

N/A N/A 0.0117

Adult exposed following mixing/loading from sachets,

spraying and dislodgeable residues

N/A N/A 0.0075

Infant exposed to dislodgeable residues

0.0080 N/A N/A

2.2.1.3. Risk characterisation

Primary exposure

The risks to human health from primary exposure are acceptable for mixing and loading and application of Ficam W (containing bendiocarb) in sachet form when impermeable coveralls, gloves and eye/face protection are worn in addition to RPE with a 10-fold protection factor.

For mixing/loading and application of Ficam W from HDPE containers the MOE is 82 with RPE (10-fold protection factor) impermeable coveralls, gloves and eye/face protection. The UK CA considers this is a borderline case and this MOE is acceptable for this exposure scenario for the following reasons. The NOAEL used for calculating the MOE in this exposure scenario is taken from a 2 year dog study in which no severe toxicity was noted at dose levels higher than the NOAEL. The acetylcholinesterase effects on which the NOAEL is based are likely to be rapidly reversible. The majority of the exposure likely to occur within this scenario will be by the dermal route and it is noted that the dermal absorption value applied is considered to be a worst case. As described in Section 1.1.3.1 (Document II-C), the risk



assessment could be further refined using a dermal absorption value of 4.4 %; this would give an MOE value of 148 for this scenario. If the assessment assumed a dermal absorption of 9 % and that the operators would be using the biocide for 48 minutes (the median duration for spraying) the MOE would be 203. Using the figure of 4.4 % for dermal absorption and spraying for 48 minutes the MOE would be 361. In addition, if other risk assessment methodology was applied to the exposure scenario resulting in an MOE of 82, allometric scaling could be used to modify the interspecies assessment factor given that a dog study is used. This would give an overall assessment factor of 35, which supports the UK proposal that the MOE of 82 derived for this exposure scenario represents an acceptable risk to human health.

Secondary exposure

Dermal The risks from secondary exposure to Ficam W (containing bendiocarb) through the dermal route have been assessed in a range of relevant exposure scenarios. The risks from exposure to adults, children and infants at the Tier 1 or 2 level (MOEs >283), assuming a dermal penetration of 0.4 % w/w, are considered to be low. Oral As infants and companion animals are considered to be the only groups which are likely to consume non-foodstuffs from surfaces, the risk assessment for oral exposure only focuses on these groups. In the Tier 1 assessment the acute/medium-term and long term risks from an infant consuming the product even without vacuuming are considered to be low. In a Tier 2 assessment, a kitten would need to ingest 961.5 cm2 and 11,363 cm2 of treated carpet before and after vacuuming, respectively, to achieve a body burden equivalent to the systemic NOAEL for short-term exposure. The risks to infants and companion animals from oral exposure to Ficam W (containing bendiocarb) are considered to be low. Inhalation The risks from acute/medium-term and long-term inhalation exposure to bendiocarb are considered to be acceptable. Therefore, Ficam W (containing bendiocarb) does not present a risk via inhalation in this scenario to adults, children and infants. According to Curry et al (1995) a substance should only be considered volatile if it has a vapour pressure >10 mPa at 20 0C. As the vapour pressure of bendiocarb is 1.9 mPa at 20 oC, it is not considered to be volatile.



It is considered that Ficam W (containing bendiocarb) does not present a risk to human health via inhalation. Combined exposure Except for those exposures during application of the product (which as discussed earlier are based on the worst-case spraying time and worst-case dermal absorption figure), the greatest contribution to the exposures is from the inhalation of residue dislodged from a treated carpet. This is a worse case assessment as the scenario assumes that the air concentrations would persist over the long term. In reality, air levels would be expected to decline because of settlement of particles, natural ventilation of the treated premises and the progressive reduction of bendiocarb in the carpet by repeated vacuuming. The exposure to airborne bendiocarb would be expected to be transient. Because only relatively long-term NOAELS from 13-week and a 2-year studies are available for the risk assessment, the combined MOEs are excessively conservative and therefore considered acceptable.

2.2.2. Environmental Risk Assessment

2.2.2.1. Fate and distribution in the environment

Fate in the aquatic compartment

Bendiocarb has been shown to hydrolyse at a moderate rate under environmental temperatures and pH with a predicted DT50 of 5.7 d (at 12 °C and pH 7). At pH 7, a major hydrolysis product, NC 7312 was identified, which was recorded to reach 87.9 % of the applied parent compound under the conditions tested (25 °C). Photolysis was shown to be only a minor route of removal of bendiocarb with a DT50 of 187 d predicted from the available data after adjustment for natural sunlight.

Based on the data provided bendiocarb was not shown to be readily biodegradable, but did undergo biodegradation (DT50 17.1 d at 12 °C, k = 0.041 d-1) to a single major metabolite, NC 7312, which further degraded to CO2 in aerobic sediment/water systems. NC 7312 was shown to reach a maximum mean level of 28 – 32 % applied radioactivity (AR) in the water phase after 7 d and 17 - 18 % AR in the sediment after 2 – 3 d. The rate of degradation of the metabolite was shown to be enhanced in the presence of sediment, with DT50s between 22.6 d (sediment-water system) to 132.8 d (filtered water) calculated for 12 °C. Degradation of bendiocarb under anaerobic conditions was shown to follow the same route as under aerobic conditions but at a slightly higher rate (DT50 8.9 d adjusted to 12 ºC). Degradation of the major metabolite, NC 7312, was not investigated further in the anaerobic system.

Data was submitted which demonstrated that bendiocarb has a low potential to bioconcentrate and hence bioaccumulate in fish with a bioconcentration factor (BCF) of 6.0 found for the whole body of the fish. These findings are further supported by the results from calculating a BCF using a QSAR from the ‘Technical Guidance Document on Risk Assessment in support of Commission Directive 93/67/EEC (new notified substances), Commission Regulation (EC) No 1499/94 (existing substances) and Directive 98/8/EC (biocidal products)’ (EC, 2003). This returned a value of 5.55, which agrees very closely with the study results.



Fate in air

The fate of bendiocarb in air was investigated using the quantitative structure activity relationship estimation method (QSAR; TGD, 2003), which considers the reaction with the daily air concentrations of hydroxyl (OH) radicals. A maximum estimated half-life of 13.2 h was predicted but as the active substance is not considered volatile, as shown by the reported vapour pressure of 1.9 mPa (at 20 ºC), the air compartment is not considered further within the following exposure assessment.

Fate in the terrestrial compartment

A study of the effect of sunlight on a soil surface indicated that bendiocarb could undergo rapid photolysis, with a DT50 of 1.4 d assuming a temperature of 12 ºC. The major photolysis products were shown to be strongly bound to the soil and not readily extracted.

Biodegradation of bendiocarb was investigated under aerobic conditions in 3 soils, a sandy loam, a silty clay loam and sand (< 1.5 % organic matter) and shown to be reasonably rapid with DT50s of between 2.1 and 9.9 (when adjusted to 12 ºC). However, the degradation endpoints from the sand soil has been discounted as this does not represent the normal range of soils. Therefore, the DT50 of 9.9 d is considered an appropriate worst-case value for use in an environmental risk assessment for refinement of exposure values where applicable.

