FAO/PL:1969/M/17/1 WHO/FOOD ADD./70.38 1969 EVALUATIONS OF SOME PESTICIDE RESIDUES IN FOOD THE MONOGRAPHS Issued jointly by FAO and WHO The content of this document is the result of the deliberations of the Joint Meeting of the FAO Working Party of Experts and the WHO Expert Group on Pesticide Residues, which met in Rome, 8 - 15 December 1969. FOOD AND AGRICULTURE ORGANIZATION OF THE UNITED NATIONS WORLD HEALTH ORGANIZATION Rome, 1970 FENITROTHION IDENTITY Chemical name dimethyl 3-methyl-4-nitrophenyl phosphorothionate Synonyms 0,0-dimethyl 0-(3-methyl-nitrophenyl) phosphorothioate, Sumithion(R), Folition(R), Accothion(R), Danathion(R) (Denmark), Metathion(R) (Czechoslovakia), methylnitrophos (countries in Eastern Europe) Structural formulaOther relevant chemical properties Properties of fenitrothion - melting point 0.3°C, boiling point 109°C/0.1 mm Hg; d420 1.3084; yellowish-brown liquid with unpleasant odour; soluble in alcohols, ethers, ketones, aromatic hydrocarbons; insoluble in water; completely stable for 2 years, at 20-25°C; storage temperature should not exceed 40°C; unstable in alkaline media. Formulations - 95% concentrate, 50% emulsifiable concentrate, 40% wettable powder, 2.5% and 5% dust. Deburol(R) (Ciba) contains 15% fenitrothion and 62% mineral oil. One company indicates that their 95% concentrate contains 95% fenitrothion (minimum) and 0.5% 3-methyl-4-nitrophenol (maximum). EVALUATION FOR ACCEPTABLE DAILY INTAKE BIOCHEMICAL ASPECTS Absorption, distribution and excretion Various comprehensive studies in mouse, rat, and guinea-pig have dealt with the pharmacodynamic and biochemical aspects of fenitrothion and its metabolites (Nishizawa et al., 1961; Miyamoto, 1964a, 1964b, 1969; Miyamoto et al., 1963a; Vandanis and Crawford 1964; Hollingworth et al., 1967 Hladká and Nosál, 1967 and Douch et al., 1968). Fenitrothion is presumably rapidly absorbed from the mammalian intestinal tract as evidenced by the appearance of radioactivity in blood from guinea-pigs and rats administered phosphorus32 -labelled fenitrothion orally. The presence of the oxygen analogue was demonstrated in all tissues examined (brain, heart, lung, liver, kidney, spleen and muscle) and it was detectable in blood one minute after an intravenous injection of fenitrothion. This oxygen analogue (II of Fig. 1) is the important metabolite with respect to toxicity. It is formed in the microsomal fraction of the cell, the main organs responsible for the transformation being the liver and kidney. Fenitrooxon is further metabolized as indicated in Fig. 1. The major excretion product found is 3-methyl-4-nitrophenol (VII) which can further be oxidized to 3-carboxy-4-nitrophenol (VIII). Other metabolites are the demethyl-derivatives (V and VI) which, with increasing doses, are excreted in increasing amounts. A total of nine metabolites has been isolated, the majority of which can also be identified. In vitro studies showed that formation of the oxygen analogue (II) was dependent on the availability of reduced nicotine adenine dinucleotide phosphate (NADPH2) and oxygen. Liver slices incubated with fenitrothion did not produce measurable amounts of fenitrooxon, while liver homogenates and the supernatant fraction of such homogenates showed appreciable activation of added fenitrothion. No correlation between the toxicity and rate of formation of the oxygen analogue could, however, be demonstrated (Miyamoto et al., 1963a; Miyamoto, 1969). No observations are available in these studies on the distribution into fatty tissue: however, residue studies on milk, meat and fat from cattle indicate amounts of approximately 0.001 ppm in these samples (Miyamoto and Sato, 1969). Fenitrothion and its metabolites are excreted mainly in the urine (90-95 per cent). Up to 10 per cent was recovered in faeces. Within three days nearly complete recovery of an orally administered dose (15 mg/kg) could be obtained. The metabolic, pattern of fenitrothion as it appears from these studies is shown in Fig. 1. The ratios between the amounts of metabolites was dependent upon the dose given, as is shown in Table 1, which gives the percentage distribution of metabolites in mouse urine after various doses of fenitrothion (Hollingworth et al., 1967). Effect on enzymes and other biochemical parameters As with other organophosphorous compounds fenitrothion acts in the animal organism as a cholinesterase inhibitor, probably after conversion to the oxygen-analogue. Some evidence presented indicates that the cholinesterase inhibiting effect in brain depends more on the rate of penetration into the brain than on the rate of oxidation and decomposition of fenitrothion (Miyamoto, 1969).
