IPCS INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY
Health and Safety Guide No. 66
TRICHLORFON
HEALTH AND SAFETY GUIDE
UNITED NATIONS ENVIRONMENT PROGRAMME
INTERNATIONAL LABOUR ORGANISATION
WORLD HEALTH ORGANIZATION
WORLD HEALTH ORGANIZATION, GENEVA 1991
This is a companion volume to Environmental Health Criteria 132:
Trichlorfon
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
Trichlorfon : health and safety guide.
(Health and safety guide ; no. 66)
1.Trichlorfon - adverse effects
2.Trichlorfon -poisoning
3.Trichlorfon - standards
4.Environmental exposure I.Series
ISBN 92 4 151066 8 (NLM Classification: WA 240)
ISSN 0259-7268
(c) World Health Organization 1991
Publications of the World Health Organization enjoy copyright
protection in accordance with the provisions of Protocol 2 of the
Universal Copyright Convention. For rights of reproduction or
translation of WHO publications, in part or in toto, application
should be made to the Office of Publications, World Health
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welcomes such applications.
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
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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
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 human beings
3. CONCLUSIONS AND RECOMMENDATIONS
4. HUMAN HEALTH HAZARDS, PREVENTION AND PROTECTION, EMERGENCY ACTION
4.1. Main human health hazards, prevention and protection,
first aid
4.1.1. Advice to physicians
4.1.1.1 Symptoms of poisoning
4.1.1.2 Medical treatment
4.1.2. Health surveillance advice
4.2. Explosion and fire hazards
4.3. Storage
4.4. Transport
4.5. Spillage and disposal
4.5.1. Spillage
4.5.2. 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
ANNEX I. TREATMENT OF ORGANOPHOSPHATE INSECTICIDE POISONING IN MAN
INTRODUCTION
The Environmental Health Criteria (EHC) documents 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. Within the Guide is a Summary of Chemical Safety
Information which should be readily available, and should be clearly
explained, to all who could come into contact with the chemical. 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 Manager
International Programme on Chemical Safety
Division of Environmental Health
World Health Organization
1211 Geneva 27
Switzerland
THE INFORMATION IN THIS GUIDE SHOULD BE CONSIDERED AS A STARTING POINT
TO A COMPREHENSIVE HEALTH AND SAFETY PROGRAMME
1. PRODUCT IDENTITY AND USES
1.1 Identity
Common name: trichlorfon (ISO)
Chemical structure:
Chemical formula: C4H8Cl3O4P
Relative molecular mass: 257.44
CAS chemical name: dimethyl2,2,2-trichloro-1-hydroxyethyl-
phosphonate
Synonyms: Chlorofos; DEP; DETF; dipterex; dimethyl
1-hydroxy-2,2,2-trichloroethane-
phosphonate; O,O-dimethyl
(2,2,2-trichloro-1-hydroxyethyl)
phosphonate; metrifonate, foschlor;
trichlorofon; trichlorphon
Trade names: Agroforotox; Anthon; L 13/59; Bilarcil;
Cekufon; Danex; Dipterex; Ditriphon;
Dylox; Dyrex; Dyvon; Masoten;
Metrifonate; Neguvon; Proxol; Tugon;
Wotex
CAS registry number: 52-68-6
RTECS registry number: TA0700000
Conversion factors: 1 ppm = 11.4 mg/m3
1 mg/m3 = 0.088 ppm,
at 25°C and 101.3 kPa (760 mmHg)
The purity of technical trichlorfon is reported to be more than 98%.
It is a racemic mixture of two isomers. The main impurities are
2,2-dichlorovinyl dimethyl phosphate, dichlorvos (0-0.2%),
trichloroacetaldehyde (0-0.05%), dichloroacetaldehyde (0-0.03%),
methyl hydrogen 2,2,2-trichloro-1-hydroxyethylphosphonate, demethyl
trichlorfon (0-0.3%), and water (less than 0.3%). The technical
product also contains phosphoric acid, 2,2,2-trichloro-1-
hydroxyethylphosphonic acid, and dimethyl phosphite.
1.2 Physical and Chemical Properties
Trichlorfon is a colourless crystalline powder that is stable at room
temperature. It is slowly hydrolysed in acid media; the half-life is
526 days at pH 1-5 and 20°C. In alkaline media, at pH 8 and 37.5°C,
it hydrolyses initially to the more toxic compound dichlorvos, but is
essentially 100% hydrolysed in 24 h to less toxic products, such as
dimethyl hydrogen phosphate, dichloroacetaldehyde, and glyoxal.
Trichlorfon also decomposes under ultraviolet irradiation.
Some physical properties are given in the Summary of Chemical Safety
Information (section 6).
1.3 Analytical Methods
Trichlorfon residues can be determined using gas liquid
chromatography. The same method can be used for product analysis;
alternative methods include thin layer chromatography and high
performance liquid chromatography.
1.4 Production and Uses
Trichlorfon was introduced as a commercial chemical in 1952. It is a
broad spectrum insecticide that is particularly effective against
Diptera. It is used mainly against insect pests in field and fruit
crops, but it is also used to control forest insects and in public
health. Further applications of trichlorfon include the control of
endo- and ectoparasites in, or on, domestic animals and fish. Under
the generic name of metrifonate, trichlorfon is used as an
antihelminthic, and in the treatment of schistosomiasis in humans.
The global consumption of trichlorfon, which was more than 3000 tonnes
in 1980, was reported to be approximately 850 tonnes in 1987.
