IPCS INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY Health and Safety Guide No. 82 CARBENDAZIM HEALTH AND SAFETY GUIDE UNITED NATIONS ENVIRONMENT PROGRAMME INTERNATIONAL LABOUR ORGANISATION WORLD HEALTH ORGANIZATION WORLD HEALTH ORGANIZATION, GENEVA 1993 This is a companion volume to Environmental Health Criteria 149: Carbendazim Published by the World Health Organization for the International Programme on Chemical Safety (a collaborative programme of the United Nations Environment Programme, the International Labour Organisation, and the World Health Organization) This report contains the collective views of an international group of experts and does not necessarily represent the decisions or the stated policy of the United Nations Environment Programme, the International Labour Organisation, or the World Health Organization WHO Library Cataloguing in Publication Data Carbendazim : health and safety guide. (Health and safety guide ; no. 82) 1.Benzimidazoles - standards 2.Benzimidazoles - toxicity 3.Fungicides, Industrial - standards 4.Fungicides, Industrial - toxicity I.Series ISBN 92 4 151082 X (NLM Classification: WA 240) ISSN 0259-7268 The World Health Organization welcomes requests for permission to reproduce or translate its publications, in part or in full. Applications and enquiries should be addressed to the Office of Publications, World Health Organization, Geneva, Switzerland, which will be glad to provide the latest information on any changes made to the text, plans for new editions, and reprints and translations already available. (c) World Health Organization 1993 Publications of the World Health Organization enjoy copyright protection in accordance with the provisions of Protocol 2 of the Universal Copyright Convention. All rights reserved. The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the Secretariat of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. The mention of specific companies or of certain manufacturers' products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters. CONTENTS INTRODUCTION 1. PRODUCT IDENTITY AND USES 1.1. Identity 1.2. Physical and chemical properties 1.3. Analytical methods 1.4. Production and uses 2. SUMMARY AND EVALUATION 2.1. Exposure 2.2. Uptake, metabolism, and excretion 2.3. Effects on organisms in the environment 2.4. Effects on experimental animals and in vitro test systems 2.5. Effects on humans 3. CONCLUSIONS AND RECOMMENDATIONS 4. HUMAN HEALTH HAZARDS, PREVENTION AND PROTECTION, EMERGENCY ACTION 4.1. Human health hazards, prevention and protection, first aid 4.1.1. Advice to physicians 4.1.2. Health surveillance advice 4.2. Explosion and fire hazards 4.3. Storage 4.4. Transport 4.5. Spillage 4.6. Disposal 5. HAZARDS FOR THE ENVIRONMENT AND THEIR PREVENTION 6. SUMMARY OF CHEMICAL SAFETY INFORMATION 7. CURRENT REGULATIONS, GUIDELINES, AND STANDARDS 7.1. Previous evaluations by international bodies 7.2. Exposure limit values 7.3. Specific restrictions 7.4. Labelling, packaging, and transport 7.5. Waste disposal BIBLIOGRAPHY INTRODUCTION The Environmental Health Criteria (EHC) monographs produced by the International Programme on Chemical Safety include an assessment of the effects on the environment and on human health of exposure to a chemical or combination of chemicals, or physical or biological agents. They also provide guidelines for setting exposure limits. The purpose of a Health and Safety Guide is to facilitate the application of these guidelines in national chemical safety programmes. The first three sections of a Health and Safety Guide highlight the relevant technical information in the corresponding EHC. Section 4 includes advice on preventive and protective measures and emergency action; health workers should be thoroughly familiar with the medical information to ensure that they can act efficiently in an emergency. The section on regulatory information has been extracted from the legal file of the International Register of Potentially Toxic Chemicals (IRPTC) and from other United Nations sources. The target readership includes occupational health services, those in ministries, governmental