TABLE I Percentage distribution of metabolites of fenitrothion in mouse urine after administering various doses Metabolite Percentage of radioactive metabolite excreted in urine after giving P52 - labelled fenitrothion at the indicated dose levels in mg/kg body-weight 3 17 200 850 Phosphoric acid 2.0 2.4 1.9 1.2 Methylphosphoric acid 1.5 2.5 2.4 1.1 Dimethylphosphoric acid 32.2 21.4 5.8 3.0 Dimethylphosphorothioic acid 12.8 20.3 8.7 6.6 Phosphate analogue (II) 2.7 1.6 3.3 2.5 O-demethylphosphate analogue (VI) 26.1 28.4 24.6 17.1 O-demethylphosphorothioate analogue (V) 20.5 20.1 50.9 66.1 Unknown 2.2 2.5 2.4 2.4 TOXICOLOGICAL STUDIES Special studies on neurotoxicity Hen Three hens protected against acute anti-cholinesterase effects with atropine and pralidoxime were given a single oral dose of 400 mg/kg body-weight of fenitrothion. No symptoms of paralysis occurred during an observation period of 28 days. Histologic examination of spinal cord and sciatic nerves revealed no pathological lesions in two hens and a few scattered degenerated fibres in the spinal cord of the third (Carshalton, 1962). Seven hens protected in the same way were given an oral dose of 250 mg/kg body-weight of fenitrothion and three other hens were given 500 mg/kg. Two of the 500 mg/kg group died within 1-2 days, while the remaining eight hens did not show any sign of paralysis during an observation period of six weeks (Kimmerle, 1962b). Special studies on potentiation Rat Female rats were given intraperitoneal doses of a combination of fenitrothion and the following organophosphorus compounds: parathion, parathion-methyl, demeton, disulfoton, malathion, EPN, azinphos-methyl, carbophenothion, mevinphos, dioxathion, schraden, ethion, diazinon, Folex, coumaphos, and fenchlorphos as well as the carbamate carbaryl. No sign of a potentiating effect was demonstrated (DuBois and Kinoshita, 1963). When male rats were given acute oral doses of mixtures of fenitrothion and phosphamidon a marked potentiation of toxicity occurred as evidenced by increased mortality. In female rats a potentiation of toxicity occurred as evidenced by increased mortality. In female rats a potentiation occurred only in mixtures containing relatively low concentrations of fenitrothion, the potention effect diminishing as the concentration of fenitrothion was increased. It was concluded that potentiation is associated with a non-linear phosphorothioate conversion (Braid and Nix, 1968). Special studies on the metabolite fenitrooxon The metabolite fenitrooxon is more toxic than the parent compound (cf. Tables II and III). TABLE II Acute toxicity of fenitrooxon Acute Animal Route LD50 mg/kg References body-weight Mouse oral 90 Miyamoto, 1969 Mouse oral 120 Hollingworth et al., 1967 Rat oral 24 Miyamoto, 1969 Rat i.v. 3.3 Miyamoto, 1969 Guinea-pig oral 221 Miyamoto, 1969 Guinea-pig i.v. 32 Miyamoto, 1969 Acute toxicity The symptoms of acute toxicity are the same as for other organophosphorus compounds, doses close to the LD50 producing symptoms which developed more rapidly after intravenous than after oral administration. The compound is considerably less toxic to mammals than its close structural analogue parathion-methyl (Miyamoto et al., 1963b). Table II gives the LD50 in several species: TABLE III LD50 mg/kg Animal Route body-weight References Mouse (M) oral 1336 Carshalton, 1964 Mouse (F) oral 1416 Carshalton, 1964 Mouse (M) i.p. 115 DuBois and Puchala, 1960 Mouse (F) i.p. 110 DuBois and Puchala, 1960 Mouse i.v. 220 Miyamoto et al, 1963b Rat (M) oral 740 Gaines, 1969 Rat (F) oral 570 Gaines, 1969 Rat (M) i.p. 135 DuBois and Puchala, 1960 Rat (M) i.p. 160 DuBois and Puchala, 1960 Rat i.v. 33 Miyamoto et al, 1963b Guinea-pig (M) oral 500 DuBois and Puchala, 1960 Guinea-pig oral 1850 Miyamoto et al, 1963b Guinea-pig (M) i.p. 110 DuBois and Puchala, 1960 Guinea-pig i.v. 112 Miyamoto et al, 1963b Cat oral 142 Nishizawa et al, 1961 Short-term studies Dog In what was described as a preliminary test, groups of dogs, each comprising one male and one female animal, were given daily oral doses by capsule of 0, 2, 9 or 40 mg/kg body-weight of fenitrothion for periods up to 98 days. Body-weights, blood biochemistry, cholinesterase levels and haemograms were checked at intervals. At the 2 mg/kg level there was no effect with respect to any other of the parameters mentioned. At 9 mg/kg a slight depression after 60 days and at 40 mg/kg a moderate depression after 29 days occurred in whole blood, plasma and red-cell cholinesterase. At 40 mg/kg there were also marked toxic symptoms typical of cholinergic stimulation, and the dogs in this group were sacrificed below the end of the 98-day period (Cooper, 1966). Rat 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. Mortality, food intake, growth, general behaviour, urinalysis, average organ-weights and histpathology were comparable to the controls in the groups fed 32, 63, 125, and 250 ppm. All the animals fed 500 ppm showed clinical symptoms of