WORLD HEALTH ORGANIZATION FOOD AND AGRICULTURE ORGANIZATION ORGANISATION MONDIALE DE LA SANTE ORGANISATION POUR L'ALIMENTATION ET L'AGRICULTURE VBC/DS/77.30 ORIGINAL: ENGLISH DATA SHEETS ON PESTICIDES No. 30 FENITROTHION It must be noted that the issue of a Data Sheet for a particular pesticide does not imply endorsement of the pesticide by WHO or FAO for any particular use, or exclude its use for other purposes not stated. While the information provided is believed to be accurate according to data available at the time when the sheet was compiled, neither WHO nor FAO are responsible for any errors or omissions, or any consequences therefrom. The issue of this document does Ce document ne constitue pas une not constitute formal publication. Il ne doit faire publication. It should not be l'objet d'aucun compte rendu ou reviewed, abstracted or quoted résumé ni d'aucune citation sans without the agreement of the l'autorisation de l'Organisation Food and Agriculture des Nations Unies pour Organization of the United l'Alimentation et l'Agriculture Nations or of the World Health ou de l'Organisation Mondiale de Organization. la Santé. CLASSIFICATION: Primary use: Insecticide Secondary use: Acaricide Chemical group: Organophosphorus compound Date issued: 1. GENERAL INFORMATION 1.1 COMMON NAME: Fenitrothion (ISO) Identity: O,O-dimethyl O-(3-methyl-4-nitrophenyl) phosphorothioate Synonyms: OMS-43, sumithion, folithion, accothion, novathion, agrothion Local synonyms: 1.2 SYNOPSIS An organophosphorus insecticide and selective acaricide of moderate mammalian toxicity. 1.3 SELECTED PROPERTIES 1.3.1 Physical characteristics Brownish yellow liquid of b.p. 145°C at 0.4 mm Hg (0.53 mbar) with decomposition. 1.3.2 Solubility Practically insoluble in water but soluble in most organic solvents; low solubility in aliphatic hydrocarbons. 1.3.3 Stability It is hydrolysed by alkali and its half-life in 0.01 N NaOH at 30°C is 272 minutes. It readily isomerizes on distillation. Completely stable for two years at 20-25°C. 1.3.4 Vapour pressure (volatility) low, 6 x 10-6 mm Hg at 20°C, or 8 x 10-6 mbar at 20°C. 1.4 AGRICULTURE, HORTICULTURE AND FORESTRY 1.4.1 Common formulations Emulsifiable concentrates 50%; dusts 2, 3 and 5%; wettable powders 40% and 50%; granules 3% and 5%, baits, ULV. 1.4.2 Susceptible pests Aphids, weevils, sandfly, raspberry beetle, tortrix, midges, moths, thrips, ermine moth, leatherjackets, leaf hoppers, rice borers, and budworms. 1.4.3 Use pattern Used on cotton and rice at up to 2 kg/ha; used on vegetables at up to 1.25 kg/ha; used on cereals at up to 1.0 kg/ha; used in forestry and on cocoa at up to 0.5 kg/ha; coffee, spray concentration 0.1%; top fruit, spray concentration 0.1%; ornamentals, spray concentration 0.1%; sugar cane, spray concentration 0.075; tea, spray concentration 0.05%. 1.4.4 Unintended effects Should not be used on flowering crops. Phytotoxicity is possible on brassicae and orchard fruit - should not be applied directly to grains. Livestock may be affected if given access to treated areas within one week of application. 1.5 PUBLIC HEALTH Successfully tested on residual insecticide for control of malaria vectors, as a 5% suspension of water dispersible powder. This is applied on the surfaces indoors at 2 g/m2 at a three-monthly interval. Also used as ULV application from ground or air, technical insecticide being applied at the rate of 250-500 ml/ha for the control of vital epidemics transmitted by Aedes aegypti or Culex sp. It has also been used as a mosquito larvicide at dosage rates varying from 224 to 336 g/ha. 1.6 HOUSEHOLD USE No known use. 2. TOXICOLOGY AND RISKS 2.1 TOXICOLOGY - MAMMALS 2.1.1 Absorption route Absorbed from the gastrointestinal tract as well as by the intact skin and by inhalation. 2.1.2 Mode of action An organophosphorus cholinesterase inhibitor. 2.1.3 Excretion Converted to the oxygen analogue. Metabolites include 3-methyl-4-nitrophenol and 3-carboxy-4-nitrophenol. Up to nine metabolites have been isolated. Excretion is mainly in the urine 90-95% and up to 10% in the faeces. 