agencies, industry, and trade unions who are involved in the safe use of chemicals and the avoidance of environmental health hazards, and those wanting more information on this topic. An attempt has been made to use only terms that will be familiar to the intended user. However, sections 1 and 2 inevitably contain some technical terms. A bibliography has been included for readers who require further background information. Revision of the information in this Guide will take place in due course, and the eventual aim is to use standardized terminology. Comments on any difficulties encountered in using the Guide would be very helpful and should be addressed to: The Director International Programme on Chemical Safety World Health Organization 1211 Geneva 27 Switzerland 1. PRODUCT IDENTITY AND USES 1.1 Identity Common name: Carbendazim Chemical formula: C9H9N3O2 Chemical structure:Common trade names (including formulations): Carbendazim, Delsene, Bavistin, Corbel, Konker, Bedazim, Derosal, Kombat, Kemdazin, Carbendor, Hoe 017411, Cekudazim, Equitdazin, Aimcozim (some are formulations with other pesticides) CAS chemical name: Methyl (1H-benzimidazol-2-yl)carbamate Synonyms: Carbendazol (ZMAF), methyl-2- benzimidazole carbamate (MBC, MCB, BCM, BMC) CAS registry number:
10605-21-7 RTECS registry number: DD 6500000 Other information: Carbendazim is a metabolite of other benzimidazole fungicides 1.2 Physical and chemical properties Carbendazim, a white crystalline solid, is a systemic fungicide of the benzimidazole family. It melts at approximately 250 °C and has a vapour pressure of <1 × 10-9 mbar at 25 °C. Carbendazim is essentially insoluble in water (8 mg/litre) at pH 7 and 25 °C. It is stable under normal storage conditions. 1.3 Analytical methods Analyses of environmental samples and residues are performed by extraction with an organic solvent and purification of the extract by a liquid-liquid partitioning procedure. Residue levels may be determined by HPLC or immunoassay. 1.4 Production and uses In 1988, the estimated global sale of carbendazim was approximately 3600 tonnes. It is the most widely used member of a family of fungicides known as the benzimidazoles. Carbendazim is a systemic and broad spectrum fungicide that is currently registered for use for the control of diseases in fruit trees, nut crops, vegetables, cereals, tropical crops and ornamentals, turf, and many field crops. It is formulated as an aqueous dispersion, aqueous suspension, flowable water dispersible granules, and a wettable powder. 2. SUMMARY AND EVALUATION 2.1 Exposure The primary source of carbendazim exposure for the general human population is dietary intake. Estimated human exposures, based on dietary analysis and crop tolerance values, indicate an expected intake substantially below the recommended Acceptable Daily Intake (ADI), based on no-observed-effect levels in animal tests. Occupational exposure during manufacture or crop application is within acceptable levels. Primary routes of exposure are inhalation and dermal contact and both are easily reduced and controlled by the use of dust masks and protective clothing. 2.2 Uptake, metabolism, and excretion Carbendazim is well absorbed after oral, but not dermal, exposure. Absorbed carbendazim is rapidly metabolized and eliminated in the urine and faeces. 2.3 Effects on organisms in the environment Because of its stability on plant material, lasting several weeks, carbendazim may become accessible to organisms feeding on leaf litter. Soil and sediments may contain residues of carbendazim for up to 3 years. However, the strong adsorption of carbendazim on soil and sediment particles reduces the exposure of terrestrial and aquatic organisms. Carbendazim applied at recommended application rates has little effect on soil microbial activity. Some adverse effects have been reported in groups of fungi. Carbendazim is algicidal and was toxic for aquatic organisms and fish in laboratory studies. Carbendazim was toxic for earthworms in laboratory studies, when applied at realistic exposure concentrations, and, in the field, at recommended levels of use. Its toxicity