anti-cholinesterase poisoning and there were minimal symptoms in four animals in the 250 ppm group. In the 500 ppm group the average organ-weights of the testes and brain were increased in comparison with those of the control group. After interim sacrifice every month of four rats from each group, measurement of the cholinesterase activity of plasma, red cells, brain cortex, liver and kidney showed a dose-dependent depression, the lowest being in the brain. The cholinesterase activity in the 32 and 63 ppm groups generally increased after 60 days of dosing to a level within the normal limits, the beet recovery being in the plasma, kidney and brain, less in the red cells and the liver (Misu et al., 1966). Two groups, each of 20 male rats, were dosed by stomach tube on six days a week for six months with 10 mg/kg and 11 mg/kg body-weight of fenitrothion, respectively. During the first weeks the rats showed a temporary deterioration of general condition and loss of weight. Haematology and urinalysis during the experiment and gross and microscopic pathology at its termination did not reveal any abnormalities (Klimmer, 1961). Male rats were given daily oral doses of 13 mg/kg body-weight of fenitrothion for 28 days. Red-cell cholinesterase activity showed severe depression, but there was recovery 30 days after withdrawal of fenitrothion (Kimmerle, 1962a). Male rats were fed 5, 10, and 20 ppm of fenitrothion in the diet for an unspecified period. Brain and red cell cholinesterase activity was normal in the 5 ppm group, whereas the 10 ppm group showed a slight depression of red cell activity after five weeks with recovery two weeks after withdrawal. The 20 ppm group showed some depression of activity both in red cells and in brain and the recovery in the brain remained incomplete two weeks after withdrawal (Carshalton, 1964). Other reported studies with fenitrothion in the rat lasting 90 days indicate that the levels causing no appreciable effect on the cholinesterase activity of plasma, red-cells and whole blood were 20 ppm in the diet and 10 ppm in drinking water. The only exception was a moderate inhibition of the activity in plasma among the male animals when given 10 ppm in drinking water. The above mentioned levels and higher, namely 92.8 ppm in the diet and 46.2 ppm and 215 ppm in drinking water, caused no effect on food or water intake, weight-gain, average organ-weights, haemogram and blood biochemistry. However, 92.8 ppm of fenitrothion in the diet and 46.4 ppm in drinking water had a moderate effect on whole blood and red-cell cholinesterase and a more marked effect on plasma cholinesterase. The cholinesterase activity recovered between 30-40 days after withdrawal of fenitrothion. The levels of 430 ppm in the diet and 1000 ppm in drinking water caused a depression of body-weight gains (Cooper, 1966). Long-term studies Rat An interim report on what appears to be a two-year feeding study in rats is available. Groups of nine or 10 male rats were fed 0, 25, 100 or 400 ppm of fenitrothion in their diet and were sacrificed after feeding these levels for 63 weeks. As a positive control a group was also fed 800 ppm of malathion. At the 400 ppm level of fenitrothion, food intake and body-weight gain were increased and only a few animals survived the 63 week period. At this level there was a 100 per cent depression of red-cell cholinesterase. At the 100 ppm level a slight (10-30 per cent) cholinesterase depression occurred in the brain and a moderate depression (30-65 per cent) in the red blood cells and plasma. At 25 ppm there was no effect on cholinesterase nor was there any effect with regard to any other parameters evaluated (Ueda and Nishimura, 1966). OBSERVATIONS IN MAN In a field spraying operation in Southern Nigeria including a village using a five per cent spray of fenitrothion, examination of 18 villagers one week later did not reveal any clinical symptoms of toxicity or plasma cholinesterase depression. The same was true of the three spraymen examined on the first, second and sixth day after spraying relative to a pre-spraying level (Vandekar, 1965). In another field spraying trial in Northern Nigeria, 10,000 huts in which about 16,500 people lived were sprayed. Field test cholinesterase determinations on whole blood did not show any appreciable difference in cholinesterase levels of 535 villagers tasted before spraying and 299 villagers tested 5-30 days after spraying. After one week of intensive spraying five out of 20 spraymen developed a 50 per cent depression of cholinesterase which returned to a stable level after a period of rest. One sprayman developed symptoms of toxicity which lasted only a few hours and disappeared without treatment (Wilford et al., 1965). Fenitrothion was given to a total of 24 human subjects in single oral doses of from 2.5 to 20 mg (0.042 to 