Formulations used in agriculture are: 50% emulsifiable concentrate,
95, 80, and 50% soluble powders, 50% wettable powders, 5 and 4% dusts,
5, 2.5, and 1% granules, and 75, 50, 40, and 25% ultra-low volume
concentrates.
The following formulations are used in the treatment of animals: 90,
80, and 50% soluble powders, 6% suspension, 11% solution, and 50%
injectable solution tablets. A 1% fly bait is also available and a
0.1% preparation against house ants.
Tablets containing 100 mg metrifonate are used in the treatment of
schistosomiasis in humans.
2. SUMMARY AND EVALUATION
2.1 Exposure
Trichlorfon is an organophosphorus insecticide that has been in use
since the early 1950s. It is considered to be a slow release
reservoir of dichlorvos.
The air concentration of trichlorfon insecticide may be as high as
0.1 mg/m3, soon after spraying, but, within days, levels decrease to
below 0.01 mg/m3. Levels of trichlorfon in runoff water from
sprayed areas may be as high as 50 µg/litre, though levels in surface
waters are usually much lower and decrease rapidly.
Trichlorfon is relatively stable in water at pH values below 5.5. At
higher pH values, trichlorfon is transformed into dichlorvos. While
micro-organisms and plants may metabolize trichlorfon, the most
important route of removal is abiotic hydrolysis.
Trichlorfon degrades rapidly in the soil, and levels generally
decrease to negligible amounts within one month of application.
With a few exceptions, levels of trichlorfon on crops are below
10 mg/kg, the day after application, and below 0.1 mg/kg, two weeks
later.
Milk from cows treated with trichlorfon for pest control may contain
residues as high as 1.2 mg/litre, 2 h after application, but the
levels decline to less than 0.1 mg/litre, 24 h after treatment.
Significant levels of trichlorfon have not been found in the meat from
treated animals. Eggs from treated hens have been found to contain
0.05 mg trichlorfon/kg.
2.2 Uptake, metabolism, and excretion
Trichlorfon is readily absorbed via all routes of exposure (oral,
dermal, inhalation) and is rapidly distributed to the tissues of the
body. Peak blood concentrations are detected within 12 h, with
disappearance from the blood stream occurring in a matter of 1.5-4 h;
only low levels are detected after 8-24 h. The biological half-life
of trichlorfon in the mammalian blood is estimated to be about 30 min.
Trichlorfon undergoes transformation, via dehydrochlorination, to form
dichlorvos (2,2-dichlorovinyl dimethyl phosphate) in water and all
biological fluids and tissues, at pH values higher than 5.5.
Dichlorvos is a physiologically active anticholinesterase. The main
routes of degradation of trichlorfon are demethylation, P-C bond
cleavage, and ester hydrolysis via dichlorvos. The major metabolites
of trichlorfon found in vivo are demethyl trichlorfon, demethyl
dichlorvos, dimethyl hydrogen phosphate, methyl hydrogen phosphate,
phosphoric acid, and trichloroethanol. The last of these metabolites
is found in the urine as a glucuronide conjugate.
The elimination of trichlorfon and its metabolic products occurs
primarily via the urine. Studies conducted with radiolabelled
(14C-methyl and 32P-) trichlorfon revealed that the bulk of the
chemical was excreted as water-soluble material, little being
chloroform-soluble. Some 66-70% of water-soluble products appeared in
the urine within 12 h. Twenty-four percent of the 14C-methyl
labelled material was eliminated in the expired air as carbon dioxide.
Low levels of trichlorfon and its metabolites have been detected in
the milk of cows treated with trichlorfon.
2.3 Effects on organisms in the environment
Trichlorfon is moderately toxic for fish (96-h LC50 values range
between 0.45 mg/litre and 51 mg/litre), and moderately to highly toxic
for aquatic arthropods (48-h/96-h LC50 values range between
0.75 µg/litre and 7800 µg/litre). However, the reported
concentrations of trichlorfon found in surface waters, after
application in forests at 6 kg/ha, fell short of these ranges. Thus,
normal use of trichlorfon will have little or no effect on populations
of aquatic organisms, since other groups, such as molluscs and
microorganisms, are less sensitive than arthropods. Trichlorfon is
moderately toxic for birds, LD50 values from laboratory studies
ranging between 40 mg/kg and 180 mg/kg body weight. However, field
studies following aerial application of trichlorfon did not reveal any
effects on the numbers, breeding pairs, nesting success, or mortality
of forest songbirds. A reduction observed in singing and an increase
in feeding activity may have resulted from a reduction in food
organisms. There is no indication that trichlorfon will adversely
affect organisms in the terrestrial environment other than arthropods.
There is no information on the effects on beneficial arthropods.
2.4 Effects on experimental animals and in vitro test systems
Trichlorfon is an insecticide that is moderately toxic for animals.
The oral LD50 values of technical trichlorfon in laboratory animals
range from 400 to 800 mg/kg body weight; the dermal LD50 values for
the rat exceed 2000 mg/kg body weight. Trichlorfon poisoning causes
the usual organophosphate cholinergic signs attributed to the
accumulation of acetylcholine at nerve endings. Technical trichlorfon
was shown to be moderately irritating to the eyes of rats, but was not
irritating in skin tests on rabbits. Skin sensitization potential was
demonstrated in guinea-pigs.