for birds is low and it is relatively non-toxic for honey bees. 2.4 Effects on experimental animals and in vitro test systems The toxicity of carbendazim through ingestion is low, with an LD50 in rats of 10 000 mg/kg. Inhalation toxicity is very low (4-h LC50 >50 mg/litre) and toxicity through dermal contact, moderate (LD50 >10 000 mg/kg). Carbendazim is not a skin irritant or sensitizer in guinea-pigs, but it may cause eye irritation. In long-term feeding studies on rats, hepatotoxicity and testicular toxicity were observed at dose levels greater than 500 mg/kg (equivalent to 25 mg/kg body weight per day). Hepatotoxicity was observed in dogs at dose levels greater than 300 mg/kg. Decreases in sperm counts and reduced fertility were found in rats at dose levels of 50 mg/kg body weight per day or more. No effect on the male reproductive system was found at a dose level of 500 mg/kg (25 mg/kg body weight per day) in the rat. Carbendazim caused increases in malformations and anomalies in the rat at dose levels greater than 10 mg/kg. Decreases in fetal weight and increases in fetal lethality were also found in the rat at dose levels of 20 mg/kg body weight per day or more. Carbendazim resulted in an increased incidence of hepatocellular tumours in certain strains of mice known to have a high background rate for these tumours. No carcinogenic effect was observed in rats. Carbendazim is not a heritable gene mutagen. However, it produced numerous chromosome aberrations or aneuploidy, caused by the same mechanism that is responsible for its fungicidal activity. Carbendazim was found to bind to fungal tubulin but to have a low affinity for mammalian tubulin. 2.5 Effects on humans No inadvertent poisoning of agricultural or factory workers has been documented. 3. CONCLUSIONS AND RECOMMENDATIONS Estimated human exposures, based on dietary analysis and crop tolerance values, indicate the expected intake to be below the recommended Acceptable Daily Intake (ADI), based on no-observed-effect levels in animal tests. Given the toxicity levels of carbendazim and the low dietary exposure levels, it is unlikely that it poses a significant health risk for the general population. Occupational exposures during manufacture or crop application are below the established Threshold Limit Values. Carbendazim is strongly adsorbed on soil organic matter and persists in the soil for up to 3 years. Carbendazim persists on leaf surfaces and, therefore, in leaf litter. Earthworms have been shown to be adversely affected (population and reproductive effects) at recommended rates of application. There is no information on other soil or litter arthropods that would be similarly exposed. The high toxicity for aquatic organisms in laboratory tests is unlikely to be seen in the field, because of the low bioavailability of sediment-bound residues of carbendazim. However, no information is available on sediment-living species, which would receive high exposure. 4. HUMAN HEALTH HAZARDS, PREVENTION AND PROTECTION, EMERGENCY ACTION 4.1 Human health hazards, prevention and protection, first aid 4.1.1 Advice to physicians The acute toxicity of carbendazim for humans is believed to be very low. There is no specific antidote. In case of skin contact, immediately wash skin with soap and water. In case of eye contact, immediately flush eyes with plenty of water for at least 15 min. 4.1.2 Health surveillance advice No specific health surveillance information is available. 4.2 Explosion and fire hazards 4.2.1 Explosion hazards Like most organic powders or crystals, under severe dust conditions, this material may form explosive mixtures in air. 4.2.2 Fire hazards Evacuate personnel to a safe area, keeping them away from, and upwind of, the fire. Wear self-contained breathing apparatus. Use water or dry chemical to extinguish the fire and water spray to cool the tank/container. 4.3 Storage Store in well ventilated area. Keep container tightly closed. Do not store or consume food, drink, or tobacco in areas where they may become contaminated with this material. 