IPCS INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY
Health and Safety Guide No. 81
BENOMYL
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
148: Benomyl
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
Benomyl: health and safety guide.
(Health and safety guide ; no. 81)
1.Benomyl - standards 2.Benomyl - toxicity 3.Fungicides, Industrial-
standards 4.Fungicides, Industrial - toxicity
I.Series
ISBN 92 4 151081 1 (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
4.2.1. Explosion hazards
4.2.2. 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: Benomyl
Chemical formula: C14H18N4O3
Chemical structure:
Common trade names
(including formulations): Benlate, Tersan, Fungicide 1991,
Fundazol
CAS chemical name: Carbamic acid, [1-(butylamino)
carbonyl]-1H-benzimidazol-2-yl]-,
methyl ester
Synonyms: Methyl 1-(butylcarbamoyl)-2-
benzimidazolecarbamate
CAS registry number: 17804-35-2
RTECS registry number: DD647500
Primary metabolite in
mammals and degradation
product in the environment: Carbendazim
1.2 Physical and chemical properties
Benomyl, a tan coloured crystalline solid, is a systemic fungicide
of the benzimidazole family. It decomposes just after melting at 140
œC and has a vapour pressure of <5.0 × 10-6 Pa at 25 °C. Benomyl
is essentially insoluble in water (3.6 ppm) at pH 5 and 24 °C. It is
stable under normal storage conditions, but will decompose to
carbendazim in water.
1.3 Analytical methods
Analyses of environmental samples and determination of residues are
performed by extraction with an organic solvent, purification of the
extract by a liquid-liquid partitioning procedure, and conversion of
the residue to carbendazim. Residue levels can be determined using
HPLC or immunoassay.
1.4 Production and uses
In 1991, the estimated value of the worldwide sales of benomyl was
US$290 million. This was about 50% of the global market for
benzimidazole products. Carbendazim (20%) and thiophanate-methyl
(20%) mainly account for the rest of the benzimidazole market.
Benomyl is a systemic and broad spectrum fungicide that is currently
registered for use in more than 50 countries on more than 70 crops
for the control of diseases in fruit trees, nut crops, vegetables,
cereals, tropical crops and ornamentals, turf, and many field crops.
It is marketed as a wettable powder and as a dry flowable
formulation (dispersible granules).
2. SUMMARY AND EVALUATION
2.1 Exposure
Dietary intake is the primary source of benomyl exposure for the
general human population. Estimates, 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 exposures during manufacture or crop application are
below established Threshold Limit Values. Primary routes of exposure
are inhalation and dermal contact, both of which are easily reduced
and controlled by the use of dust masks and protective clothing.
2.2 Uptake, metabolism, and excretion
Benomyl is well absorbed after oral, but not dermal, exposure.
Absorbed benomyl is rapidly metabolized and eliminated in the urine
and faeces.
2.3 Effects on organisms in the environment
Because they remain stable for several weeks on plant material, both
benomyl and 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.
Benomyl, at recommended application rates, has little effect on soil
microbial activity. Some adverse effects have been reported in
groups of fungi. Benomyl is algicidal and was toxic for aquatic
organisms and fish in laboratory studies.
Benomyl was toxic for earthworms in laboratory studies at realistic
exposure concentrations and when used at recommended levels in the
field. Its toxicity for birds is low and its degradation product
carbendazim is "relatively non-toxic" for honey bees.
2.4 Effects on experimental animals and in vitro test systems
The toxicity of benomyl via ingestion is very low, with an LD50 in
rats of >10 000 mg/kg. It is moderately toxic via inhalation (4-h
LC50 >4 mg/litre) and via dermal contact (LD50 >2000 mg/kg).
Application to the shaved skin of guinea-pigs produced sensitization
and mild skin irritation. Application to the eyes of rabbits
produced mild eye irritation.
The no-observed-effect level (NOEL) was 2500 mg/kg (2500 ppm), the
highest dose tested in a long-term dietary study on rats. In mice,
both benomyl and its metabolite carbendazim induced hepatocellular
tumours in certain strains of mice known to have a high background
rate for these tumours. No carcinogenic effect was observed in rats.
Reduced testicular weight, lowered sperm counts, and reduced
fertility have been observed in studies on laboratory animals. The
NOEL for reproductive effects was 15 mg/kg, in a study on male rats.