0.33 mg/kg body-weight for a 60 kg man). The excretion of the metabolite, 3-methyl-4-nitrophenol, in the urine was almost complete within 24 hours, the maximum excretion occurring in the first 12 hours. The percentage of the dose excreted during this time depended to a certain extent upon the size of the dose administered, being about 70 per cent of theoretical after a 0.042 mg/kg dose and about 50 per cent after a 0.33 mg/kg dose. Both plasma and cholinesterase activity were not depressed below normal except possibly in one person given a 0.33 mg/kg dose, where some depression of plasma cholinesterase was apparent after six and 24 hours (about 65 per cent of the pre-test level). When repeated doses of 2.5 or 5 mg approximately 0.04 to 0.08 mg/kg) were given to five individuals, four times at 24 hour intervals, most of the nitrocresol metabolite appeared in the urine within the interval 0 to 12 hours after administration. After receiving the third and fourth dose there was a trend towards a rise in red cell cholinesterase activity but in no cases was there any evidence of reduction below normal levels of the activity of this enzyme in either plasma or red cells (Nosal and Hladka, 1968). COMMENT Adequate information is available on the toxicity, biochemistry and metabolism of fenitrothion, in three species of rodent. Information is also available in man including field spraying studies and a metabolism study. Only an interim report comprising a 63-week study in rats in available and there are no 1-2 year studies in a non-rodent mammalian species. The short-term studies in the rat, using cholinesterase inhibition criteria, provide a no-effect level. No reproduction or teratogenicity studies are available and in view of the similarity in the structure of fenitrothion to parathion-methyl, it is important that such studies be undertaken. For this reason and because no adequate long-term studies are available it was decided to give only a temporary acceptable daily intake to this compound. TOXICOLOGICAL EVALUATION Level causing no toxicological effect Rat: 5 ppm in the diet, equivalent to 0.25 mg/kg body-weight/day ESTIMATE OF TEMPORARY ACCEPTABLE DAILY INTAKE FOR MAN 0-0.001 mg/kg body-weight RESIDUES IN FOOD AND THEIR EVALUATION USE PATTERN Fenitrothion is a broad-spectrum insecticide having a much lower acute mammalian toxicity than many similar organophosphorus insecticides. Its action is by direct contact or an a stomach poison. It can be applied as an emulsifiable concentrate, wettable powder, granular formulation or dust. It is toxic to bees and should not be sprayed on flowering crops. Fenitrothion can be combined with all conventional insecticides and fungicides except those having an alkaline reaction. The insecticide has been used throughout Europe, East Pakistan, East Africa, United Arab Republic, Japan, Republic of China, New Zealand, Canada, and Brazil. It is not registered for use in the United States. Pre-harvest treatments Fenitrothion is used on a wide variety of crops including fruits, field crops, vegetables, rice, cotton, cereals, cocoa, tea, and coffee for control of stem borers, hoppers, leaf miners, leaf rollers, whiteflies, fruit flies, mealybugs, mirids and bugs, thrips, aphids, mites, lady beetles, caterpillars, and soft scale insects. The recommended concentrations and rates of application vary for the different crops and pest species to be controlled. Concentrations of sprays range from 0.05 to 0.1%. active ingredient (a.i.) and rates of application from 0.5 to 2.0 kg a.i./hectare. The chemical is generally tolerated by most crops although high dosages may injure cotton, and phytotoxicity on Brassica crops and orchard fruits has been encountered. Safety intervals prior to harvest range from 10 to 21 days and differ depending on the country and the crop. Post-harvest treatments No post-harvest treatments are made in Europe. Admixture of 1 to 5 ppm of fenitrothion has been recommended to protect grains such as rice, wheat, and barley for months against various weevils and beetles. Bag treatment is acceptable in Brazil for protecting stored grains and post-harvest treatments are under development in various countries. Other uses Fenitrothion is used to control grasshoppers, locusts, and caterpillars on pastures and spruce budworm in forests. It also provides control of household and other pests, such as mosquitoes and their larvae, houseflies, cockroaches, lice, bedbugs, and poultry mites. Its action is rapid, and its residual activity is good. RESIDUES RESULTING FROM SUPERVISED TRIALS Typical maximum residues after treatment of a variety of crops are given in Table IV. TABLE IV Maximum residues after treatment of crops Maximum Dosage residues at active Pre-harvest harvest, ppm Crop ingredient interval, days respectively Reference Rice 1000 g/ha 41 