4.4 Transport All products should be transported in secure vehicles according to local regulations. Containers should be sound, adequately labelled, and kept dry. 4.5 Spillage Sections 4.1 and 4.2 of this Guide should be reviewed before proceeding with clean up. Use appropriate personnel protective equipment during clean up. Prevent liquid from entering sewers, waterways, or low areas. Shovel, or sweep, up. 4.6 Disposal Treatment, storage, transportation, and disposal must be in accordance with applicable local regulations. Remove nonusable solid materials and/or contaminated soil for disposal in an approved and permitted landfill. Do not flush into surface water or sanitary sewer systems. Do not reuse container; dispose of according to approved local procedures. 5. HAZARDS FOR THE ENVIRONMENT AND THEIR PREVENTION The strong adsorption of benomyl and its degradation product carbendazim on particulates in soil and aquatic sediment reduces its bioavailability. However, earthworm populations have been reduced at recommended application rates. There is no information on toxicity to other soil invertebrates or aquatic invertebrates living in sediments. Residues on particulates may persist for years. Excessive application of benomyl to the same area should be avoided to prevent build up of residues. Disposal should avoid contamination of both soil and surface water sediments. 6. SUMMARY OF CHEMICAL SAFETY INFORMATION This summary should be easily available to all health workers concerned with, and users of, carbendazim. It should be displayed at, or near, entrances to areas where there is potential exposure to carbendazim, and on processing equipment and containers. The summary should be translated into the appropriate language(s). All persons potentially exposed to the chemical should also have the instructions in the summary clearly explained. Space is available for insertion of the National Occupational Exposure Limit, the address and telephone number of the National Poison Control Centre, and local trade names. SUMMARY OF CHEMICAL SAFETY INFORMATION CARBENDAZIM Methyl (1H-benzimidazol-2-yl)carbamate C9H9N3O2 PHYSICAL PROPERTIES OTHER CHARACTERISTICS Relative molecular mass 191.2 White, crystalline solid Melting point (°C) 250 Water solubility (mg/litre, pH 7, 25 °C) 8.0 Specific density 0.27 Relative vapour pressure (Pa, 20 °C) <1 x 10-7 Explosion limit (LEL, g/litre in air) 0.13 HAZARD/SYMPTOM PREVENTION AND PROTECTION FIRST AID SKIN: Irritation Wear long-sleeved shirt and long Remove contaminated clothing, wash with trousers, chemical resistant gloves, soap and water, and obtain medical shoes or boots treatment EYE: Irritation Wear safety goggles or face shield Flush with plenty of water for at least 15 min and obtain medical treatment INHALATION: Irritation Avoid breathing dust or spray mist Remove from exposure; obtain medical attention INGESTION: Do not eat, drink, chew or smoke Obtain medical attention during use; keep out of reach of children HAZARD/SYMPTOM PREVENTION AND PROTECTION FIRST AID ENVIRONMENT: Presents a risk Contamination of water and soil for aquatic and soil organisms should be avoided by proper methods of application, storage, transport, and waste disposal SPILLAGE STORAGE FIRE AND EXPLOSION Wear appropriate protective Store in well ventilated area; keep Under severe dust conditions, carbendazim equipment during clean up; prevent container tightly closed; store in may form explosive mixtures in air; liquid from entering sewers, original container only, away from in case of fire, evacuate personnel waterways, or low areas; shovel, other pesticides, fertilizer, food, to a safe area, wear self-contained or sweep, up or animal feed; do not allow to breathing apparatus, use water or dry become wet during storage chemical to extinguish fire, and cool tank/container with water spray WASTE DISPOSAL Treatment, storage, transportation, National occupational exposure and disposal must be in accordance limit: with applicable local regulations; waste disposal must be in an approved and permitted landfill or by incineration; do not flush to National Poison Control Centre: surface water or sanitary sewer system 7. CURRENT REGULATIONS, GUIDELINES AND