WORLD HEALTH ORGANIZATION FOOD AND AGRICULTURE ORGANIZATION ORGANISATION MONDIALE DE LA SANTE ORGANISATION POUR L'ALIMENTATION ET L'AGRICULTURE VBC/DS/82.49 ORIGINAL: ENGLISH DATA SHEETS ON PESTICIDES No. 49 PIRIMIPHOS-METHYL 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. R 185 CLASSIFICATION: Primary use: Insecticide Secondary use: Acaricide Chemical group: Organophosphorus Compound Date issued: January 1983 1. GENERAL INFORMATION 1.1 COMMON NAME: Pirimiphos-methyl (BSI, ISO, ANSI) 1.1.1 Identity: IUPAC 0,2-diethylamino-6-methylpirimidin-4-yl O,O- dimethyl phosphorothioate CAS No. 1 phosphorothioic acid, O-(2-(diethylamino)-6- methyl-4-pyridinyl) O,O-diethyl ester Cas Reg. No. 29232-93-7 Mol. Formula C11H20N303PS Mol. Wt. 305.3 1.1.2 Synonyms: ActellicR; ActellifogR; BlexR; PP511 (discontinued name); SilosanR; SybolR; OMS 1424. 1.2 SYNOPSIS: Pirimiphos-methyl is a broad spectrum, non-cumulative organophosphorus pesticide; a cholinesterase inhibitor with fast acting fumigant, contact, and stomach action; and slightly toxic to mammals. Pirimiphos-methyl has translaminar action when sprayed on plants; short persistence on growing plants; and, long persistence on inert surfaces, including stored grain. It is fairly rapidly degraded in the environment. 1.3 SELECTED PROPERTIES 1.3.1 Physical characteristics The pure substance is a straw-coloured liquid. It has no characteristic odour; a M.P. of 15-18°C - it freezes to a white solid at 15°C; a density (d30) of 1.157; and, a refractive index (nD25) of 1.527. The U.V. spectrum is a strong absorption band at 248 nm and a weaker band at 300 nm. Weakly alkaline, it is slightly corrosive to tinplate and mild steel but not corrosive to brass, copper, stainless steel, nylon, polyethylene or aluminium. 1.3.2 Solubility 5.0 mg/l water at 30°C; miscible with, or very soluble in most organic solvents. 1.3.3 Stability Stable for up to six months at normal room temperature, readily hydrolysed by concentrated acids and alkalis; decomposes in sunlight, low biological persistence on foliar surfaces and in plant tissues but excellent persistence on inert surfaces and on stored crops. 1.3.4 Vapour pressure 1.47 x 10-5 kPa (1.1 x 10-4 mm Hg) at 30°C. 1.4 AGRICULTURE, HORTICULTURE AND FORESTRY 1.4.1 Common formulations E.c. (250 and 500 g a.i./1), U.L.V. concentrate (500 g a.i./1), encapsulated formulation (200 g a.i./1), dusts (10 and 20 g a.i./kg), w.p. (250 and 400 g a.i./kg), a fog (100 g a.i./1), an aerosol (20 g a.i./1 with pyrethroids), a solvent free formulation (900 g a.i./kg) and a smoke generator formulation. 1.4.2 Susceptible pests Pirimiphos-methyl is active against a wide variety of pests including ants, aphids, beetles, caterpillars, cockroaches, fleas, flies (including houseflies, Drosophila, and biting flies), mites, mosquitos, moths, thrips, whiteflies and scales. 1.4.3 Use pattern Pirimiphos-methyl is used as a general insecticide; in pre- harvest clean up of fruits and vegetables; and on horticultural plants. It is not recommended for use on celery. Pre-harvest withholding intervals of three to seven days are recommended following spray application, no such intervals are necessary following the use of fogs or smokes. Pirimiphos-methyl is also used for eradication of a wide range of stored product pests for long duration protection and, to control nuisance and disease vector insects. 1.4.4 Unintended effects None reported. 1.5 PUBLIC HEALTH USE 1.5.1 Common formulations E.c. (250 and 500 g a.i./1), U.L.V. concentrate (500 g a.i./1), encapsulated formulation (200 g a.i./1), dusts (10 and 20 g a.i./kg), w.p. (250 and 400 g a.i./kg), a fog (100 g a.i./1), an aerosol (20 g a.i./1 with pyrethroids), a solvent-free formulation (900 g a.i./kg) and a smoke generator formulation. 1.5.2 Susceptible pests Ants, beetles, bed-bugs, cockroaches, fleas, flies, lice, mites, mosquitos, and others as in 1.4.2. 