Review findings report



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carbendazim
REVIEW findings report

The reconsideration of the active constituent carbendazim, registration of products containing carbendazim and approvals of their associated labels

© Australian Pesticides and Veterinary Medicines Authority 2012


ISBN 978-0-9873591-0-0 (electronic)
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This publication is available from the APVMA website: www.apvma.gov.au.

FOREWORD

The Australian Pesticides and Veterinary Medicines Authority (APVMA) is an independent statutory authority with responsibility for the regulation of agricultural and veterinary chemicals in Australia. Its statutory powers are provided in the Agvet Code scheduled to the Agricultural and Veterinary Chemicals Code Act 1994.

The APVMA can reconsider the approval of an active constituent, the registration of a chemical product or the approval of a label for a container for a chemical product at any time. This is outlined in Part 2, Division 4 of the Agvet Code.

A reconsideration may be initiated when new research or evidence has raised concerns about the use or safety of a particular chemical, a product containing that chemical, or its label.

The reconsideration process includes a call for information from a variety of sources, a review of that information and, following public consultation, a decision about the future use of the chemical or product. The information and technical data required by the APVMA to review the safety of both new and existing chemical products must be derived according to accepted scientific principles, as must the methods of assessment undertaken.

In undertaking reconsiderations (hereafter referred to as reviews), the APVMA works in close cooperation with advisory agencies including the Office of Chemical Safety in the Department of Health and Ageing, the Department of Sustainability, Environment, Water, Population and Communities, and state departments of agriculture, as well as other expert advisers as appropriate.

The APVMA has a policy of encouraging openness and transparency in its activities, and welcomes community involvement in decision making. The publication of review reports is a part of that approach.

The APVMA also makes these reports available to the regulatory agencies of other countries as part of bilateral agreements. The APVMA recommends that countries receiving these reports not use them for registration purposes unless they are also provided with the raw data from the relevant applicant.

The basis for the current reconsideration is whether the APVMA is satisfied that continued use of the active constituent carbendazim and products containing carbendazim in accordance with the instructions for their use:

  • would not be an undue hazard to the safety of people exposed to it during its handling

  • would not be likely to have an effect that is harmful to human beings.

This document relates to all products containing carbendazim.

The Review Findings, containing the APVMA’s assessments (including the technical reports) for all registrations and approvals relating to carbendazim, are available from the APVMA website at www.apvma.gov.au/products/review/index.php

ACRONYMS AND ABBREVIATIONS

g gram

ADI Acceptable Daily Intake

APVMA Australian Pesticides and Veterinary Medicines Authority

ARfD Acute Reference Dose

bw bodyweight

Codex FAO/WHO Codex Alimentarius Commission

EC emulsifiable concentrate

EFSA European Food Safety Authority

FAISD Handbook of first aid instructions, safety directions and warning statements for agricultural and veterinary chemicals

JMPR Joint FAO/WHO Meeting on Pesticide Residues

kg kilogram

L litre

LOAEL Lowest Observable Adverse Effect Level

LOEL Lowest Observable Effect Level

mg milligram

mg/kg bw/day mg/kg bodyweight/day

mL millilitre

MRL Maximum Residue Limit

NEDI National Estimated Dietary Intake

NHMRC National Health and Medical Research Council

OCS Office of Chemical Safety

OHS occupational health and safety

PPE personal protective equipment

SC suspension concentrate

SUSMP Standard for the Uniform Scheduling of Medicines and Poisons

US United States

US EPA United States Environmental Protection Agency

WHO World Health Organization

WP wettable powder

CONTENTS


EXECUTIVE SUMMARY

Carbendazim is a systemic benzimidazole fungicide that was used to control fungal diseases on pulses, fruits, macadamia nuts, cucurbits, pastures, roses, timber and turf; it was also used in post-harvest storage of fruits. Carbendazim is both a metabolite and breakdown product of benomyl and a breakdown product of thiophanate-methyl in plants and the environment.

Carbendazim product registrations and label approvals were under review as part of the Australian Pesticides and Veterinary Medicine Authority’s (APVMA) Chemical Review Program because of specific concerns about public health, occupational health and safety and residues in treated produce.

The review of carbendazim was commenced as part of a joint review of carbendazim and thiophanate-methyl. However, the review of thiophanate-methyl was separated from the joint review and completed in November 2010.

