WORLD HEALTH ORGANIZATION FOOD AND AGRICULTURE
ORGANIZATION
ORGANISATION MONDIALE DE LA SANTE ORGANISATION POUR L'ALIMENTATION
ET L'AGRICULTURE
WHO/PCS/DS/94.87
Original: ENGLISH
Distr.: LIMITED
Date of issue: February 1994
WHO/FAO DATA SHEET ON PESTICIDES No. 87
BENOMYL
It must be noted that the issue of a Data Sheet for a
particular pesticide does not imply endorsement of the pesticide by
WHO or FAO for any particular use, or exclude its use for other
purposes not stated. While the information provided is believed to
be accurate according to data available at the time when the sheet
was compiled, neither WHO nor FAO are responsible for any errors or
omissions, or any consequences therefrom.
The issue of this document does Ce document ne constitue pas une
not constitute formal publication. Il ne doit faire
publication. It should not be l'objet d'aucun compte rendu ou
reviewed, abstracted or quoted résumé ni d'aucune citation sans
without the agreement of the l'autorisation de l'Organisation
Food and Agriculture des Nations Unies pour
Organization of the United l'Alimentation et l'Agriculture
Nations or of the World Health ou de l'Organisation Mondiale de
Organization. la Santé.
CLASSIFICATION:
Primary use: Systemic fungicide
Secondary use: Acaricide, mite ovicide
Chemical group: Benzimidazole carbamate
1.0 GENERAL INFORMATION
1.1 COMMON NAME: Benomyl (ISO)
1.1.1 Identity:
IUPAC chemical name: Methyl 1-[(butylamino)carbonyl]-1H-
benzimidazol-2-ylcarbamate
CAS chemical name: Carbamic acid, [1-(butylamino)carbonyl]-
1H-benzimidazol-2-yl]-, methyl ester.
CAS registry number: 17804-35-2
RTECS registry number: DD6475000
Molecular formula: C14H18N4O3
Relative molecular mass: 290.3
Structural formula:
Trade names and synonyms: BenlateR;TersanR;
Fungicide 1991; methyl
1-(butylcarbamoyl)-2-benzimidazolecarbamate.
1.2 SYNOPSIS:
Benomyl is a systemic, broad spectrum benzimidazole carbamate
fungicide. Acute toxicity is low, and there is no evidence of
accumulation. It is only mildly irritant to skin and eyes, but
sensitizes skin. Foetotoxic and teratogenic effects have been
observed in laboratory animals following gavage administration of
high doses, but not following dietary exposure. Inhalation and
oral exposure reduced spermatogenic activity in laboratory
animals.
1.3 SELECTED PROPERTIES
1.3.1 Physical characteristics: A tan-coloured odourless
crystalline solid which decomposes at 140 °C just after
melting. Technical benomyl is greater than 98% (w/w) pure.
1.3.2 Solubility: In water at 25 °C and pH 5 its
solubility is 3.6 mg/L. Soluble in several organic solvents,
especially heptane and chloroform (40 and 9.4 g/100 g solvent at
25 °C respectively).
1.3.3 Stability: Rapidly hydrolysed in dilute aqueous
solutions and in soil to butyl isocyanate and the fungicide
methyl-2-benzimidazole carbamate (carbendazim). Decomposed by
strong acids and alkalis. Stable to light.
1.3.4 Vapour pressure:
Negligible (less than 5 x 10-6 Pa).
1.4 AGRICULTURE, HORTICULTURE AND FORESTRY
1.4.1 Common formulations: Wettable powder (50%) and oil
dispersion (50%). In combination with other pesticides as a
wettable powder (10-50%) or as a dust (6%).
1.4.2 Pests mainly controlled: Controls a wide range
of fungal diseases of fruits, nuts, vegetables, field crops, turf
and ornamentals. Powdery mildew, apple scab and grey mould fungus
are well controlled. It is also effective against mites.
1.4.3 Use pattern: Effective as a pre-harvest
systemic fungicide, and as a post-harvest dip or dust treatment
for the protection of fruits, seeds and vegetables in storage.
Compatible in mixtures with non-alkaline pesticides.
1.4.4 Unintended effects:
Toxic to fish and to earthworms.
1.5 PUBLIC HEALTH PROGRAMMES: No recommended
usage.
1.6 HOUSEHOLD USE:
1.6.1 Common formulations: Wettable powder (50%), wettable
powder (2%) in combination with other pesticides.