The route of degradation in soil was shown to be similar to that in water-sediment studies with the formation of the metabolite NC 7312 followed by unextractable residues (~ 45 % applied radioactivity [AR]) and carbon dioxide (~ 55 % AR) by the end of the test (26 weeks). However, the known metabolite, NC 7312 degraded rapidly in soil and was only reported to exceed 10 % AR in sand, which was used primarily to explore the effect of volatility on the test. Therefore, it has been assumed that whilst degradation of bendiocarb in soil would occur, the known metabolite NC 7312 would not trigger a level of concern for soil compartment under the proposed use patterns.

The adsorption and desorption of bendiocarb has been shown to be influenced by the organic content of the soil matrix. The geometric mean Koc value of 33.35 suggest that bendiocarb would not adsorb strongly to soil and would very easily undergo desorption, suggesting a potential for high mobility in soil compartment. The known metabolite (NC 7312) has an estimated Koc of 202.5, which suggests that this substance (formed at < 10 % applied parent in the laboratory) would have a tendency to be mobile in soil.

Overall, the available fate and behaviour studies suggest that bendiocarb would be subject to removal from the soil compartment as a result of degradation to NC 7312, pyrogallol, bound residues and subsequent mineralisation to CO2. The parent and main metabolite, NC 7312 would also be subject to mobility pressures, which would further remove any residues from this compartment. Therefore, the overall fate profile for this compound suggests that even if repeated exposures of the soil compartment was to occur, it is unlikely that accumulation of this compartment would be of concern.



2.2.2.2. Effects assessment

In the aquatic compartment, the most sensitive species to bendiocarb was shown to be the water flea (Daphnia magna) following both acute and chronic exposure with a 21 d NOEC, based on reproduction, length and weight, of 0.88 µg l-1. This result is consistent with the view that invertebrates are usually more sensitive than fish or algae to insecticidal actives. Therefore, in consultation with the TGD, an assessment factor of 10 is considered appropriate and a PNEC of 0.088 µg l-1 has been used for risk assessment.

NC 7312 shows considerably lower aquatic toxicity than bendiocarb, and even though only the base set acute data are available and an assessment factor of 1000 was used, the derived PNEC of 10 µg l-1 is 100 times higher than that of the parent.

A PNEC for the sediment compartment for neither the parent nor metabolite has been derived because the trigger values for a sediment assessment, as given by the TGD (Koc > 500 and/or log Kow > 3), were not reached for bendiocarb (mean 35.65, and 1.7 respectively). As for NC 7312; whilst the log Kow is 3.15, the predicted Koc is 202.5, which suggests that a sediment assessment should not be performed. Furthermore, the fate of bendiocarb and NC 7312 in sediment-water systems suggested that both substances tended to be associated predominantly with the water phase.

For the effects assessment of the soil compartment, endpoints are available for bendiocarb from an acute earthworm (Eisenia fetida) study with an LC50 (14 d) of 188 mg a.s. kg-1 dw reported in addition to a series of chronic soil microorganisms that suggest the NOEC for bendiocarb of 50 mg kg dw and is appropriate for the limited soil exposures being considered. As only one chronic terrestrial study is available and no plant data have been submitted a precautionary approach has been taken, which is to use an assessment factor of 1000 instead of 100 as recommended by the TGD (Table 20) to give a PNEC of 0.19 mg a.s kg-1 dw soil.

NC 7312 was not shown to be a metabolite of concern in all but sand soils, which is not considered to represent average soil conditions and was only used in the study to investigate the volatility of bendiocarb from a soil surface.

2.2.2.3. PBT assessment

According to the TGD, ‘The Persistent, Bioaccumulative and Toxic (PBT) assessment is considered to be different from the local and regional assessments approaches, as it seeks to protect ecosystems where risks are more difficult to estimate’. Under the Biocidal Products Directive (BPD), a PBT assessment is needed to demonstrate that a substance does not fulfil selection under the United Nations Environment Programme – Persistent Organic Pollutants convention (UNEP-POPs) to limit emissions to the environment of those chemicals with high potential for persistence, bioaccumulation, long-range transport and adverse effects on human health and the environment. Any substance which is found to be either a PBT or very Persistent very Bioaccumulative (vPvB) substance shall not be allowed on Annex I unless releases to the environment can be effectively prevented.



Persistence

Data have been presented, which shows that bendiocarb did degrade reasonably rapidly in the aquatic environment with a worst-case DT50 value of 17.1 d at 12 °C under aerobic conditions in a sediment/water system. Therefore, the a.s. does not fulfil the criteria for a persistent compound according to the TGD (> 40 d in freshwater and/or > 120 d in freshwater sediment).

The rate of degradation of the major metabolite, NC 7312, was shown to be enhanced in the presence of sediment, a DT50s of 22.6 d (sediment-water system) to 132.8 d (filtered water) reported at 12 °C. Therefore, this metabolite is not considered to be of concern with regards to persistence in the aquatic environment and need not be considered further.

Bioaccumulation

A substance is considered to have the potential to fulfil the criterion of bioaccumulation when the log Kow exceeds 4.5, but as a log Kow of 1.7 has been derived for bendiocarb there is no trigger for an assessment of the bioaccumulation potential of this a.s in aquatic organisms. Therefore, the bioaccumulation criterion is not fulfilled.

Toxic

According to the available data, the most sensitive chronic endpoint for bendiocarb is that derived for a 21 d Daphnia study (NOEC of 0.88 µg l-1). This means that the trigger of < 0.01 mg l-1 given in the TGD is exceeded and bendiocarb can be considered to have fulfilled the criterion for toxic.

No data on the effects against birds have been submitted (or are considered necessary) for this assessment.

As bendiocarb has only fulfilled one criterion (T) out of the 3 considered, it can be accepted that it is not a PBT substance.

2.2.2.4. Exposure assessment

The environmental exposure assessment for bendiocarb has been produced using all available information. This has been taken from submitted studies and the Organisation for Economic Co-operation and Development (OECD) Task Force document; 4th Draft Emission Scenario Document (ESD) for ‘Insecticides, acaricides and products to control arthropods (PT 18) for household and professional use’ (OECD, March 2007). Information and guidance was also taken from part II of the Technical Guidance Document on risk assessment (TGD; EC, 2003). All calculations within the exposure scenario apply to bendiocarb only, as other constituents of the Ficam W product formulation are not considered to be compounds of concern. With regards to metabolites, NC 7312 is only considered as a major metabolite (of concern) in the aquatic compartment.

The environmental exposure assessment for Ficam W (a wettable powder formulation which contains 80 % pure bendiocarb w/w) is based on use by professionals only, for both indoor and outdoors treatments using an application rate of 96 mg pure bendiocarb m-2. The potential



environmental releases of bendiocarb resulting from the use of Ficam W will largely depend on the target pest being treated. For example, indoor infestations of cockroaches/ants will be largely associated with hard surface treatment limited to food preparation areas i.e. kitchens, whereas flea infestations are more likely to occur throughout the house where carpeted areas or pet bedding exist. Outdoors, occasional treatments against pests such as ants, wasps and wild bees (nest treatment) are considered to be the most common use for Ficam W.

