IPCS INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY
Health and Safety Guide No. 72
FOLPET
HEALTH AND SAFETY GUIDE
UNITED NATIONS ENVIRONMENT PROGRAMME
INTERNATIONAL LABOUR ORGANISATION
WORLD HEALTH ORGANIZATION
WORLD HEALTH ORGANIZATION, GENEVA 1992
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
Folpet : health and safety guide.
(Health and safety guide ; no. 72)
1.Fungicides, Industrial - standards 2.Fungicides, Industrial - toxicity
3.Phthalimides - standards 4.Phthalimides - toxicity
5.Environmental exposure I.Series
ISBN 92 4 151072 2 (NLM Classification: WA 240)
ISSN 0259-7268
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(c) World Health Organization 1992
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The mention of specific companies or of certain manufacturers'
products does not imply that they are endorsed or recommended by the
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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. Human exposure to folpet
2.2. Effects on the environment
2.3. Uptake, metabolism, and excretion
2.4. Effects on animals
2.5. Effects on human beings
3. CONCLUSIONS AND RECOMMENDATIONS
3.1. Conclusions
3.2. Recommendations
4. HUMAN HEALTH HAZARDS, PREVENTION AND PROTECTION, EMERGENCY ACTION
4.1. Main human health hazards, prevention and protection,
first aid
4.1.1. Prevention and protection
4.1.2. First aid
4.2. Advice to physicians
4.3. Explosion and fire hazards
4.4. Storage and transport
4.5. Spillage
4.6. Disposal
5. HAZARDS FOR THE ENVIRONMENT AND THEIR PREVENTION
6. CURRENT REGULATIONS, GUIDELINES, AND STANDARDS
6.1. Exposure limit values
6.2. Specific restrictions
6.3. Transport and labelling
BIBLIOGRAPHY
INTRODUCTION
This Health and Safety Guide is not based on an existing
Environmental Health Criteria document, but on critical national
reviews. The hazard evaluation in the Health and Safety Guide was
made on the basis of carefully selected studies, after scrutiny of
the original publications.
In order to assist the peer-review process of the present Health and
Safety Guide, a background companion document was prepared by the
IPCS and can be obtained from the Director on request; the IPCS does
not intend that the background document should be published.
The first three sections of this Health and Safety Guide present
essential technical information and the hazard evaluation. 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.
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
Chemical formula: C9H4CL3NO2S
Chemical structure:
Relative molecular mass: 296.58
Common trade names: Acryptan; Folpan; Folpet; Ftalan;
Orthophaltan; Phaltan; Phthaltan;
Thiophal; Troysan anti-mildew 0;
Splacid; Folnit; Fungitrol-II;
Vinicoll; Intercide-TMP; Cosan-I
Mixtures include: Acylon Super F;
Ridomil Combi (folpet + metalaxyl);
Caltan (folpet + ofurace); Caltam C
(folpet + captafol + ofurace);
Galben F, WP (folpet + benalaxyl);
Mycodifol, Mycodifol F
(folpet + captafol); Sandofan F
(folpet + oxadixyl)
CAS chemical name: 1H-isoindole-1,3 (2H)-dione,
2-((trichloromethyl)thio)-;
Synonyms: N-(trichloromethylmercapto)
phthalimide;
N-(trichlormethylthio)-
phthalimide;
2-((trichloromethyl)-thio)-
1H-isoindole-1,3(2H)-dione;
N-(trichloromethylthio)phthalimide;
N-(trichlor-methylthio)-phthalamid
(German)
CAS registry number: 133-07-3
RTECS registry number: TI1575000
Technical folpet is usually 90% pure. The main impurities are
phthalimide (up to 4.0%) and sodium chloride (up to 5%).
1.2 Physical and chemical properties
Pure folpet is a white crystalline solid with a reported melting
point of 177 °C. At 20 °C, the vapour pressure of the pure compound
is very low. Its solubility in water is 1 mg/litre at room
temperature and it is slightly soluble in organic solvents (ethanol,
acetone).
In the dry state, it is stable at room temperature, but it is
hydrolysed in an aqueous solution at a rate that depends on the pH.
In alkaline solution, this breakdown is rapid, occurring within
minutes. The hydrolysis products are carbon dioxide, hydrochloric
acid, hydrogen sulfide, phthalamic acid, and phthalic acid.