This document summarises the findings of the carbendazim review. All public comment received since the release of the Preliminary Review Findings documents (May 2011) was considered in the preparation of this report.

Review assessments

Toxicological assessment



The toxicological assessment for the review of carbendazim was undertaken by the Office of Chemical Safety (OCS), which considered all the toxicological data and related information submitted for the review.

The OCS examined the available data and concluded that carbendazim has the potential to cause birth defects and impair human fertility at levels above a threshold dose.

As these effects are observed only above a threshold dose, which is significantly higher than the public and occupational health standards set for carbendazim in this review, the OCS had no objection on public or occupational health grounds to the continued approval of the active ingredient carbendazim and the continued registration of products containing carbendazim.

Public health standards

The OCS review reaffirmed the existing acceptable daily intake (ADI) for carbendazim of 0.03 mg/kg bw/day (milligrams of carbendazim per kilogram of bodyweight per day), established an acute reference dose (ARfD) of 0.05 mg/kg/bw for carbendazim (no Australian value had previously been established) and recommended a new National Health and Medical Research Council (NHMRC) health-based guideline value for carbendazim in drinking water of 0.09 mg/L (milligrams per litre) (similar to the present health value of 0.10 mg/L).

The poison schedule of carbendazim was revised from Schedule 6 to Schedule 7 of the Standard for the Uniform Scheduling of Medicines and Poisons (SUSMP) in January 2011, as recommended by the OCS in 2009.

As of January 2010, the warning statement on products containing carbendazim includes a caution about male infertility in addition to the caution for women of child-bearing age, as recommended by the OCS in 2009. The OCS also advised that existing first aid instructions for carbendazim remained appropriate.

The use of carbendazim on publicly accessible turf (eg. parks, ovals, sport fields) was suspended by the APVMA in January 2010. This was based on advice from the OCS that this use pattern was likely to present an unacceptable risk.

Occupational health and safety assessment



As part of the occupational health and safety assessment for the review of carbendazim, the OCS considered all the occupational health and safety data and related information that had been submitted for the review.

The APVMA considered the advice provided by the OCS and found that safety directions should be updated to include face shields for all liquid formulation products and the use of respirators for wettable powder products during mixing and loading of the concentrate.

Based on exposure modelling at the maximum anticipated daily work rates, the OCS had no objections to the continuation of uses for spray operators applying carbendazim with airblast or groundboom equipment. The OCS did not support the application of carbendazim to ornamental plants and turf by hand-held equipment as the risks could not be mitigated even with the correct personal protective equipment (gloves and overalls).

The OCS risk assessment determined that re-entry exposure in grapes, stone fruits, custard apples, apples, pears, turf and roses was unacceptable, and these use patterns could no longer be supported. Additional re-entry statements were also established for pasture, red clover and strawberries.

Residues assessment



The residue assessment for the review of carbendazim was undertaken by the APVMA Residue Section, which considered all the residue data and information submitted for the review, and took into account the recommendations made by the OCS in its toxicological assessment.

The residues report noted that consumers of large portions of a treated commodity in a single day could potentially be exposed to levels of carbendazim above the ARfD, if the instructions on the existing labels for use of carbendazim on grapes, citrus, custard apples, mangoes, cucurbits (including melons), pome fruits (apples and pears) and stone fruit were followed. Dietary exposure to levels of carbendazim above the ARfD could occur even in the absence of maximum residue limit (MRL) violations. The APVMA suspended the labels of all carbendazim products in January 2010 and issued new use instructions that prohibit these uses.

For certain other existing label uses, residues data were not available to ensure that the established MRLs were appropriate. These MRLs will be replaced with temporary MRLs during a two-year phase-out period for these uses. This relates to all uses for bananas, strawberries, ginger seed pieces, sugar cane setts, pasture, red clover and subterranean clover.

Use patterns for chickpeas, faba beans, lentils, vetch and macadamias were acceptable. As a result, these uses were affirmed as a result of this review.

Environmental assessment



The scope of this review did not include an assessment of the environmental effects of carbendazim. This decision was based on advice from the then Department of Environment and Heritage on 24 April, 2006, that did not provide the APVMA with a basis to consider that carbendazim could be likely to have a harmful effect on the environment.