The environmental emissions associated with the local scale are considered to present the worst-case scenario in terms of predicted environment concentrations (PECs). The use patterns have been considered separately in terms of indoor and outdoor applications to avoid an excessive or over prediction of exposure of the wider environmental compartments due to the existing worst-case assumptions of the use patterns already present within the scenarios used (see Document II-B, Section 3.3.3). In the scenarios presented the underpinning assumption is that the associated product, Ficam W, is for professional use only and will be used responsibly in such a way as to maximise the effectiveness of the treatment and minimise unnecessary exposure of non-target groups (people, animals and environment). The potential environmental emissions identified are:

Indoor use

1. Emissions from treated hard surfaces (tiles, laminate, concrete etc) as a result of wet cleaning resulting in:

• Direct exposure to the sewage treatment plant (STP) compartment via drains with,

i. indirect exposure to surface waters (including sediment) via STP effluent,

ii. indirect exposure to soil compartment (including groundwater) via STP sludge application to land and

iii. indirect exposure to biota via surface waters (bioconcentration in fish leading to secondary poisoning of fish eating birds).

2. Emissions from treated soft surfaces/furnishings as a result of dry cleaning resulting in: • Direct exposure of municipal waste sites/landfill with,

i. indirect exposure to STP of landfill leachate and ii. indirect exposure to surface waters (including sediment) via STP

effluent. 3. Emissions from treated soft surfaces/furnishings (carpets, sofas, mattresses etc) as a

result of wet cleaning resulting in: • Direct exposure to the sewage treatment plant (STP) compartment via drains

with i. indirect exposure to surface waters (including sediment) via STP

effluent, ii. indirect exposure to soil compartment (including groundwater) via STP

sludge application to land and iii. indirect exposure to biota via surface waters (bioconcentration in fish

leading to secondary poisoning of fish eating birds).



Outdoor use

1. Emissions from product washed off/from treated surfaces (walls, concrete) as a result of weathering/precipitation resulting in:

• Direct exposure to the STP compartment via surface drains adjacent to treated area,

i. indirect exposure to surface waters (including sediment) via STP effluent (run-off assumed to be negligible),

ii. indirect exposure to soil compartment (including groundwater) via STP sludge application to land and

iii. indirect exposure to biota via surface waters (bioconcentration in fish leading to secondary poisoning of fish eating birds).

• Direct exposure to soil compartment adjacent to treated area, i. indirect exposure to biota via soil (secondary poisoning of worm eating

birds) and ii. indirect exposure to groundwater compartment via soil.

2. Exposure of non-target species to bait used on hard surfaces outdoors resulting in: i. direct exposure to non-target birds/mammals to bait (primary poisoning)

and ii. indirect exposure to non-target birds/mammals to bait via consumption

of target pest (secondary poisoning). It should be noted that the air compartment is unlikely to be exposed because the available vapour pressure data (vapour pressure for bendiocarb = 1.9 mPa at 20 °C) suggests that it would not be regarded as volatile in the product Ficam W. This is further supported by the fact that the Ficam W product is formulated as a wettable powder. Therefore, it has been concluded that the air compartment is not of concern and no assessment has been presented. Indoor application scenario

The major route of environmental exposure is considered to be that resulting from the wet cleaning of hard surfaces, as cleaning of this nature is also more likely to occur as a matter of routine hygiene in both domestic and commercial premises. This treatment is restricted to professional use and advice will be given not to clean the treated area until the infestation is under control. Where regular cleaning is essential, it is unlikely that this type of formulation would be selected by the professional pest controller. Similarly, use of this product on carpeted areas must remain undisturbed for a period of time (3 weeks to allow for unhatched eggs and pupae) to allow for the infestation to be brought under control and re-infestation from unhatched eggs prevented. Therefore, environmental emissions of bendiocarb resulting from the vacuuming of carpets are likely to be limited, with shampooing of carpets unlikely as a normal practice in order to maintain the residual insecticidal effect and these have not been considered as part of the exposure assessment. This is considered a reasonable series of assumptions, as this is intended as a professional product and will only be used in premises that have a significant infestation problem to warrant the likely expense.



Further to the above assumptions, the indirect environmental exposure via domestic/industrial waste disposal to landfill (as a result of dry (vacuum) cleaning) has not been considered in this exposure assessment. This is because this route of exposure is much less likely to be of concern when compared to the direct exposure via the STP compartment. In addition, the effect of its dilution with other wastes, biodegradation of the active substance (a.s.) and the significant containment measures at landfill sites according to European Union (EU) waste regulations (EU Directive 99/31/EC) reduce any concerns further.

The PEC values for the main compartments of concern resulting from the indoor use of Ficam W are presented in the Table 2.4 below.

Table 2.4 Predicted environmental concentrations resulting from the indoor use of Ficam W

Environmental compartment of concern Substance STP

(mg l-1) Aquatic*

(mg l-1) Soil**

(mg kg-1 dw) Bendiocarb 1.83 x 10-4 6.78 x 10-6 see outdoor use NC 7312 N/A 4.38 x 10-6 N/A

N/A – not applicable * - refined values (biodegradation taken into account) ** - exposure via the STP route was shown to be far higher from outdoor use and therefore only this value has been presented.

Outdoor application scenario Widespread use of Ficam W as a treatment for flies at refuse and landfill sites is possible but this has not been addressed as the leachate, recycling and recovery from landfill are covered by additional regulations such that BPD would not be the primary consideration. The main direct environmental exposure route to be considered is via the STP as a result of run-off to facility drains from hard surfaces following outdoor use. Direct exposure of the soil compartment adjacent to treated buildings, resulting from run-off, is also considered possible as a result of the use of Ficam W. However, no direct application to soil or plants should be allowed to occur. The PEC values for the main compartments of concern resulting from the indoor use of Ficam W are presented in Table 2.5.



Table 2.5 Predicted environmental concentrations resulting from the outdoor use of Ficam W

Environmental compartment of concern Substance STP

(mg l-1) Aquatic* (mg l-1)

Soil (mg kg-1 dw)

Bendiocarb 6.8 x 10-3 2.53 x 10-4 0.408 a

2.85 x 10-4 b

NC 7312 - 1.63 x 10-4 - * - refined values (biodegradation taken into account) a – PEC due to run-off from hard surfaces b – Highest PEC calculated from spreading sewage sludge to land

2.2.2.5. Risk characterisation

Risks to the aquatic compartment

According to the data presented in Table 2.4, the proposed use pattern of the insecticide product Ficam W should not pose an unacceptable risk to surface waters when exposed via STP effluent as a result of indoor treatments. However, when used out-of-doors the risk of exposure to bendiocarb (not its metabolite) to surface waters is unacceptable. This is despite the scenario allowing for aquatic degradation and restricted use to around domestic properties only. Whilst this is of concern the risks may be reduced through restricting the scale of use outdoors by professionals (see Table 2.6).

