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.
See Also: Azinphos methyl (PIM 739)