Short-term, oral toxicity studies were carried out on rats, dogs,
monkeys, rabbits, and guinea-pigs. In a 16-week study on rats, a
4-year study on dogs, and a 26-week study on monkeys,
no-observed-effect levels (NOELs) of 100 mg/kg diet, 50 mg/kg diet,
and 0.2 mg/kg body weight (based on plasma, erythrocyte, or brain ChE
activity) respectively, were determined. Inhalation exposure of rats,
over a 3-week period, indicated a NOEL of 12.7 mg/m3, based on the
inhibition of plasma, erythrocyte, and brain ChE activity. Long-term
toxicity/carcinogenicity studies were carried out on mice, rats,
monkeys, and hamsters, after oral, intraperitoneal, or dermal
administration. An adverse effect on the gonads was demonstrated
following the oral exposure of mice and rats at dose levels of
30 mg/kg body weight and 400 mg/kg diet, respectively. From a
24-month study on rats and a 10-year study on monkeys,
no-observed-adverse-effect levels (NOAELs) of 50 mg/kg diet and
0.2 mg/kg body weight, respectively, were determined.
No evidence of carcinogenicity has been found following the long-term
exposure of test animals using several routes of administration.
Under physiological conditions, trichlorfon has been reported to have
a DNA-alkylating property. The trichlorfon mutagenicity results have
been both positive and negative. Dichlorvos may be either partly or
fully responsible for the effects observed. The results of most of
the in vitro mutagenicity studies on both bacterial and mammalian
cells were positive, while few of the in vivo studies produced
positive results.
Studies on mice, rats, and hamsters indicate that trichlorfon produces
a teratogenic response in rats at doses high enough to produce
maternal toxicity. Exposure of rats to 145 mg/kg diet during
gestation caused fetal malformations. A dose of 400 mg/kg body
weight, administered by gavage to hamsters, also produced both
maternal toxicity and a teratogenic response. The lowest dose by
gavage that produced teratogenic effects in rats was 80 mg/kg body
weight. The effects appeared to be time specific in the gestation
period. The NOEL in this study was 8 mg/kg. NOAELS of 8 mg/kg body
weight for rats and 200 mg/kg body weight for hamsters were
demonstrated. Teratogenic responses involving the central nervous
system have been reported for the pig and guinea-pig. However, no
teratogenic effects were observed in a 3-generation reproduction study
on rats, in which high dose levels induced adverse reproductive
effects. The NOEL in this study was 300 mg/kg diet.
Very high doses have produced neurotoxicity in animals.
The active transformation product in mammals is dichlorvos, which is
estimated to be at least 100 times more potent as an
anticholinesterase than trichlorfon.
2.5 Effects on Human Beings
Several cases of acute poisoning from intentional (suicide) or
accidental exposure have occurred. Signs and symptoms of intoxication
included characteristics of AChE inhibition, such as exhaustion,
weakness, confusion, excessive sweating and salivation, abdominal
pains, vomiting, pinpoint pupils, and muscle spasms. In severe cases
of poisoning, unconsciousness and convulsions developed and death
usually resulted from respiratory failure. In cases where victims
survived because of medical intervention, a delayed polyneuropathy
associated with weakness of the lower limbs occurred a few weeks after
exposure. In fatal cases, autopsy findings have shown ischaemic
changes in the brain, spinal cord, and vegetative ganglia, damage to
the myelin sheath in the spinal cord and brain peduncles, and
structural changes in the axons of peripheral nerves.
A few cases of occupational poisoning have occurred, mainly because
safety precautions were neglected. Occupational exposure at a
workplace where air concentrations exceeded 0.5 mg/m3, resulted in
decreased levels of plasma cholinesterase and changes in the EEG
pattern. However, these effects were completely reversible on
cessation of exposure. No cases of skin sensitization have been
reported.
Trichlorfon has been extensively used for the treatment of
schistosomiasis in humans. Administration of a single dose
(7-12 mg/kg) resulted in 40-60% inhibition of cholinesterase in the
plasma and erythrocytes, without the manifestation of any cholinergic
symptoms. However, mild symptoms were observed in cases with a
repeated dose regimen. A high dose level (24 mg/kg) caused severe
cholinergic symptoms.
3. CONCLUSIONS AND RECOMMENDATIONS
3.1 Conclusions
Trichlorfon is a moderately toxic organophosphorus ester insecticide.
Overexposure through handling during manufacture or use, or accidental
or intentional ingestion may cause serious poisoning.
The general population is exposed to trichlorfon mainly as a result of
agricultural and veterinary practices, and in the treatment of
Schistosoma haematobium.
The reported trichlorfon intakes are far below the Acceptable Daily
Intake established by FAO/WHO and should not constitute a health
hazard for the general population.
With good work practices, hygienic measures, and safety precautions,
trichlorfon is unlikely to present a hazard for those occupationally
exposed.
Despite its high toxicity for non-target arthropods, trichlorfon has
been used with little or no adverse effect on populations of organisms
in the environment.
3.2 Recommendations
For the health and welfare of workers and the general population, the
handling and application of trichlorfon should only be entrusted to
competently supervised and well-trained operators, who will follow
adequate safety measures and apply trichlorfon according to good
application practices.
The manufacture, formulation, agricultural use, and disposal of
trichlorfon should be carefully managed to minimize contamination of
the environment, particularly surface waters.
Regularly exposed workers and patients should undergo periodic health
evaluations.
The rates of application of trichlorfon should be limited, to avoid
effects on non-target arthropods. The insecticide should never be
sprayed over water bodies or streams.