The APVMA assessed adverse experience reports alleging the involvement of carbendazim in fish developmental problems. However, given the lack of reliable supporting data, the reports did not lead to a decision to extend this current review to include the environmental aspects of the use of products containing carbendazim.

Carbendazim has been also placed on the Priority List for Spray Drift Review and a spray drift review of carbendazim will initiated by the APVMA in due course.

Review findings

On the basis of the evaluation of the submitted data and information, the review outcomes for carbendazim may be summarized as follows:

  1. the active constituent approval can be affirmed (Table ).

  2. older label approvals will be cancelled and the relevant particulars of the most recently approved label for each product will be varied (Table ). Many of these variations were applied by the APVMA in January 2010 via a suspension of labels and issuance of new instructions. The relevant label particulars have been varied as follows:

  • Apply the warning statement regarding male infertility: ‘Contains carbendazim which causes birth defects and (irreversible) male infertility in laboratory animals. Avoid contact with carbendazim’ (included in the suspension of January 2010).

  • Delete instructions for treatment of turf from the labels because of unacceptable potential risks to the public (included in the suspension of January 2010).

  • Delete instructions for use on grapes, citrus, custard apples and mango, cucurbits (including melons), pome fruits and stone fruit from labels because of unacceptable potential dietary risks to humans (included in the suspension of January 2010).

  • Delete instructions for use on bananas, strawberries, ginger seed pieces, sugar cane setts, pasture, red clover and subterranean clover from labels because of a lack of data to assess potential residues.

  • Delete instructions for use on roses because of unacceptable potential OHS risks.

  • Amend the safety directions to include:

      1. the statements ‘Very dangerous, particularly the concentrate’ and ‘Poisonous if absorbed by skin contact, inhaled or swallowed’

      2. the use of a face shield when mixing and loading 80–500 g/L suspension concentrate (SC) products

      3. the use of a full face-piece respirator (with dust cartridge or canister) when mixing and loading wettable powder products

      4. additional instructions ‘Will damage the eyes and skin’ for the 75 g/L timber protection product.

(c) Affirm label approvals that have been varied to comply with the findings of the review.

(d) Affirm registrations of those products with appropriately varied labels. Currently there are 12 registered products (Table ) to be affirmed once labels have been appropriately varied.

INTRODUCTION



The Australian Pesticides and Veterinary Medicines Authority (APVMA) has reviewed the approval of the active constituent carbendazim, registered products containing carbendazim and the associated label approvals for products containing carbendazim. This document summarises the data evaluated and the findings of the review. This report supersedes the PRF published in May 2011.

Regulatory status of carbendazim in Australia



Carbendazim (methyl benzimidazol-2-ylcarbamate) is a systemic benzimidazole fungicide previously used in Australia to control a broad range of diseases on pulses, fruits, macadamias, turf, pastures and ornamentals. It was also used in post-harvest food storage, as a pre-planting ginger and sugar cane treatment and as a timber treatment fungicide. Carbendazim is both a metabolite and breakdown product of benomyl (not registered since December 2004) and a breakdown product of thiophanate-methyl in plants and the environment.

Carbendazim products are available as suspension concentrates (SC), emulsifiable concentrates (EC) and wettable powders (WP). There are 18 registered carbendazim products and eight active constituent approvals at the time of writing, August 2012 (these are listed in Appendix A).

Agricultural products contain 500 g/L (grams per litre) of carbendazim and were previously approved to be applied by various ground-based methods such as spraying (low and high volume), dipping (either post-harvest on fruits or pre-planting in the case of ginger and sugar cane), with multiple applications depending upon the crop and disease.

Three timber products were included in the review; they were formulated as carbendazim (75 to100 g/L) in combination with zinc napthenate (370 g/L), oxine copper (80 g/L) or chlorothalonil (450 g/L). They are applied by dipping and spraying. Of these timber products, only the 75 g/L emulsifiable concentrate (EC) carbendazim formulation remained registered at the time of preparation of the review findings.

The review of carbendazim and thiophanate-methyl commenced in February 2007 and covered occupational health and safety (OHS), residues and public health concerns. This followed the APVMA review of the related compound benomyl, which commenced in 2003 but was not completed because of the voluntary cancellation of all products and actives in December 2004.