1.6.2 Pests mainly controlled: Powdery mildew,
botrytis, fusarium basal rot, black spot and blossom rot.
1.6.3 Use pattern: As a spray application to
ornamentals, domestic fruit, trees and lawns. Application
procedures and re-application intervals should be made according
to manufacturers' directions.
2.0 TOXICOLOGY AND RISKS
2.1 TOXICOLOGY - MAMMALS
2.1.1 Absorption route: Benomyl is readily absorbed after
oral and inhalation exposure, but much less following dermal
exposure.
2.1.2 Mode of action: Benomyl and its main metabolite
carbendazim bind to microtubuli, an essential structure of all
cells, thereby interfering with their functions (cell division,
intracellular transports, etc.). Selective toxicity of benomyl is
thought to be due to its higher affinity for fungal as compared
with mammalian microtubuli.
2.1.3 Excretion products: Benomyl is almost
completely transformed and excreted in the urine as
methly(5-hydroxy-1H-benzimidazol-2-yl)-carbamate (5-HBC) and to a
less extent as carbendazim. 5-HBC is the major metabolite in
milk.
2.1.4 Toxicity, single dose:
Oral LD50
Rat (M & F) „ 10 000 mg/kg b.w. (peanut oil)
Rat (M & F) „ 10 000 mg/kg b.w.
(aqueous suspension of BenlateR, 53%a.i.)
Dermal LD50
Rabbit (M & F) 10 000 mg/kg b.w. (50% w.p.)
Inhalation LC50 - 4 hour exposure
Rat >4.01 mg/L (50% w.p.)
Dog >1.65 mg/L (50% w.p.)
Oral administration of benomyl to rats and inhalation exposure to
dogs caused testicular toxicity. Doses were >100 mg/kg and 1.65
mg/L for oral and inhalation exposure respectively.
Primary irritancy: Mild erythema was observed following
application of an aqueous suspension of 25% benomyl to shaved
guinea pig skin. Mild conjunctival irritation was observed in
rabbit eyes following instillation of 10 mg of a dry powder
formulation (5 mg a.i.) or 0.1 ml of an oil suspension (10 mg
a.i.).
2.1.5 Toxicity, repeated doses:
Oral: Gavage studies in rats of various age showed that benomyl
(„200 mg/kg/day for 10 days and „45 mg/kg/day for about 80 days)
caused reduced sperm count and various histopathological lesions
of testes and epididymus indicating disruption of all stages of
spermatogenesis.
Inhalation: Nose exposure of rats to benomyl (6 h/day for 90
days) caused degeneration of olfactory epitelium at „50 mg
benomyl/m3.
Dermal: Skin exposure of rabbits to 50% benomyl formulation
equivalent to 1000 mg/kg (6 h/day, 5 days/week for 3 weeks) caused
mild erythema and moderate desquamation of the sites of
application. Testicular toxicity (degeneration of spermatogenic
elements) was observed at microscopic examination. Benomyl was
found to produce sensitization in guinea pigs.
Cumulation of compound: No evidence of cumulative residues was
seen in the tissues of laboratory and domestic animals.
Cumulation of effects: No evidence of cumulative effects was
observed in rats following gavage, dietary or inhalation exposure.
2.1.6 Dietary studies:
Short term: No signs of toxicity were observed in rats following
90 days administration of benomyl up to and including 2500
mg/kg/diet. In a 90-day study, beagle dogs received 0, 100, 500
and 2500 mg/kg/diet (up to 84 mg/kg b.w./day). Minor changes in
clinical chemistry and some histopathological lesions observed, at
the high dose level only, were probably not due to benomyl.
Long term: Administration of up to and including 2500 mg/kg
diet to rats for two years was without adverse effect on growth,
clinical chemistry, haematologic or histopathologic parameters.
No adverse effects on clinical chemistry parameters or
haematological indices were observed in male and female CD-1 mice
receiving up to 5000 mg/kg/diet for two years. Compound related
changes were found in the absolute and relative liver weights for
males (highest dose) and females (up to and including 1500 mg/kg
diet). Male mice had decreased testes weights and testes
degeneration at the highest dose.
2.1.7 Supplementary studies of toxicity:
Carcinogenicity: Rats were exposed up to 2500 mg/kg benomyl in
the diet for two years and no oncogenic effects were detected.