4. HUMAN HEALTH HAZARDS, PREVENTION AND PROTECTION, EMERGENCY ACTION
4.1 Main Human Health Hazards, Prevention and Protection, First Aid
Trichlorfon is an organophosphorus insecticide. Technical trichlorfon
and concentrated formulations are slightly toxic (acute, oral LD50
for the rat: 560 mg/kg), but can be hazardous for human beings if
incorrectly handled. Trichlorfon is hazardous through ingestion and
skin contact, because of rapid absorption. Typical signs and symptoms
of organophosphorus poisoning may occur rapidly with overexposure.
Cases of delayed neurotoxicity have been reported as well as sporadic
cases of effects on spermatogenesis.
The human health hazards associated with certain types of exposure to
trichlorfon, together with preventive and protective measures and
first aid recommendations are listed in the Summary of Chemical
Information (section 6).
4.1.1 Advice to physicians
4.1.1.1 Symptoms of poisoning
Trichlorfon is an indirect inhibitor of cholinesterase, i.e., it is
converted in the body into the active transformation product,
dichlorvos. As a result, signs and symptoms of overexposure develop
after a latent period and may continue to increase after exposure has
been discontinued. Initially, there may be feelings of exhaustion,
headache, weakness, and confusion. Then, vomiting, abdominal pain,
and excessive sweating and salivation may develop. The pupils are
small. Difficulty in breathing may be experienced, due to either
congestion of the lungs or weakness of the respiratory muscles. In
severe cases of poisoning, muscle spasms, unconsciousness, and
convulsions may develop. Death results from respiratory failure.
For a more complete treatise on the effects of organophosphorus
insecticides, especially their short- and long-term effects on the
nervous system, refer to Environmental Health Criteria 63:
Organophosphorus insecticides - a general introduction (WHO 1968).
4.1.1.2 Medical treatment
Since trichlorfon formulations may contain petroleum distillates, it
is preferable not to induce vomiting. In the case of ingestion of
liquid formulations containing hydrocarbon solvents, vomiting involves
a risk of aspiration pneumonia. Instead, the stomach should be
emptied, as soon as possible, by careful gastric lavage using 5%
sodium bicarbonate (with a cuffed endotracheal tube already in place).
If possible, identify the solvents present in the formulation and
observe the victim for additional toxic effects. As early as
possible, administer 2 mg of atropine sulfate intravenously and
1000-2000 mg of pralidoxime chloride or 250 mg of obidoxime chloride
(adult dose), intramuscularly or intravenously, to patients suffering
from severe respiratory difficulties, convulsions, or unconsciousness.
Repeated doses of 2 mg of atropine sulfate should be given, as
required, based on the respiration, blood pressure, pulse frequency,
salivation, and convulsion conditions. For children, the doses are
0.04-0.08 mg of atropine/kg body weight, 250 mg of pralidoxime
chloride per child or 48 mg of obidoxime chloride/kg body weight.
Diazepam 10 mg (adult dose) should be given, subcutaneously or
intravenously, in all but the mildest cases.
Artificial respiration should be applied, if required.
Morphine, barbiturates, phenothiazine derivatives, tranquillizers, and
all kinds of central stimulants are contraindicated.
The diagnosis of intoxication should be confirmed as soon as possible
by the determination of the cholinesterase activity (ChE) in venous
blood.
For more information on the treatment of poisoning by organophosphorus
insecticides see Environmental Health Criteria 63: Organophosphorus
insecticides: - a general introduction (WHO 1986). The section on
therapy from this publication is attached as Annex 1 of this guide.
4.1.2 Health surveillance advice
Occupational exposure to organophosphorus insecticides can be
monitored by the measurement of erythrocyte- and whole blood-ChE
activity. Physiological variations in erythrocyte- and blood-ChE
values occur in a healthy persons.
Inhibition of acetyl-cholinesterase (AChE) or ChE activities of less
than 20-25% is considered diagnostic of exposure, but not necessarily
indicative of hazard. However, work procedures and hygiene should be
checked. Inhibition of 30-50% or more is considered an indication
that an exposed individual should be removed from further contact with
ChE-inhibiting pesticides, until values return to normal. Work
procedures and hygiene should also be checked.
4.2 Explosion and Fire Hazards
Liquid formulations may be flammable. Inform the fire service that
skin contamination and the breathing of fumes must be avoided.
Protective clothing and self-contained breathing apparatus must be
worn.
Extinguish fires with alcohol-resistant foam or powder. The use of
water spray should be confined to the cooling of unaffected stock, to
avoid polluted runoff from the site.
4.3 Storage
Technical trichlorfon and its formulations should be stored in locked,
well-ventilated buildings, preferably buildings specifically used for
insecticide storage. Do not expose to direct sunlight. Keep products
out of reach of children and unauthorized personnel. Do not store
near animal feed or foodstuffs.
4.4 Transport
Comply with any local regulations regarding the movement of hazardous
goods. Do not load with animal feed or foodstuffs. Check that
containers are sound and labels undamaged before despatch.
4.5 Spillage and Disposal
4.5.1 Spillage
Stay upwind, avoid skin contamination and inhalation of vapour.
Absorb spilled liquid, and cover contaminated areas with a 1:3 mixture
of sodium carbonate crystals and damp sawdust, lime, sand, or earth.
Sweep up and place the sweepings in a closeable, impervious container.
Ensure that the container is tightly closed and suitably labelled
before transfer to a safe place for disposal.