1.3 Analytical methods
Capillary gas-liquid chromatography with an electron-capture
detector is a suitable method for the routine determination of
folpet residues in the presence of captan, captafol, vinclozolin,
and iprodione.
1.4 Production and uses
Folpet was first marketed in the early 1950s. The world production
in 1989 is believed to have been in excess of 5000 tonnes. Folpet is
a broad spectrum phthalimide fungicide that is used in the
cultivation of both food and non-food crops, as well as in the
manufacture of oil-based interior and exterior paints and coatings,
and in the manufacture of plastics. Methods of application include
dusting, spraying, or direct incorporation into paints, coatings,
and plastic formulations.
In agriculture and horticulture, it is mainly applied, as a
protective fungicide, to the foliage of grapes, apples, avocados,
citrus, cucumbers, soft fruit, lettuces, melons, onions, flowering
ornamentals, and tomatoes. It is generally available as a wettable
powder, dust, flowable concentrate, and as water-soluble pellets.
2. SUMMARY AND EVALUATION
2.1 Human exposure to folpet
The heaviest occupational exposure to folpet is associated with its
use in agriculture; other occupational exposures, for example in the
production of paints, are negligible. Owing to its widespread use,
the general population may be exposed to this pesticide through
residues in food. However, folpet is extensively hydrolysed by
cooking, and as a result of the maceration of plant materials.
Because of the nature of the folpet residues, they are readily
removed by washing, blanching, peeling, etc.
2.2 Effects on the environment
The acute toxicity of folpet for birds is extremely low and it is
relatively non-toxic for honey bees. On the other hand, it is highly
toxic for fish; 96-h LC50s in the range of 0.04-0.3 mg/litre have
been reported for various species of fish. It is also toxic for
freshwater invertebrates, such as daphnids (water fleas).
Folpet is not persistent, and its use is not considered to
constitute a threat to terrestrial wildlife. The environmental
impact of the pesticide is likely to be limited by its high rate of
biodegradation. It does not bioaccumulate.
2.3 Uptake, metabolism, and excretion
Folpet may be absorbed by ingestion as well as by inhalation, and to
a very limited extent by skin exposure. It is rapidly hydrolysed in
the blood and gives rise to phthalamic acid and phthalimide, and to
derivatives of the trichloromethylthioside chain. Neither folpet nor
its metabolites appear to accumulate in the tissues of mammals, but
are rapidly excreted in the urine (95% within 24 hours). Degradation
in the gut appears to play a major role in the metabolism of folpet.
Here, the reactive intermediate thiophosgene is generated, and
further metabolized.
2.4 Effects on animals
The acute toxicity of folpet following ingestion or dermal contact
is low, the acute oral LD50 in rats being greater than 5000 mg/kg
body weight. There are indications that folpet is more toxic when
inhaled.
Folpet is irritating to the eyes and has been found to cause
sensitization in the guinea-pig.
The no-observed-adverse-effect level (NOAEL) in the dog, with oral
administration for 1 year,was about 10 mg/kg body weight per day.
The main adverse effects were related to organ weight changes,
mainly of the testes, adrenals, and liver. None of these findings
were associated with macro- or microscopic pathological findings. A
reduction in the rate of body weight gain in the high- and
intermediate-dose groups was noted. A decrease in food intake was
found only in the high-dose group. Dose-related increases in benign
and malignant tumours of the gastrointestinal tract were noted in
two strains of mice after life-long administration. However, the
results of long-term studies on rats have been negative. Folpet has
been proved to be genotoxic in several in vitro systems; however,
in vivo, it has not been possible to demonstrate any mutagenic
effects in mammals.
Several studies to evaluate the teratogenic potential of folpet have
been carried out on rabbits and rats. In none of these
investigations could teratogenic effects be demonstrated at levels
below a maternal toxic dose. The NOAEL for fetotoxic effects in the
rat was 10 mg/kg body weight per day in these studies.
2.5 Effects on human beings
No serious adverse health effects have been reported for this
pesticide. It is an irritant to the eyes and skin.
3. CONCLUSIONS AND RECOMMENDATIONS
3.1 Conclusions
No serious adverse health effects have been demonstrated in humans
It is a compound of low acute mammalian toxicity. It is irritant to
the eyes and skin, and might cause sensitization. At high exposure
levels, folpet induces general toxic effects. Tumours were found in
mice following long-term, high-dose, oral administration. Tumours
were not observed in similar studies on rats, and therefore the
evidence for the carcinogenicity of this compound in experimental
animals is inadequate. It seems that the potential for causing
heritable effects in mammals is very low.
