WORLD HEALTH ORGANIZATION FOOD AND AGRICULTURE
ORGANIZATION
ORGANISATION MONDIALE DE LA SANTE ORGANISATION POUR L'ALIMENTATION
ET L'AGRICULTURE
VBC/DS/79.38
ORIGINAL: ENGLISH
LEPTOPHOS
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: Insecticide
Secondary use: Fungicide
Chemical group: Organophosphorus compound
Date issued: April 1979
1. GENERAL INFORMATION
1.1 COMMON NAME: Leptophos (ISO)
1.1.1 Identity: O-(4-bromo-2,5-dichlorophenyl) 0-methyl
phenylphosphonothioate
1.1.2 Synonyms:
VCS 506
Phosvel
Abar
Local synonyms:
1.2 SYNOPSIS - An organophosphorus insecticide of high mammalian
toxicity which may produce a delayed neurotoxic effect. It
should not be used if an alternative exists.
1.3 SELECTED PROPERTIES
1.3.1 Physical characteristics - A white amorphous solid of melting
point 70.2-70.6°C (99.4% purity).
1.3.2 Solubility - Only very slightly soluble in water, 2.4 mg/i at
25°C. Very soluble in benzene, 1.3 kg/l; cyclohexane 142 g/l;
acetone, 470 mg/l.
1.3.3 Stability - Very stable; it hydrolyses slowly under strongly
alkaline conditions and is stable under prolonged acid exposure
at normal temperatures. Decomposition occurs above 350°C.
1.3.4 Vapour pressure - 1.5 x 10-5 mmHg at 25°C.
1.4 AGRICULTURE, HORTICULTURE AND FORESTRY
1.4.1 Common formulations - Emulsifiable concentrates 3 Ib a.i./US
gall (300 g/1). Wettable powder 45%; dust 3%, granulets 5%.
1.4.2 Pests mainly controlled - Effective against lepidoptera
especially Prodenia litura, grasshoppers, bugs, fleas.
1.4.3 Use pattern - There is positive evidence of a temperature
coefficient against lepidoptera which may make it more useful in
warmer climates. Moderately persistent. Used as e.c. on cotton
at 1.5 lb a.i./acre (1.7 kg/ha). Used as e.c. on vegetables and
fruit at 1.0 lb a.i./100 galls (1 g/1). Use as granules on
maize at 1.5 kg a.i.,/hectare.
1.4.4 Unintended effects - Reported to have only minimal irritating
effect on eyes if handled with usual care.
1.5 PUBLIC HEALTH PROGRAMMES - Not recommended for any use in public
health programmes.
1.6 HOUSEHOLD USE: No household use.
2. TOXICOLOGY AND RISKS
2.1 TOXICOLOGY - MAMMALS
2.1.1 Absorption route - Leptophos may be absorbed through the intact
skin, by inhalation and from the gastrointestinal tract.
2.1.2 Mode of action - Inhibition of cholinesterase and "neurotoxic
esterase" after metabolic conversion to the oxygen analogue.
2.1.3 Excretion products - Most of an oral dose is eliminated within
24 hours. By 96 hours 80-87% of C14 labelled leptophos is
accounted for in the urine and approximately 12% in the faeces.
Metabolites include the oxygen analogue, 0-methyl
phenylphosphonothioate and 1-bromo-2,5-dichlorophenol.
2.1.4 Toxicity, single dose
Oral: LD50 rat (M): 53 mg/kg
rat (F): 43 mg/kg
Dermal: LD50 rabbit > 800 mg/kg
2.1.5 Toxicity, repeated doses
Oral: Rats of both sexes were fed 1.0, 5.0, 10.0 mg/kg diet of
leptophos for 90 days. All survived and there were no
alterations in body weights, plasma biochemistry or in brain,
plasma and erythrocyte cholinesterase. Rats of both sexes were
fed 3.0, 10.0, 30.0 and 100 mg/kg diet for 10 days. One rat
died at the 100 mg/kg level and there was marked inhibition of
brain and erythrocyte cholinesterase at 30 ppm in all but one
rat. The rats surviving for 10 days at 100 mg/kg showed similar
cholinesterase inhibition.
Inhalation: The aerosol inhalation LC50 was found to be
2.7 g/m3 air based on a fourhour period of exposure for albino
rats. Cholinesterase inhibition in blood was observed at
concentrations of 0.84 mg/litre of air. Tremors, lacrimation,
salivation and blood stained ocular and nasal discharge were
observed.