Mice were exposed to 0, 500, 1500 and 5000 mg/kg/diet for two
years. The incidence of hepatocellular adenomas and carcinomas
in female mice was increased in a dose-dependent manner. In male
mice, the number of hepatocellular adenomas and carcinomas were
significantly increased at 500 and 1500 mg/kg but not at 5000
mg/kg dose. The increased number of lung alveolar carcinomas in
male mice was still within the range of historical controls.
Teratogenicity: A mouse gavage study (0, 50, 100 and 200 mg/kg
per day on days 7 to 17 of gestation ) showed teratogenic effects
at all dose levels. Abnormalities included; exencephaly,
hydrocephaly, cleft palate, hydronephrosis, polydactyly,
oligodactyly, umbilical hernia, fused ribs, fused vertebrae and
short/kinky tail.
Teratogenicity was also observed in a rat gavage study (0, 3, 10,
30, 62.5 and 125 mg/kg per day on days 7 to 16 of gestation).
Malformations included, microphthalmia, anophthalmia and
hydrocephaly. The NOEL was 30 mg/kg benomyl. In another study in
rats the NOEL for similar teratogenic effects was found to be 31.2
mg/kg.
In a rat study aimed at evaluating the effects of low levels of
benomyl as the pups aged the compound was administered by gavage
at dose levels of 0, 15.6, and 31.2 mg/kg per day from day 7 of
gestation to day 15 of lactation). No teratogenicity was found
but testes weight was significantly reduced in males given 31.2
mg/kg.
A further gavage study in rats produced similar teratogenic
effects at 62.4 mg/kg per day on day 7 - 21 of gestation. The
incidence of these effects increased when a semipurified protein-
deficient diet was given together with the same level of benomyl.
Some malformations (primarily hydrocephaly) also appeared at the
lower dose when the same diet was provided.
Reproduction: No adverse effect was observed in a three
generation reproduction study with ChR-CD rats receiving 2500
mg/kg diet (the maximum dose administered).
Pre-pubertal exposure of Sprague-Dawley rats to 10 daily gavage
doses of 200 mg technical benomyl/kg b.w./day in oil had no effect
on the time of puberty onset or on the sperm count at that time.
However, the same regimen caused depression of the total
epididymal and vas deferens sperm counts at doses of 200 or 400
mg/kg b.w./day in adult rats. At the 400 mg/kg b.w./day dose the
testes weights were maintained but showed evidence of
hypospermatogenesis.
Dietary administration of 1, 6.3 or 203 mg/kg (diet) for 70 days
had no effect on reproductive behaviour of adult Wistar rats.
Decreased ejaculate sperm concentration was observed in the high
dose group and testes weights were decreased at all doses. Both
effects were reversed during a 70 day recovery period.
Permanent reductions were observed in the size of testes and male
accessory glands in 100 day old offspring of Wistar rat dams
receiving 31.2 mg benomyl/kg b.w./day on gestation day 7 through
to day 15 of lactation.
Reduced spermatogenic activity has been reported in rats following
acute inhalation exposure, acute and sub-chronic oral exposure and
dogs following a single four hour inhalation exposure (section
2.1.4).
Mutagenicity: In a dominant lethal mutation study administration
of upto 203 mg benomyl/kg/diet for 46-53 days to Wistar rats, or
2500 mg/kg/diet for 7 days to ChR-CD rats did not induce
mutations. Intraperitoneal administration of 1000 mg benomyl/kg
b.w. to rats induced mitotic arrest in bone-marrow cells within
four hours of dosing. Serum from these rats collected 30 minutes
after dosing was cytotoxic to mammalian cell lines in vitro.
Orally administered doses of 1000 mg/kg b.w. did not affect the
bone marrow, and the serum was only weakly cytotoxic.
Benomyl was not mutagenic in Escherichia coli WP2 hcr, or
Salmonella typhimurium, nor in mitotic gene conversion studies
in Saccharomyces cerevisiae, but was a mitotic spindle poison in
Aspergillus nidulans .
2.2 TOXICOLOGY - MAN
2.2.1 Absorption route: No specific information published
but animal data suggest rapid absorption from the gastro-
intestinal tract, and by the inhalation route. Benomyl is probably
absorbed only slowly through intact skin.
2.2.2 Dangerous doses:
Single: No published information available.
Repeated: No published information available.
2.2.3 Observations on occupationally exposed workers:
No inadvertent poisoning of agricultural or forestry workers has
been documented.
Benomyl caused contact dermatitis and dermal sensitization in some
farm workers. Cross-sensitization between benomyl and other
pesticides such as diazinon, daconil, saturon and 2-bordeaux has
been reported.
