WORLD HEALTH ORGANIZATION FOOD AND AGRICULTURE ORGANIZATION ORGANISATION MONDIALE DE LA SANTE ORGANISATION POUR L'ALIMENTATION ET L'AGRICULTURE VBC/DS/84.

51 ORIGINAL: ENGLISH DATA SHEET ON PESTICIDES No. PERMETHRIN 51

CLASSIFICATION: Primary use: Insecticide Secondary use: Chemical group: Pyrethroid 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 not constitute formal publication. It should not be reviewed, abstracted or quoted without the agreement of the Food and Agriculture Organization of the United Nations or of the World Health Organization. 1. 1.1 GENERAL INFORMATION COMMON NAME: Permethrin (ISO, BSI, ANSI) Ce document ne constitue pas une publication. Il ne doit faire l'objet d'aucun compte rendu ou rsum ni d'aucune citation sans l'autorisation de l'Organisation des Nations Unies pour l'Alimentation et l'Agriculture ou de l'Organisation Mondiale de la Sant.

1.1.1 Identity: IUPAC: 3-phenoxybenzyl (1RS)-cis,trans-3-(2,2-dichlorovinyl)2,2-dimethylcyclopropanecarboxylate CAS No. 1: (3-phenoxyphenyl)methyl (1RS)-cis,trans-3-(2,2dichloroethenyl)-2,2-dimethylcyclopropanecarboxylate CAS Reg. No.: 52645-53-1 Molecular formula: C12H20O3 Molecular weight: 391.29 Structural formula:

1.1.2 Synonyms: Acion(R); AI3-;29158; Ambush(R); AMbushfog(R); BW-21-7; CO-Opex(R); Ectiban(R); Eskmin(R); FMC 33297; Indothrin(R); Kafil(R); Matadon(R); NIA 33297; NRDC 143; Outflank; OMS-1821; Perthrine(R); Picket(R); Picket G(R); Pounce(R); Perigen(R); Pramex(R); PP557; Qamlin(R); R86557; Stockade(R); Stomoxin(R); (R) S-3151; SBP-1513; Talcord ; WL43479. 1.2 SYNOPSIS: Permethrin is a composite synthetic pyrethroid; a broad spectrum, non-cumulative pesticide; and, a fast acting neurotoxin with good contact, limited stomach and no fumigant action. It is moderately stable in the environment and has good residual action on inert surfaces. Permethrin is nonsystemic in plants; of low mammalian toxicity,, and is readily metabolized with immediate loss of toxicity. SELECTED PROPERTIES

1.3

1.3.1 Physical characteristics - The pure isomers are colourless crystals at ambient temperatures changing to a clear, pale yellow, viscous liquid above the melting points of 63-65C for the cis isomers and 44-47C for trans isomers. The boiling point is 200C/0.01 mmHg. The technical product is a viscous, brown liquid which may partially crystallize at ambient temperatures and is completely liquid above 60C. The technical products boil at 210-220C/0.05 mmHg. The specific gravity is 1.190-1.272 at 20C. 1.3.2 Solubility - at 20C, less than 0.1 mg/l water at 30C, 0.2 mg/l water +450.0 g/l acetone +450.0 g/l cyclohexanone +450.0 g/l ethanol +450.0 g/l xylene +450.0 g/l chloroform

it is soluble in or mixable with most organic solvents except ethylene glycol. 1.3.3 Stability - Permethrin has good stability on plant surfaces under severe conditions of temperature, humidity and solar radiation but it is relatively unstable in most soils. In solution it is stable under neutral and acidic pHs but relatively unstable in alkaline conditions. 1.3.4 Vapour pressure - at 20C, cis isomer 2 x 10-9 kPa trans isomer 1 x l0-9 kPa 1.4 AGRICULTURE, HORTICULTURE AND FORESTRY