Prevent liquid from spreading and contaminating other cargo,
vegetation, or waterways with a barrier of the most suitable material
available, e.g., earth or sand. If the spill occurs into a waterway
and the trichlorfon-containing material is immiscible with water and
sinks, dam the waterway to stop the flow and to retard dissipation by
water movement. Use a bottom pump, dredging, or underwater vacuum
equipment to remove undissolved material.
Empty any of the product remaining in a damaged/leaking container into
a clean empty container, which should then be tightly closed and
suitably labelled.
Decontaminate emptied leaking containers with a 10% sodium carbonate
solution added at the rate of at least 1 litre per 20-litre drum.
Swirl round to rinse walls, empty, and add rinsings to sawdust, etc.
Puncture empty containers to prevent re-use.
4.5.2 Disposal
Contaminated absorbents, containers, surplus product, etc., should be
burnt in a proper incinerator, at high temperatures, with effluent gas
scrubbing. When no incinerator is available, bury in an approved
dump, or in an area where there is no risk of contamination of surface
or ground water. Before burying, liberally mix with sodium carbonate
(washing soda) crystals to help neutralize the product and mix with
soil rich in organic matter. Comply with any local legislation.
5. HAZARDS FOR THE ENVIRONMENT AND THEIR PREVENTION
Trichlorfon is moderately toxic for birds and fish, but highly toxic
for arthropods. It does not bioaccumulate, and it breaks down rapidly
in the environment.
Avoid contamination of the soil, water, and atmosphere by proper
methods of storage, transport, handling, and waste disposal.
In case of spillage, use the methods advised in section 4.5.1.
6. SUMMARY OF CHEMICAL SAFETY INFORMATION
This summary should be easily available to all health workers
concerned with, and users of, trichlorfon. It should be displayed at,
or near, entrances to areas where there is potential exposure to
trichlorfon, 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.
TRICHLORFON
Chemical formula: C4H8Cl3O4P
CAS chemical name: dimethyl 2,2,2-trichloro-1-hydroxyethylphosphonate
CAS registry number: 52-68-6
PHYSICAL PROPERTIES OTHER CHARACTERISTICS
Appearance colourless crystals Colourless crystalline powder; stable at room temperature;
Melting point 83-84°C slowly hydrolysed in acid media, with half-life of 526 days at
Boiling point 100°C (0.1 mmHg) pH 1-5 (20°C); at pH 8 (37.5°C) hydrolyses to dichlorvos,
Vapour pressure 7.8 × 10-6mmHg (20°C) but 100% transformed to less toxic products within 24 h;
Volatility 0.022 mg/m3(20°C) decomposes under ultraviolet radiation
20
Density d 1.73
4
Solubility at 25°C in g/100 ml
water 15.4
benzene 15.2
chloroform 75.0
diethyl ether 17.0
n-hexane 0.08
Partition coefficient
(octanol/water) log Pow 0.57
Corrosiveness corrosive to metals
HAZARDS/SYMPTOMS PREVENTION AND PROTECTION FIRST AID
GENERAL: readily absorbed via
skin, ingestion, and inhalation; may
cause organophosphate poisoning:
weakness, headache, vomiting,
excessive sweating and salivation,
pinpoint pupils; in severe cases:
convulsions, unconsciousness, and
death due to respiratory paralysis
SKIN: irritation; redness; extensive Wear PVC or neoprene gloves Remove and wash contaminated clothing;
contamination may cause poisoning and apron; rubber boots wash contaminated skin with water and
soap; obtain medical attention immediately
EYES: irritation; redness Wear safety goggles or face shield Flush eyes with clean water for at least
15 min; if irritation persists, obtain
medical attention immediately
INHALATION: overexposure may Avoid breathing the vapour; use In case of signs and symptoms, remove from
cause poisoning proper (exhaust) ventilation or contaminated area and obtain medical
suitable respiratory protection attention immediately
INGESTION: an unlikely Wash hands before eating, drinking, Induce vomiting, if the subject is conscious,
occupational hazard using the toilet, and after work except in the case of an emulsifiable
concentrate; obtain medical attention
immediately
Accidental or intentional ingestion Obtain medical attention immediately; if
may rapidly lead to severe poisoning breathing has stopped, apply artificial
respiration
HAZARDS/SYMPTOMS PREVENTION AND PROTECTION FIRST AID
REPEATED EXPOSURE BY As above As above
INHALATION OR INGESTION,
OR THROUGH SKIN may gradually
lead to signs and symptoms associated
with inhibition of cholinesterase
activity
7. CURRENT REGULATIONS, GUIDELINES, AND STANDARDS
The information given in this section has been extracted from the
International Register of Potentially Toxic Chemicals (IRPTC) legal
file. A full reference to the original national document from which
the information was extracted can be obtained from IRPTC. When no
effective date appears in the IRPTC legal file, the year of the
reference from which the data are taken is indicated by (r).
The reader should be aware that regulatory decisions about chemicals
taken in a certain country can only be fully understood in the
framework of the legislation of that country. Furthermore, the
regulations and guidelines of all countries are subject to change and
should always be verified with appropriate regulatory authorities
before application.
7.1 Previous Evaluations by International Bodies
Trichlorfon was evaluated by the Joint FAO/WHO Meeting on Pesticide
Residues (JMPR) in 1971, 1975, and 1978. In 1978, the JMPR
established an Acceptable Daily Intake (ADI) for humans of
0-0.01 mg/kg body weight.
