WORLD HEALTH ORGANIZATION FOOD AND AGRICULTURE ORGANIZATION
ORGANISATION MONDIALE DE LA SANTE ORGANISATION POUR L'ALIMENTATION ET
L'AGRICULTURE
VBC/PDS/DS/85.59
ORIGINAL: ENGLISH
DATA SHEET ON PESTICIDES No. 59
AZINPHOS-METHYL
CLASSIFICATION:
Primary use: Insecticide
Secondary use: Acaricide
Chemical group: Organophosphorus compound
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.
1. GENERAL INFORMATION
1.1 COMMON NAME: Azinphos-methyl (ISO, BSI; exception - USSR;
metiltriazotion)
1.1.1 Identity:
IUPAC: S-(3,4-dihydro-4-oxobenzo (d)-(1,2,3)-triazin-3-
ylmethyl-O,O-dimethyl phosphorodithioate
CAS No. 1: Phosphorodithioic acid, O,O-dimethyl ester, S-ester
with 3(mercaptomethyl)-1,2,3-benzotriazin-4(3H)-one
CAS Reg. No: 86-50-0
Molecular formula: C10H12N3O3PS2
Molecular weight: 317.1
Structural formula:
1.1.2 Synonyms: Azinfos-methyl; Azinophos-methyl; Azinphos methyl;
Azinphosmetile; Bay 9027; Bay 17 147; CarfeneR; CotneonR;
CotnionR; Cotnion-methylR; CrysthionR; CrysthyonR; DBDR;
Ent 23,233; GothnionR; GusathionR; GuthionR, Methyl GusathionR;
Methyl GuthionR; Metiltriazotion; NCI-CO0066; R 1582.
1.2 SYNOPSIS: Azinphos-methyl is a broad spectrum, non-cumulative,
non-systemic organophosphorus insecticide/acaricide; an
irreversible cholinesterase inhibitor with good contact and
stomach action. It has good residual activity and is highly toxic
to mammals and some wildlife. It is toxic to some ornamental and
fruit trees. Toxicity is increased following metabolism.
1.3 SELECTED PROPERTIES
1.3.1 Physical characteristics - Azinphos-methyl forms colourless
crystals melting at 73-74°C. It has a density (d2O/4) of 1.44
and a refractive index n76/D) of 1.6115.
1.3.2 Solubility - In water, 33 mg/l at room temperature; it is soluble
in most organic solvents except aliphatics.
1.3.3 Stability - Azinphos-methyl is unstable at temperatures above
200°C and is rapidly hydrolysed by cold alkali and acid.
Solutions in ethanol and propylene glycol are stable for at least
3 weeks.
1.3.4 Vapour pressure - Less than 3.8 x 10-4 mmHg at 20°C.
1.4 AGRICULTURE, HORTICULTURE AND FORESTRY
1.4.1 Common formulations - These include emulsifiable concentrates,
200 g a.i./l; wettable powders, 200-500 g a.i./kg; dust
preparations, 25 and 50 g a.i./kg; ULV preparations, 150-200 g/l.
1.4.2 Pests controlled - These include aphids, mites, codling moths,
lygusbugs, bollworms, armyworms, bollweevils, thrips,
grasshoppers, stinkbugs, spittle bugs, plum curculio, pear
psylla, scale and the European brown snail.
1.4.3 Use pattern - Azinphos-methyl is used on alfalfa, almonds,
apricots, apples, artichokes, beans, barley, caneberries,
blueberries, broccoli, brussel sprouts, cabbage, cauliflower,
celery, cherries, citrus, clover, coffee, cotton, crabapples,
cranberries, cucumbers, eggplant, filberts, grapes, melons,
nectarines, oats, onions, peaches, pears, pecans, plums, peppers,
potatoes, prunes, quinces, rice, rye, soybeans, spinach,
strawberries, sugar cane, sugar beets, tobacco, tomatoes, trees,
walnuts, watermelons, wheat, ornamentals and others. It is
applied at a rate of 4.5-6.5 kg/ha.
1.4.4 Unintended effects - Azinphos-methyl is toxic to Hawthorn and
American Linden trees at high concentrations and the EC has
caused russetting to some fruit varieties.
1.5 PUBLIC HEALTH USES - No recommended use.
1.6 HOUSEHOLD USE - No recommended use.
2. TOXICOLOGY AND RISKS
2.1 TOXICOLOGY - MAMMALS
2.1.1 Absorption route - Azinphos-methyl is absorbed from the
gastrointestinal tract; through the intact skin; and, by
inhalation of fine spray mist or dusts.