Table 2.6 Risk characterisation (PEC:PNEC) values for bendiocarb and NC 7312 in the aquatic compartment as a result of using the insecticidal product Ficam W

Compartment Use pattern Substance PEC:PNEC

Indoor treatment 2.61 x 10-4STP Outdoor treatment Bendiocarb 9.71 x 10-3

Bendiocarb 0.075 Indoor treatment NC 7312 4.38 x 10-4

Bendiocarb 2.78*Surface waters Outdoor treatment NC 7312 0.016

* - unacceptable risk as PEC:PNEC > 1

No PEC-PNECsediment values have been determined for bendiocarb or its major metabolite (NC 7312) as it was concluded that neither pose any significant threat to the sediment compartment (see Document II-A, Section 4.1.1.2.1, 4.1.1.2.2 , 4.3.3. and Document II-B, Section 3.3.3.1.3). Bendiocarb has a low log Kow of 1.7, a mean Koc of 33.35 and was shown to remain predominantly in the water phase of a water-sediment environment. Despite a log Kow of 3.15 being at the trigger point for concern, a predicted Koc of 202.5 (QSAR) and sediment-water results (max. 32 % in water after 7 d, max. 18 % in sediment after 3 d) suggests that NC 7312 would also be predominantly associated with the aqueous phase and not sediment.



Risks to the soil compartment

From the proposed use pattern for Ficam W there are 2 areas of concern regarding the risks to soil as follows:

• the risks to the local or adjacent soil compartment from the outdoor use of the product (assuming 50 % emission from a single annual application of Ficam W used outdoors) as a result of a weathering event; and

• the risks to soil from applied sewage sludge containing bendiocarb as a result of losses to drains from either indoor or outdoor use.

The available risk characterisation data (see Table 2.7) show that the use of bendiocarb as an insecticide in Ficam W, according to the proposed use pattern for this product, does not pose an unacceptable risk to any soil compartment via the application of sewage sludge. However, the data for the local (in-situ) soil, exposed as a result of the use of bendiocarb in Ficam W outdoors, indicate that bendiocarb would pose an unacceptable risk to the immediate soil compartment. This risk is considered to be an artefact of the size of receiving compartment for soil, which if extended to a depth of 0.3 m would no longer be of concern.

Table 2.7 Risk characterisation (PEC:PNEC) values for bendiocarb and NC 7312 in the soil compartment as a result of using the insecticidal product Ficam W

Compartment Use pattern Depth PEC:PNEC

0.1 m 2.15*Soillocal adjacent to

treatmentOutdoor treatment 0.3 m 0.72

Soillocal/agri. soil Outdoor/indoor treatment 0.1 m 1.78 x 10-6

* - unacceptable risk as PEC:PNEC > 1

In soil bendiocarb has the potential to be mobile (Koc 33.35) and been shown to metabolise via the known metabolite, NC 7312, which in turn forms bound residues in the soil compartment and eventually mineralises to CO2. Whilst it is reasonable to assume that bendiocarb would move beyond the 10 cm depth, according to a PEARL assessment, neither bendiocarb nor NC 7312 would be expected to pose a significant risk to groundwater when applied to the perimeters of domestic buildings.

Risks to non-target biota

From the proposed use pattern and formulation the only non-target biota considered to be at risk from the use of bendiocarb in Ficam W are honey bees. It can be accepted that exposure of these organisms would result in a toxic response, particularly as the product is sold for use against wasp and wild bees. However, as the product is restricted to professional users appropriate risk mitigation measures via labelling has been proposed by the Applicant; “Action should be taken to prevent foraging bees gaining access to the treated bees nests preferably by removing the combs or blocking nest entrance. After treatment nests should be removed, if possible, and disposed of in a controlled manner (i.e. Pesticide Waste Disposal Scheme)”.



Risks for other non-targets such as birds and small mammals have not been considered because of the formulation and application type. Therefore, changes to the formulation may trigger the need for additional data and risk assessment to assess this risk at Member State level.

2.2.3. List of endpoints

In order to facilitate the work of Member States in granting or reviewing authorisations, and to apply adequately the provisions of Article 5(1) of Directive 98/8/EC and the common principles laid down in Annex VI of that Directive, the most important endpoints, as identified during the evaluation process, are listed in Appendix I.

3. DECISION

3.1. Background to the Decision

The human health risk assessment indicates that the risks from secondary exposure to bendiocarb are acceptable. The greatest risk from secondary exposure to bendiocarb is from the inhalation of residue dislodged by vacuuming a treated carpet. However, this risk assessment is excessively conservative as comparison for this transient exposure has been compared with NOAELs from long-term studies. Exposure to airborne bendiocarb would be expected to be transient because air levels would be expected to decline due to settlement of particles, natural ventilation of treated premises and the progressive reduction of bendiocarb in the carpet by repeated vacuuming. The major risks from exposure to bendiocarb are to the person carrying out the bendiocarb treatment. It is considered that the assessments for primary exposure are likely to be highly conservative as they are based on a person carrying out a bendiocarb treatment every day for their working life, which is unlikely to occur as the majority of professional treatments with bendiocarb will occur in the summer months to treat insect problems. In addition the NOAEL on which the assessments are based is taken from a 2 year dog study in which no severe toxicity was noted at dose levels higher than the NOAEL and the figure (9 %) used for dermal absorption is the highest recorded value, with the average being 4.4 %. The assessments on which the risks are identified require the operator to wear appropriate and suitable PPE (including RPE) when using Ficam W and this should be a requirement of its use (section 3.3). It is considered that, based on the assessment of the risks to human health, bendiocarb can be included on Annex I of the BPD.

The scenario used for the environmental risk assessment has assumed treatment against crawling insects (such as ants) using a crack and crevice treatment in wet rooms (i.e. kitchens and bathrooms) followed by wet cleaning. This risk assessment of this use pattern has shown that bendiocarb would not pose an unacceptable risk to surface waters. Therefore, the use of Ficam W in rooms where ‘wet cleaning’ is likely must be restricted to crack and crevice applications and areas inaccessible to cleaning (i.e. behind kitchen cupboards and appliances).

Indoor use of Ficam W against fleas can be expected, which would involve application to soft furnishings and carpets, where losses to the aquatic compartment following wet cleaning of carpets and treated furniture are possible e.g. shampooing. However, it has been assumed that exposure via this route will in reality be low, as treatments will have to be left (no vacuum or shampooing) in place for full control to be achieved. As this is a professional product, and it



contains a substance with residual activity (i.e. ideal for controlling pests that reproduce in situ), it will only be used where it can be left undisturbed to achieve maximum effectiveness. However, label instructions recommending a minimum period for a substance to be left in place (depending on product efficacy) will reduce any concern with regards to freshly applied bendiocarb being removed to landfill or washings down the drain.

The risk assessment presented to address the use of Ficam W outdoors can be considered as restricted in terms of both frequency (a single annual treatment was assumed for resistance reasons) and scale (small scale via domestic properties was used with 20 % use assumed). From the results presented, the use of Ficam W outdoors could pose an unacceptable risk to surface waters from exposure to the active substance, bendiocarb. Therefore, the use of Ficam W outdoors where exposure to drains cannot be prevented should not be permitted. However, the limited use around the perimeter of buildings to treat wasp and wild bees nests should continue to be allowed, providing clear labelling is given to avoid losses to drains as far as is practicable.