Cumulation of compound: Leptophos is not cumulative in body
tissues.
Cumulation of effect: Continued exposure to leptophos is likely
to have a cumulative effect on cholinesterase inhibition.
2.1.6 Dietary studies
Short-term: Dogs of both sexes were fed leptophos at 3.0, 10.0
and 30.0 mg/kg diet for 90 days. No biochemical abnormalities
were observed. Body weight, food consumption, haematology and
urine analyses were normal. At the completion of this study,
organ weights and gross and histopathologic examinations were
within normal limits .
Long-term: A two-year dietary feeding study in rats at 10, 20,
30 and 60 mg/kg diet revealed no significant abnormalities apart
from some inhibition of erythrocyte cholinesterase at 60 mg/kg
after 18 and 24 months exposure. No significant effect on brain
cholinesterase was observed at any of the feeding levels.
2.1.7 Supplementary studies on toxicity
Carcinogenicity: During the two-year feeding study described
above (2.1.6) a tumour incidence was assessed at the conclusion
of the investigation. The incidence of tumours in the treated
and control animals was comparable and considered normal.
Teratogenicity: Rabbits dosed with leptophos at 1.0 and 3.0
mg/kg from days 6-18 of gestation revealed no increase in
resorptions, foetal mortality or abnormal offspring. Body
weights of foetuses from both test groups compared well with the
untreated contro group.
Mutagenicity: A dominant lethal mutagenic study designed to
evaluate the potential effects of leptophos upon male germinal
cells in mice was conducted. Both orai and intraperitoneal
dosage were employed and by both routes, doses of 15 and 30
mg/kg were used. None of the animals showed any impairment in
mating ability.
Delayed neurotoxicity: Delayed ataxia and paralysis in hens has
been reported with this compound after single oral doses of 400
and 500 mg/kg. The oxon metabolite of leptophos is an extremely
active inhibitor of the "neurotoxic esterase" in vitro, normally
a clear warning of potential hazard.
Local irritative effect: Transient conjunctival irritation has
been observed in rabbits after instillation of 100 mg of
leptophos. The reaction was most marked at 24 hours and had
disappeared 72 hours after exposure.
2.1.8 Modifcation of toxicity - No information available.
2.2 TOXICOLOGY - MAN
2.2.1 Absorption - Leptophos may be absorbed through the intact skin,
by inhalation and frothe gastrointestinal tract.
2.2.2 Dangerous doses
Single: Not known.
Repeated: Not known.
2.2.3 Observations on occupationally exposed workers - No information
available.
2.2.4 Observations on exposure of the general population - No
information available.
2.2.5 Observations of volunteers - No information available.
2.2.6 Reported mishaps - 1200 water buffalo were suspected of being
poisoned with leptophos. Some fatalities were recorded and there
were reports of persistent paralysis in some of the survivors.
2.3 TOXICITY TO NON-MAMMALIAN SPECIES
2.3.1 Fish - Harmful - rainbow trout: as toxic as DDT
goldfish: much more toxic than DDT
2.3.2 Birds - Subacutely toxic to quail. Neurotoxic to hens at high
dosage.
2.3.3 Other species - No harmful effects reported following widespread
foliar and soil treatments at 1-2 kg/ha on arable and
horticultural crops in several countries. Regarded however as
potential toxicant to wild life if used contrary to labels.
3. FOR REGULATORY AUTHORITIES - RECOMENDATIONS ON REGULATION OF
COMPOUND
3.1 RECOMMENDED RESTRICTIONS ON AVAILABILITY
(for definition of categories, see Introduction to data sheets)
All formulations Category 1: This compound has an adjusted
classification in the WHO Recommended Classification of
Pesticides by Hazard due to its potential to cause delayed
neurotoxicity.
Granular formulations only below 2%, category 5.
3.2 TRANSPORTATION AND STORAGE
All formulations - Should be transported in clearly labelled
rigid and leakproof containers and in a separate compartment not
containing any food or drink. Storage should be under lock and
key and secure from access by unauthorized persons and children.
3.3 HANDLING
All formulations - Full protective clothing (see Part 4) should
be provided for all handling of the compound. Adequate washing
facilities should be available at all times during handling and
should be close to the site of handling. Eating, drinking and
smoking should be prohibited during handling and before washing
after handling.