0.005 Sumitomo 1969 Rice 0.07% spray or Miyamoto, Sato 5% granules 1-2 months n.d. 1965 Apple 0.05% spray 21 0.05 Sumitomo 1969 Apple 0.2% spray 7 and 14 0.5 and 0.35 Bayer 1969 Apple, Golden 0.15% spray 10 and 15 1.0 and 0.75 Bayer 1969 cherry 0.2% spray 7 and 14 0.5 and 0.2 Bayer 1969 Grape* 0.05% spray 10 0.50 Sumitomo 1969 Tomato* 0.05% spray 7 0.18 Sumitomo 1969 Cocoa 0.1% spray 14 0.10 Miyamoto et al 1965b Red cabbage 0.15%; 1000 7 Outside leaves 1/ha 0.65 Cabbage less outside leaves 0.25 Bayer 1969 Sugar beets 0.15%; 1000 8 n.d. Bayer 1969 1/ha TABLE IV (cont'd) Maximum residues after treatment of crops Maximum Dosage residues at active Pre-harvest harvest, ppm Crop ingredient interval, days respectively Reference Green tea 0.1% spray 14 0.27 Sumitomo 1969 Cauliflower 0.1%; 1000 7 n.d. Bayer 1969 1/ha Lettuce 0.1%; 1000 7 and 14 1.05 and 0.3 Bayer 1969 1/ha Lettuce 0.05%; 600 1, 7, and 14 0.65, 0.06, Möllhoff 1968 1/ha 0.01 Peas and pod 0.25%; 560 0 and 5 0.7 and <0.15 Bayer 1969 1/ha *These green-house trials gave residues higher than those of field trials. FATE OF RESIDUES General comments Fenitrothion may be metabolized as shown in Figure 1. The major route in animals appears to be through splitting of the P-O-aryl bond to give the corresponding dimethyl esters of phosphorothioic and phosphoric acids. Another means of degradation is demethylation of the methoxy group to give desmethyl fenitrothion. Although formation of the oxygen analogue, fenitrooxon, is minor compared to products formed via hydrolysis, fenitrooxon must be taken into account because the mammalian toxicity of oxons is generally much higher than that of parent thiono pesticides. In plants the metabolism of fenitrothion appears to be similar to that in animals. In animals Orally administered 32P-labelled fenitrothion was readily absorbed from the digestive tract of guinea pigs or rats and the major portion of the radioactivity excreted in the urine. Neither fenitrothion nor fenitrooxon was detected and desmethyl fenitrothion, dimethyl phosphorothioic and dimethyl phosphoric acids were identified in the urine (Miyamoto et al., 1963a). Following intravenous injection of radioactive 32P fenitrothion into guinea pigs and rats, fenitrothion rapidly disappeared from the blood. Fenitrothion and fenitrooxon were found in the tissues, and their amounts decreased rapidly. The desmethyl compound and the dimethyl esters mentioned in the foregoing paragraph were found mostly in the liver and kidneys (Miyamoto, 1964a). Excretion of metabolic products is rapid and chiefly in the form of 3-methyl-4-nitrophenol (the nitrocresol hydrolysis product) (Hladka and Nosal, 1967; Nosal and Hladka, 1968); the cresol methyl may be oxidized to COOH (Douch et al., 1968). The desmethyl compounds are also excreted (Hollingworth et al., 1967; Miyamoto et al., 1963b). Between 60 and 90% of the insecticide is excreted within two days, chiefly in the aforementioned forms. Only up to 10% is excreted in the feces. Detoxication via the desmethyl compounds is dose-dependent. After oral administration of up to 40 grams of fenitrothion per lactating cow, residues in the milk were as high as 0.4 ppm after 6 hours and below the limit of detection after one day (Hais and Franz, 1965). Detoxication in bovine rumens is rapid owing to reduction of fenitrothion to the amino compound (Miyamoto et al., 1967). Cows fed 3 mg/kg body weight of fenitrothion for seven consecutive days produced milk having up to 0.002 ppm residue of fenitrothion on the second day, and no residue one day after administration was stopped. Less than 0.003 ppm aminofenitrothion and about 0.1 ppm p-nitrocresol were detected during treatment, and no fenitrooxon was found (Miyamoto et al., 1967). Thirty calves (1-1.5 yr. av. wt. 243 kg) confined on a pasture sprayed with 375 g/ha of fenitrothion (11.8 ppm initial residue on grass) were periodically sacrificed and breast muscle and omental fat analysed. On the first day residues in the meat and fat were about 0.01 ppm. No residue of fenitrothion was found in the meat from the third day on and only 0.004-0.007 ppm was found in the fat on the third day; these amounts decreased almost to control levels by the seventh day (Republic of Argentina, 1968; Miyamoto and Sato, 1969). Lactating dairy cattle were fed 50 ppm of fenitrothion in the feed (dry basis) for 29 days. No residue of fenitrothion, fenitrooxon, or the cresol appeared in the milk. A maximum of 0.006 ppm of aminofenitrothion was found (Bowman, 1969). In plants About 50% of 32P-labelled fenitrothion sprayed on rice plants penetrated into the tissues in 24 hours; at the end of this period only 10% was left, indicating rapid decomposition. Some fenitrooxon formed but it disappeared from the tissues more rapidly than fenitrothion. Rice grains harvested 46 days after