2.1.2 Mode of action - Azinphos-methyl is an inhibitor of
cholinesterase activity in vitro mammalian, avian and piscene
studies have shown, however, that it is a poor inhibitor of brain
cholinesterase. The oxygen analogue, gutoxon is a more potent
anticholinesterase agent in brain tissue. After cessation of
treatment it usually takes several weeks for normal enzyme
activities to resume.
2.1.3 Excretion products - Azinphos-methyl is readily absorbed and
metabolised in mammals. Dimethylphosphorothioic and
dimethylphosphoric acids, desmethyl azinphosmethyl and azinphos-
methyloxon are principal metabolites as demonstrated in in vitro
mouse tissue studies. The benzotrianzine moiety is rapidly
excreted without degradation, less than 0.1% of the radioactivity
of peroral or intraperitoneal doses (0.1-0.2 mg/kg bw) of 14C-
labelled azinphos-methyl is eliminated as CO2. Approximately 65%
of the radioactivity of these doses was eliminated in urine,
about 25% in faeces. In studies with dairy cows no residues of
azinphos-methyl or gutoxon appeared in milk, four unidentified
non-phosphorus containing metabolites were present in low
concentration.
2.1.4 Toxicity, single dose:
Oral LD50:
Rat (M) 16 (13-25) mg/kg bw
Rat (F) 13.5 (11-16.4) mg/kg bw
Mouse (M) 7.15 mg/kg bw
Guinea-pig (M) 80 mg/kg bw
Dermal LD50:
Rat (M) 455 mg/kg bw
(F) 220 mg/kg bw
Mouse 65 mg/kg bw
I.P. LD50:
Rat (M) 11.6 mg/kg bw
Rat (F) 5.1 mg/kg bw
Mouse (M) 5.4 mg/kg bw
Mouse (F) 3.4 mg/kg bw
Guinea-pig (M) 40.0 mg/kg bw
I.V. LD50:
Rat (M & F) 7.5 mg/kg bw
I.V. LD50:
Mouse (M) 8.0 mg/kg bw
Inhalation LC50
Rat (M) 69.0 mg/kg bw
(F) 79.0 mg/kg bw
Most susceptible species - Females, in all species tested, appear
to be more sensitive than males, the mouse appears to be the
most susceptible species.
2.1.5 Toxicity, repeated doses:
Oral: See Dietary studies, section 2.1
Dermal: In animals given 2 or 20 mg/kg bw doses five times a
week for three weeks there was a slight depression of
cholinesterase activity at the highest dose only. The no-
observed-effect level was reported to be 2.0 (mg/kg bw)/day.
Inhalation: Male and female rats exposed to 4.72 mg/m3 for 6
hours a day, 5 days a week for 12 weeks showed depressed
erythrocyte and plasma cholinesterase activity, males showed
depression growth rates. Concentrations of 0.195 and 1.24 mg/m3
produced no ill effects.
2.1.6 Dietary studies:
Short term: Groups of male rats were fed azinphos-methyl at
dosage levels of 0, 5, 10, 20, 50 or 100 mg/kg (diet) for 9
weeks. At the two highest dose levels clinical signs of toxicity
and decreased body weight gains were observed. Whole blood
cholinesterase activity was depressed in all treatment groups.
Groups of male and female rats were fed azinphos-methyl at dosage
levels of 0, 2, 5, and 20 mg/kg (diet) for 120 days. No clinical
or laboratory evidence of toxicity was evident at 60 days. At
the highest dose, at 120 days, there was some inhibition of brain
and erythrocyte cholinesterase (10 and 30 per cent respectively).
There were no observed treatment related changes in gross or
microscopic anatomy.
Weanling male rats fed 50 or 100 mg/kg (diet) for 16 weeks showed
increased mortality rates (50%), severe clinical signs of
toxicity, which stabilized after 30 days, and showed a dose
dependent decrease in body weight gain. All cholinesterase
activities were markedly depressed throughout the dosing period.
Brain and erythrocyte activities were not fully restored to
normal 30 days after cessation of treatment. No evidence of
testicular atrophy was evident in the survivors.
Groups of male and female dogs given azinphos-methyl in 5, 10, 20
or 50 mg/kg diets for 12 weeks showed no treatment related
depression of weight gain or clinical signs of toxicity. At 50
mg/kg cholinesterase activity was significantly decreased by the
end of the 12 weeks.