The data on the active substance and the insecticide products have demonstrated sufficient efficacy against a large range of insects (e.g. cockroaches and ants) for inclusion into Annex I to be recommended. Bendiocarb is a carbamate insecticide and some resistance to carbamates has been found to varying degrees, depending on the pest species and location. Data has been provided that shows that although there is a potential for resistance to occur the applicant has proposed an adequate resistance management strategy. In addition it is proposed that information is added to the label of bendiocarb-containing products to prevent/reduce the potential for resistance to occur (see section 3.3). It is considered that the submitted data and information on resistance are sufficient to support Annex I inclusion of the active substance. The physico-chemical properties of the active substance and biocidal products have been evaluated and are deemed acceptable for the appropriate use, storage and transportation of the active substance and biocidal products.

3.2. Decision regarding Inclusion in Annex I

That bendiocarb shall be included in Annex I to Directive 98/8/EC as an active substance for use in product-type 18 (Insecticides, acaricides and products to control other arthropods). The information outlined below will be included in the entry for Annex I inclusion:

Identity:

• IUPAC Name: 2,2-dimethyl-1, 3-benzodioxol-4-yl methylcarbamate • CAS No.: 22781-23-3 • EINECS No.: 245-216-8

Purity:

• 97 % w/w

Proposed product type:



• 18 (Insecticides, acaricides and products to control other arthropds)

Proposal for conditions of particular uses:

• In rooms where regular wet cleaning are envisaged crack and crevice treatments only. • Recommendations shall be made by the user that the treatment remains undisturbed for

a minimum period (to be defined by the pest being treated against to ensure that newly hatched offspring are exposed).

• Use outdoors shall be restricted to the treatment of wasp and wild bee nests where losses to drains can be prevented.

• No direct applications to soil are permitted. 3.3. Elements to be taken into account by Member States when authorising products

It is considered that, should bendiocarb receive Annex I inclusion, those aspects of the label claims for Ficam W that are not addressed in this evaluation, can be addressed at the product authorisation stage.

In addition it is considered that, the following three items of advice on resistance should be present on the label or associated leaflet for the associated biocidal product Ficam W and all bendiocarb containing products:

• Where an extended period of control is required, treatments should be alternated with products with different modes of action.

• Levels of effectiveness should be monitored, and instances of reduced effectiveness should be investigated for possible evidence of resistance, noting that sanitary conditions and the proximity of untreated refuse can contribute to the risk of re-infestation.

• In cases where label rates are correctly applied, but fail to give the expected level of control, and resistance is demonstrated, use of any product containing the same class of chemistry should cease.

It is proposed that Member States consider including on the product label for Ficam W (containing bendiocarb) information such as the following:

• When using, do not eat, drink or smoke. • Remove soiled clothing immediately. • Clean hands and face at work intervals and after work. • Work in an adequately ventilated room. • Do not breathe spray. • Wash any contamination from skin or eyes immediately. • Avoid excessive contamination of coveralls and launder regularly. • Unprotected persons and animals should be kept away from treated areas until dry. • Do not spray bed linen or other materials which come into direct contact with occupants

of the bed. • Do not apply to clothing and bedding.



• Do not handle treated fabrics until dry and air thoroughly before use. • Do not contaminate foodstuffs, eating utensils or food contact surfaces. • Wear suitable protective clothing, gloves and eye/face protection.

It is considered that adequate and suitable PPE for workers using Ficam W should include as a minimum:

• Respiratory protection which offers a 10-fold protection factor. • Hand protection: Chemical resistant gloves. • Eye protection: Chemical resistant goggles. • Skin and body protection: Impermeable coveralls

3.4. Requirement for further information

It is considered that the evaluation has shown that sufficient data have been provided to verify the outcome and conclusions, and permit the proposal for the inclusion of bendiocarb on to Annex I to Directive 98/8/EC.

3.5. Updating this Assessment Report

This assessment report may need to be updated periodically in order to take account of scientific developments and results from the examination of any of the information referred to in Articles 7, 10.4 and 14 of Directive 98/8/EC. Such adaptations will be examined and finalised in connection with any amendment of the conditions for the inclusion of bendiocarb in Annex I to the Directive.



Appendix I: List of endpoints Chapter 1: Identity, Physical and Chemical Properties, Classification and

Labelling

Active substance (ISO Common Name) Bendiocarb

Product-type 18 (Insecticides, acaricides and products to control other arthropods)

Identity

Chemical name (IUPAC) 2,2-dimethyl-1-3-benzodioxol-4-yl methylcarbamate

Chemical name (CA) Carbamic acid, methyl-, 2,3-(Isopropylidenedioxy) phenyl ester

CAS No 22781-23-3

EC No 245-216-8

Other substance No. CIPAC No. 232

Minimum purity of the active substance as manufactured (g/kg or g/l)

g/kg

970

g/l

-

% w/w

97

% v/v

-

Identity of relevant impurities and additives (substances of concern) in the active substance as manufactured (g/kg)

The identity and concentrations of the impurities in Bendiocarb, and the additives are confidential. This information is provided in the Confidential Annex document.

Molecular formula C11H13NO4

Molecular mass 223.23

Structural formula

N

O

O

OO



Physical and chemical properties

Melting point (state purity) 129 °C (purity: 98.5 %)

Boiling point (state purity) Not measurable, substance decomposes.

Temperature of decomposition 264 °C

Appearance (state purity) At 23 - 26 oC and 101.3 kPa:

Physical state: Crystalline powder (purity: 98.5 %) Colour: Beige (purity: 98.5 %) Odour: None (purity: 98.5 %)

Relative density (state purity) 1.29 at 20 °C (purity: 99.0 %)

Surface tension 63.29 mN/m at 20 ºC (purity: 98.9 %)

Vapour pressure (in Pa, state temperature) 1.9 x 10-3 Pa at 20 °C (purity: 99.8 %) 4.6 x 10-3 Pa at 25 °C (purity: 99.8 %)

Henry’s law constant (Pa m3 mol -1) 1.54 x 10-3 Pa m3 mol-1 (calculated)

Solubility in water (g/l or mg/l, state temperature) Results at 20 °C (purity: 99.3 %)

pH 3 – 5: 0.31 g/l pH 7: 0.28 g/l pH 9 - 11: 0.03 g/l (significant hydrolysis)

Solubility in organic solvents (in g/l or mg/l, state temperature)

Results at 20 °C (purity: 99.3 %): Acetone: 150 – 200 g/l Dichloromethane: 200 – 300 g/l Ethyl acetate: 60 – 75 g/l n-Hexane: 0.225 g/l Methanol: 75 – 100 g/l p-Xylene: 11.7 g/l

Stability in organic solvents used in biocidal products including relevant breakdown products

Not applicable, the product will not be formulated with organic solvents.

Partition coefficient (log POW) (state temperature) log Pow = 1.7 at 25 °C

The partition coefficient was determined to be independent of temperature and pH.