3.4 DISPOSAL AND/OR DECONTAMINATION OF CONTAINER
All formulations - Container must either be burned or crushed
and buried below topsoil. Care must be taken to avcid
subsequent contamination of water sources. Decontamination of
containers in order to use them for other purposes should not be
permitted.
3.5 SELECTION, TRAINING AND MEDICAL SUPERVISION OF WORKERS
All formulations - Prc-employment medical examination of workers
necessary. Workers suffering from active haptic, renal or
neurological disease should be excluded from contact. Pre-
employment and periodic cholinesterase test for workers
desirable. Special account should be taken of the workers'
ability to comprehend and follow instructions.
3.6 ADDITIONAL REGULATIONS RECOMMENDED IF DISTRIBUTED BY AIRCRAFT
All formulations - Should not be applied from the air.
3.7 LABELLING
All formulations "POISON" (skull and crossbones insignia).
Minimum cautionary statement - Leptophos is an organophosphorus
compound which inhibits cholinesterase, an may cause delayed
disorders of the nervous system. Contact with the skin,
inhalation of'dust or spray or swallowing may be fatal'. Wear
protective gloves, clean protective clothing and a respirator of
the organic-vapour type when handling this material. Bathe
immediately after work. Ensure that containers,are kept under
lock and key. Keep the material out of the reach of children
and well away from foodstuffs, animal feed and their containers.
If splashed, irmnediately remove contaminated clothing and wash
the skin thoroughly with soap and water. For splashes in eyes,
flush with water for 15 minutes.
If poisoning occurs, call a physician. Atropine and pralidoxime
are specific antidotes for acute poisoning and repeated doses
may be necessary. Artificial respiration may be needed.
3.8 RESIDUES IN FOOD: Maximum residue limits have been recommended
by the Joint FAO/WHO Meeting on Pesticide Residues. These are
subject to review by the Joint Meeting which is held annually.
4. PREVENTION OF POISONING IN MAN AND EMERGENCY AID
4.1 PRECAUTIONS IN USE
4.1.1 General - Leptophos is an organophosphorus pesticide of high
toxicity. It penetrates The intact skin and is also absorbed by
inhalation and from the gastrointestinal tract. All
formulations should be handled by trained personnel wearing
protective clothing.
4.1.2 Manufacture and formulation
T.L.V.: No information available.
4.1.3 Mixers and applicators - When opening the container and when
mixing, protective impermeable boots, clean overalls, gloves and
respirator should be worn. Mixing, if not mechanical, should
always be carried out with a paddle of appropriate length. When
spraying tall crops a respirator should be worn as well as an
impermeable hood, clothing, boots and gloves. The applicator
should avoid working in spray mist and avoid contact with the
mouth.
Particular care is needed when equipment is being washed after
use. All protective clothing should be washed immediately after
use, including the insides of the gloves. Splashes must be
washed immediately from the skin or eyes with large quantities
of water. Before eating, drinking or smoking, hands and other
exposed skin should be washed.
4.1.4 Other associated workers - Persons exposed to leptophos 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 - With good agricultural
practice subject to 4.2 below, other populations should not be
exposed to hazardous amounts of leptophos.
4.2 ENTRY OF PERSONS INTO TREATED AREAS - Unprotected persons should
be kept out of treated areas for at least one day.
4.3 SAFE DISPOSAL OF CONTAINERS AND SPILLAGE - Residues in
containers should be emptied in a diluted form into a deep pit
taking care to avoid contamination of ground waters.
Decontamination of containers in order to use them for other
purposes should not be permitted. Spillage of leptophos and its
formulations should be removed by washing with 5% sodium
hydroxide solution and then rinsing with large quantities of
water.
4.4 EMERGENCY AID
4.4.1 Early symptoms of poisoning - May include excessive sweating,
headache, weakness, giddiness, nausea, vomiting, stomach pains,
blurred vision, slurred speech, and muscle twitching. Later
there may be convulsions, coma, loss of reflexes and loss of
sphincter control.