In a second experiment male and female dogs were given azinphos-
methyl in 0, 20, 50, 100, 200 or 400 mg/kg diets for 19 weeks.
Cholinesterase activity was slightly depressed in the 20 and 50
mg/kg groups after four weeks, reactivation occurred after 6 and
9 weeks respectively. On the 100 mg/kg diets and above,
cholinesterase activity was depressed to 50% of control level.
Slight though unequivocal reactivation occurred in the 100 mg/kg
group only, after 17 weeks.
Long term: In a 2 year rat study, both sexes were given azinphos-
methyl at 0, 2.5, 5 or 20 mg/kg (diets), an additional group was
given 50 mg/kg (diet) for 47 weeks followed by a 100 mg/kg (diet)
for the remainder of the study period. In the highest dosage
groups, severe clinical signs of toxicity were observed in over
10% of the females. There were no treatment induced changes in
mortality, body weight gain, food consumption, or haematology.
In males at 20 mg/kg (diet) and above erythrocyte and plasma
cholinesterase activities were significantly depressed; at 5
mg/kg (diet) the plasma activity was inhibited up to the 39th
week. In females these activities were consistently depressed at
the highest dosage level only; at 20 mg/kg (diet) the plasma
activity was depressed up to week 65; at 5 mg/kg (diet)
erythrocyte activity was depressed up to week 10 only. Brain
cholinesterase activity was depressed in the highest dosed
animals only which also experienced some increase in liver
weight. There was no indication that tumour incidence was
increased by azinphos-methyl treatment.
Groups of male and female dogs were fed azinphos-methyl at both
constant and progressively increasing dosage levels: 5 mg/kg
(diet) for 2 years; 20 mg/kg (diet) for 36 weeks increased to 50
mg/kg (diet) for 15 months; 50 mg/kg (diet) for two years; 50
mg/kg (diet) for 36 weeks, followed by 100 mg/kg (diet) for 21
weeks, 150 mg/kg (diet) for 27 weeks and, finally 300 mg/kg
(diet) for 21 weeks. In males at 300 mg/kg (diet) severe
clinical signs of toxicity with slight weight loss were observed.
Fewer females showed severe signs of toxicity at the highest
dosage level and there was a slight reduction in food consumption
at both highest dosages. Erythrocyte cholinesterase activity was
slightly decreased at 20 mg/kg (diet), markedly at 50 mg/kg
(diet) and higher. In the second year, all dogs showed a
decrease in plasma cholinesterase activity at dosage levels of 50
mg/kg (diet) and above. There were no treatment related changes
in mortality rates, laboratory parameters or in gross or
histopathological incidences.
The no-effect-levels have been demonstrated in the rat and dog to
be approximately 0.125 (mg/kg bw)/day.
2.1.7 Supplementary studies of toxicity
Carcinogenicity: Azinphos-methyl has been classified as a
tumorogen with no carcinogenic potential. Azinphos-methyl was
given at time weighted average dietary levels of 78 and 156 mg/kg
(diet) to male rats, 62.5 and 125 mg/kg (diet) to female rats,
3.13 and 62.5 mg/kg (diet) for male mice, and 62.5 and 125 mg/kg
(diet) for female mice. Compound related tumours of the pancreas
and of thyroid follicle cells were observed. Mutagenicity
studies have also provided no clear support of a carcinogenic
potential for azinphos-methyl.
Mutagenicity: Results of a dominant lethal mutation study in
which male mice received 1.125 or 1.25 mg/kg bw doses (i.p.) were
negative. In a Chinese hamster cell culture study, azinphos-
methyl was mutagenically active only at doses of 600 ppm or more.
Similar results, at high doses, were observed in human cell
culture studies. Azinphosmethyl was inactive in several
microbial pre-screening tests for mutagenicity.
Teratogenicity: There was no evidence of teratogenic potential
for azinphos-methyl in several mammalian reproductive studies
including a mouse dominant lethal mutagenicity test. It was also
inactive in a chick embryo study (1 mg/egg); though embryotoxic
(66% mortality), the survivors showed no morphologic abnormality.
Reproduction: In a rat 3-generation study, 0, 5, 10, 25 or 50
mg/kg (diet) doses were continuously fed to males and females
from thirty days prior to first mating of the FO generation. A
high mortality rate among females forced the elimination of the
highest dose group after the first mating; poor weanling survival
was also observed at this dosage level. In the remaining groups
no treatment related adverse effects were observed relative to
reproductive behaviour and success, and no embryotoxic or fetal
toxic effects were observed. Gross and microscopic anatomy of
the F3b weanlings were normal.