The thiophanate-methyl review was separated from the carbendazim review and has been finalised (November 2010). This is because the toxicological outcomes and findings of the review were significantly different for these two actives. It appears that thiophanate-methyl is not significantly metabolised to carbendazim in mammals, and there were no concerns with respect to birth defects or male infertility.

The APVMA suspended the label approval of all products containing carbendazim in May 2007 and issued new instructions for the use of products containing carbendazim, which included revised safety directions for the 500 g/L products and the addition of a birth defect warning statement. This suspension of labels was renewed in June 2009 for those products with labels that had not been updated to include those new instructions.

The APVMA acted again in January 2010 to suspend all labels of carbendazim and issue new instructions for dealing with or using products with suspended labels. These new instructions included an extended warning statement (that included male infertility effects as well as developmental defects), signal heading and storage instructions appropriate for Schedule 7, and the removal of uses for turf and on certain food crops. This action was based on preliminary advice received from the OCS and the APVMA Residues Section.

Table : Formulation types of carbendazim products included in this review



Formulation type

Level of active constituent

Product type

EC (emulsifiable concentrate)

75 g/L with 90 g/L zinc napthenate and 370 g/L n-methyl-2-pyrrolidone

Timber preservative

SC (suspension concentrate)

100 g/L with 450 g/L chlorothalonil

Timber preservative

SC (suspension concentrate)

80 g/L with 80 g/L oxine copper and 428 g/L n-methylpyrrolidone

Timber preservative

SC (suspension concentrate)

500g/L

Agricultural plant protection, post-harvest storage and turf uses.

WP (wettable powder)

500 g/L

Agricultural plant protection and post-harvest storage

Reasons for carbendazim review

The active constituent carbendazim, all products containing carbendazim and their associated labels were placed under review because of concerns about public health, OHS and residues.

This followed the APVMA review of the related compound, benomyl, which commenced in 2003 but was not completed because of the voluntary cancellation of all products and active ingredients in December 2004.

Scope of the review



The extent of the review was scoped on the basis of the reasons for the nomination of carbendazim, the information already available on this chemical and the approved uses of product containing carbendazim in Australia.

The basis for a reconsideration of the registration and approvals for a chemical is whether the APVMA can be satisfied that the requirements for continued registration and approval are being met, as prescribed by the Agvet Codes scheduled to the Agricultural and Veterinary Chemicals Code Act 1994. In this case, these requirements are that the use of any product containing carbendazim in accordance with the instructions for its use:

  • would not be an undue hazard to the safety of people exposed to it during its handling; and

  • would not be likely to have an effect that is harmful to human beings.

The APVMA reviewed the toxicological, OHS and residue conditions of product registrations and active constituent approvals for carbendazim.

The APVMA also considered whether carbendazim product labels carried adequate instructions and warning statements; instructions include:

  • the circumstances in which the product should be used

  • how the product should be used

  • times when the product should be used

  • frequency of the use of the product

  • the withholding period after the use of the product

  • disposal of the product and its container

  • safe handling of the product.

On the basis of these concerns, it was decided to review the active constituent approvals, product registrations and label approvals for carbendazim, under the provisions of Part 2, Division 4 of the Agvet Codes.

Regulatory options



There can be three possible outcomes to the reconsideration of the approvals of the active constituent carbendazim, registration of products containing carbendazim and all associated labels. Based on the information reviewed the APVMA may be:

  • satisfied that the products and their labels continue to meet the prescribed requirements for registration and approval, and therefore affirms the registrations and approvals

  • satisfied that the conditions to which the registration or approval is currently subject can be varied in such a way that the requirements for continued registration and approval will be complied with, and therefore varies the conditions of registration or approval

  • not satisfied that the requirements for continued registration and approval continue to be met, and suspends or cancels the registrations and/or approvals.

APPROVEd carbendazim USE PATTERNS

  1. Introduction

At the time of preparation of these review findings, there were eight active constituent approvals for carbendazim and 18 registered products containing the active constituent carbendazim.

Details of these active constituents and products can be found in Appendix A, Tables 21-24.

Of the 18 previously registered products containing carbendazim, 17 contained 500 g/L carbendazim, 16 were suspension concentrates, one was a wettable powder (500 g/kg), and one timber product was an emulsifiable concentrate (75 g/L).