1.4.1 Common formulations Agronomic uses: Emulsifiable concentrates (100-500 g a.i./l); fogging solutions (50 g/l) ; ULV concentrates (50- 470 g/l) . Veterinary uses: Emulsifiable concentrates (25-200 g a.i./l) and dusts (2.5-10 g a.i./kg). For plant use the cis:trans isomer ratio is 40:60 or higher, a lower ratio of 25:75 is available for use on animals and on animal shelter surfaces. 1.4.2 Susceptible pests - Permethrin is effective, at low doses, as an ovicide, larvicide and adulticide; and, as a repellent and a feeding suppressor against a wide variety of insect ectoparasites of plants and animals. It is particularly effective against members of the Lepidoptera, Coleoptera, Diptera and Heteroptera orders. However, as a lipophilic substance lacking fumigant action it is not usually effective against aphids, systemic parasites and soil pests except by direct contact application. Mites, cockroaches, locusts and grasshoppers are well controlled at high dose levels. In addition to biting insects, other arthropod ectoparasites such as ticks are well controlled on animals. 1.4.3 Use pattern - Permethrin is used in the protection of a wide variety of field crops (cotton, tobacco, hops, fruits and vegetables), in greenhouses, market gardens and vineyards. Successful use in large-scale silviculture programmes is under review. Permethrin may be applied from ground or from air dispensers to field crops. It may be sprayed on plants in enclosed areas and on inert surfaces for quick knockdown or repellent effect or used as a dip or spray for animals. Some biting insects are well controlled for several weeks by simply applying the formulation to one or two dominant members of a small herd (10-30 animals). 1.4.4 Unintended effects - Permethrin is not phytotoxic when used as recommended, rapid degradation in soils, aquatic environment and low mobility limit adverse effects on non-target organisms. It

is very toxic to bees. 1.5 PUBLIC HEALTH PROGAMMES

1.5.1 Common formulations - See 1.4.1, also available in hand held aerosol and fogging formulations; as a transparent emulsion; and, in a variety of formulations in combination with several other active ingredients including, bioallethrin, copper sulfate, dichlorvos, pirimicarb, pirimiphos-methyl, tetramethrin and triforine. 1.5.2 Susceptible pests - Pemethrin is effective in the control of several insect vectors of disease, ticks, ants, mosquitos, lice, fleas, blackflies, tsetse fly, domestic flies and other pests which contaminate food and water sources. 1.5.3 Use pattern - Most commonly permethrin is used as a spray or fogging treatment of surfaces, buildings, plants, confined spaces or larval habitats. Permethrin is very effective as a direct contact poison or as a residual substance. It has been experimentally absorbed onto fabric with good effect retained after the fabric was washed. Permethrin has also been effective when used as a low concentration dusting powder directly on humans against body lice in experimental trials. 1.6 HOUSEHOLD AND INDUSTRIAL USE

1.6.1 Common formulations - See 1.4.1; also available in hand held aerosol sprays or fogging devices; as a transparent emulsion; and, in a variety of formulations in combination with several other active ingredients including bioallethrin, copper sulfate, dichlorvos, pirimicarb, pirimiphos-methyl, tetramethrin and triforine. 1.6.2 Susceptible pests - See 1.5.2; Permethrin is also effective against termites and woodboring beetles, silverfish, bed-bugs, cockroaches, crickets and other undesirable arthropods. 1.6.3 Use pattern - Permethrin may be used as a space or surface spray; as a residual film on inert surfaces, in fabrics and on exposed wood. It is used for its knockdown and kill properties and as a repellent. 2. 2.1 TOXICOLOGY AND RISKS TOXICOLOGY - MAMMALS

2.1.1 Absorption route - Permethrin is readily absorbed from the gastrointestinal tract; minimally through the intact skin, in non-polar solvents more rapidly than in aqueous solutions; and, by inhalation of dust and fine spray mist. 2.1.2 Mode of action - Permethrin is a neurotoxin which acts directly on neuron membranes. It prolongs sodium ion permeability during the excitatory phase of the action potential thus effecting repetitive activity in the sensory and motor pathways. The parent