4.4.2 Treatment before person is seen by a physician, if these
symptoms appear following exposure - The person should stop work
immediately, remove contaminated clothing and wash the affected
skin with soap and water, if available, and flush the area with
large quantities of water. If swallowed, vomiting should be
induced if the person is conscious. In the event of collapse,
artificial respiration should be given, bearing in mind that if
mouth-to-mouth resuscitation is used, vomit may contain toxic
amounts of leptophos.
5. FOR MEDICAL AND LABORATORY PERSONNEL
5.1 MEDICAL DIAGNOSIS AND TREATMENT IN CASES OF POISONING
5.1.1 General information - An organophosphorus pesticide of high
acute toxicity which can be absorbed through the intact skin as
well as by inhalation and from the gastrointestinal tract. It
is partially converted in vivo to the oxon analogue which is an
active inhibitor of acetylcholinesterase. Continued exposure to
low amounts may inhibit blood cholinesterase to dangerous
levels. By a different mechanism (inhibition of "neurotoxic
esterase"), dying-back process may be initiated in which the
long axons are particularly affected (delayed neurotoxic
effect).
5.1.2 Symptoms and signs - Initial symptoms of poisoning may include
excessive sweating, headache, weakness, giddiness, nausea,
vomiting, stomach pains, blurred vision, slurred speech and
muscle twitching. More advanced symptoms may include
convulsions, coma, loss of reflexes, and loss of sphincter
control. In survivors, delayed neurotoxicity may become
manifest by persistent ataxia and paralysis of the limbs.
5.1.3 Laboratory - The most important laboratory findings is reduction
in blood cholinesterase activity.
5.1.4 Treatment - If the pesticide has been ingested, unless the
patient is vomiting, rapid gastric lavage should be performed
using 5% sodium bicarbonate, if available. if skin contact has
occurred the skin should be washed with soap and water. If the
compound has entered the eyes, they should be washed with a
large quantity of isotonic saline or water. Persons without
signs of respiratory inefficiency but with manifest peripheral
symptoms, should be treated with 2-4 mg of atropine sulfate and
1000-2000 mg of pralidoxime chloride or 250 mg of Toxogonin
(adult dose) by slow intravenous injection. More atropine
should be given as needed. Persons with severe intoxication,
with respiratory dif f iculties, convulsions and unconsciousness
should immediately be given atropine and a reactivator. In such
severe cases 4-6 mg of atropine sulfate at 5-10 minute
intervals. The patient's condition, including respiration,
blood pressure, and pulse rate, should be carefully observed as
a guide to further administration of atropine. If the patient
is cyanotic, atropine and artificial respiration or oxygen as
required may be administered simultaneously. If necessary,
intubation should be performed. Diazepam may be given to
control fits. Contraindicated are morphine, barbiturates, other
tranquillizers and central stimulants of all kinds.
5.1.5 Prognosis - There is no specific treatment for delayed
neurotoxic effects. In people surviving the acute toxic effect
the chances of complete recovery are not certain as it is
possible that persistent ataxia and paralysis of limbs may be a
sequel of poisoning.
5.1.6 Reference of previously reported case - No cases of poisoning in
man have so far reported.
5.2 SURVEILLANCE TESTS
Test Normal level* Action level*
Plasma cholinesterase 100% 50%
Erythrocyte cholin-
esterase 100% 70%
Symptomatic level
variable
usually 40%
Urinary levels of ether extractable organic phosphorus may also
be used to determine the degree of exposure.
5.3 LABORATORY METHODS - References are given only.
5.3.1 Detection and assay of compound - It is unlikely that unchanged
leptophos will be detectable in human tissue after exposure as
it will be fairly rapidly broken down to a number of
metabolites.
Product analysis is by infra-red absorption at 9.62 microns.
Residues are determined by electron capture G.L.C. Particulars
of the methods can be obtained from the Velsicol Chemical
Corporation, Chicago, or from Bowman, M. C. & Beroza, M. (1969)
J. Agr. Food Chem., 17, 1054.
5.3.2 Other tests in cases of poisoning - Levels of cholinesterase in
the blood, particularly plasma, provide the most useful
diagnosis of poisoning, see: Michel, N. 0. (1949) J. Lab.
Clin. Med., 34, 1564 and Ellman, G. L. et al. (1961)
Biochem. Pharmacol., 7, 88.
Levels of phosphate esters in urine may also be determined in
order to give an indication of the extent of exposure. See
methods given in 5.3.1 above.
* Expressed as percentage of pre-exposure activity.
= = =