Six of the active constituent approvals and 11 of the product registrations are subject to this review. Those active constituent approvals and product registrations that were approved after the commencement of the review are not included in the review but are subject to the outcomes of the review.

Use patterns



When this review started, carbendazim products were registered for use on field crops, ornamentals, tree and vine crops, post-harvest dipping, pre-planting treatments and timber preservation. There were no products registered for use in home gardens.

Field crop and ornamental uses included application by boom spray on pulses (chickpeas, faba beans, lentils and vetch), cucurbits, pasture, red clover, subterranean clover, strawberries, turf and roses for the treatment of various fungal diseases.

Tree and vine crop uses included application by boom spray or airblast on apples and pears (pome fruits), custard apples, grapes, macadamia nuts and stone fruit for the treatment of various fungal diseases.

Post-harvest uses included dipping of apples and pears, bananas, citrus fruit, mangoes, rockmelons and stone fruit to prevent post-harvest rots and moulds.

Pre-planting treatments included dipping or spraying of cut seed pieces of ginger and sugar cane.

Timber protection uses included dipping, boron bath or spraying of sawn lumber, poles and rounds to control sap stain, mould and decay fungi.

Many of these uses were effectively removed from use in January 2010, when the APVMA acted to suspend all labels of products containing carbendazim and issued new instructions for use that included the restraint: ‘DO NOT apply to turf, grapes, cucurbits (including melons), citrus fruit, custard apple, mango, pome fruit (apples or pears) or stone fruit (including cherries).’

Public submissions



In response to the release of the Preliminary Review Findings (PRF) report in May 2011, the APVMA received one submission from the then Queensland Department of Employment, Economic Development and Innovation (DEEDI) (now DAFF) about the proposed findings. One of the concerns raised in this submission was that the methodology used to determine the dietary risk for carbendazim was too conservative compared to other international regulatory bodies. Examination of this issue by the APVMA found additional studies were considered by the OCS during its assessment of carbendazim compared to the identified overseas assessments. In addition, the OCS included gavage studies which resulted in a more conservative estimate of dietary risk during its assessment. This is consistent with the OCS policy when conducting risk assessments for the APVMA.

In addition, the following warning statement was queried by DEEDI:

Contains carbendazim which causes birth defects and (irreversible) male infertility in laboratory animals. Avoid contact with carbendazim’. However, this warning is consistent with current labelling of similar products (e.g. procymidone).

Changes to the re-entry statements for pasture, red clover and strawberries were also suggested for improved clarity. However, these uses are not supported following the residues assessment of carbendazim (refer Section 4.3) therefore the changes to re-entry statements are not required.

SUMMARY OF DATA ASSESSMENTS



The following provides a summary of the data assessments for carbendazim (refer to Volumes 2 and 3, published May 2011).

Toxicology

Introduction

The toxicological assessment for the review of carbendazim was undertaken by the Office of Chemical Safety (OCS). The OCS considered all the toxicological data and related information submitted for the review. The toxicological findings are summarised below. These are unchanged from the May 2011 PRF for carbendazim.

Carbendazim was nominated for review under the APVMA’s Chemical Review and Adverse Experience Reporting Program because of concerns over its potential to cause birth defects and impair human fertility and the consequent risks to workers using carbendazim products. In reviewing this concern, the OCS examined all of the available data and concluded that carbendazim has the potential to cause birth defects and impair human fertility. They concluded that a warning statement should be required for products containing carbendazim. As these effects are observed only above a threshold dose well in excess of the public and occupational health standards set for carbendazim in this review, the OCS had no objection on public or occupational health grounds to the continued registration of all existing carbendazim products. However, a number of use patterns are no longer supported by the OCS, as set out in the findings of this review.

Evaluation of toxicology

The toxicological database for carbendazim consists primarily of toxicity tests that have been conducted using animals. In interpreting the data, it should be noted that toxicity tests generally use doses that are high compared with likely human exposures. The use of high doses increases the likelihood that potentially significant toxic effects will be identified. Findings of adverse effects in any one species do not necessarily indicate such effects might be generated in humans. From a conservative risk assessment perspective, however, adverse findings in animal species are assumed to represent potential effects in humans, unless convincing evidence of species specificity is available. Where possible, considerations of the species-specific mechanisms of adverse reactions weigh heavily in the extrapolation of animal data to likely human hazard. Equally, consideration of the risks to human health must take into account the likely human exposure levels compared with those, usually many times higher, which produce effects in animal studies. Toxicity tests should also indicate dose levels at which the specific toxic effects are unlikely to occur. Such dose levels as the no observable effect level (NOEL) are used to develop acceptable limits for dietary or other intakes (ADI and ARfD) at which no adverse health effects in humans would be expected.