Azinphos-methyl was fed to pregnant rabbit does from day 8 to day
16 of pregnancy at dosage levels of 5 or 25 mg/kg (diet). No
treatment related changes were observed in litter size, number of
stillbirths, sex ratios, fetal weight, fetal development, or pup
survival to 30 days.
Neurotoxicity: There was no evidence of demylenation in rats fed
azinphos-methyl at dosage levels up to 20 mg/kg (diet) for 120
days. Azinphos-methyl is a neuroactive agent with immediate
neurotoxic action and no known delayed neurotoxic effect.
2.1.8 Modification of toxicity - No information available.
2.2 TOXICOLOGY - MAN
2.2.1 Absorption route - Azinphos-methyl may be absorbed from the
gastrointestinal tract, through the intact skin; and by
inhalation of fine spray mist or dusts.
2.2.2 Dangerous doses:
Single: Azinphos-methyl has a toxicity rating 5 - extremely
toxic, the probable lethal oral dose for humans is from 5 to 50
mg/kg bw, approximately seven drops or one teaspoon (0.2 g) for
a 70 kg person.
Repeated: No information available.
2.2.3 Observations of occupationally exposed workers - Cholinesterase
activity in 15 male agricultural field workers was only slightly.
lower than in controls. No clinical signs of toxicity were
observed in the workers exposed to the pesticide. One spray-
aircraft pilot experienced severe symptoms of azinphos-methyl
poisoning while flying his craft. Probable source of the
contamination was a concentrate spill on his hands and a spray
directly onto his face. He was able to land safely and was
treated in hospital; his recovery was uneventful.
2.2.4 Observations on exposure of the general population - No
information available.
2.2.5 Observations of volunteers - In several experimental exposure
studies male volunteers were given peroral doses ranging from 4
to 20 (mg/man)/day for 30 days. No clinical signs of toxicity
were observed and there was significant depression of
cholinesterase levels only at the highest dose levels (18 and 20
mg).
In a second study, 2 male volunteers received 16 mg of azinphos-
methyl for 30 days. Neither subject showed any depression of
blood cholinesterase during treatment. Excretion of the
degradation products reached maximum level 24 hours after the
initial treatment and continued at that level until the day
following cessation of treatment.
2.2.6 Reported mishaps - No information available.
2.3 TOXICITY TO NON-MAMALIAN SPECIES
2.3.1 Fish - Azinphos-methyl is quite toxic to fish.
LC50 (48 hour):
Channel cat fish 9.0 mg/l
Sunfish 0.025 mg/l
Golden shiner 0.1 mg/l
Large mouth bass 0.025 mg/l
Bluegills 0.025 mg/l
Goldfish 2.0 mg/l
Median tolerance limits:
TL50 (96 hour):
Rainbow trout 0.0032
Chinook salmon 0.0043
Coho salmon 0.0042
Guppies 0.12
Fathead minnow 0.093
Stickleback 0.012; (0.5% salinity)
Stickleback 0.005; (2.5% salinity)
2.3.2 Birds - Both laboratory and field tests have shown that birds
have a significantly high tolerance to azinphos-methyl regardless
of the route of absorption.
Acute LD50:
Chicken 277 mg/kg bw
The 100 day cumulative LD50, 250 mg/kg (diet):
Juvenile bobwhite quail 5500 mg/kg bw
Juvenile ringneck pheasant 2000 mg/kg bw
Bobwhite quail showed no adverse effects after exposure to 6
spray applications (0.83-0.89 kg a.i./ha) at 6 day intervals over
a two month period. Ringneck pheasants similarly exposed to
spray applications of 5.5 kg a.i./ha showed no ill effects and
their reproductive success was not affected.
2.3.3 Other species - Azinphos-methyl is acutely toxic to a variety of
wildlife species including amphibians, crustaceans, molluscs, and
many beneficial insects such as honey bees. There is no evidence
however that it is accumulative in aquatic environments and it is
not persistent on plants.