The International Agency for Research on Cancer (IARC) evaluated
trichlorfon in 1987, and concluded that the data were inadequate to
evaluate its carcinogenicity for experimental animals, and that no
data on its carcinogenicity for humans were available. It was
therefore classified in Group 3.
The International Programme on Chemical Safety (WHO) classified
technical trichlorfon as "slightly hazardous" (Class III). WHO has
issued a data sheet on trichlorfon (No. 27).
7.2 Exposure Limit Values
Some exposure limit values are given in the table on pp. 28-29. When
considering exposure limits, however, it is important also to include
any residues of its major conversion product, dichlorvos (see HSG
No. 18: Dichlorvos).
7.3 Specific Restrictions
Trichlorfon has been officially approved for use as a pesticide in
most countries. In some countries, specific uses as well as
limitations and precautions are defined. In the USSR, it was banned
for use in livestock farming in 1987. In Norway, its use is not
permitted for medical treatment.
EXPOSURE LIMIT VALUES
Medium Specification Country/ Exposure limit description Value Effective
organization date
AIR Workplace Hungary Maximum allowable concentration (MAC)
- Ceiling value 0.5 mg/m3 1988
USSR Maximum allowable concentration (MAC)
- Ceiling value (vapour + aerosol) 0.5 mg/m3 1977
AIR Ambient USSR Maximum allowable concentration (MAC)
(average per day) 0.04 mg/m3 1984
- Ceiling value 0.5 mg/m3
FOOD Intake from FAO/WHO Acceptable daily intake (ADI) 0-0.01 mg/kg 1978
body weight
FOOD Residue FAO/WHO Maximum residue limit (MRL) 0.05-2 mg/kg 1986, 1988,
products specified as follows: 1989
- Carrots, eggplants (aubergines), milk, parsley,
sugar beets 0.05 mg/kg
- Artichokes, beans (black-eyed, green, lima),
cattle (carcass, meat, byproducts, fat), cereal
grains, cherries, citrus fruits, cotton seed,
cow peas, linseed, mustard greens, peanuts
(shell-free), pigs (carcass meat, byproducts,
fat), pumpkins, radishes, rapeseed, safflower
seed (plus cob), sheep (carcass meat), soya
beans, turnips 0.1 mg/kg
- Bananas (pulp), beet root, brussels sprouts,
cauliflower, celery, kale, peaches, sweet corn
(kernels + cob), tomatoes 0.2 mg/kg
- Cabbage, grapes, lettuce, spinach 0.5 mg/kg
- Banana, peppers, strawberries 1.0 mg/kg
- Apples 2.0 mg/kg
Medium Specification Country/ Exposure limit description Value Effective
organization date
WATER Surface USSR Maximum allowable concentration 0.05 mg/kg 1983
fishing USSR Maximum allowable concentration 0.00 mg/kg 1983
SOIL USSR Maximum allowable concentration 0.05 mg/kg 1976
7.4 Labelling, Packaging, and Transport
The United Nations Committee of Experts on the Transportation of
Dangerous Goods classifies trichlorfon in:
Hazard Class 6.1: poisonous substance;
Packing Group III: a substance presenting a relatively low
risk of poisoning in transport, for
material containing 70% (solid) or 23%
(liquid).
The label should be as follows:
The European Economic Community legislation requires labelling as
dangerous substance using the symbol:
The label must read:
Harmful by inhalation, in contact with skin and if swallowed;
keep out of reach of children; keep away from food, drink and
animal feeding stuffs.
The European Economic Community legislation on the labelling of
pesticide preparations classifies trichlorfon in Class IIB for the
purpose of determining the labels for preparations containing
trichlorfon and other active ingredients.
WHO gives the following product specification for technical
trichlorfon for use in public health:
"The material shall consist of trichlorfon together with related
manufacturing compounds and shall be in the form of a white
crystalline powder free from extraneous impurities or added modifying
agents."
The material should contain at least 970 g trichlorfon per kg. The
acidity and water content are specified and analytical methods for
checking are given.
The specification continues:
"The technical trichlorfon shall be packed in suitable, clean
containers, as specified in the order.
"All packages shall bear, durably and legibly marked on the container,
the following:
Manufacturer's name
Technical trichlorfon to specification WHO/SIT/13.R3
Batch or reference number, and date of test
Net weight of contents
Date of manufacture
and the following minimum cautionary notice:
"Trichlorfon is an organophosphorus compound that inhibits
cholinesterase. It is poisonous if swallowed or absorbed
through the skin. Avoid skin contact; wear protective gloves
and clean protective clothing while using the material. Wash
thoroughly with soap and water after using.
"Keep the material out of the reach of children, and well away
from foodstuffs, and animal feed, and their containers.
"If poisoning occurs, call a physician. Atropine and
pralidoxime are specific antidotes, and artificial respiration
may be needed."
Similar specifications and instructions are given for trichlorfon
emulsifiable concentrate and water-soluble powder.
FAO gives similar product specifications for trichlorfon for its use
in plant protection. In this case, the technical material should
contain at least 97% active material. Containers must comply with
pertinent national and international transport and safety regulations.
7.5 Waste Disposal
In the USA, any waste containing trichlorfon is considered a hazardous
waste and permits are required for its handling, transport, treatment,
storage, discharge, and disposal.
BIBLIOGRAPHY
FAO (1985a) Guidelines for the packaging and storage of pesticides.
Rome, Food and Agriculture Organization of the United Nations.
FAO (1985b) Guidelines for the disposal of waste pesticides and
pesticide containers on the farm. Rome, Food and Agriculture
Organization of the United Nations.