compound is the neurotoxic agent. 2.1.3 Excretion - The metabolism of permethrin has been extensively studied in rats and mice and in lactating cows and goats. The two sets of cis and trans isomers are metabolized by liver microsomal esterases and oxidases; however, the sequence of enzyme activity and the relative contribution of each enzyme are quite variable among the isomers and within animal species for individual isomers. A concise and thorough review has been published by D. R. Hutson (Prog. Drug. Metab., 3; Chap. 4, p. 215, 1979). The trans isomer metabolism is dominated by hydrolysis whereas the cis isomers are less easily hydrolised and more toxic. Oxidase activity in both isomers involves stereospecific oxidation of the acid moiety, cyclopropanecarboxylic acid; oxidation of the alcohol moiety, 3phenoxybenzyl alcohol (3-PB alc) to 3-phenoxybenzoic acid (3-PBA); and hydroxylation of the alcohol moiety at positions 4', 6 and to a limited extent at position 2. Trans isomers are excreted more rapidly than the cis isomers and excretion of the acid radioisotope label is more rapid than that of the alcohol. Hydrolysis resistance is associated with low urinary (45-55%) and high faecal excretion of the cis isomers whereas trans isomers are primarily eliminated in urine (81-90%). The major excretion products of the alcohol moiety in both isomers are 4'HO-3-PBA sulfate in rats; 4'-HO-3-PBA (trans) and 6-HO-3-PBA cis) sulfates in mice; and, N-(3-phenoxybenzoyl) glutamate in cows. These, along with the cyclopropanecarboxylic acid glucuronides and 3-PBA glucuronides are the primary excretion products in most of the species studied. In rats the metabolism of racemic permethrin is very rapid, some 42 metabolites have been identified none of which have known toxic effects. Elimination is rapid, following a single oral dose of a racemic mixture over 50% of the radioactive lable was excreted within 48 hours. It is completely eliminated within 8 to 12 days of administration. 2.1.4 Toxicity, sinple dose - The toxicity of the racemic mixture varies with the cis/trans ratio and the characteristics of the vehicle uged. In general the cis isomers are the most toxic and non-polar carriers increase the toxicity of both isomers. Oral LD50: Rat (M) Rat (F) Mouse (M, F) Mouse (M, F) Mouse (M, F) Mouse (M) Mouse (M) Mouse (M) Mouse (M) Mouse (M) Rabbit (F) Guinea-pig (M) 430 470 150 96 000 310 470 620 490 000 000 000 mg/kg mg/kg mg/kg mg/kg mg/kg mg/kg mg/kg mg/kg mg/kg mg/kg mg/kg mg/kg b.w.; b.w.; b.w.; b.w.; b.w.; b.w.; b.w.; b.w.; b.w.; b.w.; b.w.; b.w.; racemic permethrin in corn oil racemic permethrin in corn oil 1R, trans-permethrin 1R, cis-permethrin 1S, cis/trans-permethrin racemic cis/trans = 75/25 racemic cis/trans = 50/50 racemic cis/trans = 25/75 racemic permethrin in corn oil racemic permethrin in water racemic permethrin in water racemic permethrin in water

3 +5 1 +4 +4 +4

Dermal LD50: Mouse (M, F) Rat (M, F) Rat (M, F) Rabbit (F) +2 500 mg/kg +2 500 mg/kg 750 mg/kg +4 000 mg/kg b.w.; b.w.; b.w.; b.w.; racemic racemic racemic racemic permethrin permethrin permethrin permethrin no no in no solvent solvent xylene solvent

Subcutaneous LD5O: Mouse (M, F) Rat (M, F) +10 000 mg/kg b.w.; 6 500 mg/kg b.w.; racemic permethrin in corn oil racemic permethrin in corn oil

Intraperitoneal LD50: Rat (M, F) Mouse (M, F) +3 500 mg/kg b.w.; 540 mg/kg b.w.; racemic permethrin in water racemic permethrin no solvent

Inhalation LC50: Mouse (M, F) Rat (M, F) +685 mg/m3; +685 mg/m3; racemic permethrin in kerosine racemic permethrin in kerosine

In general pyrethroid poisoning is characterized by hyperactivity and hypersensitivity (somatosensory). Permethrin is included among those pyrethroids which produce the T-syndrome in rats, consisting of hypersensitivity to external stimuli and fine whole body tremors progressing to gross tremors and prostration. 2.1.5 Toxicity, repeated doses Oral: Beagle dogs were given permethrin in gelatin capsules for three months at dosage levels of 5, 100 or 500 (mg/kg b.w.)/day in one study and 10, 100 or 5000 (mg/kg b.w.)/day in a second study. Transient clinical signs of toxicity were observed at 500 and 5000 mg/kg b.w. and liver to body weight ratios were increased at 5000 mg/kg b.w./day. Dermal: Rabbits administered up to 1.0 (g/kg b.w.)/day on intact and abraded skin for 21 days showed no clinical signs of toxicity other than moderate skin irritation and no other ill-effects. In a 21 day wear-test, cotton cloth impregnated with permethrin (0.125or 1.25 mg/cm2) applied to shaved, intact rabbit skin produced no observed ill-effects. Inhalation: Sprague Dawley rats subjected to permethrin at 0, 125, 250 or 500 mg/m3 for six hours a day, five days a week for 13 weeks in a metabolism and excretion study exhibited no observed toxicological effects. Cumulation of compound: Permethrin does not accumulate in body tissues due to rapid metabolism and excretion. Cumulation of effects: No evidence of adverse effects were presented in the reports of subacute studies. 2.1.6 Dietary studies -