Blood profiles from workers involved in the manufacture of benomyl
were not different from those of a control group of workers.
Workers exposed for 1-95 months during benomyl manufacture were
examined for reproduction performance. There was no reduction in
fertility as shown by the birth rates, which were generally higher
than those of the control populations.
2.2.4 Observations on exposure of the general population:
No published information available. With good agricultural
practice, exposure of the public to hazardous quantities of
benomyl is unlikely.
2.2.5 Observations on volunteers:
No published information available.
2.2.6 Reported mishaps: None reported.
2.3 TOXICITY - NON-MAMMALIAN SPECIES
2.3.1 Fish:
LC50 (96 hour):
Carp 7.5 mg/L
Fathead minnow 2.2 mg/L
Bluegill 1.3 mg/L
Rainbow trout 0.17 mg/L
Channel catfish 0.031 mg/L
2.3.2 Birds:
LC50 (5 days)
Mallard duck > 10 000 mg/kg diet
Bobwhite quail > 10 000 mg/kg diet
Body weight gain, feed consumption and egg production in Leghorn
hens were unaffected by 25 mg benomyl/kg diet (as BenlateR 50%
w.p.) for 28 days. No residues were found in the fat or breast
tissue. A low concentration of the methyl 5-hydroxy-metabolite
was found in the eggs during exposure, but not 7 days after
cessation of exposure.
2.3.3 Beneficial insects:
Benomyl is not toxic to bees.
2.3.4 Other species:
LC50 Daphnia magna 0.64 mg/L
Exposure of earthworms to residues or suspensions of benomyl may
have a delayed lethal effect. Low concentrations on the foliage
may suppress feeding. Reduced populations of earthworms have been
reported in benomyl treated orchards.
3.0 FOR REGULATORY AUTHORITIES - RECOMMENDATIONS OF COMPOUND
3.1 RECOMMENDED RESTRICTIONS ON AVAILABILITY
[For definition of categories see the 'Introduction to Data Sheets'].
All liquid formulations of 50% or less and all solid formulations
- Category 5
3.2 TRANSPORT AND STORAGE
Formulations in Category 5: Should be stored and transported in
clearly labelled leakproof containers out of the reach of
children, away from food and drink.
3.3 HANDLING
Formulations in Category 5: Handling of large quantities of
solid formulations (2 kg bags or greater) requires use of a dust
mask and protective clothing (see section 4.1.3 - 4.1.4). For
handling small quantities and liquid formulations no facilities
other than those required for handling of any chemical are
required.
3.4 DISPOSAL AND/OR DECONTAMINATION OF CONTAINERS
Decontamination of containers is probably not practical due to the
low water solubility of benomyl. Containers must be disposed of in
an approved manner. Care must be taken to avoid contamination of
water sources.
3.5 SELECTION, TRAINING AND MEDICAL SUPERVISION OF WORKERS
Formulations in Category 5: Warning of workers to minimize
contact is essential particularly in view of the sensitizing
effects of benomyl.
3.6 ADDITIONAL REGULATIONS RECOMMENDED IF DISTRIBUTED BY AIRCRAFT
All formulations: Benomyl is normally not distributed by
aircraft. If it is, pilots and loaders should have special
training in application methods. All workers must wear a dust
mask, overalls and impermeable gloves.
3.7 LABELLING
Formulations in category 5 - Minimum cautionary statement.
This formulation contains the fungicide benomyl which is poisonous
if swallowed or if the dust is inhaled. Keep out of reach of
children and pets, and well away from foodstuffs or animal feeds.
3.8 RESIDUES IN FOOD
Maximum levels have been recommended for a variety of agricultural
products and foodstuffs by the FAO/WHO Joint Meeting on Pesticide
Residues on Food and the Environment. In 1983 the JMPR
established an Acceptable Daily Intake (ADI) of 0-0.02 mg/kg/b.w.
4.0 PREVENTION OF POISONING IN MAN AND EMERGENCY AID
4.1 PRECAUTIONS IN USE
4.1.1 General: Benomyl is a benzimidazole fungicide.
Acute toxicity of benomyl is low, but it has the potential of
causing sensitization.
4.1.2 Manufacture and formulation: TLV 10 mg/m3.
Dusts should be controlled, preferably by mechanical means.
Protective equipment for respiratory tract and skin is necessary.