Hydrolytic stability (DT50) (state pH and temperature)

pH_5__: 1116 h (25 ºC)

major metabolite: pyrogallol (30 % of a.s)

pH_7__: 48.1 h (25 ºC)

major metabolite: NC 7312 (87.9 % of a.s)

pH_9__: 0.73 h (25 ºC)


Dissociation constant Not accessible as Bendiocarb hydrolyses rapidly in alkaline solution

UV/VIS absorption (max.) (if absorption > 290 nm Spectra confirm the chemical structure



state ε at wavelength)

Photostability (DT50) (aqueous, sunlight, state pH)

DT50 = 187 d (extrapolated for natural sunlight), major metabolite NC 7312 (max. ~ 12 %), with up to 40 % reported as a mixture of unidentified polar products that could not be isolated or identified separately.

Quantum yield of direct phototransformation in water at Σ > 290 nm

Not available

Flammability Bendiocarb is not highly flammable according to EC Test Method A.10. It shows no spontaneous combustion behaviour at temperatures up to 200 oC. Tests for flammability on contact with water and pyrophoric properties were not conducted, as experience in use show negative results would be obtained.

Explosive properties No positive results were obtained with respect to thermal and mechanical sensitivity.



Doc I – Overall Summary and Assessment

Classification and proposed labelling

with regard to physical/chemical data Not Classified

with regard to toxicological data T: R23: Toxic by inhalation T: R25: Toxic if swallowed Xn: R21: Harmful in contact with the skin

with regard to fate and behaviour data N: R53: May cause long-term adverse effects in the aquatic environment.

with regard to ecotoxicological data N: R50: Very toxic to aquatic organisms.

Chapter 2: Methods of Analysis Analytical methods for the active substance

Technical active substance (principle of method)

Impurities in technical active substance (principle of method)

High Performance Liquid Chromatography using UV detection for the analysis of Bendiocarb and impurities in the active substance and formulated product. The method was suitably validated.

Analytical methods for residues

Soil (principle of method and LOQ) High Performance Liquid Chromatography using Mass Spectrometry, for the analysis of Bendiocarb in soil. The method was suitably validated. Limit of quantification (LOQ): 5 µg kg-1

Air (principle of method and LOQ) Liquid Chromatography, using Mass Spectrometry, for the analysis of Bendiocarb in air. The method was suitably validated. Limit of quantification (LOQ) = 0.12 µg/m3

Water (principle of method and LOQ) High Performance Liquid Chromatography using UV detection for the analysis of Bendiocarb residues in drinking water. The method was suitably validated. Limit of quantification (LOQ): 0.1 µg/l

High Performance Liquid Chromatography using Mass Spectrometry, for the analysis of Bendiocarb in drinking and surface water. The method was suitably validated. Limit of quantification (LOQ): 0.05 µg/l

Body fluids and tissues (principle of method and LOQ)

Capillary Gas Chromatography, using Mass Selective Detection, for the analysis of Bendiocarb in whole blood. The method was suitably validated.

Limit of quantification (LOQ): 50 ng/ml

Food/feed of plant origin (principle of method and LOQ for methods for monitoring purposes)

Food/feed of animal origin (principle of method and LOQ for methods for monitoring purposes)

Relevant when an active substance is used to treat food-handling surfaces or to treat surfaces when uncovered food is present. This is not the case for bendiocarb, therefore, an analytical method is not required.

of 48


Chapter 3: Impact on Human Health

Absorption, distribution, metabolism and excretion in mammals

Rate and extent of oral absorption: In rats, following single (up to 10 mg kg-1) and repeated (0.125 mg kg-1 d-1) administration, bendiocarb was rapidly and extensively absorbed.

At these dose levels, an oral absorption value of 100 % is considered appropriate.

Rate and extent of dermal absorption: There are no data available on absorption following dermal exposure to bendiocarb. Data are available on two representative bendiocarb formulations. The dermal absorption of an aqueous dilution (Ficam W) and a dustable powder (Ficam D) were tested in vitro on human skin.

From these data, a worst-case dermal absorption value of 9 % bendiocarb has been chosen, although this will represent a very conservative approach. However, where refinement of the risk characterisation is necessary, the less conservative dermal absorption value of 4.4 % is applied. Additionally, a worst-case dermal absorption value of 0.4 % for bendiocarb applied as a dust is proposed for use, as appropriate. Again, where refinement of the risk characterisation is necessary, the less conservative dermal absorption value of 0.26 % is applied.

Rate and extent of inhalation absorption: There are no data on the absorption of bendiocarb following inhalation exposure. However, based on the almost complete absorption from the gastro-intestinal tract, it can be predicted that it will be well absorbed from the respiratory tract. Therefore, a worst-case default of 100 % absorption following inhalation exposure is proposed.

Distribution: Once absorbed, bendiocarb and/or its metabolites are widely distributed around the body.

Potential for accumulation: Bendiocarb does not appear to have potential for bioaccumulation.

Rate and extent of excretion: In the rat, elimination of bendiocarb and/or its metabolites after oral administration is rapid, occurs mainly in the urine and is complete by 48 hours after dosing.

Toxicologically significant metabolite(s) None

Acute toxicity

Rat LD50 oral Rat: 25-156 mg kg-1 in males and 27-40 mg kg-1 in females

Rat LD50 dermal Rat: 566 - 800 mg kg-1



Rat LC50 inhalation Rat: 0.61 mg l-1 in males and 0.47 mg l-1 in females

Skin irritation Not classified

Eye irritation Not classified

Skin sensitization (test method used and result) Negative in a Buehler test.

Repeated dose toxicity

Species/ target / critical effect Inhibition of erythrocyte and brain cholinesterase activity is considered to be the most sensitive marker of toxicity in rats and dogs.

Lowest relevant oral NOAEL / LOAEL NOAELacute/medium-term: 1.0 mg kg-1 d-1 (112 day dog study).

NOAELlong-term: 0.65 mg kg-1 d-1 (2 year dog study).

Lowest relevant dermal NOAEL / LOAEL NOAEL: 1.67 mg kg-1 d-1 (21 day rabbit study).

Lowest relevant inhalation NOAEL / LOAEL NOAEC: 1 mg m-3 equivalent to a systemic dose equivalent of 0.6 mg kg-1 d-1 (13 week rat study).

Genotoxicity Bendiocarb gave a positive result in an in vitro cytogenicity assay on human lymphocytes with metabolic activation. However, it was negative in several other in vitro (bacterial reverse mutation assays and unscheduled DNA synthesis assay) tests and in three in vivo assays (clastogenicity, chromosome aberrations in bone marrow and dominant lethal mutations in germ cells). The available data do not support classification for mutagenicity.

Carcinogenicity

Species/type of tumour No treatment-related tumours identified in lifetime studies in rats or mice exposed to bendiocarb in the diet.

lowest dose with tumours Not applicable.

Reproductive toxicity

Species/ Reproduction target / critical effect No treatment-related effects on fertility

Lowest relevant reproductive NOAEL / LOAEL >18 mg kg-1 d-1

Species/Developmental target / critical effect Post-implantation losses occurred only in the presence of maternal toxicity in both rats and rabbits. A slight delay in ossification in rabbit foetuses, secondary to maternal toxicity, was attributed to bendiocarb but was not sufficient to classify for developmental toxicity.