FAO (1985c) Guidelines on good labelling practice for pesticides.
Rome, Food and Agriculture Organization of the United Nations.
FAO (1986) International code of conduct on the distribution and use
of pesticides. Rome, Food and Agriculture Organization of the United
Nations.
FAO/WHO (1964-present) Evaluation of some pesticide residues in food.
Rome, Food and Agriculture Organization of the United Nations.
FAO/WHO (1986a) Guide to Codex recommendations concerning pesticide
residues. Part 8. Recommendations for methods of analysis of
pesticide residues. 3rd ed., Rome, Codex Committee on Pesticide
Residues.
FAO/WHO (1986b) Codex maximum limits for pesticide residues.
CAC/Vol.XIII - ed. 2, Rome, Codex Alimentarius Commission, Food and
Agriculture Organization of the United Nations, - plus Supplement 1
(1988) and Supplement 2 (1989).
GIFAP (1982) Guidelines for the safe handling of pesticides during
their formulation, packing, storage and transport. Brussels,
Groupement International des Associations Nationales des Fabricants de
Produits Agrochimiques.
GIFAP (1983) Guidelines for the safe and effective use of pesticides.
Brussels, Groupement International des Associations Nationales des
Fabricants de Produits Agrochimiques.
GIFAP (1984) Guidelines for emergency measures in cases of pesticide
poisoning. Brussels, Groupement International des Associations
Nationales des Fabricants de Produits Agrochimiques.
GIFAP (1987) Guidelines for the safe transport of pesticides.
Brussels, Groupement International des Associations Nationales des
Fabricants de Produits Agrochimiques.
IARC (1972-present) IARC monographs on the evaluation of carcinogenic
risk of chemicals to man. Lyon, International Agency for Research on
Cancer.
IRPTC (1985) IRPTC file on treatment and disposal methods for waste
chemicals. Geneva, International Register of Potentially Toxic
Chemicals, United Nations Environment Programme.
IRPTC (1987) IRPTC legal file. Geneva, International Register of
Potentially Toxic Chemicals, United Nations Environment Programme.
PLESTINA, R. (1984) Prevention, diagnosis, and treatment of
insecticide poisoning. Geneva, World Health Organization (unpublished
document No.VBC/84.889).
SAX, N.I. (1984) Dangerous properties of industrial materials. New
York, Van Nostrand Reinhold Company Inc.
UNITED NATIONS (1986) Recommendations on the transport of dangerous
goods. 4th ed., New York, United Nations.
US NIOSH/OSHA (1981) Occupational health guidelines for chemical
hazards. 3 Vols, Washington DC, US Department of Health and Human
Services, US Department of Labor (Publication No. DHHS(NIOSH) 01-123).
WHO (1986) Environmental Health Criteria 63: Organophosphorus
insecticides : a general introduction. Geneva, World Health
Organization, 181 pp.
WHO (1990) The WHO recommended classification of pesticides by hazard
and guidelines to classification 1990/91. Geneva, World Health
Organization (Unpublished document WHO/PCS/90.1).
WHO (in preparation) Environmental Health Criteria 132: Trichlorfon.
Geneva, World Health Organization.
WHO/FAO (1975-87) Trichlorfon, Data sheets on pesticides, No. 27.
Geneva, World Health Organization (Unpublished document).
WORTHING, C.R. & WALKER, S.B. (1987) The pesticide manual. 8th ed.,
Lavenham, Lavenham Press Limited, British Crop Protection Council.
ANNEX I
TREATMENT OF ORGANOPHOSPHATE INSECTICIDE POISONING IN MAN
(From EHC 63: Organophosphorus Insecticides - A General Introduction)
All cases of organophosphorus poisoning should be dealt with as an
emergency and the patient sent to hospital as quickly as possible.
Although symptoms may develop rapidly, delay in onset or a steady
increase in severity may be seen up to 48 h after ingestion of some
formulated organophosphorus insecticides.
Extensive descriptions of treatment of poisoning by organophosphorus
insecticides are given in several major references (Kagan, 1977;
Taylor, 1980; UK DHSS, 1983; Plestina, 1984) and will also be included
in the IPCS Health and Safety Guides to be prepared for selected
organophosphorus insecticides.
The treatment is based on:
(a) minimizing the absorption;
(b) general supportive treatment; and
(c) specific pharmacological treatment.
I.1 Minimizing the Absorption
When dermal exposure occurs, decontamination procedures include
removal of contaminated clothes and washing of the skin with alkaline
soap or with a sodium bicarbonate solution. Particular care should be
taken in cleaning the skin area where venepuncture is performed.
Blood might be contaminated with direct-acting organophosphorus esters
and, therefore, inaccurate measures of ChE inhibition might result.
Extensive eye irrigation with water or saline should also be
performed. In the case of ingestion, vomiting might be induced, if
the patient is conscious, by the administration of ipecacuanha syrup
(10-30 ml) followed by 200 ml water. This treatment is, however,
contraindicated in the case of pesticides dissolved in hydrocarbon
solvents. Gastric lavage (with addition of bicarbonate solution or
activated charcoal) can also be performed, particularly in unconscious
patients, taking care to prevent aspiration of fluids into the lungs
(i.e., only after a tracheal tube has been put in place).
The volume of fluid introduced into the stomach should be recorded and
samples of gastric lavage frozen and stored for subsequent chemical
analysis. If the formulation of the pesticide involved is available,
it should also be stored for further analysis (i.e., detection of
toxicologically relevant impurities). A purgative can be administered
to remove the ingested compound.