1.5.3 Use pattern Pirimiphos-methyl is used as a residual insecticide in malaria control programmes, applied indoors on walls and ceilings at 1 or 2 g a.i./m2, usually as a 2.5-5% suspension at three-monthly intervals. It is also used as a U.L.V. spray and in thermal fogs to control mosquitos vectoring viral infections and, as a mosquito larvicide. It is extensively used as a residual spray in fly control programmes and as a 2% dust in rodent burrows to control DDT resistant fleas. It should not be used directly on humans or on processed foods. 1.5.4 Unintended effects None reported. 1.6 HOUSEHOLD USE 1.6.1 Common formulations It is available in emulsifiable concentrates (80 g a.i./1), dusts and aerosols (with pyrethroids) for home and garden use. 1.6.2 Susceptible pests Ants, beetles, bed-bugs, cockroaches, fleas, flies, lice, mites, mosquitos, wasps, and many nuisance insects and other arthropods. 1.6.3 Use pattern As recommended by manufacturer; do not use on processed food. Do not harvest food crops until at least seven days after the last spray application. 1.6.4 Unintended effects None reported. 2. TOXICOLOGY AND RISKS 2.1 TOXICOLOGY - MAMMALS 2.1.1 Absorption route Pirimiphos-methyl may be absorbed from the gastrointestinal tract; through the intact skin; and less commonly, by inhalation of fogs, smokes or spray mists. 2.1.2 Mode of action Cholinesterase inhibition by pirimiphos-methyl. The degradation products desethyl pirimiphos-methyl and pirimiphos-methyloxon are also active but of transient stability and have not figured significantly in mammalian studies. 2.1.3 Excretion products Detoxification of pirimiphos-methyl by metabolism and excretion is very rapid in mammals. In 14C-labelled pirimiphos-methyl dosed rats, over 70% of the radioactivity was excreted within 24 hours and 100% within five to six days, 85% in urine and 15% in faeces. Twelve metabolites, none with cholinesterase inhibiting activity, were detected in the urine of treated rats and dogs. Metabolism, quantitatively similar in both species, proceeds primarily by cleavage of the P-O bond. The oxon product appears to be an important active intermediary which is rapidly detoxified in homeotherms. 2.1.4 Toxicity, single dose Oral: LD50 Rat (M) 1450 mg/kg b.w. Rat (F) 1840-2260 mg/kg b.w. Rabbit (M) 1154-2300 mg/kg b.w. Mouse (M) 1030-1360 mg/kg b.w. Guinea-pig (F) 1000-2000 mg/kg b.w. Dog (M) > 1500 mg kg b.w. Cat (F) 575-1150 mg kg b.w. In acute oral toxicity studies on rats the onset of toxicity signs was delayed 12-14 hours after dosing and persisted for 10-12 days. Dermal: LD50 Rat (F) > 4500 mg/kg b.w. I.P.: LD50 Rat (M) 800 mg/kg b.w. Most susceptible species: No appreciable species variability among the mammals tested; the hen (LD50 79-80 mg/kg) is the most susceptible. 2.1.5 Toxicity, repeated doses Oral: Groups of male and female rats were dosed for two weeks, five days a week. At 200 mg/kg only mild signs were observed, toxicity was delayed and reversible. There were no mortalities; body weights and haemoglobin were reduced; reticulocytosis and spleenic haematopoesis were observed. At 400 mg/kg severe signs of poisoning appeared after the second dose; the severity of toxicity increased with each successive dose; the cumulative mortality was nine of 10 rats from day 4 for males and three of 10 from day 6 for females. Inhalation: Male and female rats exposed to a nominal vapour concentration of 3.5 ppm for three weeks showed no signs of toxicity during the study period, no change in blood cholinesterase levels and no gross or histopathologic effects. Dermal: In rabbits, a daily application of 1000 mg/kg b.w. of pirimiphos-methyl for two weeks produced mild, reversible signs of poisoning and the onset of poisoning was delayed for several days. In a later 21-day study, the insecticide was applied to intact or abraded skin of male and female rabbits in occluded applications of 0, 4, 40 or 400 mg/kg b.w. No treatment related adverse clinical signs, gross or histopathologic changes were observed. At the highest dose, on abraded skin, food consumption and plasma cholinesterase levels were depressed in both sexes; body weights were reduced in the females only. It was concluded that 40 mg/kg b.w. is a clear "no-effect" level for rabbits. Cumulation of compound: There was no evidence of accumulation of pirimiphos-methyl, or its metabolites in liver, kidney or adipose tissue of rats following four successive 7.5 mg/kg b.w. per oral daily doses of the 14C-labelled insecticide. In similar studies on domesticated animals there was no evidence of residue accumulation in either body tissues or animal produce. Cumulation of effects: Repeated exposure of rats to high doses of pirimiphos-methyl produced cumulative inhibitory effects on cholinesterase activity. 