2.1.4 Toxicity, single dose Oral LD50 rat (M) 504 mg/kg Dermal LD50 rat (M & F) 3500 mg/kg Most susceptible species, cat (M) oral LD50 142 mg/kg 2.1.5 Toxicity, repeated doses Oral: No fatalities occurred among male rats dosed for 28 days at 13 mg/kg/day, however, erythrocyte cholinesterase activity was reduced and recovery took 30 days after cessation of dosing. Twenty male rats dosed orally six days a week for two months at 10 and 11 mg/kg, showed some deterioration of general condition and weight loss during the first weeks. However, haematology and urinalysis during the experiment and histological examination at its termination, did not reveal any abnormalities. Dogs of both sexes were dosed orally by capsule at 2.9 or 40 mg/kg for 98 days. Body weights, blood biochemistry, cholinesterase levels and haemograms were checked at intervals. No effect was found at 2 mg/kg. At 9 mg/kg there was a slight reduction of whole blood, plasma and erythrocyte cholinesterase activities, after 60 days, and at 40 mg/kg a moderate reduction after 29 days. At 40 mg/kg, marked cholinergic symptoms were observed. Inhalation: Groups of six male and female rats, Sprague Dawley strain, were exposed to fenitrothion mist during two hours per day for five consecutive days. The aerial concentration of fenitrothion in the chamber was approximately 62, 15 and 8 mg/m3. Plasma, erythrocyte and brain cholinesterase activities of the rats exposed to 7 mg/m3 of fenitrothion for five days showed no reduction as compared with the control, while at the dose of 15 mg/m3 of fenitrothion plasma cholinesterase activity was reduced approximately by 30-50%. At 62 mg/m3 erythrocyte cholinesterases were inhibited by 50% or more. Brain cholinesterase activity was not affected at the lower dosages and only by exposure to 62 mg/m3 of fenitrothion was it reduced to about 50% of the control. In another trial, groups of 16 male and 16 female rats and 15 each of male and female mice, were exposed to 1 and 0.2% fenitrothion mist for two hours, six days per week for four weeks; plasma and erythrocyte cholinesterase recovered within seven days after termination of the exposure to 0.2% fenitrothion, and at the higher dosage (1%) both cholinesterases were still 10-20% below the control values after 14 days. None of the rats died during four weeks of exposure, and there were no adverse effects on weight gain, haematology, clinical biochemistry, organ weight and histopathology. Similar results were obtained with mice. Cumulation of compound: Does not accumulate in body tissues to any significant extent. Cumulation of effect: Repeated exposure may produce cumulative inhibitory effect on cholinesterase. Acute effects are prolonged and recovery of erythrocyte cholinesterase activity after severe inhibition may take up to 30 days. 2.1.6 Dietary studies Short-term: Groups of male rats (16 or 17 in number), were fed 0, 32, 63, 125, 250, and 500 ppm of fenitrothion in the diet for 90 days. All the animals fed 500 ppm showed clinical symptoms of anticholinesterase poisoning and there were minimal symptoms in four animals in the 250 ppm group. In the 500 ppm group, the average weight of testes and brain were increased in comparison with those of the control group. Cholinesterase activity of plasma, erythrocyte, brain cortex, liver and kidneys showed a dose-dependent reduction, the lowest being in the brain. The cholinesterase activity in the 32 and 63 ppm groups generally recovered after 60 days of dosing to a level within the normal limits, the best recovery being in the plasma, kidney and brain, less in the erythrocyte and the liver. Long-term: Fenitrothion was fed to groups of male and female beagle dogs at concentrations ranging from 5 to 200 ppm for periods of one to two years. In the first trial, groups of dogs (six males and six females per group) were fed fenitrothion for two years at doses of 30, 100 or 200 ppm in the diet. No measurable deviations from the control were found in the treated groups with respect to growth, food consumption, behavioural reactions, mortality haematology and clinical blood chemistry values, urinary analysis, organ weights and their ratio to body weight and gross and microscopic pathological examinations. At 30 ppm, erythrocyte cholinesterase activity was unaltered but plasma cholinesterase was reduced throughout the two-year experiment. Brain cholinesterase activity was not affected at the highest dose level. Additional sub-acute feeding study was carried out to check blood cholinesterase activity at the doses of 5 and 10 ppm for one year. Five out of eight beagles exposed to 5 ppm of fenitrothion showed slight reduction of plasma enzyme activity for the first three months, but the activity recovered thereafter. Brain cholinesterase was normal. The "no effect" level of fenitrothion for cholinesterase activity was determined to be 5 ppm. Several studies on long-term oral toxicity of fenitrothion, including carcinogenicity study have been carried out in rats. It was found that fenitrothion fed at concentrations from 2.5 to 150 ppm for periods ranging from six months to two years produced no measurable deviation from the normal with respect to the parameters investigated except cholinesterase activity. Fenitrothion fed to rats at a concentration of 5 ppm was determined as the "no effect" level with regard to cholinesterase activity. 