4.1.1 Toxicology hazard profile



Carbendazim is a mitotic spindle poison that interferes with the process of cell division by blocking the action of the protein tubulin and results in chromosomes not dividing correctly. When present in cells at levels above a threshold dose, carbendazim can induce chromosome damage (broken or duplicated chromosomes). This mechanism of action affects rapidly dividing cells and is likely to be responsible for the testicular toxicity observed in some laboratory animals (as chromosome duplication is part of the process of sperm generation) and teratogenicity (birth defects observed when carbendazim was force-fed to laboratory animals at high doses).

Carbendazim-induced teratogenic effects (affecting the head and eyes) were observed in rats following gavage (force feeding by stomach tube) dosing at 30 mg/kg bw/day (no effects seen at 10 mg/kg bw/day); however, exposure via the diet at greater than 700 mg/kg bw/day did not cause significant developmental or reproductive toxicity. A similar profile is seen for benomyl.

Thus these effects were observed only after giving animals single large doses by stomach tube. They did not occur when the compound was mixed in with their food. This difference probably arises because a single large dose in the stomach cannot be detoxified by the liver or excreted from the body quickly enough to prevent it from crossing the placenta and causing malformations in the developing foetus. However, animals exposed to a sustained dose in their diet are able to metabolise (detoxify) and excrete the chemical so that levels are not high enough to cross the placental barrier and thus affect the developing foetuses.

Testicular toxicity is considered to be another critical endpoint for carbendazim. In two studies in rats, a single dose of 50 mg/kg bw was sufficient to induce either an increase in the frequency of micronuclei in spermatids or premature release of germ cells two days post-exposure, atrophy of seminiferous tubules, decreased seminiferous tubule diameter, and abnormal growth of efferent ductules. These effects persisted for at least 70 days post-exposure. A NOEL could not be established for testicular toxicity from the available studies, therefore an extra safety factor was applied to the lowest observable effect level (LOEL) value.

The OCS also concluded that there was no evidence that carbendazim is carcinogenic.

4.1.2 Conclusions



Active approvals

No change is required to the approval status of carbendazim.

Product registration

There is no objection on public and occupational health grounds to the continued registration of several use patterns of existing carbendazim products. The use of carbendazim on ornamentals is no longer supported on OHS grounds, and the use on turf is no longer supported from both an occupational and public health perspective. From a re-entry perspective, use on grapes, stone fruits, custard apples, apples, pears, turf and roses is no longer supported.

Health standards

The present review reaffirmed the current ADI for carbendazim of 0.03 mg/kg bw/day, based on a NOEL of 2.5 mg/kg bw/day from a two-year dog study and applying a safety factor of 100. The NOEL is based on chronic hepatitis observed at the next highest dose (12.5 mg/kg bw/day) and is protective of developmental and testicular effects observed at higher doses.

The OCS set a new ARfD of 0.05 mg/kg/bw for carbendazim by applying a safety factor of 1000 to the LOEL of 50 mg/kg bw derived from a study on testicular toxicity in rats.

It was recommended that the National Health and Medical Research Council (NHMRC) revise the current Health Value for carbendazim in drinking water to 0.09 mg/L. The existing NHMRC health value is 0.1 mg/L.

Poisons schedule

The OCS also recommended that the poison schedule of carbendazim be revised from Schedule 6 to Schedule 7 of the Standard for Uniform Scheduling of Medicines and Poisons (SUSMP). This was considered by the National Drugs and Poisons Schedule Committee in October 2009 and January 2010 and implemented on 01 January 2011. In addition, the scheduling of several products that are not regulated by the APVMA (paints, jointing compounds and sealants) was considered, and the cut-off value for exemption from scheduling was reduced from 0.5% to 0.1% carbendazim.