2.1.6 Dietary studies Short-term: Pirimiphos-methyl was fed to four groups of rats (male and female) for 90 days at levels of 0, 8, 80 and 360 mg/kg diet. There were no mortalities in any of the dose groups. No effects were observed in the 8 mg/kg diet group. In the groups fed 80 and 360 mg/kg significant signs of toxicity were observed; plasma and brain cholinesterase were inhibited; and, in females, there was a significant reduction in weight gain. In the group fed 360 mg/kg diet, the same effects were observed as in the 80 mg/kg group, but they were more severe and more rapid in onset; and, erythrocyte cholinesterase was inhibited. With the exception of brain cholinesterase activity the above effects were rapidly reversed upon cessation of treatment. Pirimiphos-methyl was given groups of dogs, both male and female, for 90 days at dose levels of O, 2, 10 or 25 mg/kg b.w. There were no mortalities. Females in the 10 and 25 mg/kg groups and males in the 25 mg/kg group showed reduced weight gains which were easily reversed on cessation of treatment. At all dose levels there was a mild and reversible depression of plasma cholinesterase activity. At 10 and 25 mg/kg erythrocyte cholinesterase depression was marked and recovery was slow. Bile duct proliferation was observed in four out of 16 high dose dogs, three of those had received the 25 mg/kg dose. In a repeat study at 25 mg/kg, minimal bile duct proliferation was seen in two of the 10 animals but it was not observed in two dogs whose dose had been progressively raised to 50 mg/kg b.w. from the eighth week onwards. Long-term: Pirimiphos-methyl was fed to groups of female and male mice for 80 weeks at concentrations of 0, 5, 250 or 500 mg/kg of diet. Animal deaths and rumour incidence were comparable between controls and treatment groups. At 250 and 500 mg/kg, plasma and erythrocyte cholinesterase was inhibited. The mouse "no-effect" level was determined from the 5.0 mg/kg diet to be equivalent to 0.5 (mg/kg b.w.)/day. Pirimiphos-methyl was fed to groups of male and female rats for two years at concentrations of 0, 10, 50 or 300 mg/kg of diet. A few animals from each test group were kept on normal diet for an additional four to eight weeks, for recovery observations. With one exception, in males at 300 mg/kg between weeks 54 and 72, there was no treatment related increase in cumulative mortalities within the test groups. No adverse effects were seen apart from cholinesterase inhibition. Marked plasma cholinesterase depression and some erythrocyte and brain cholinesterase inhibition were observed at 300 mg/kg. At 50 mg/kg, only female plasma cholinesterase activity was depressed. In all cases these enzyme activities returned to normal within four weeks after cessation of dosing. On the 10 mg/kg diet, no ill-effects were observed and therefore this dose was selected for the "no-effect" level for rats, equivalent to 0, 5 (mg/kg b.w.)/day. In a two-year study of dogs, pirimiphos-methyl was given per oral in doses of 0, 0.5, 2 or 10 (mg/kg b.w.)/day. Mild signs of toxicity were seen in all the high dose animals. There was no increase in gross or histopathologic incidences in any of the treatment groups. Erythrocyte and plasma cholinesterase activities were depressed in the 2 and 10 mg/kg groups, brain cholinesterase was inhibited at the 10 mg/kg level only. Cholinesterase activity was normal at the lower dose level, 0.5 (mg/kg b.w.)