2.1.7 Supplementary studies of toxicity Carcinogenicity: See 2.1.6, dietary studies, long-term. Reproduction study: Fenitrothion was administered in the diet to albino rats at dosage levels of 10, 30 and 150 ppm through weaning of the first (F1A litters) filial generation and 10, 30 and 100 ppm thereafter. Body weight reduction occurred due to the feeding of 150 ppm fenitrothion to the P1 generation animals and 100 ppm fenitrothion to the P2 generation animals. Lactation index was significantly depressed for all the filial generations at the highest dietary levels of fenitrothion. At these levels, weaning body weights of both sexes of the F1A, males of the F1B, and both sexes of the F2A generations were significantly lower than the respective control values. The organs of representative weanlings sacrificed from control and test groups showed no gross compound-related changes at any of the test levels. No microscopic evidence of compound-related histomorphologic alterations were present in sections of thyroid, liver, kidney, stomach and small intestine taken from male and female F3B weanlings which received the highest level (100 ppm) of fenitrothion. Teratogenicity: Technical fenitrothion was administered to pregnant albino rabbits at daily rates of 0.3 mg/kg and 1.0 mg/kg of body weight during early gestation. No adverse effects on body weight gain were noted which could be attributed to fenitrothion. No deaths or unusual reactions were noted among females. Foetal mortality was not affected by the treatment with fenitrothion, nor were any external and skeletal abnormalities observed among the foetuses. Delayed neurotoxicity: Tests in hens at 250, 400 and 500 mg/kg have not revealed any paralysis or associated nerve damage. In rats fed 10 mg/kg/day for six months, fine structure of neuromuscular junctions was unchanged. 2.1.8 Modification of toxicity In potentiation studies among several organophosphorus compounds tested in combination with fenitrothion, only phosphamidon has shown positive effects in both male and female rats, as evidenced by increased mortality. 2.2 TOXICOLOGY - MAN 2.2.1 Absorption Absorbed from the gastrointestinal tract as well as by inhalation and by the intact skin. 2.2.2 Dangerous doses Single: Not known. Repeated: Not known. 2.2.3 Observations of occupationally exposed workers Fenitrothion is applied as a residual indoor spray for adult mosquito control. When supervision, including cholinesterase monitoring, has been adequate, there have been no cases of poisoning during residual indoor spraying. Only in a few instances has it been necessary to remove individuals from spraying due to symptomless reduction of whole blood cholinesterase activity, usually observed towards the end of six to eight weeks spraying cycles. No cases of poisoning occurred. 2.2.4 Observations on exposure of the general population In a malaria control trial in northern Nigeria involving 10 000 and 16 500 people, whole blood cholinesterase levels were unaffected in 299 villagers representative of this population, tested 5-30 days after their houses had been sprayed. This represents a higher exposure than encountered by its proper agricultural use. Fenitrothion has been used in agriculture for a number of years without any cases of poisoning being reported. 2.2.5 Observations of volunteers Single dose: Twenty-four volunteers were given a single oral dose of from 2.5 to 20 mg of fenitrothion. In one case there was some reduction of plasma cholinesterase activity, six and 24 hours after receiving the largest dose. The excretion of the metabolite 3-methyl-4-nitrophenol in urine was maximal at 12 hours and almost complete at 24 hours. Repeated: Five individuals were given four daily doses of 2.5 and 5 mg fenitrothion. Metabolites appeared in the urine at 0-12 hours after administration. After the third and fourth doses there was a tendency towards a rise in erythrocyte cholinesterase levels. No cholinesterase inhibition was seen in the plasma. 2.2.6 Reported mishaps Accidental poisoning has occurred but no large-scale mishaps have been reported. 2.3 TOXICITY TO NON-MAMMALIAN SPECIES 2.3.1 Fish Toxic (4.4 ppm/h for carp; 1.0 ppm/h for trout). 