Short-term: Technical permethrin dissolved in corn oil was fed to mice at dietary levels of 200 to 4000 mg/kg and to an additional group, 80 mg/kg for two weeks increased to 10 000 mg/kg for the remainder of the 28-day study; to rats in several studies of different durations (from 4-26 weeks) and several ranges of dietary levels up to 3000 mg/kg for 26 weeks, 4000 mg/kg for 13 weeks and 10 000 mg/kg for four weeks; and, to lactating cows at dietary levels of 0.2 to 50 mg/kg for 28 days. Acetone solutions of permethrin were given to rats at dietary levels up to 13 000 mg/kg for 90 days and 17 280 mg/kg for 14 days. There were no observed compound related changes in growth. Mortality was not an observed effect of permethrin administration except in rats fed very high dose levels which were usually associated with reduced food consumption. Corn oil solutions appear to be more toxic than acetone solutions. In Sprague Dawley rats the observed minimum lethal level for corn oil solutions was 5000 mg/kg (diet) compared to 8640 mg/kg (diet) for acetone solutions. Transient, early clinical signs of toxicity were observed in rats at high sublethal doses only. Consistently in mice and rats, liver weight and liver-to-body weight ratios were elevated by permethrin administration and were accompanied by slight hypertrophy and fatty changes; these changes were not permanent. Compound-induced changes in histo-pathology suggestive of tumorigenicity were not observed. In lactating cows permethrin residues, originating from the cis isomer primarily, were found to plateau at low levels in milk and body tissues within a few days of initial administration. These residues were quickly eliminated after cessation of exposure. The observed no-effect level in rats was 2000 mg/kg diet in a 90day study, equivalent to 175 (mg/kg b w.)/day and 1500 mg/kg (diet) in a 26-week study, equivalent to 93 (mg/kg b.w.)/day. Long-term: At the time of preparation of this data sheet, only four of several long-term studies were available in published form. In two mouse chronic studies the dietary levels were 250, 1000 and 2500 mg/kg in one and, 20, 100 and 500 mg/kg in the other. In the second study, after 2-3 weeks of administration, the two highest dose levels were increased to 4000 and 5000 mg/kg respectively, the latter increase was reversed after two weeks however. In two chronic rat studies, dietary levels of 20, 100 and 500 mg/kg and 500, 1000 and 2500 mg/kg were administered. There were no consistent compound-related changes in growth or food consumption in either species. In general, mortality was not an observed effect of permethrin administration although in mice, at 4000 mg/kg, the incidence of mortality in the later stage of the study was increased significantly. Permethrin caused a dose-dependent increase in liver weights and liver-tobody weight ratios in both species. In mice, and to a lesser extent in rats, hepatocellular hypertrophy, pleomorphism and hepatic degeneration were highest in the treatment groups and were possibly dose dependent in mice. There was no oncogenic effect due to permethrin in these studies. The rat chronic study no effect level was observed to be 100 mg/kg (diet) equivalent to 5.0 (mg/kg b.w.)/day.