/day was selected as the "no-effect" level for dogs. 2.1.7 Supplementary studies of toxicity Carcinogenicity: No evidence of carcinogenic activity was observed in the several diet studies described in section 2.1.6. In addition, no evidence supportive of a carcinogenic potential for pirimiphos-methyl was found in several mammalian mutagenicity studies. Teratogenicity: No evidence of teratogenicity was observed in studies of pregnant rats and rabbits fed pirimiphos-methyl in their diets at concentration levels of 10 and 20 mg/kg and 1 and 16 mg/kg respectively, for the duration of gestation. In both studies the litter size was increased and the foetus weights were decreased by the treatment. Pirimiphos-methyl has been shown to be teratogenic in chick-egg injection studies only, inducing micromelia and abnormal feathering after dosing on the fourth day of incubation. However, no teratogenic effects were observed in a dietary study in laying-hens at dose levels of 4' to 40 mg/kg of diet. Reproduction: Pirimiphos-methyl was fed continuously to rats in two three-generation studies, in one the dose levels were 5, 10 and 100 mg/kg (diet) and in the other were 20 and 200 mg/kg (diet). No treatment related embryotoxic effects were observed in either study. The pesticide had no adverse effect on reproduction performance at dose levels up to 100 mg/kg (diet), at 200 mg/kg (diet) the pregnancy rate was slightly depressed. (See also the section on teratogenicity above.) Mutagenicity: Pirimiphos-methyl showed no mutagenic potential in several mammalian studies including two three-generation studies, a micronucleus test in young female ICR mice, or in a mouse dominant lethal study. It was found to be mutagenically active in a plate assay of six out of seven S. typhimurium strains but in none of the E. coli strains used in microbial screening tests. Irritation and sensitization: There were no signs, of sensitization nor primary irritation in a 24-hour occluded patch test in which a 50% pirimiphos-methyl solution in olive oil was applied to the dorsal skin of guinea-pigs and in another study in which the undiluted compound was applied to the dorsal skin of rats. Neurotoxicity: Two groups of five hens were given single oral doses of pirimiphosmethyl at 50 and 60 mg/kg. One hen died in the first dose group and three in the latter, at 21 days the dead animals were replaced, all the hens in each group were redosed and protected with atropine and pralidoxime. The hens were observed for an additional 21 days, no neurotoxicity was found in the treatment groups that could be attributed to pirimiphos-methyl. In another study, 10 birds received 0, 0.5, 1.0, 2.5, 5.0 or 10 mg/kg b.w. by direct intubation daily for 90 days. There were no clinical or histopathological findings associated with neurotoxicity. 2.2 TOXICOLOGY - MAN 2.2.1 Absorption It may be absorbed from the gastrointestinal tract; through the intact skin; and, by inhalation of fogs, smokes or spray mist when used in confined spaces. 2.2.2 Dangerous doses Single: Not known. Repeated: Not known. 2.2.3 Observations of occupationally exposed workers A total of 35 trained personnel participated in two separate WHO-supervised public health spray programmes, none showed any ill- effects attributable to pesticide poisoning. At the termination of one programme three of the 12 spraymen showed plasma cholinesterase activities which were 70-75% of the mean of two pre-exposure values. 2.2.4 Observations on exposure of the general public The inhabitants of two locations involved in the above- mentioned pirimiphos-methyl spray programmes did not show or complain of any ill-effects attributable to pesticide poisoning; no observations of cholinesterase activity were reported. 2.2.5 Observations on volunteers Liver function and blood test results were within the normal limits in two groups of volunteers given 0.25 (mg/kg)/day, five males for 28 days and three males and four females for 56 days. From these results, 0.25 (mg/kg)/day was accepted as the "no observed effect" level. The acceptable daily intake (ADI) was established at 0.01 mg/kg; the ADI represents the sum of the oxygen analogue, n-desmethyl pirimiphos-methyl and the parent compound in total expressed as pirimiphos-methyl. 2.2.6 Reported mishaps There are no reports of human poisoning attributed to pirimiphos-methyl. 