4.1.3 Mixers and applicators: Light respiratory
protection should be used when handling dusty formulations. For
all formulations clean overalls and gloves should be used to
prevent skin contamination. When opening the container and when
mixing, care should be taken to avoid contact with the eyes and
mouth. Mixing if not mechanical, should always be carried out
with a paddle of appropriate length. The applicator should avoid
working in spray mist and avoid contact with the mouth. Splashes
must be washed from the skin or eyes immediately with large
volumes of water. Before eating, drinking or smoking, hands and
exposed skin should be washed.
4.1.4 Other associated workers: Persons exposed to
benomyl and associated with its application should wear protective
clothing and observe the precautions described above in 4.1.3.
under "Mixers and Applicators".
4.1.5 Other populations likely to be affected:
Subject to 4.2 below, other persons are not likely to be exposed
to hazardous amounts of benomyl.
4.2 ENTRY OF PERSONS INTO TREATED AREAS
No exclusion from treated areas is indicated.
4.3 DECONTAMINATION OF SPILLAGE AND CONTAINERS
Residues in containers should be buried in a deep dry pit
(>0.5 m) taking care to avoid contamination of water sources.
Spillage of liquid formulations should be contained and absorbed
by absorbent material. This material, or spillage of dry
formulations, should be collected and buried in a deep dry pit.
Care must be taken to avoid contamination of water sources.
Residues should be washed from the spillage site with water and
detergent.
4.4 EMERGENCY AID
4.4.1 Early symptoms of poisoning: No details reported.
4.4.2 Treatment before person is seen by physician, if
these symptoms appear following exposure:
The person should stop work immediately, remove contaminated
clothing and wash contaminated skin with soap and water and flush
with large volumes of clean water. If the eyes are contaminated,
they should be flushed with large volumes of clean water.
5.0 FOR MEDICAL AND LABORATORY PERSONNEL
5.1 MEDICAL DIAGNOSIS AND TREATMENT IN CASE OF POISONING
5.1.1 General information: Benomyl is a benzimidazole
fungicide of low acute toxicity. At high doses benomyl has been
shown in animals to be teratogenic and to cause testicular
changes.
5.1.2 Symptoms and signs: No cases of human poisoning
have been recorded.
5.1.3 Laboratory: No tests in humans to measure
exposure have been reported.
5.1.4 Treatment: Symptomatic, because no specific
antidote is available. In the case of skin contamination the
exposed area should be washed with soap and water. If the
compound has entered the eyes they should be washed with copious
volumes of isotonic saline or water.
5.1.5 Prognosis: Unknown.
5.1.6 References to previously reported cases:
No reports.
5.2 SURVEILLANCE TESTS: There are no readily
available field techniques to determine the degree of exposure.
5.3 LABORATORY METHODS
5.3.1 Detection and assay of compound and residues:
Assay methods may not distinguish between benomyl and methyl 2-
benzimidazole carbamate, which forms rapidly when benomyl is in
aqueous solution.
Douch PGC (1973), Xenobiotica, 3(6), 367-383.
Kirkland JJ, Holt RH, Pease HL (1973), J Agric Food Chem, 21(3):
368-371.
Pressley TA, Longbottom JE (1982), The determination of benomyl and
carbendazim in Municipal and Industrial Wastewater. Method 631.
EPA-600/4-82-012. PB82-156068.
Teubert W, Stringham R (1984), J Assoc Off Anal Chem 67(2):
303-305.
5.3.2 Other tests in case of poisoning: None.
REFERENCES
1. WHO (1994) The WHO Recommended Classification of Pesticides by Hazard
and Guidelines to Classification 1994-1995, Geneva, World Health
Organization mimeographed document (WHO/PCS/94.2).
2. The Pesticide Manual, A World Compendium (9th edition 1991), Worthing,
C.R. and Hance, R.J., eds., British Crop Protection Council, 20
Bridport Road, Thornton Heath, CR4 7QG, United Kingdom.
3. WHO (1990), Environmental Health Criteria 148; Benomyl; Geneva,
World Health Organization.
4. WHO (1990), Health and Safety Guide 81; Benomyl; Geneva, World
Health Organization.
5. FAO/WHO (1985), Evaluations 1983 of Pesticide Residues in Food, FAO
Plant Production and Protection Paper, 61, 8-32.
6. Thomson WT (1984), Agricultural Chemicals, Book IV. Fungicides.
Thomson Publications, California, 93791, USA
7. Ireland CM, Gull K, Guttridge WE, Pogson CI (1979), Biochem Pharmacol
28: 2680-2682.
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