2.1.7 Supplementary studies of toxicity Carcinogenicity: Administration of high doses of permethrin to mice in long-term dietary studies was associated with significant increases in very frequently occurring benign lung adenomas. This apparent induction activity was restricted to only one sex in any given study and to only one species. The lesion was not seen in comparable rat studies. In mice, the increased incidence was not associated with increased mortality, decreased latency or increased malignancy. Furthermore, extensive mutagenicity testing including point mutation, chromosomal aberration, dominant lethal, Ames, DNA repair and mammalian cell transformations (in vivo and in vitro studies) produced no evidence of permethrin-induced genetic activity. Although tumorigenic activity has been demonstrated in mice, collectively these findings do provide any evidence of carcinogenic potential for permethrin. Teratogenicity: Permethrin was neither embryotoxic nor teratogenic in a mouse study at dosage levels of 5-150 mg/kg b.w. administered from days 7 through 12 of gestation nor in two rat studies, one at 22.5 to 225 mg/kg b.w. from days 6 through 15 and another study at 4-83 mg/kg b.w. (in corn oil) from days 6 through 16. It also did not adversely affect weaning efficiency following normal deliveries in the mouse study nor in a third rat study at dosage levels of 10-50 mg/kg b.w. administered from day 9 through 14 of gestation. In the latter rat study, the only observed effect was a slightly increased incidence of non-ossified sternebrae in the Caesarean delivered pups at 50 mg/kg b.w. Mutagenicity: See carcinogenicity section above. Reproduction: In a standard rat three-generation study, permethrin at dosage levels of 20 and 100 mg/kg (diet) produced no adverse reproductive effect (including indices of fertility, gestation, viability and lactation). In a second rat study also, permethrin at dosage levels of 500, 1000 and 2500 mg/kg (diet) produced no adverse changes in standard indices of reproductive success. In the F3 b-litters females displayed transient clinical signs of acute toxicity, and dose-dependent increased incidences of hepatic centrilobular hypertrophy and cytoplasmic eosinophilia were observed in both sekes. (No teratogenic effects were observed in a third set of litters of the F3 generations at 21 days of gestation.) Neurotoxicity: In rats, high doses of pemethrin (6.0 g/kg of diet for 14 days), caused some neuropathy, including minimal demyelination and myelin ovoids on the sciatic nerve. Clinical signs of neurotoxicity were observed at doses of 5.0 g/kg diet and above. Hens given 1.0 g/kg b.w. doses of permethrin in DMSO (p.o.) showed no evidence of delayed neuropathy or other adverse effects during three weeks of post-treatment observation. Changes in EEG

spike and slow wave patterns were observed in rabbits, cats and guinea-pigs given 100 mg/kg b.w. in a single dose, no EEG changes were observed at 30 mg/kg b.w. Primary irritation and sensitization: In rabbits, technical permethrin produced mild primary skin irritation following 24hour application of 0.5 ml to intact and abraded skin and mild primary eye irritation (conjunctivitis) following ocular instillation of 0.1 ml without rinsing. Technical pemethrin did not produce sensitization reactions in guinea-pigs in a standard Draize test nor acneform dermatitis in rabbits following 30 daily applications of 0.1 ml to the ears. It also did not cause dermal photochemical reactions in rabbits under test conditions. Special pharmacological effects: In rabbits, 4 mg/kg b.w. produced hypotension, reduced respiration and an increased heart rate with no attendant changes in ECG wave pattern. In mice, dosage levels up to 2000 mg/kg b.w. did not change hexobarbital induced sleeping time. 2.1.8 Modifications of toxicity - Esterase and oxidase enzyme systems are important in the detoxification process, inhibitors of these enzymes will increase the toxicity to permethrin in both mammals and target organisms. 2.2 TOXICOLOGY - MAN

2.2.1 Absorption route - Permethrin may be readily absorbed from the gastrointestinal tract; minimally through the intact skin, especially in non-polar solvents; and by inhalation of dust and fine spray mist. 2.2.2 Dangerous doses - No information available. 2.2.3 Observations of occupationally exposed workers - In Sweden 33% of workers polled reported skin and eye irritation following occupational exposure. 2.2.4 Observations on exposure of the general public - No information available. 2.2.5 Observations of volunteers - In WHO trials in Nigeria, following indoor use at doses of 0.5 g/m3, volunteers to exposure made no complaint about adverse effects nor were any observed. 2.2.6 Reported mishaps - No information available. 2.3 TOXICITY TO NONMAMMALIAN SPECIES

2.3.1 Fish - Permethrin is highly toxic to fish, however the risk is of short duration due to rapid loss from water by adsorption and degradation. There have been no reports of problems of fish toxicity during commercial use (including aerial application).

LC50 (96 h):

Technical material g/l g/l g/l g/l g/l

Rainbow trout 0.1-0.5 Channel catfish 1.10 Large-mouth bass (fingerlings) 8.50 Mosquito fish 15.0 Salmon 12.0 LC50 (24 h): Rainbow trout 25.0 14.0 18.0 LD50 (I.P.): Rainbow trout 22.0 7.0 14.0

g/l (cis) g/l (trans) g/l (technical grade)

mg/kg b.w. (cis) mg/kg b.w. (trans) mg/kg b.w. (technical grade)

2.3.2 Birds - Permethrin is of very low toxicity to birds. Hens treated with coarse spray mist (3.77-11.94 mg/bird) showed no adverse effects and no significant accumulation in body tissues or eggs. Oral LD50 acute: Starlings Mallard duck Oral LD50 subacute: Pheasants Japanese quail Starlings +23 000 mg/kg b.w. +23 000 mg/kg b.w. +23 000 mg/kg b.w. Technical material +32 000 mg/kg b.w. +11 275 mg/kg b.w.