treatment contained 0.0007 ppm fenitrothion and less than 1 ppm of p-nitrocresol and dimethyl phosphorothioic acid (Miyamoto and Sato, 1965). Fenitrothion does not appear to have much systemic action. After treatment of rice plants with fenitrothion, more residue is found in the bran than in the polished grains (Miyamato and Sato, 1965). Very little active ingredient passed from peel to fruit in stored bananas (Miyamoto et al., 1965a). The half-life of fenitrothion in green plants ranges between the values established for parathion and parathion-methyl, i.e. between one and two days; the half-life of the oxon is estimated to be only a few hours (Möllhoff, 1968). Although the oxon may form in plants it occurs only during the first few days after treatment and in proportions (ca. 1% smaller than those in animals (Miyamoto et al., 1963; Miyamoto and Sato 1965; Möllhoff, 1968). Desmethyl compounds occur only in minor amounts in plants. Phytotoxicity of fenitrothion on cabbage was ascribed to high penetration of the insecticide and accumulation of the cresol hydrolysis product (Tomizawa and Kobayashi, 1964). In soil The soil bacteria Bacillus subtilis, converted more than half of radiolabelled 32P fenitrothion to the amino analogue under aerobic conditions at 37°C in 24 hours. The desmethyl derivatives of fenitrothion and aminofenitrothion as well as dimethyl phosphorothioic acid formed. None of the oxon or oxons of the degradation products were found (Miyamoto et al., 1966). Fenitrothion is gradually inactivated by other bacterial species including gram-positive and gram-negative rods, but not by fungi and yeasts (Yasuno et al., 1965). Fenitrothion is readily absorbed onto various kinds of soil and decomposed by alkalinity or microorganisms (Muramoto, 1967). Persistence in soil does not appear to be great. In storage and processing Fenitrothion shows promise for control of grain insects in storage. Applied at 2 and 1 ppm to barley, it decreased to 0.4 ppm after 15 weeks' storage (Green and Tyler, 1966). On barley in silos the half-life of fenitrothion was about 100 days (Green and Tyler, 1966) and on stored bananas about 15 days (Miyamoto et al., 1965a). Applied to wheat 11% moisture) at rates of 1, 2 and 4 ppm, 0.2, 0.4., and 1.1 ppm of fenitrothion remained, respectively, after 9 months of storage at 25°C and 60% relative humidity (Kane and Green, 1968). In extensive trials as a wheat protectant, fenitrothion levels steadied below 2 ppm after about 2 months regardless of application rate between 2.5 and 10 ppm. In one trial 6 ppm applied to grain decreased to 2.4, 1.7, and 1.1 ppm, respectively, after 1´, 4, and 6 months. Flour made from the 2.4-ppm sample contained 0.3 ppm fenitrothion, while only traces were found in the flour and bread from the later samples (Cooper Technical Bureau, 1968). Evidence of residues in food in commerce or at consumption No report of residues of fenitrothion in food in commerce or at consumption has been found. Reference is made under "In storage and processing" to the finding of only "traces" of fenitrothion in flour and bread prepared from grain containing 1.7 and 1.1 ppm of the insecticide. METHODS OF RESIDUE ANALYSIS Metabolic studies on plants and mammals indicate that residues of fenitrooxon and aminofenitrooxon, when they do form, occur in small amount and are degraded or excreted more rapidly than the parent compound. Once pilot experiments establish that no more than traces of these compounds form on a given crop, there does not seem to be any need to analyse for these compounds on that crop in commerce. (For purposes of this discussion, a trace shall be considered less than 10% of the tolerance level of the parent compound). Analyses for the p-nitrocresol have been made and measurable amounts of the compound are found following good agricultural practice. A determination of the cresol is sometimes reported. However, if a pilot experiment on a given crop shows no excessive amount of the cresol to be present at harvest, there does not appear to be any need for its analysis on that crop in commerce. Other metabolites are generally rather polar and do not tend to be stored. In essence then, the analyst will be concerned with residues of fenitrothion itself unless pilot experiments indicate that other metabolites should be taken into account. This same view is expressed by Frehse and Möllhoff in a IUPAC report by Egan (1969). Fenitrothion in so similar to parathion and methyl parathion that analytical methods used for them may be used for fenitrothion. However, many of the earlier methods lack specificity. Numerous procedures for a wide variety of harvest products are based on thin-layer chromatography, spectroscopy and gas chromatography. Information relating to these analyses follow. No reference to inter-laboratory collaborative studies