2.3 TOXICITY TO NON-MAMMALIAN SPECIES 2.3.1 Fish LC50, static tests: Carp (24-hour) 1.6 mg/l Carp (48-hour) 1.4 mg/l Rainbow trout (48-hour) 0.25 mg/l LC50, flow through tests: Rainbow trout (24-hour) 0.78 mg/l Rainbow trout (48-hour) 0.53 mg/l Fathead minnow (24-hour) 5.60 mg/l Fathead minnow (48-hour) 4.10 mg/l The threat to fish is greatly reduced by the strong tendency of pirimiphos-methyl to decompose in aqueous solutions and, to undergo photo-oxidation. 2.3.2 Birds Oral: LD50 Chickens 79-80 mg/kg Japanese quail 140 mg/kg Green finches 200-400 mg/kg I.P.: LD50 Japanese quail 140 mg/kg Diet: LC50 Mallard ducklings 630 mgkg Bobwhite quail chicks 207 mg/kg In two diet studies, chickens were fed pirimiphos-methyl in doses ranging from 4 to 40 ppm, there was no lasting adverse effect on hens, chicks; or, egg production, quality, or hatchability. The relatively high toxicity of pirimiphos-methyl to birds appears to be related to a deficiency of esterases that hydrolyze pirimiphos-methyloxon. In 14 species of birds representing six avian orders the rate of hydrolysis of the oxon by in vitro plasma A-esterase ranged from a non-detectable-level to 71 (nmoles/min.)/ml plasma, at best it was less than 10% of the lowest recorded mammalian rate. 2.3.3 Other species No information. 3. FOR REGULATORY AUTHORITIES - RECOMMENDATIONS ON REGULATION OF COMPOUND 3.1 RECOMMENDED RESTRICTIONS ON AVAILABILITY (For definitions of categories, see introduction). Liquid and solid formulations above 10 and 30% respectively: category 4. Other formulations: category 5. 3.2 TRANSPORT AND STORAGE Formulations in category 4 - Should be transported and stored in clearly labelled, rigid and leakproof containers, under lock and key, secure from access by unauthorized persons and children. No food or drink should be transported or stored in the same compartment. Formulations in category 5 - Should be transported and stored in clearly labelled leak-proof containers out of reach of children, away from food and drink. 3.3 HANDLING Formulations in category 4 - Protective clothing (see 4.1.3- 4.1.4) should be used by all persons handling the compound. Adequate facilities should be available at all times during the handling and should be close to the site of handling. Eating, drinking and smoking should be prohibited during handling and before washing of hands and face. Formulations in category 5 - No facilities other than those needed for handling of any chemical are required. 3.4 DISPOSAL AND/OR DECONTAMINATION OF CONTAINER Containers may be decontaminated. Decontaminated containers should not be used for food or drink. If not decontaminated, empty containers should be burned or crushed and buried below topsoil. Care must be taken to avoid subsequent contamination of water resources. 3.5SELECTION, TRAINING AND MEDICAL SUPERVISION OF WORKERS Formulations in category 4 - Pre-employment medical examination of workers is desirable. Workers suffering from active hepatic or renal disease should be excluded from contact. Special account should be taken of workers' mental ability to comprehend and follow instructions. Training of workers in techniques to avoid contact is essential. Formulations in category 5 - No pre-employment medical examination for workers is necessary. Warning to workers to minimize contact is essential. 3.6 ADDITIONAL REGULATIONS RECOMMENDED IF DISTRIBUTED BY AIRCRAFT All formulation - Pilots and loaders should have special training in application methods and in recognition of early symptoms of poisoning. Loaders must wear overalls, rubber gloves and goggles. Flagmen should wear overalls and an impermeable brimmed hat; and should be located well away from the dropping zone. 3.7 LABELLING Formulations in category 4 - Minimum cautionary statement - Pirimiphos-methyl is an organophosphorus compound. It is of low toxicity and should not be used by people under medical advice not to work with such compounds. Avoid all mouth contact, skin contact or inhalation of spray, dust, fog or smoke. Wash splashes from skin and eyes immediately