Products in Schedule 7 have additional controls on their sale and supply and must bear the signal heading ‘Dangerous Poison’ and the storage instructions: ‘Store in a locked room or place away from children, animals, food, feedstuffs, seed and fertilisers.’

Warnings, first aid and safety directions

The OCS recommended that all registered products containing carbendazim should bear the following warning statement: ‘Contains carbendazim which causes birth defects and (irreversible) male infertility in laboratory animals. Avoid contact with carbendazim.’

The OCS determined that the existing first aid instructions for carbendazim remain appropriate.

Occupational health and safety



4.2.1 Overview

The OHS assessment for the review of carbendazim was undertaken by the OCS, which considered all the OHS data and information submitted for the review. The OHS findings are summarised below.

The OCS recommended that the APVMA should be satisfied that persons involved in preparing and applying carbendazim products, according to the revised label directions (details below), would not be likely to suffer from adverse effects.

However, based on the likelihood of toxicologically unacceptable levels of dermal and oral exposure to the public, uses of carbendazim on parks, golf courses, bowling greens and other sport-playing fields, as well as on commercial turf, should cease.

The following uses of carbendazim are supported with minor changes to the Safety Directions (details below):

  • application to field crops by boom spray

  • application to orchard crops by airblast

  • application to plant materials by dipping

  • application to timber by spraying and dipping.

The following uses of carbendazim are no longer supported, from an OHS perspective:

  • application to ornamental plants and commercial turf by hand-held equipment.

The following uses of carbendazim are supported without changes to the current use pattern, with a re-entry period of ‘until the spray has dried’, based on the occupational health risk assessment for application and re-entry:

  • cucurbits

  • chickpeas

  • faba beans

  • lentils

  • macadamia nuts.

The following uses of carbendazim are supported by the OCS with a re-entry period of ‘until the spray has dried’ unless wearing appropriate PPE (cotton overalls and chemical-resistant gloves):

  • pasture

  • red clover

  • strawberries.

4.2.2 Worker exposure during mixing, loading and application

The OCS OHS assessment found that operators mixing and loading suspension concentrate (SC) 80–500 g/L and wettable powder (WP) carbendazim products should wear gloves because of the potential for slight skin irritation. In addition, face shields should be worn during this process to prevent accidental ingestion of the SC formulation. Respirators should be worn during mixing and loading of WP formulations to mitigate the risk of inhalation and accidental ingestion.

The assessment found that operators applying carbendazim are likely to be exposed mainly by the dermal and inhalational routes. Based on exposure modelling, even at the maximum anticipated daily work rates, spray operators applying carbendazim with airblast or groundboom equipment are not heavily exposed, and engineering controls are not required to protect them. Therefore, the OCS has no objections to the continuation of these uses when appropriate personal protective equipment is worn.

The OCS found that it is likely that operators applying carbendazim to ornamental plants and turf by hand-held equipment will be significantly exposed to the chemical. Even with the application of personal protective equipment (gloves and overalls), this risk cannot be mitigated. Therefore, the OCS does not support these uses.

4.2.3 Worker exposure during re-entry



Carbendazim has a long half-life on foliage (up to six months), and therefore occupational re-entry exposure can occur for a significant length of time following application. The OCS risk assessment found that re-entry exposure in grapes, stone fruits, custard apples, apples, pears, turf and roses is unacceptable, and recommended that these use patterns can no longer be supported. Furthermore, additional re-entry statements are required for pasture, red clover and strawberries to mitigate the risk of exposure to foliar residues on re-entry.

The OCS recommended the following re-entry statement for the use of carbendazim on cucurbits, chickpeas, faba beans, lentils and macadamia nuts:

‘Do not allow entry into treated areas until the spray has dried, unless wearing cotton overalls buttoned to the neck and wrist (or equivalent clothing) and chemical resistant gloves. Clothing must be laundered after each day's use.’

The OCS supported the use of carbendazim on pasture, red clover and strawberries with the following re-entry statements, which include a requirement to wear chemical resistant gloves after the spray has dried. This assessment was based on several pre-season applications and the high contact activities of harvesting for strawberries and handweeding for pasture and red clover.

‘Do not allow entry into treated areas until the spray has dried, unless wearing cotton overalls buttoned to the neck and wrist (or equivalent clothing) and chemical resistant gloves. Clothing must be laundered after each day's use.’