If good agricultural practices are observed, particularly as regards
the recommended pre-harvest application interval, the exposure of
the public is unlikely to exceed the recommended maximum residue
limits for folpet.
Folpet is highly toxic for freshwater fish and toxic for freshwater
invertebrates. It is not a hazard for terrestrial organisms in
normal usage.
3.2 Recommendations
Occupational exposure to folpet should be kept to a minimum,
particularly in view of its irritant effects.
Because of the high aquatic toxicity of folpet, adequate precautions
should be taken to prevent contamination of surface waters.
In order to avoid high levels of residue in fresh fruits and
vegetables, the recommended pre-harvest intervals for the
application of folpet to these crops should be strictly enforced.
4. HUMAN HEALTH HAZARDS, PREVENTION AND PROTECTION, EMERGENCY ACTION
4.1 Main human health hazards, prevention and protection, first aid
4.1.1 Prevention and protection
The acute oral toxicity of technical folpet is low, but the compound
may be more toxic by inhalation, may cause eye irritation, and may
induce allergic dermatitis.
The main goal of preventive measures is to ensure a safe work
environment and proper work practices. The following precautions
should be observed during handling and use, in order to reduce the
risk of accidental contamination:
* Avoid contact with the skin and eyes.
* Do not smoke, drink, or eat while handling folpet. Wash the
hands and any exposed skin before eating, drinking, smoking,
and after work.
* Avoid breathing folpet dust or spray mist, and wear disposable
dust masks wherever appropriate.
* When unloading and handling containers of concentrates, wear
protective PVC or neoprene gloves.
* When handling any leaking containers, or when dealing with
leaks and spills, wear overalls and PVC or neoprene aprons,
gloves, and boots. If overalls become contaminated, change and
wash them thoroughly before re-use.
* Store products in closed, original, labelled containers, out of
the reach of children and away from food and animal feed.
4.1.2 First aid
Acute poisoning by folpet is unlikely unless large amounts have been
ingested. In cases of overexposure, apply routine first aid
measures. If material has been spilled on the skin, immediately
remove the patient from the source of contamination, remove all
contaminated clothing, and wash the affected areas with soap and
water. If the material is in the eyes, flush with clean water for at
least 5-10 minutes. In case of ingestion of significant quantities,
if the patient is conscious give water to drink and induce vomiting.
In serious cases, medical attention should be sought.
4.2 Advice to physicians
The acute toxicity of folpet for humans is believed to be low. There
is no specific antidote. Treat symptomatically as required. In cases
of ingestion, gastric lavage may be indicated.
4.3 Explosion and fire hazards
Folpet itself is not flammable, but when heated it may produce toxic
fumes, such as sulfur dioxide, hydrochloric acid, and phosgene. If
folpet is involved in a fire, extinguishers that dispense
alcohol-resistant foam, carbon dioxide, or dry powder should be
used. Confine the use of water sprays to the cooling of unaffected
stock only, thus avoiding polluted run-off from the site. Fire
service personnel should be advised that self-contained breathing
apparatus may be necessary, because of the generation of noxious
fumes.
4.4 Storage and transport
All products should be stored in secure buildings, out of the reach
of children and animals, and local regulations should be complied
with. Containers should be sound and adequately labelled.
Folpet should be transported in a separate compartment to prevent
the contamination of any food or animal feed.
4.5 Spillage
Avoid direct personal contact with solids or liquids containg folpet
and keep spectators away from any leakage. This pesticide is highly
toxic for fish. Prevent contamination of other goods or cargo, or
surface waters.
Absorb spillage of liquid products with sawdust, earth, or sand,
sweep up and place in separate container. Empty any product
remaining in damaged or leaking containers into a clean empty
container, and ensure that it is suitably labelled. Sweep up any
spilt powder with damp sawdust, taking care not to raise a dust
cloud. Remove trapped material with suction hoses. Place in a
separate container for subsequent disposal.
4.6 Disposal
Do not deposit unwanted folpet or folpet waste in a landfill, or in
sewers or surface waters. Wastes should be incinerated in plants
with an effluent-gas scrubbing device.
Folpet may be also disposed of by mixing with excess calcium oxide
or sodium hydroxide and sand or other absorbents, in a pit or trench
at least 0.5 m deep, in damp soil.