2.3.2 Birds Moderately toxic (LD50 523 mg/kg for chickens; for wild birds: mallard duck 1190 mg/kg, pheasant 55.6 mg/kg). 2.3.3 Other species Toxic to bees and livestock, game and wild animals. 3. FOR REGULATORY AUTHORITIES - RECOMMENDATIONS ON REGULATION OF COMPOUND 3.1 RECOMMENDED RESTRICTIONS ON AVAILABILITY (for definition of categories, see introduction) All formulations 10% or above, Category 4 Formulations below 10%) Category 5 3.2 TRANSPORTATION AND STORAGE All formulations in Category, 4: Should be transported or stored in clearly labelled, rigid and leakproof containers. No food or drink should be transported in the same compartment. Storage should be under lock and key and secure from access by unauthorized persons and children. Formulations in Category 5: Should be transported in clearly labelled, leakproof containers, out of reach of children and away from food and drink. 3.3 HANDLING All formulations in Category 4: Full protective clothing should be used by all those handling the compound. Adequate washing facilities should be available at all times during handling and should be close to the site of handling. Eating, drinking and smoking should be prohibited during handling and before washing after handling. Some liquid formulations contain flammable volatile solvents. Formulations in Category 5: No facilities other than those needed for handling of any chemical need be required. 3.4 DISPOSAL AND/OR DECONTAMINATION OF CONTAINERS All formulations: Containers may be decontaminated (for method see para. 4.3). Decontaminated containers should not be used for food or 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 All formulations in Category 4: Pre-employment medical examination of workers desirable. Workers suffering from active hepatic or renal disease should be excluded from contact. Special account should be taken of the workers' mental ability to comprehend and follow instructions. Training of workers in techniques to avoid contact essential. Pre-employment and routine cholinesterase test for workers is desirable. Formulations in Category 5: Warning of workers to minimize contact essential. 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 symptoms of poisoning. Use of flagmen not recommended. Flagmen if used should wear protective clothing and be located well away from the dropping zone. 3.7 LABELLING All formulations in Category 4: Fenitrothion is an organophosphorus compound that inhibits cholinesterase. It is poisonous if swallowed or inhaled. It may be absorbed through the skin. Avoid skin contact; wear hand protection, clean protective clothing, and, if in poorly ventilated area, a respirator when handling the material. Wash thoroughly with soap and water after using. Keep out of reach of children and well away from foodstuffs, animal feed and their containers. If poisoning occurs, call a physician. Atropine and pralidoxime are specific antidotes and artificial respiration may be needed. Formulations in Category 5: Fenitrothion is a toxic substance. It is poisonous if swallowed. It may be absorbed through the skin or inhaled as dust or mists. Avoid skin contact, wear protective gloves and clean protective clothing while using this material. Wash thoroughly with soap and water after using. Keep the material out of reach of children and well away from foodstuffs, animal feed and their containers. 3.8 RESIDUES IN FOOD Maximum residue limits for fenitrothion have been recommended by the Joint FAO/WHO Meeting on Pesticide Residues. 4. PREVENTION OF POISONING IN MAN AND EMERGENCY AID 4.1 PRECAUTIONS IN USE Fenitrothion is an organophosphorus insecticide of moderate toxicity. It can be absorbed by mouth, by inhalation of the dust and through the intact skin. Most formulations should be handled by trained personnel wearing protective clothing. 4.1.1 Manufacture and formulation TLV: No information. Although volatility is low, vapour and dust should be controlled preferably by mechanical means. Protective equipment for the skin and respiratory protection is usually necessary. 4.1.2 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. The applicator should avoid working in spray mist and avoid contact with the mouth. Particular care is needed when equipment is being washed after use. All protective clothing should be washed immediately after use, including the inside of gloves. Splashes must be washed immediately from the skin or eyes with large quantities of water. Before eating, drinking or smoking, hands and other exposed skin should be washed. 