‘Do not allow entry into treated areas after the spray has dried, unless wearing chemical resistant gloves.’

However, the residue assessment did not support the continued use of carbendazim products on strawberries, pasture and red clover (refer below) therefore this specific re-entry statement is not required.

Residues



The residues assessment for the review of carbendazim was undertaken by the APVMA Residues Section. The residues assessment is summarised below.

The residues report noted that the use of carbendazim according to the instructions on the previously approved product labels for grapes, citrus, custard apples, mangoes, cucurbits (including melons), pome fruits and stone fruit could result in consumers of large portions of these commodities ingesting levels of carbendazim above the ARfD established by the OCS. Dietary exposure to levels of carbendazim above the ARfD could occur even in the absence of maximum residue limit (MRL) violations. These concerns have effectively been dealt with by suspensions and new use instructions including label restraints issued in January 2010 and February 2012.

The report notes that for certain other existing label uses, residues data are not available to ensure that the established MRLs are appropriate. It recommends that these MRLs be replaced with temporary MRLs during a two-year phase-out period. This relates to all uses for bananas, strawberries, ginger seed pieces, sugar cane setts, pasture, red clover and subterranean clover.

Use patterns for chickpeas, faba beans, lentils, vetch and macadamias are acceptable. It is proposed that these be affirmed as a result of this review.

The chronic dietary exposure to carbendazim is estimated by the national estimated daily intake (NEDI) calculation, which encompassed all registered and temporary uses of the chemical and the mean daily dietary consumption data derived from the 1995 National Nutrition Survey of Australia. The NEDI calculation is made in accordance with World Health Organization (WHO) Guidelines and is a conservative estimate of dietary exposure to chemical residues in food. On the basis of carbendazim uses supported by this review, the NEDI for carbendazim is equivalent to 4 per cent of the ADI and thus is acceptable.

On the basis of an assessment of registered and permitted carbendazim uses in food production, available residues data and application of the revised acute reference dose, the Residues report recommended the following:

  1. The following use patterns be deleted from labels because of the risks from short-term dietary exposure and the MRL for such uses being inappropriate:

  • grapes: all uses

  • citrus fruit: all uses

  • custard apple: all uses

  • mango: all uses

  • cucurbits: all uses

  • pome fruit: all uses

  • stone fruit: all uses.

    Note: These uses were effectively removed in January 2010 when the APVMA acted to suspend all labels of products containing carbendazim and issued new instructions for use that included the restraint: ‘DO NOT apply to turf, grapes, cucurbits (including melons), citrus fruit, custard apple, mango, pome fruit (apples or pears) or stone fruit (including cherries)’.



  1. The following use patterns be deleted from labels as data are not available to ensure current MRLs are appropriate and that human health is protected. These uses will be subject to a two year phase-out period for those cancelled labels that are consistent with the previous suspensions.

  • banana – all uses

  • strawberries – all uses

  • ginger – all uses

  • sugar cane – all uses

  • pasture and clover – all uses.

  1. The following established use patterns are supported by a contemporary risk assessment:

  • pulses (chickpeas, faba beans, lentils and vetch) – to control chocolate spot and grey mould

  • macadamia nuts – to control macadamia husk spot

  • the grazing withholding periods for macadamia plantations should be four weeks.

  1. MRLs that are no longer associated with a registered or permitted use will be removed from the MRL Standard.

The following entries (Table 2) will need to be established in the MRL Standard for carbendazim:

Table : MRL Standards based on the review of carbendazim



MRL Table 1

Compound

Food

MRL (mg/kg)

Carbendazim

MO 0105

PE 0112

TN 0669

MM 0095

ML 0106

PO 0111

PM 0110

VD 0070

Edible offal (mammalian)

Eggs

Macadamia nuts

Meat [mammalian]

Milks

Poultry, Edible offal of

Poultry meat

Pulses

0.2

*0.1

0.1

0.2

*0.1

*0.1

*0.1

0.5

MRL Table 3

Compound

Residue

Carbendazim

Sum of carbendazim and 2-aminobenzimidazole, expressed as carbendazim

MRL Table 4










Compound

Animal feed commodity

MRL (mg/kg)

Carbendazim

AL 0157

Legume animal feeds

25



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