Benomyl is embryotoxic in rats and mice and has been shown to
adversely effect postnatal development at dose levels greater than
15.6 mg/kg in the rat, when administered by gavage.
Benomyl is not a heritable gene mutagen. However, it produced
numerous chromosome aberrations or aneuploidy. This was caused by
the mechanism through which benomyl exerts its fungicidal activity.
Benomyl was found to bind to fungal tubulin but had a low affinity
for mammalian tubulin.
2.5 Effects on humans
The mammalian toxicity of benomyl is low . No inadvertent poisoning
of agricultural or factory workers has been documented. The primary
toxic effect of benomyl is dermal sensitization and contact
dermatitis. These effects can be reduced by wearing long-sleeved
shirts, long trousers, and gloves.
3. CONCLUSIONS AND RECOMMENDATIONS
Estimates of 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. As both the toxicity of
benomyl and the dietary exposure levels are low, 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. The primary toxic
effects of benomyl under these conditions of exposure are dermal
sensitization and contact dermatitis, but these effects can be
significantly reduced by limited exposure. Benomyl is rapidly
converted to carbendazim in various environmental compartments.
Carbendazim is strongly adsorbed on soil organic matter and persists
in the soil for up to 3 years. It persists on leaf surfaces and,
therefore, in leaf litter. Earthworms have been shown to be
adversely affected (population and reproductive effects) at
recommended application rates. 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 the sediment-living species that receive the highest
exposure.
4. HUMAN HEALTH HAZARDS, PREVENTION AND PROTECTION, EMERGENCY
ACTION
4.1 Human health hazards, prevention and protection, first aid
The human health hazards associated with certain types of exposure
to benomyl, together with preventive and protective measures and
first-aid recommendations, are listed in the Summary of Chemical
Safety Information (section 6).
4.1.1 Advice to physicians
The acute toxicity of benomyl for humans is believed to be very low.
There is no specific antidote. In case of skin contact, immediately
wash the 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
The primary toxic effects of benomyl are dermal sensitization and
contact dermatitis. Contaminated skin should be monitored for signs
of skin irritation.
4.2 Explosion and fire hazards
4.2.1 Explosion hazards
Like most organic powders or crystals, under severe dusting
conditions, this material may form explosive mixtures in air.
Hazardous gases/vapours produced during a fire include
n-butylisocyanate.
4.2.2 Fire hazards
Evacuate personnel to a safe area, keeping them away from, and
upwind of, fire. Wear self-contained breathing apparatus. Use water
or dry chemical to extinguish fire and water spray to cool
tank/container.
4.3 Storage
Store in a 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.
Never allow benomyl to become wet during storage. This may lead to
certain chemical changes that could increase its toxicity
(lacrimation because of the formation of butyl isocyanate) and
reduce the effectiveness of benomyl as a fungicide.
4.4 Transport
All products should be transported in secure vehicles following
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 non-usable
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 the soil and aquatic sediment reduces
its bioavailability. However, earthworm populations have been
reduced by benomyl applied at recommended rates. There is no
information on its toxicity for 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 the 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, benomyl. It should be displayed at, or
near, entrances to areas where there is potential exposure to
benomyl, 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.