I.2 General Supportive Treatment
Artificial respiration (via a tracheal tube) should be started at the
first sign of respiratory failure and maintained for as long as
necessary.
Cautious administration of fluids is advised, as well as general,
supportive and symptomatic pharmacological treatment and absolute
rest.
I.3 Specific Pharmacological Treatment
I.3.1 Atropine
Atropine should be given, beginning with 2 mg iv and given at
15-30-min intervals. The dose and the frequency of atropine treatment
varies from case to case, but should maintain the patient fully
atropinized (dilated pupils, dry mouth, skin flushing, etc.).
Continuous infusion of atropine may be necessary in extreme cases and
total daily doses of up to several hundred mg may be necessary during
the first few days of treatment.
I.3.2 Oxime reactivators
Cholinesterase reactivators (e.g., pralidoxime, obidoxime)
specifically restore AChE activity inhibited by organophosphates.
This is not the case with enzymes inhibited by carbamates. The
treatment should begin as soon as possible, because oximes are not
effective on "aged" phosphorylated ChEs. However, if absorption,
distribution, and metabolism are thought to be delayed for any
reasons, oximes can be administered for several days after
intoxication. Effective treatment with oximes reduces the required
dose of atropine. Pralidoxime is the most widely available oxime. A
dose of 1 g pralidoxime can be given either im or iv and repeated
2-3 times per day or, in extreme cases, more often. If possible,
blood samples should be taken for AChE determinations before and
during treatment. Skin should be carefully cleansed before sampling.
Results of the assays should influence the decision on whether to
continue oxime therapy after the first 2 days.
There are indications that oxime therapy may possibly have beneficial
effects on CNS-derived symptoms.
I.3.3 Diazepam
Diazepam should be included in the therapy of all but the mildest
cases. Besides relieving anxiety, it appears to counteract some
aspects of CNS-derived symptoms, which are not affected by atropine.
Doses of 10 mg s.c. or i.v. are appropriate and may be repeated as
required (Vale & Scott, 1974). Other centrally acting drugs and drugs
that may depress respiration are not recommended in the absence of
artificial respiration procedures.
I.3.4 Notes on the recommended treatment
I.3.4.1 Effects of atropine and oxime
The combined effect far exceeds the benefit of either drug singly.
I.3.4.2 Response to atropine
The response of the eye pupil may be unreliable in cases of
organophosphorus poisoning. A flushed skin and drying of secretions
are the best guide to the effectiveness of atropinization. Although
repeated dosing may well be necessary, excessive doses at any one time
may cause toxic side-effects. Pulse-rate should not exceed 120/min.
I.3.4.3 Persistence of treatment
Some organophosphorus pesticides are very lipophilic and may be taken
into, and then released from, fat depots over a period of many days.
It is therefore quite incorrect to abandon oxime treatment after
1-2 days on the supposition that all inhibited enzyme will be aged.
Ecobichon et al. (1977) noted prompt improvement in both condition and
blood-ChEs in response to pralidoxime given on the 11th-15th days
after major symptoms of poisoning appeared due to extended exposure to
fenitrothion (a dimethyl phosphate with a short half-life for aging of
inhibited AChE).
I.3.4.4 Dosage of atropine and oxime
The recommended doses above pertain to exposures, usually for an
occupational setting, but, in the case of very severe exposure or
massive ingestion (accidental or deliberate), the therapeutic doses
may be extended considerably. Warriner et al. (1977) reported the
case of a patient who drank a large quantity of dicrotophos, in error,
while drunk. Therapeutic dosages were progressively increased up to
6 mg atropine i.v. every 15 min together with continuous i.v. infusion
of pralidoxime chloride at 0.5 g/h for 72 h, from days 3 to 6 after
intoxication. After considerable improvement, the patient relapsed
and further aggressive therapy was given at a declining rate from days
10 to 16 (atropine) and to day 23 (oxime), respectively. In total,
92 g of pralidoxime chloride and 3912 mg of atropine were given and
the patient was discharged on the thirty-third day with no apparent
sequelae.
References to Annex I
ECOBICHON, D.J., OZERE, R.L., REID, E., & CROCKER, J.F.S (1977)
Acute fenitrothion poisoning. Can. Med. Assoc. J.,116: 377-379.
KAGAN, JU.S. (1977) [Toxicology of organophosphorus pesticides.]
Moscow, Meditsina, pp. 111-121, 219-233, 260-269 (in Russian).
PLESTINA, R. (1984) Prevention, diagnosis, and treatment of
insecticide poisoning. Geneva, World Health Organization (Unpublished
WHO document. VBC/84.889).
TAYLOR, P. (1980) Anticholinesterase agents. In: Goodman, L.S. &
Gilman, A., ed. The pharmacological basis of therapeutics. 6th ed. New
York, Macmillan Publishing Company, pp. 100-119.
UK DHSS (1983) Pesticide poisoning: notes for the guidance of medical
practitioners, London, United Kingdom Department of Health and Social
Security, pp. 41-47.
VALE, J.A. & SCOTT, G.W. (1974) Organophosphorus poisoning. Guy's
Hosp. Rep., 123: 13-25.
WARRINER, R.A., III, NIES, A.S., & HAYES, W.J., Jr (1977) Severe
organophosphate poisoning complicated by alcohol and terpentine
ingestion. Arch. environ. Health, 32: 203-205.