Developmental toxicity

Lowest relevant developmental NOAEL / LOAEL Rat: NOAEL of 2 mg kg-1 d-1 for maternal and foetal



effects

Rabbit: NOAEL of 1 mg kg-1 d-1 for maternal effects and 2.5 mg kg-1 d-1 for foetal effects.

Neurotoxicity / Delayed neurotoxicity

Species/ target/critical effect No signs of delayed neurotoxicity were reported in hens following a single oral gavage dose of bendiocarb that resulted in mortalities

Lowest relevant developmental NOAEL / LOAEL. NOAELneurotoxicity : >757 mg kg-1

Summary Value Study Safety factor

ADI (if residues in food or feed) Not Required N/A N/A

AEL (acute) 0.01 mg kg-1 d-1 112 d dog study 100

AEL (medium-term) 0.01 mg kg-1 d-1 112 d dog study 100

AEL (long-term) 0.0065 mg kg-1 d-1 2-year dietary study in the dog 100

Drinking water limit Not Required N/A N/A

ARfD (acute reference dose) Not Required N/A N/A

Acceptable exposure scenarios (including method of calculation)

Professional users Exposure route: Combined dermal and inhalation

Method of calculation: MOE and AEL

Values used in the assessment Scenario

MOE AEL Mixing/loading Ficam W from the HDPE container + application by spray

82 1.2

Mixing/loading Ficam W using sachets + application by spray

176

0.6

Production of active substance: N/A (Technical bendiocarb is manufactured outside the

EU)



Formulation of biocidal product Formulated infrequently in the EU over 5 days per annum. Production line is a closed system. Loading and packaging carried out in semi-venitlated areas by people wearing appropriate PPE. Neither inhalation or dermal exposure is expected.

Intended uses Ficam W is diluted with water and applied by spray to treat a wide spectrum of public health and stored-product insect pests.



Secondary exposure Exposure route: Dermal, inhalation and oral routes Method of calculation: MOE, AEL and reverse-reference 1. Acute/medium-term dermal exposure

NOAEL of 1.0 mg kg-1 d-1 (112-day oral dog study)

Infant Child Adult Scenario

MOE AEL MOE AEL MOE AEL Adult, child and infant come into contact with smooth, treated surfaces

312500 0.0003 344828 0.00029 454545 0.0002

Infant exposed to soft furnishings before vacuuming.

1493 0.067 N/A N/A N/A N/A

Infant exposed to soft furnishings after vacuuming.

16667 0.006 N/A N/A N/A N/A


435 0.23 769 0.13 833 0.12

Adult launders contaminated clothing N/A N/A N/A N/A 10000 0.01

2. Long-term dermal exposure

NOAEL of 0.65 mg kg-1 d-1 (2-year dietary study in dogs)


MOE AEL MOE AEL MOE AEL Adult, child and infant come into contact with smooth, treated surfaces

203125 0.0005 224138 0.0005 295455 0.0003

Infant exposed to soft furnishings before vacuuming.

970 0.1 N/A N/A N/A N/A

Infant exposed to soft furnishings after vacuuming.

10833 0.009 N/A N/A N/A N/A


283 0.35 500 0.2 542 0.18

Adult launders contaminated clothing N/A N/A N/A N/A 6500 0.02



3. Acute/medium-term oral exposure

NOAEL of 1.0 mg kg-1 d-1 (112-day oral dog study)

Infant Scenario

MOE AEL Contamination of hands and ingestion of deposits before vacuuming 50000 0.002

Contamination of hands and ingestion of deposits after vacuuming 500000 0.0002

NOAEL of 0.5 mg kg-1 (single oral administration in cats)

Scenario Reverse reference scenario Ingestion of residue from treated carpet before vacuuming

to achieve the NOAEL a kitten would need to ingest pure bendiocarb from 961.5 cm2 of treated carpet before vacuuming.

Ingestion of residue from treated carpet after vacuuming

to achieve the NOAEL a kitten would need to ingest pure bendiocarb from 11363.6 cm2 of treated carpet following vacuuming..

4. Long-term oral exposure


Infant Scenario

MOE AEL Contamination of hands and ingestion of deposits before vacuuming 32500 0.003

Contamination of hands and ingestion of deposits after vacuuming 325000 0.0003

5. Acute/medium-term inhalation exposure

13-week rat inhalation study, a NOAEC of 2 mg m-3 (equivalent to 0.6 mg kg-1 d-1)


MOE AEL MOE AEL MOE AEL

Inhalation of dislodged residues during vacuuming

92 1.08 102 0.98 162 0.62

6. Long-term inhalation exposure





MOE AEL MOE AEL MOE AEL

Inhalation of dislodged residues during vacuuming

100 1 110 0.91 176 0.57

Combined exposure Exposure route: Dermal, inhalation and oral routes Method of calculation: MOE and AEL Long-term NOAEL: 0.65 mg kg-1 d-1 (2-year dietary study in dogs)

Acute/medium-term NOAEL: 1.0 mg kg-1 d-1 (112-day oral dog study) for infrequent combined exposures


MOE AEL MOE AEL MOE AEL Long-term - Adult and

child exposed to dislodgeable residues. Adult laundering of

clothing.

N/A N/A 110 0.9 171 0.6

Acute/medium term- Adult exposed following

mixing/loading from HDPE containers,

spraying and dislosgeable residues

N/A N/A N/A N/A 86 1.17

Acute/medium-term- Adult exposed following

mixing/loading from sachets, spraying and dislosgeable residues

N/A N/A N/A N/A 133 0.75

Long-term - Infant exposed to dislodgeable

residues 81 1.2 N/A N/A N/A N/A

Non-professional users Not required as product is professional only.

Indirect exposure as a result of use N/A

Chapter 4: Fate and Behaviour in the Environment



pH_5__: 1116 h (25 ºC)

major metabolite: pyrogallol (30 % of a.s)

Hydrolysis of active substance and relevant metabolites (DT50) (state pH and temperature)

pH_7__: 48.1 h (25 ºC)


pH_9__: 0.73 h (25 ºC)


Photolytic / photo-oxidative degradation of active substance and resulting relevant metabolites

DT50 = 187 d (extrapolated for natural sunlight), major metabolite NC 7312 (max. ~ 12 %), with up to 40 % reported as a mixture of unidentified polar products that could not be isolated or identified separately.

Readily biodegradable (yes/no) No

Biodegradation in seawater No data

Distribution in water / sediment systems (active substance)

Arnold 1984: Bendiocarb was rapidly hydrolysed (99 % in 2 days) resulting in the formation of NC 7312 (2,2-dimethyl-l,3-benzodioxol-4-ol) which was further degraded.

Purser (1997a): Immediately after (14C)-bendiocarb application >97 % of applied radioactivity (AR) was recovered in the surface water. Over the incubation period a slow transfer of radioactive material to the sediment was observed with the surface water containing 31 to 35 % of applied radioactivity after 30 days. The radioactivity extracted from the sediment with acetonitrile increased from ca 3 % of applied radioactivity at day 0 to 7 to 13 % after 30 days. The major component in the surface water and sediment acetonitrile extracts in all samples analysed up to 7 days after application was (14C)-bendiocarb.