3. FOR REGULATORY AUTHORITIES - RECOMMENDATIONS OF COMPOUND
3.1 RECOMMENDED RESTRICTION ON AVAILABILITY
(For definition of categories see the Introduction to data sheets)
Liquid formulations of 8% and over, Category 2
Other liquid formulations, Category 3
Solid formulations of 32% and over, Category 2
Other solid formulations, Category 3
3.2 TRANSPORTATION AND STORAGE
All formulations - Should be transported and stored in clearly
labelled impermeable containers under lock and key, secure from
access by unauthorized persons and children. No food or drink
should be stored in the same compartment.
3.3 HANDLING
All formulations - Full protective clothing (see 4.3, part 4)
should be used by those handling the compound. Adequate washing
facilities should be available at all times during the handling
and should be close to site of handling. Eating, drinking and
smoking should be prohibited during handling and before washing
after handling.
3.4 DISPOSAL AND/OR DECONTAMINATION OF CONTAINERS
All formulations - Container must either be burned or crushed and
buried below topsoil. Care must be taken to avoid subsequent
contamination of water sources. Decontamination of containers in
order to use them for other purposes should not be permitted.
3.5 SELECTION AND TRAINING AND MEDICAL SUPERVISION OF WORKERS
All formulations - Pre-employment medical examination of workers
necessary. Workers suffering from active hepatic or renal disease
should be excluded from contact. Pre-employment and periodic
cholinesterase test for workers desirable. A periodic urinary p-
nitrophenol test may be used as an alternative. Special account
should be taken of the workers' mental ability to comprehend and
follow instructions. Training of workers in techniques to avoid
contact essential.
3.6 ADDITIONAL REGULATIONS RECOMMENDED IF DISTRIBUTED BY AIRCRAFT
All formulations - Pilots and loaders should have special
training in application methods and early symptoms of poisoning,
and must wear a suitable respirator. Use of flagmen not
recommended. Flagmen, if used, should wear protective clothing, a
broad brimmed hat and be located well away from the dropping zone.
3.7 LABELLING
Minimum cautionary statement - All formulations. "DANGER -
POISON" (skull and cross-bones insignia). Azinphos-methyl is an
organophosphorus compound of very high toxicity, which inhibit
cholinesterase activity. 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 stored under lock and key.
Empty containers must be disposed of in such a way as to prevent
all possibility of accidental contact with them. Keep the
material out of reach of children and well away from foodstuffs,
animal feed and their containers.
In case of contact, immediately remove contaminated clothing and
wash the skin thoroughly with soap and water; for eyes, flush with
water for 15 minutes. If poisoning occurs, call a physician.
Atropine sulfate is a specific antidote, repeated doses may be
necessary. Artificial respiration also may be needed.
3.8 RESIDUES IN FOOD
3.8.1 Maximum residue levels - The Joint FAO/WHO Meeting on Pesticide
Residue recommended maximum residue levels.
4. PREVENTION OF POISONING IN MAN AND EMERGENCY AID
4.1 PRECAUTIONS IN USE
4.1.1 General - Azinphos-methyl is a highly toxic organophosphorus
pesticide. It penetrates the intact skin and is also absorbed by
inhalation and via the gastrointestinal tract. Most formulations
should be handled by trained personnel wearing protective
clothing.
4.1.2 Manufacture and formulation - T.L.V. - 0.2 mg/m3, STEL - 0.6
mg/m3. Closed systems and forced ventilation may be required to
reduce, as much as possible, the exposure of workers to the
chemical.
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 or during aerial application, 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 by 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
gloves. Splashes must be washed immediately from the skin and
eyes with large quantitites of water. Before eating, drinking or
smoking, hands and other exposed skin should be washed.
4.1.4 Other associated workers (including flagmen in aerial operations)
- Persons exposed to azinphos-methyl and associated with its
applications 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 application
practice subject to 4.2 below, other populations should not be
exposed to hazardous amounts of azinphos-methyl.
4.2 ENTRY OF PERSONS INTO TREATED AREAS - Unprotected persons should
be kept out of tall crops for four days and out of other crops for
24 hours after application.
4.3 DECONTAMINATION OF SPILLAGE AND CONTAINERS - Residues in
containers should be emptied in a diluted form into a deep pit,
taking care to avoid ground waters. The empty container may be
decontaminated by rinsing two or three times with water and
scrubbing the sides. An additional rinse should be carried out
with 5% sodium hydroxide solution which should remain in the
container overnight. Impermeable gauntlets should be worn during
this work, and a soakage pit should be provided for the rinsings.
Decontaminated containers should not be used for other purposes.