4.1.3 Other associated workers (including flagmen in aerial operations) Persons exposed to fenitrothion and associated with its application should observe the precautions described in 4.1.3 under "mixers and applicators". 4.1.4 Other populations likely to be affected With good agricultural practice, subject to 4.2 below, other populations should not be exposed to hazardous amounts of fenitrothion. 4.2 ENTRY OF PERSONS INTO TREATED AREAS Unprotected persons should be kept out of treated areas for at least one day. 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. In additional rinse should be carried out with 5% sodium hydroxide solution which should remain in the container overnight. Impermeable gloves should be worn during this work and a soakage pit should be provided for the rinsings. Decontaminated containers should not be used for food and drink. Spillage of fenitrothion 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 Early symptoms may include excessive sweating, headache, weakness, giddiness, nausea, and vomiting, stomach pains, joint and muscle pains, slurred speech, blurred vision and constricted pupils. 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, 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 fenitrothion. 5. FOR MEDICAL AND LABORATORY PERSONNEL 5.1 MEDICAL DIAGNOSIS AND TREATMENT OF CASES OF POISONING 5.1.1 General information An organophosphorus pesticide of moderate toxicity which is absorbed through the intact skin as well as by inhalation and from the gastrointestinal tract. It is converted in vivo to the oxygen analogue (fenitrothion) which is an active cholinesterase inhibitor. Prolonged and 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, muscle and joint pains, blurred vision, slurred speech, muscle twitching and hypersalivation. More advanced symptoms of poisoning may include coma, cyanosis, loss of sphincter control and loss of reflexes. 5.1.3 Laboratory The most important laboratory finding is reduction in activity of blood cholinesterases. 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 isotonic saline or water. Persons without signs of respiratory inefficiency but with manifest peripheral symptoms should be treated with 2-4 mg of atropine sulfate and 1000-2000 mg of pralidoxime chloride or 250 mg of toxogonin (adult dose) by slow intravenous injection. More atropine may be given as needed. Persons with severe intoxication 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 5-10 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, artificial respiration should be administered 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. 5.1.5 Prognosis If the acute toxic effects are survived and these may be prolonged, and adequate artificial respiration has been given, the chances of complete recovery are good. However, in very severe cases, particularly if artificial respiration has been inadequate, prolonged hypoxia may give rise to permanent brain damage. 5.1.6 References of previously reported cases No clear-cut poisoning cases. However, the following references may be helpful: Matsushima, S. (1972) Baioteku, 3(4), 258 Tshikawa, T. (1972) Baioteku, 3(4), 263 5.2 SURVEILLANCE TESTS Test Normal level* Action level* Symptomatic level Plasma cholinesterase 100% 50% Variable Erythrocyte cholinesterase 100% 70% Usually 40% *Expressed as percentage of pre-exposure activity. 5.3 LABORATORY METHODS 5.3.1 Detection and assay of compound It is unlikely that unchanged fenitrothion will be detectable in human tissues after exposure. Determination of levels of blood cholinesterase and urinary 3-methyl-4-nitrophenol (see 5.3.2 below) should be used in cases of suspected poisoning. Residues may be determined by hydrolysis to 3-methyl-4-nitrophenol which is measured at 400 mu by difference in absorbency in acid and alkaline solution or by gas liquid chromatography; see Möllhoff (1968). For an intra-red method, see Delves & Williams (1966). The most sensitive methods for fenitrothion utilize gas chromatography with either a plasma-photometric detector (Bowman & Beroza, 1969) or a thermionic detector (Miyamoto et al., 1967); detection limits are usually 0.01-0.001 ppm. 5.3.2 Other tests in cases of poisoning Levels of cholinesterase in the blood provide the most useful diagnosis of poisoning; for methods of estimation see: Michel (1949) and Stubbs (1960) for electrometric method, Ellman et al. (1961) for spectrophotometric method and Edson (1958) for tintometric method.
See Also: Fenitrothion (EHC 133, 1992) Fenitrothion (PIM 659)