Distribution in water / sediment systems (metabolites)

Arnold 1984: The rate of degradation of NC 7312 was influenced by microcosm type and was greatly accelerated in the presence of sediment. The half- lives of NC 7312 were: <2 weeks (+ sediment), 6 weeks (unfiltered water) and an estimated 10 weeks (filtered water).

Purser (1997a): At 7 days NC 7312 was present at similar levels to that of bendiocarb in the sediment and water extracts. Thereafter, the proportion of parent compound decreased, such that at the end of the study period the amount detected declined to ca 7 % of applied radioactivity.

Mineralization Arnold 1984: The increased rate of 14CO2 evolution in the sediment/water microcosms (35 % in 8 weeks) compared with that in both non-filtered and filtered water alone (24 % and 7 % respectively) suggests enhanced microbial activity in the presence of sediment.



Purser (1997a): Between 21 and 30 days, however, significant amounts of the applied radioactivity were trapped in the ethanediol traps (2.8 to 4.7 %). The quantity of radioactivity in the ethanolamine traps increased with time, and contained a total of 20 to 22 % of the applied radioactivity after 30 days.

Non-extractable residues Arnold 1984: Non reported

Purser (1997a): Unextracted sediment residues increased from <0.1 % to 15 to 23 % of AR over the incubation period.

Route and rate of degradation in soil

Laboratory studies (range or median, with number of measurements, with regression coefficient)

DT50lab (12 °C aerobic): 9.9 (worst-case) or 6.5 (mean, n=2) [excluding sand soil]

DT90lab (20 °C, aerobic): Not reported

Mineralization (aerobic) 20 – 35 % on day 21 (Allen, 1989)

55 % after 26 d (Mackenzie and Allen, 1990)

DT50lab (20 °C, anaerobic): Not available.

degradation in the saturated zone: Not available.

Field studies (state location, range or median with number of measurements)

DT50f: Not available

DT90f: Not available

Anaerobic degradation Not available

Soil photolysis DT50: 7.8 h (extrapolated for natural sunlight)

Non-extractable residues Soil bound material also significantly increased in the irradiated samples from 15.8 % at 3.5 hours to 40.5 % at 21.1 hours.

Relevant metabolites - name and/or code, % of applied a.i. (range and maximum)

No significant amounts of degradation products could be detected in the acetonitrile extracts from the irradiated or non-irradiated soil samples. HPLC analysis showed that the radioactivity was not due to bendiocarb or its hydrolysis products (NC 7312 and pyrogallol).

Soil accumulation and plateau concentration Not available

Laboratory studies (range or median, with number of measurements, with regression coefficient)

DT50lab (12 °C aerobic): 6.5 (mean)

Adsorption/desorption



Ka , Kd

Kaoc , Kdoc

pH dependence (yes / no) (if yes type of

dependence)

Ka 0.1 – 1.85, Kd 0.24 – 4.44

Kaoc 33.35 (geometric mean), Kdoc 66.26 (geometric mean)

No

Fate and behaviour in air

Direct photolysis in air DT50 = 13.2 h estimated

Quantum yield of direct photolysis Not available

Photo-oxidative degradation in air Latitude: .N/A.. Season: ...N/A. DT50 ..N/A

Volatilization Not applicable.

Monitoring data, if available

Soil (indicate location and type of study)

Surface water (indicate location and type of study)

Ground water (indicate location and type of study)

Air (indicate location and type of study)

Not available

Chapter 5: Effects on Non-target Species

Toxicity data for aquatic species (most sensitive species of each group) ACTIVE: Bendiocarb

Species Time-scale Endpoint Toxicity

Fish

Cyprinodon variegatus 96 h LC50 0.86 mg l-1

Salmo gairdneri 78 d NOEClarval growth 0.07 mg l-1

Invertebrates

Daphnia magna 48 h EC50 0.038 mg l-1

Daphnia magna 21 d NOECreproduction 0.00088 mg l-1

Algae

Pseudokirchneriella subcapitata

72 h ErC50

NOErC*

0.408 mg l-1

0.087 mg l-1

* - not considered acceptable for risk assessment due to failure in controls after 48 h to maintain exponential growth rate.

Microorganisms

Activated sewage sludge 3 h EC50 70.1 mg l-1 (corrected for hydrolysis)



Toxicity data for aquatic species (most sensitive species of each group) Metabolite: NC 7312

Species Time-scale Endpoint Toxicity

Fish

Salmo gairdneri 96 h LC50 10 mg l-1

Invertebrates

Daphnia magna Straus 48 h EC50 25.4 mg l-1

Algae

Desmodesmus subspicatus 72 h ErC50

NOErC

88.3 mg l-1

0.95 mg l-1

Microorganisms

Not available

Effects on earthworms or other soil non-target organisms

Acute toxicity to Eisenia fetida andrei

14 d LC50 188 mg kg-1 soil

Reproductive toxicity to …………………………

Not available



Effects on soil micro-organisms

Nitrogen mineralization Not available Carbon mineralization NOEC > 50 mg l-1

Effects on terrestrial vertebrates

Acute toxicity to mammals

Acute toxicity to birds

Dietary toxicity to birds

Reproductive toxicity to birds

Not available

Effects on honeybees

Acute oral toxicity Not available

Acute contact toxicity Not available

Effects on other beneficial arthropods

Acute oral toxicity Not available

Acute contact toxicity Not available

Acute toxicity to ………………………………….. Not available

Bioconcentration

Bioconcentration factor (BCF) 5.55 (calculated)

6.0 (experimentally determined)

Depration time (DT50)

(DT90)

> 89 % in 1d

> 97 % in 3d

Level of metabolites (%) in organisms accounting for > 10 % of residues

No identification was possible due to negligible

Chapter 6: Other End Points

No other end points are considered relevant.

Appendix II: List of Intended Uses



Bendiocarb has been evaluated for its use in insecticide formulations for controlling a wide range of crawling and flying insects such as cockroaches, houseflies, mosquitoes, ants, beetles, fleas, wasps, moths, crickets and silverfish (product type 18).

The Applicant has submitted 1 biocidal product for evaluation in support of Annex I inclusion:

• Ficam W – a concentrate product containing 80 % pure bendiocarb. The product is diluted with water to control a wide spectrum of public health and stored-product insect pests. The product is intended for use both indoors and outdoors by professional operators only.

Data on the active substance bendiocarb and the biocidal product have demonstrated sufficient efficacy against insects for inclusion onto Annex I to be recommended. Data so far from published studies has demonstrated the occurrence of resistance to bendiocarb in insects (cockroaches, houseflies and mosquitoes), and the variability in the extent of such resistance. As resistance to bendiocarb is a well-known and long-established problem, measures to manage resistance are well-established. These measures, which are detailed in Document II-A (Section 2.5), should be taken into account when authorising products containing bendiocarb.




Appendix III: List of studies

See separate document.