Folpet containers made of permanent materials may be decontaminated
and used for purposes other than the storage of food, water, and
animal feed, provided that the following procedure is strictly
followed:
The container should be rinsed by filling with water up to at
least half its volume, and emptied. The container should then
be soaked by being entirely filled with water and allowed to
stand for 24 hours. The rinsing water and the first soaking
water must be disposed of in a dry pit, in order not to
contaminate surface waters. The soaking procedure must be
repeated for at least two more periods of 24 hours. The
original pesticide label must be obliterated. The container
must be clearly re-labelled, "Not to be used for food, drink,
or animal feed".
Arrangements for decontamination will vary in different countries,
and centralized decontamination centres might be established in some
cases.
5. HAZARDS FOR THE ENVIRONMENT AND THEIR PREVENTION
Folpet is not persistent and small quantities of the compound are
readily hydrolysed in soil and surface waters. However, it is highly
toxic for aquatic organisms. Contamination of ponds, waterways, and
ditches with folpet, or with equipment used for dispersing the
chemical or used containers, should therefore be avoided. In case of
spills, and for decontamination of equipment and containers, apply
the methods recommended in section 4.6. Empty containers made of
permanent materials must be decontaminated as indicated in section
4.6.
6. CURRENT REGULATIONS, GUIDELINES, AND STANDARDS
6.1 Exposure limit values
No threshold limit values (TWA) have been set for folpet.
In 1990, the Joint FAO/WHO Meeting on Pesticide Residues in Food
(JMPR) established a temporary ADI of 0-0.01 mg/kg body weight. Some
tolerances for food products are given in the table opposite.
6.2 Specific restrictions
The use of folpet is banned in Finland and Sweden. All registrations
for the use of folpet on food crops were voluntarily withdrawn in
the United States of America in 1987.
6.3 Transport and labelling
Conveyance labelling should be as follows:
Tolerances and maximum residue limits for food products
Country/ Food product Exposure limit Value Effective
organization description (mg/kg) date
Brazil Onions, cucumbers, melons Acceptable limit 2.0 1985
Other fruits and vegetables 10-20
Canada Fruits and vegetables Tolerance 15-30 1990
Codex Cucumber, melons except water melon, onion, bulb,
Alimentarius tomato Maximum residue limit 2-5 1991
Commission Apple, citrus fruits, cherries, lettuce head,
strawberry, grapes 10-25
European Pome fruit, berries and small fruit, grapes, tomatoes Maximum residue limit a 3 1988
Community
legislation Beans, broad-leaved endives, peas, endives, leeks,
stone-fruit, lettuce 2
Germany Fruits and vegetables Maximum residue limit a 0.1-3.0 1989
Sweden Fruits and vegetables Maximum acceptable 0.1-3.0 1989
concentrationa
USA Fruits and vegetables Tolerance 15-50 1987
a Sum of captan and folpet.
Supply and use labelling. European Economic Community legislation
requires labelling as a dangerous substance, using the symbol:
The label must read:
Irritating to eyes; possible risks of irreversible effects: may
cause sensitization by skin contact; wear suitable protective
clothing and gloves.
BIBLIOGRAPHY
ACGIH (1988) TLV's, threshold limit values and biological exposure
indices for 1987-1988.
FAO/WHO (1991) Joint FAO/WHO Meeting of Pesticide Residues in Food
(JMPR), 1990 Evaluations. Part II - Toxicology. Rome, Food and
Agriculture Organization of the United Nations, 1990, pp. 69-80.
WHO (1992) The WHO recommended classification of pesticides by
hazard and guidelines to classification 1992-1993. Geneva, World
Health Organization (unpublished document, WHO/PCS/92.14).
IRPTC (1989) IRPTC legal file 1988. Geneva, International Register
of Potentially Toxic Chemicals, United Nations Environment
Programme.
Reiter A (1986) Folpet exposure assessment. Report to the Hazard
Assessment Branch from the Exposure Assessment Branch, Office of
Pesticides and Toxic Substances, US EPA, Washington, DC.
Rinde E (1986) Peer review of folpet. Toxicology Assessment Branch,
Office of Pesticides and Toxic Substances, US EPA, Washington, DC.
US EPA (1986) Registration standard for folpet - ecological effects
chapter. Office of Pesticides and Toxic Substances, June 9, 1986,
Washington, DC.
Worthing CR & Hance RJ (1991) The pesticide manual. Farnham, British
Crop Protection Council, 9th ed., pp. 431-432.