on analytical procedures was found. Extraction and partitioning It is not sufficient simply to wash the analytical samples since small amounts of the active ingredient penetrate into the plant. It is therefore important that complete extraction of the insecticide and metabolites (e.g. by exhaustive Soxhlet extraction) be compared against the extraction method used. Harvest products with a high content of water have been macerated with acetone (Horler, 1966; Möllhoff, 1967, 1968), acetonitrile (Coffin and Savary, 1964; Thier and Bergner, 1966), or ethanol (Fischer, 1968). Very good recoveries were obtained by Soxhlet extraction with chloroform-methanol (9:1 v/v) (Bowman and Beroza, 1969). For milk, a combination of polar and nonpolar extractants is required, e.g. acetone-methylene chloride (Bowman and Beroza, 1969), ethanol-hexane (Franz and Kovac, 1965). Extraction with methanol-acetonitrile also proved suitable for milk samples (Miyamoto et al., 1967). For oil-containing harvest products with a low water content, use is made of benzene (Dawson et al., 1964; Horler, 1966), petroleum ether (Kovac and Sohler, 1965), hexane (Horler, 1966), or chloroform (Yuen, 1966). On account of the favourable partition coefficients (Bowman and Beroza, 1965; Kovac, 1963), fats and waxes are best removed by partitioning between hexane and acetonitrile (Franz and Kovac, 1965; Miyamoto et al., 1967; Möllhoff, 1967; Bowman and Beroza, 1969). Qualitative analysis Although no reports of fenitrothion being separated from similar residues by column chromatography have been noted, separation is possible with thin-layer or gas chromatography. Interfering active ingredients are parathion, parathion-methyl, malathion, and fenthion and the resolution is just sufficient for distinguishing fenitrothion from these active ingredients (see e.g. Möllhoff, 1968). By comparing gas chromatograms recorded with a phosphorus detector and an electron capture detector, fenitrothion can often be clearly differentiated from malathion and fenthion owing to differences in sensitivity. Colorimetry Colorimetric determinations are carried out by the method of Averell and Norris (1948) or by determination of the cresol after saponification of the active ingredient with alkali. The limits of determination are about 0.05 ppm. Thin-layer chromatography Thin-layer chromatography has been used for clean-up of the extracts with final determination by colorimetry after deleting the appropriate spot from the plate, or for direct determination on the plate after spraying. Quantitative evaluation is possible in the first instance; in the second, the evaluation is semiquantitative and more suitable for confirming identity. About 0.1 ppm of fenitrothion can be determined in most harvested products. Determination of lesser amounts is possible with procedures utilizing cholinesterase inhibition (Ackermann, 1966; Mendoza et al., 1968; Schutzmann and Barthel, 1969; Winterlin et al., 1968). Column chromatography For extract cleanup or separation of metabolites, columns are suitable, especially those packed with deactivated silica gel (Bowman and Beroza, 1969), deactivated Florisil (Möllhoff, 1967, 1968), or deactivated acid aluminum oxide (Horler, 1966). Columns packed with active Florisil (Beckman and Garber, 1969), magnesium oxide (Coffin and Savary, 1964), polyethylene-impregnated aluminum oxide (Coffin and Savary, 1964), and Sephadex LH-20 (Horler, 1968; Ruzicka, et al., 1968) have also been used. Gas chromatography The most reliable and highly sensitive methods for fenitrothion utilize gas chromatography with either the flame-photometric (Bowman and Beroza, 1969) or the thermionic detector (Miyamoto et al., 1967, Sato et al., 1968). These detectors respond to the phosphorus in the molecule with very high specificity. No cleanup is usually required with the flame-photometric detector when analysing for either fenitrothion or its oxygen analogue unless a fatty food is being analysed. In this case a simple hexane-acetonitrile partition is used. A cleanup was used with the thermionic detector but it may often be omitted. Limit of determination is usually 0.01-0.001 ppm. In the analysis for fenitrooxon a separation from fenitrothion on silica gel is used. The compound is then determined by gas chromatography (Bowman and Beroza, 1969) or enzymatically (Miyamoto et al., 1967). The cresol is determined by electron-capture gas chromatography (Bowman and Beroza, 1969) or colorimetrically (Miyamoto et al., 1967) after column separation. Analysis of fenitrothion, fenitrooxon, and the cresol by electron-capture gas chromatography is possible (Bowman and Beroza, 1969; Dawson et al., 1964; Horler, 1966; Möllhoff, 1967) but less specific; sensitivity, about 0.1 ppm, can be improved with a suitable cleanup. Determination of metabolites Gas