wash hands before eating or smoking after handling the pesticide and, wash oneself and change clothing immediately after work. When handling concentrates wear protective gloves, a face shield, and clean protective clothing. When using foggers or when fumigating indoors, wear protective gloves, rubber boots, a rubber coat, sou'wester and a respirator and do not re-enter treated spaces until they have been thoroughly ventilated. Remove or cover all food and animal feedstuffs prior to application and do not apply to food preparation surfaces or utensils. Store pesticide in the original container, tightly closed and in a safe place away from children. Wash out empty containers thoroughly and dispose of safely. Do not contaminate ponds, waterways, ditches or ground waters with either the chemical directly or the used container. Do not harvest the indicated food crops for human consumption before the specified interval has elapsed between last application and harvest. Avoid application when bees are active. If poisoning occurs take the patient to the hospital immediately. Atropine and pralidoxime are specific antidotes. No sedatives should be given. Oxygen and artificial respiration may be necessary. Formulations in category 5 - Minimum cautionary statement - This formulation contains pirimiphos-methyl, a cholinesterase inhibitor. Avoid all mouth and skin contact, or inhalation of spray mist, dust, fog or smoke. Wash hands after use. Store in the original container in a safe place away from children and pets. Wash out empty container thoroughly and dispose of safely. In addition, for aerosol preparations, keep away from heat (including sun) and do not puncture or incinerate even when empty. Do not apply directly on to food, food utensils or food preparation surfaces. Do not harvest food crops until at least seven days after the last application. 3.8 RESIDUES IN FOOD Maximum residue limits for pirimiphos-methyl have been recommended by the WHO/FAO Meeting on Pesticide Residues. 4. PREVENTION OF POISONING IN MAN AND EMERGENCY AID 4.1 PRECAUTIONS IN USE 4.1.1 General Pirimiphos-methyl is an organophosphorus pesticide of low mammalian toxicity which inhibits cholinesterase activity. 4.1.2 Manufacture and formulation T.L.V.: No information. 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, care should be taken to avoid contact with the mouth and eyes. If necessary, a facial visor and gloves should be worn. Mixing, if not mechanical, should always be carried out with a paddle of appropriate length. Splashes should be washed immediately from the skin or eyes with large quantities of water. Before eating, drinking or smoking, hands and exposed skin should be washed. If contaminated, clothing should be washed at the end of a working day. 4.1.4 Other associated workers (including flagmen in aerial operations) Persons exposed to pirimiphos-methyl and associated with its application should wear clean overalls and observe the precautions described above in 4.1.3 under "Mixers and applicators". 4.1.5 Other populations likely to be affected With correct use in agriculture, public health and in the home, the general population should not be exposed to hazardous amounts of pirimiphos-methyl. Harvesting intervals should be observed, as shown on the label they range from three to seven days depending upon the crop. 4.2 ENTRY OF PERSONS INTO TREATED AREAS Unprotected persons may enter a treated area immediately after spraying, however, they should not enter premises recently treated by sprays, fogs or smokes before those premises have been thoroughly ventilated. 