BENOMYL
Carbamic acid, [1-(butylamino) carbonyl]-1 H-benzimidazol-2-yl]-methyl ester
C14H18N4O3
PHYSICAL PROPERTIES OTHER CHARACTERISTICS
Relative molecular mass 290.3 Tan coloured, crystalline solid; high humidity or moisture
Melting point (°C) 140 levels and/or high temperatures can lead to the
Boiling point (°C) decomposes generation of n-butyl isocyanate, a strong lacrimator
Water solubility (mg/litre, pH 5, 25°C) 3.6
Specific density 0.38
Relative vapour pressure (Pa, 25 °C) <5.0 × 10-6
Explosion limit (LEL, g/litre in air) 0.05
HAZARD/SYMPTOMS PREVENTION AND PROTECTION FIRST AID
SKIN: Irritation, possible Wear long-sleeved shirt and long Remove contaminated clothing, wash with
sensitization trousers, chemical resistant gloves, soap and water and obtain medical treatment;
shoes or boots treat as an allergic dermatitis
EYES: 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/SYMPTOMS PREVENTION AND PROTECTION FIRST AID
ENVIRONMENT: Presents Contamination of water and soil should
a risk for aquatic and soil be avoided by proper methods of
organisms application, storage, transport, and
waste disposal
SPILLAGE: STORAGE FIRE AND EXPLOSION
Wear appropriate protective Store in well ventilated area; keep Benomyl is a flammable solid; keep away
equipment during clean up; prevent container tightly closed; store in from sources of ignition; under severe dust
liquid from entering sewers, original container only, away from conditions, benomyl may form explosive
waterways, or low areas; shovel, or other pesticides, fertilizer, food, mixtures in air; hazardous gas/vapour
sweep, up or animal feed; do not allow to produced in a fire contains n-butylisocyanate;
become wet during storage in case of fire, evacuate personnel to a safe
area, wear self-contained breathing apparatus,
use water or dry 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
dispose of non-usable solid
matter, contaminated soil
and/or empty containers in an National Poison Control Centre:
approved and permitted landfill
or by incineration; do not flush into
surface water or sanitary sewer
systems
7. CURRENT REGULATIONS, GUIDELINES AND STANDARDS
7.1 Previous evaluations by international bodies
Benomyl was evaluated by the Joint FAO/WHO Meeting on Pesticide
Residues in 1973, 1975, 1978, 1983, and 1988. The 1978 meeting
agreed that the Maximum Residue Levels for benomyl, carbendazim, and
thiophanate-methyl should be combined and expressed as carbendazim.
The 1983 meeting evaluated benomyl toxicity and set the following
benomyl no-observed-effect levels (NOELs) and ADI:
Rat 2500 mg/kg (2500 ppm) in the diet,
equivalent to 125 mg/kg body weight
Dog 100 mg/kg (100 ppm) (carbendazim) in the
diet, equivalent to 2.5 mg/kg body weight
Rat (teratology) 30 mg/kg body weight per day.
The estimated ADI for benomyl was established at 0-0.02 mg/kg body
weight.
7.2 Exposure limit values
Exposure limit values are presented in the table on pp. 20-21.
7.3 Specific restrictions
There are no specified restrictions on the use of benomyl.
7.4 Labelling, packaging, and transport
European Economic Community legislation requires labelling as a
dangerous substance using the symbol Xn.
Exposure limit values
Medium Specification Country/ Exposure limit description Value
organization
Food apples & pears Argentina Maximum limit (MXL) 5 mg/kg
Food plant (specified) Brazil Acceptable limit (AL) 0.05-35 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 food products Kenya Maximum residue limit (MRL) 0.2-15.0 mg/kg
(specified)
Food food products Russian Maximum residue limit (MRL) 0.1-0.5 mg/kg
(specified) Federation
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/kga
Air occupational Argentina Maximum permissible concentration (MPC) 10 mg/m3
Air occupational Mexico Maximum limit (8-h) (MXL) 10 mg/m3
Maximum limit (15-min) (MXL) 10 mg/m3
Air occupational Russian Preliminary safety level (PSL) 0.01 mg/m3
Federation
Medium Specification Country/ Exposure limit description Value
organization
Air ambient Russian Maximum allowable concentration (MAC) 0.35 mg/m3 (1 time/day)
environment Federation 0.05 mg/m3 (daily
average)
Air occupational USA Time-weighted average (TWA) 10mg/m3
Water surface water Russian Maximum allowable concentration (MAC) 0.5 mg/litre
Federation
Air occupational United Time-weighted average (8-h) (TWA) 10 mg/m3
Kingdom Short-term exposure limit (10-min) (STEL) 15 mg/m3
a Expressed as carbendazim.
The following label statements are required:
F Flammable
R11 Highly flammable
R40 Possible risk of irreversible effects
S7 Keep container tightly closed
S36/37 Wear suitable protective clothing and gloves.
US EPA requires labelling with a "Caution" signal word.
Benomyl 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 benomyl and/or
its container must be disposed of as hazardous waste. US EPA
regulations require the wastes be disposed of on site or at an
approved waste disposal facility. Containers must be disposed of in
a sanitary landfill or by incineration.
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
Benomyl (EHC 148, 1993)
Benomyl (ICSC)
Benomyl (WHO Pesticide Residues Series 3)
Benomyl (WHO Pesticide Residues Series 5)
Benomyl (Pesticide residues in food: 1983 evaluations)
Benomyl (JMPR Evaluation 1995 Part II Toxicological and environmental)