2.3.3 Beneficial insects - In laboratory studies permethrin is found to be toxic to bees; however, hazard in the field is limited by repellancy, low rates of application and lack of toxic effect once the spray has dried. 2.3.4 Others - Permethrin is toxic to some groups of aquatic invertebrates, amphibian larval forms, insects and crustaceans. However, due to the short persistence of permethrin, most populations soon recover. 3. 3.1 FOR REGULATORY AUTHORITIES - RECOMMENDATIONS ON REGULATION OF COMPOUND RECOMMENDED RESTRICTIONS ON AVAIIABILITY - (For definition of categories see introduction) All current formulations: Category 5 3.2 TRANSPORTATION AND STORAGE

Formulations in category 5 - Should be transported and stored in clearly labelled, leakproof containers out of reach of children, away from food and drink. Avoid contact with metals other than aluminium and tin. 3.3 HANDLING Formulations in Category 5 - No facilities other than those needed for the handling of any chemical are required. 3.4 DISPOSAL AND/OR DECONTAMINATION OF CONTAINERS All formulations - Containers may be decontaminated (for method see paragraph 4.3 of Part 4). Decontaminated containers should not be used for food and drink. Containers that are not decontaminated should be burned or should be crushed and buried below topsoil. Care must be taken to avoid subsequent contamination of water sources. 3.5 SELECTION, TRAINING AND MEDICAL SUPERVISION OF WORKERS Formulations in Category 5 - Warning of workers to minimize contact is essential. Persons under medication with neuroactive drugs should avoid contact. 3.6 ADDITIONAL REGULATIONS RECOMMENDED IF DISTRIBUTED BY AIRCRAFT All formulations - Pilots and loaders should have special training in application methods and recognition of early warning symptoms of poisoning and, they must wear a suitable respirator. Flagmen should wear overalls and a broad brimmed hat and be well away from the dropping zone. 3.7 LABELLING Formulations in Category 5 - Minimum cautionary statement "CAUTION" - This formulation contains permethrin, it may be poisonous if swallowed. Keep the material out of reach of children and well away from foodstuffs, animal feed and food containers. 3.8 RESIDUES IN FOOD Maximum residue limits for permethrin have been recommended by the joint FAO/WHO Meeting on Pesticide Residues. 4. 4.1 PREVENTION OF POISONING IN MAN AND EMERGENCY AID PRECAUTIONS IN USE

4.1.1 General - Permethrin is a synthetic pyrethroid and a neurotoxic agent of low toxicity to mammals. It may be readily absorbed from the gastrointestinal tract; by inhalation of dust and spray mist; and, minimally through the intact skin. The health hazard is considerably diminished by the low concentrations of the

active ingredient in all formulations. 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 a container and when mixing, protective impermeable boots, clean overalls, impermeable gloves, eye protection and a respirator should be worn. Mixing, if not mechanical, should always be carried out with a paddle of appropriate length. Avoid contact with mouth and eyes. Before eating, drinking or smoking, hands and other exposed skin should be thoroughly washed with alkaline soap. 4.1.4 Other associated workers (including flagmen in aerial operations) - Persons exposed to permethrin and associated with its application should observe the precautions described above in 4.1.3. 4.1.5 Other populations likely to be affected - With good agricultural practice, subject to 4.2 below, other populations are not likely to be exposed to hazardous amounts of permethrin. 4.2 ENTRY OF PERSONS INTO TREATED AREAS - Though permethrin is relatively persistent, low application rates ensure low residue levels. Unprotected persons may enter treated areas almost immediately after spraying without being exposed to hazardous amounts of permethrin. SAFE DISPOSAL OF CONTAINERS AND SPILIAGES - 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 detergent and scrubbing the sides. The hands should be protected during this work. Decontaminated containers should not be used for food and drink. EMERGENCY AID