4.3 DECONTAMINATION OF SPILLAGE AND CONTAINERS Residues in containers should be emptied in diluted form into a deep pit taking care to avoid contamination of groundwaters. The empty containers may be decontaminated by rinsing two or three times with water and scrubbing the sides. An additional rinse should be carried out with a 5% sodium hydroxide solution which should remain in the container overnight. Impermeable gauntlets should be worn during the work and a soakage pit should be provided for the rinsings. Decontaminated containers should not be used for food or drink. Spillage of pirimiphos-methyl 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 These 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 physician, if these symptoms appear following exposure The person should stop work immediately, remove contaminated clothing and wash contaminated skin with soap and water, if available, and flush with large quantities of water. Vomiting should not be induced unless it is reasonably certain that a potentially lethal dose has been swallowed and, provided that the person is conscious - inhalation of the solvent must be avoided. In the event of collapse artificial respiration should be given bearing in mind that if mouth to mouth respiration is used, vomit may contain toxic amounts of pirimiphos-methyl. 5. FOR MEDICAL AND LABORATORY PERSONNEL 5.1 MEDICAL DIAGNOSIS AND TREATMENT IN CASE OF POISONING 5.1.1 General information Pirimiphos-methyl is an organophosphorus pesticide of low mammalian toxicity which may be absorbed from the gastrointestinal tract; through the intact skin; and by inhalation when fog and smoke generators are used or when spraying in a confined space. It acts by inhibiting acetycholinesterase. Continuous exposure to low amounts may inhibit blood cholinesterase to hazard levels. 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 of poisoning may be convulsions, coma, loss of reflexes and loss of sphincter control. 5.1.3 Laboratory The most important finding is reduction in activity of blood cholinesterases. Urinary levels of organic phosphorus containing metabolites could also be used as a measure of exposure. Neither method is specific for pirimiphos-methyl. 5.1.4 Treatment If a potentially lethal dose has been ingested, unless the patient is vomiting, rapid gastric lavage should be performed. For skin contact, the skin should be washed with soap and water. If the compound has entered the eyes, they should be washed with isotonic saline. 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 may be given as needed. Persons with severe intoxication and with respiratory difficulties, convulsions and unconsciousness 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 five to 10 minute intervals. 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 may be required, preferably by mechanical means. If necessary, intubation should be perforated. Contraindications are morphine, barbiturates, phenothiazine, tranquillizers and central stimulants of all kinds. 5.1.5 Prognosis If the acute toxic effect is survived and adequate artificial respiration has been given, if needed, the chances of 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 References to previously reported cases None. 5.2 SURVEILLANCE TESTS Test Normal Action Symptomatic level* level* level* Plasma cholinesterase 100% 50% variable Whole blood or erythrocyte cholinesterase 100% 70% * Expressed as percentage of pre-exposure activity. Urinary levels of ether-extractable phosphorus compounds may also be used to determine the degree of exposure. 5.3 LABORATORY METHODS References only are given, 5.3.1 Detection and assay of compound Yuen, S. A. (1976) Analyst (London), 101, 533 Bullock, D. J. W. (1976) Analytical methods in pesticides and plant growth regulators, Vol. VIII, Chapter 9, 185 Kirasnykh, A. A. (1978) Kimiya V Sel'Skom Khozaistve, 16, 36 5.3.2 Other tests in cases of poisoning The level of cholinesterase in the blood, particularly the plasma, provides the most useful diagnosis of poisoning, see: Ellman, G. L. et al. (1961) Biochem. Pharmacol., 7, 88. Michel, N. O. (1949) J. Lab. Clin. Med., 34, 1564. Plasma and urine levels of methanol extractable pirimiphos- methyl and pirimiphos-methyl metabolites may also be useful in diagnosis of poisoning, see: Brealey, C. J. & Lawrence, D. K. (1979) Journal of Chromatography, 168, 461. Note: This data sheet was drafted in the Bureau of Chemical Standards, Environmental Health Directorate, Health and Welfare, Canada, and subsequently underwent medical, scientific, and industrial review.
See Also: Pirimiphos methyl (PIM 361)