Spillage of the compound or 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 - Early symptoms of poisoning may
include excessive sweating, headache, weakness, giddiness,
nausea, vomiting, hypersalivation, stomach pains, blurred vision,
slurred speech and muscle twitching. Later there may be
convulsions and coma.
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 azinphos-methyl.
5. FOR MEDICAL AND LABORATORY PERSONNEL
5.1 MEDICAL DIAGNOSIS AND TREATMENT IN CASES OF POISONING
5.1.1 General information - Azinphos-methyl, an organophosphorus
pesticide of very high mammalian toxicity, is active against a
variety of agricultural and public health pests. It is readily
absorbed from the gastrointestinal tract; through the intact
skin; and, by inhalation. It is converted in vivo to the oxygen
analogue guthionoxon which inhibits cholinesterase. It does not
accumulate in body tissues.
5.1.2 Symptoms and signs - Initial symptoms of poisoning may include
excessive sweating, headache, weakness, giddiness, nausea,
hypersalivation, vomiting, stomach pains, blurred vision, slurred
speech and muscle twitching. More advanced symptoms of poisoning
may be convulsions, coma, loss of reflexes and loss of sphincter
control.
5.1.3 Laboratory - The most important finding is reduction of blood
cholinesterase activity. Urinary levels of organophosphorus
metabolites may also be used as a measure of exposure. Neither
method is specific for the compound.
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. For skin contact, the
skin should be washed with soap and water. If the compound has
entered the eyes, they should be washed with large quantities 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 by intravenous injection
and 1000 mg of pralidoxime chloride or 250 mg of toxogonin (adult
dose) by slow intravenous injection. More atropine may be given
as needed. Persons with severe intoxication, respiratory
difficulties, convulsions or unconscious should immediately be
given atropine and a reactivator. In such severe cases 4-6 mg of
atropine sulfate should be given initially followed by repeated
doses of 2 mg at 5-10 minute intervals. Diazepam may be given to
control convulsions. The patient's condition including
respiration, blood pressure, pulse frequency, salivation, and
convulsions should be carefully observed as a guide to further
administration of atropine. If the patient is cyanotic, oxygen
should be given at the same time as atropine sulfate. The
airways should be kept free and artificial respiration should be
applied, if required, preferably by mechanical means. If
necessary, intubation should be performed.
Contraindications are morphine, barbiturates, phenothiazine
tranquillizers and central stimulants of all kinds. Pralidoxime
and toxogonin alone are not regarded as effective antidotes in
organophosphorus poisoning. In cases of severe poisoning, when
administered early, pralidoxime may be used to relieve nicotinic
effects.
5.1.5 Prognosis - If the acute toxic effect is survived and adequate
artificial respiration has been given, if needed, the chances of
complete recovery are good. However, in very severe cases,
particularly if artificial respiration has been inadequate,
prolonged anoxia may give rise to permanent brain damage.
5.1.6 Reference of previously reported cases - No information
available.
5.2 SURVEILLANCE TESTS
5.3 LABORATORY METHODS - References are given only,
Test Normal Action Symptomatic
level* level* level*
Plasma
Cholinesterase 100% 50% variable
Whole Blood or Erythro-
cyte Cholinesterase 100% 70% usually 40%
* Expressed at percentage of pre-exposure activity.
5.3.1 Detection and assay of compound - Abbot D. C. et al. (1967)
Analyst, 92 171. Bowman M. C. & Beroza M. (1967),
J. Assoc. Off. Anal. Chem., 50, 1228. Burke J. A. &
Holswade W. (1966) J. Assoc. Off. Anal. Chem., 49, 377. Getz M.
E. & Wheeler H. G. (1968) J. Assoc. Off. Anal. Chem., 51,
1101. MacDougall D. (1964) Anal. Methods Pestic., Plant Growth
Regul., 2, 231. ibid, (1972) Anal. Methods Pestic., Plant Growth
Regul., 6, 397. Meager W. R. et al. (1960) J. Agric. Food Chem.,
8, 282. Norris M. U. et al. (1954) J. Agric. Food Chem., 2,
570.
5.3.2 Other tests in case of poisoning - Levels of cholinesterase in
the blood, particularly plasma, provide the most useful diagnosis
of poisoning. Michel, N.O. (1949) J. Lab. Clin. Med., 34, 1564-
1568. Ellman, G.L. et al. (1961) Biochem. Pharmacol., 7, 88-95
Measurements of urine metabolites may also be determined in order
to give an indication of exposure for methods. See section
5.3.1, Detection and Assay.