4.3

4.4

4.4.1 Early symptoms of poisoning - These may include nausea and vomiting; shortness of breath and laboured breathing; fine or coarse tremors, hypersensitivity to external stimuli and general weakness, and prostration. A burning and itching sensation often follow contact. 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 clean the affected skin area. First, soak-up any liquid remaining on the skin with readily disposable material (e.g., talcum powder or absorbant cloth or paper), wash the affected area with warm water and alkaline soap. For eye contamination, wash with copious amounts of 4% sodium bicarbonate or water. Avoid exposing affected skin or eyes to bright light. If the material was swallowed and signs of toxicity are severe, induce vomiting if the person is

conscious and aspiration of vomit can be avoided. In the event of collapse, apply artificial respiration. Keep in mind that if mouth to mouth respiration is used, vomit may contain toxic amounts of permethrin. Keep the person calm and comfortable and, obtain medical help as soon as possible. 5. 5.1 FOR MEDICAL AND LABORATORY PERSONNEL MEDICAL DIAGNOSIS AND TREATMENT OF POISONING

5.1.1 General information - Permethrin is a synthetic pyrethroid pesticide of low toxicity to mammals. It is readily absorbed from the gastrointestinal tract; by inhalation of dust and spray mist; and, through the intact skin to a limited extent. The hydrolysis and oxidation products of metabolism are rapidly excreted in the urine and faeces. Permethrin is a neurotoxic agent most probably acting on the central nervous system to cause repetitive nerve activity. 5.1.2 Signs and symptoms - Little information is available on the acute toxic effects of permethrin in humans. Based upon animal studies, high doses may cause repetitive activity in sensory and motor nerves. Early signs of poisoning may include nausea and vomiting; dyspnoea and hyperpnoea; fine or coarse tremors, hypersensitivity to stimuli and a feeling of general weakness and prostration. A burning and itching sensation often follow contact. 5.1.3 Laboratory - There are no established, practical methods for determining permethrin in body fluids. Urinary levels of 3phenoxybenzyl degradation products may be a useful index of exposure. In addition, electrophysiological monitoring of sensory nerve potentials and, central nervous and cardiac activities (EEG and ECG) may be useful in diagnosis and in assessment of therapy. 5.1.4 Treatment - There are no specific antidotes, treatment must be symptomatic. Keep the patient warm and calm. In cases of severe intoxication, therapy should include a sedative and anticonvulsant (e.g. barbiturates, diazepam, paraldehyde, etc.). The use of antispasmodic drugs is of limited value, mephenesin and atropine have been found to effectively alleviate the symptoms of pyrethroid poisoning in laboratory animals. If a large quantity of permethrin has been swallowed, unless the patient is unconscious or vomiting, gastric lavage should be perfomed using a 5% sodium bicarbonate solution, follow with powdered activated charcoal. For skin contact, soak up any liquid remaining on skin with readily disposable absorbent material, then wash the affected area with warm water and alkaline soap. If skin irritation occurs treat with a soothing skin cream and avoid exposure to direct light. For eye contamination, wash the eye with 4% sodium bicarbonate or any other non-irritating, alkaline aqueous solution. 5.1.5 Prognosis - There have been no reports of overt symptoms resulting from poisoning of man by permethrin; the prognosis

therefore is not known. However, by analogy with laboratory animals it may be assumed that if the acute toxic effect is survived the chances of complete recovery are good. 5.1.6 References to previously reported cases - No information. 5.2 5.3 SURVEILLANCE TESTS - None. LABORATORY METHODS - References only are given,

5.3.1 Detection and assay of compound and residues Chapman, R. A. & Harris, C. R. (1978) Journal of Chromatography, 166(2), 513-516 Chiba, M. (1978) J. Environ. Sci. Health, B13(3), 261-268 Fujie, G. H. & Fullmar, D. H. (1978) J. Agric. Food Chem., 26(2), 395-398 Horiba, M., Akira, K. & Murano., A. (1977) Agric. Biol. Chem., 41(3), 581-586 Kikta, E. J. & Shierling, J. P. (1978) Journal of Chromatography, 150, 229-232 Lam, S. & Grushka, E. (1978) Journal of Chromatography, 154, 318-320 Oshler, D. D. (1979) J. Assoc. Off. Anal. Chem., 62(6), 1309-1311 Papadopoulou-Mourikidou, E., Iwata, Y. & Gunther, F. A. (1980) J. Agric. Food Chem., 28(6), 1043-1049 Siegel, M. W., Hildebrand, B. E. & Hall, D. R. (1980) Intern. J. Environs Anal. Chem., 8, 107-126 5.3.2 Other tests in case of poisoning - No information.