STANDARDS 7.1 Previous evaluations by international bodies Carbendazim was evaluated by the Joint FAO/WHO Meeting on Pesticide Residues (JMPR) in 1973, 1975, 1978, 1983, and 1988. The 1978 meeting agreed that the Maximum Residue Limits for benomyl, carbendazim, and thiophanate-methyl should be combined and expressed as carbendazim. The 1983 meeting evaluated benomyl toxicology and set the following carbendazim no-observed-effect levels (NOELs) and ADI: Rat 500 mg/kg diet, equivalent to 25 mg/kg body weight Dog 100 mg/kg diet, equivalent to 2.5 mg/kg body weight Rat (teratology) 30 mg/kg body weight per day (benomyl). The estimated ADI for carbendazim was established at 0-0.01 mg/kg body weight. 7.2 Exposure limit values Exposure limit values are presented in the table on p. 20. 7.3 Specific restrictions There are no specific restrictions on the use of carbendazim. 7.4 Labelling, packaging, and transport European Economic Community legislation requires labelling as a dangerous substance using the symbol Xn.Table 1. Exposure limit values Medium Specification Country/ Exposure limit Values organization description Food plant (specified) Brazil Acceptable limit (AL) 0.1-0.5 mg/kg Food plant (specified) Germany Maximum residue limit (MRL) 0.2-7.0 mg/kg Food plant (specified) India Maximum tolerable concentration (MTC) 0.1-5.0 mg/kg Food plant (specified) Russian Maximum residue limit (MRL) 0.1 mg/kg Federation Food cereals Sweden Maximum tolerable concentration (MTC) 0.1 mg/kg Food plant (specified) United Maximum residue limit (MRL) 0.1-10.0 mg/kg Kingdom Food FAO Acceptable daily intake (ADI) 0.02 mg/kg body weight Food plant (specified) FAO Maximum residue limit (MRL) 0.1-50 mg/kg Air occupational Russian Maximum allowable concentration (MAC) 0.1 mg/m3 (aerosol) Federation Water surface water Russian Maximum allowable concentration (MAC) 0.1 mg/litre Federation a From: IRPTC Legal File (1992). The following label statements are required: R40 - Possible risk of irreversible effects S36/37 - Wear suitable protective clothing and gloves Carbendazim has been classified as a Marine Pollutant and a Flammable Solid by the International Maritime Organization. 7.5 Waste disposal European Economic Community regulations require that carbendazim and/or its container must be disposed of as hazardous waste. BIBLIOGRAPHY FAO/WHO (1985a) Benomyl. In: Pesticide residues in food - 1983: evaluations 1983. Rome, Food and Agriculture Organization of the United Nations, pp. 7-46. FAO/WHO (1985b) Carbendazim. In: Pesticide residues in food - 1983: evaluations 1983. Rome, Food and Agriculture Organization of the United Nations, pp. 89-121. FAO/WHO (1988a) Benomyl. In: Pesticide residues in food - 1988: evaluations 1988. Rome, Food and Agriculture Organization of the United Nations, pp. 5-15. FAO/WHO (1988b) Carbendazim. In: Pesticide residues in food - 1988: evaluations 1988. Rome, Food and Agriculture Organization of the United Nations, pp. 41-54. ILO (1991) Occupational exposure limits for airborne toxic substances. Geneva, International Labour Organisation (Occupational Safety and Health Series, No. 37). UNEP IRPTC (1992) IRPTC legal file 1992. Geneva, International Register of Potentially Toxic Chemicals, United Nations Environment Programme. WHO (1993) Environmental Health Criteria 148: Benomyl. Geneva, World Health Organization. WHO (1993) Environmental Health Criteria 149: Carbendazim. Geneva, World Health Organization.
See Also: Toxicological Abbreviations Carbendazim (EHC 149, 1993) Carbendazim (ICSC) Carbendazim (WHO Pesticide Residues Series 3) Carbendazim (Pesticide residues in food: 1976 evaluations) Carbendazim (Pesticide residues in food: 1977 evaluations) Carbendazim (Pesticide residues in food: 1978 evaluations) Carbendazim (Pesticide residues in food: 1983 evaluations) Carbendazim (Pesticide residues in food: 1985 evaluations Part II Toxicology) Carbendazim (Pesticide residues in food: 1995 evaluations Part II Toxicological & Environmental) Carbendazim (Pesticide residues in food: 1995 evaluations Part II Toxicological & Environmental) Carbendazim (JMPR Evaluations 2005 Part II Toxicological)