chromatographic methods have been described for the simultaneous determination of fenitrothion, fenitrooxon (Bowman and Beroza, 1969; Möllhoff, 1968), 3-methyl-4-nitro phenol (Bowman and Beroza, 1969; Miyamoto et al., 1967) and the amino compound of fenitrothion (Miyamoto et al., 1967). As noted, for market controls determination of fenitrothion is generally sufficient (Möllhoff, 1968). NATIONAL TOLERANCES AND WITHHOLDING PERIODS Tolerance Withholding Country Crop (ppm) period (days) Austria 2.0 proposed Belgium Top fruits and vegetables 0.5 14 China, Rice - 21 Republic of Vegetables - 10 Denmark Beets, apples, peas, clover - 15 Tolerance Withholding Country Crop (ppm) period (days) East Africa Mango, cereals - 7 Germany, Field crops, vegetables, fruits, and - 10 Eastern special crops Crops for Infant food and remedies - 21 Germany Vegetables, root and field crops, 0.4 10 (Fed. Rep.) legumes, fruits, grapes Finland - 21 France Vegetables, fruits - 15 Italy - 15 Netherlands Cereals, fruits 0.5 21 New Zealand - 14 (7 for pasture) Poland Top fruits (except strawberries and - 14 raspberries) Portugal Vegetables, citrus, fruits, cocoa, coffee - 21 Pasture grass - 10 Spain Vegetables, citrus, fruits - 15-21 Sweden Peas, rape, wheat, barley - 10 Switzerland Top fruits 0.2 in combination with Amidithion APPRAISAL Fenitrothion is a broad spectrum insecticide with a much lower acute mammalian toxicity than many similar insecticides. It is not covered by patents and is produced by at least six companies. Use of fenitrothion is almost worldwide (excluding the U.S.A.) for such crops as rice, fruits, vegetables, cotton, cereals, soybeans, coffee and tea. Application rates are 0.5-2.0 kg a.i./ha. Waiting intervals are generally 10-21 days. It is used against spruce budworm (in forests), insects attacking man, and in some countries to protect stored products. Its use on pasture land (375 g/ha) results in almost no residues of fenitrothion in milk or meat (<0.01 ppm). The insecticide is available as a 95% concentrate, 50% emulsifiable concentrate, 40% wettable powder, 2.5 and 5% dusts. Composition of technical materials is not known and is apt to vary depending on manufacturer. Residue data are available mostly from Europe and Japan. Although several metabolites of fenitrothion are known to form (fenitrooxon, desmethyl fenitrothion, aminofenitrothion, and 3-methyl-4-nitrophenol), they do not accumulate in significant amounts or they appear to be comparatively non-toxic. Unless experimental trials indicate otherwise, fenitrothion appears to be the only toxic residue to be determined in products in commerce. Many methods are available for residue analysis of fenitrothion. The best of these utilize gas chromatography with the flame photometric or thermionic detector. Some of these methods may also be used for analysis of metabolites. Sensitivity is usually better than 0.01 ppm. Evaluation of these procedures for regulatory purposes is suggested. Few data on residues in food in commerce or in diets have been reported. RECOMMENDATIONS FOR TOLERANCES, TEMPORARY TOLERANCE OR PRACTICAL RESIDUE LIMITS TEMPORARY TOLERANCES (effective to June 1973) Apples, cherries, grapes, lettuce 0.5 ppm ) Preharvest interval to ) be such that these Tomatoes 0.2 ppm ) tolerances are not ) exceeded) Red cabbage, green tea 0.3 ppm Cocoa 0.1 ppm The 3-methyl-4-nitrophenol is not included in the recommendations at this time but the Joint Meeting should review this aspect in due course. PRACTICAL RESIDUE LIMITS Milk (whole) 0.002 Meat or fat 0.03 FURTHER WORK OR INFORMATION REQUIRED (before 30 June 1973) 1. Reproduction and teratogenicity studies in animals preferably in non-human primates. 2. Adequate long-term studies in rodent and non-rodent mammalian species. 3. Data on residue levels in raw agricultural commodities moving in commerce and in total diet studies. 4. Data on disappearance of residues during storage, processing and cooking. 5. Data on rate of residue decline in rice and pre-harvest interval. 6. Before use as a grain protectant, data on persistence of residues in storage of the grains concerned and definitive data on residues in bread are needed. 7. Data on occurrence of 4-nitro-3-methylphenol residues and their significance toxicologically. 8. Information on ingredients in technical products produced by several manufacturers. DESIRABLE 1. Observations in man. 2. Evaluation of gas chromatographic methods for regulatory purposes. REFERENCES Ackermann, H. (1966) Enzymatischer Nachweis phosphororganischer Insektizide nach dünnschicht-chromatographischer Trennung. Nahrung, 10:273-4 Averell, P.R. and Norris, M.V. (1948) Estimation of small amounts of O,O-diethyl-O,p-nitro-phenyl thiophosphate. Anal. Chem. 20:753-6 Bayer (1969) (Farbenfabriken Bayer AG.). Fenitrothion. Unpub. Rept. Beckman, H. and Garber, D. (1969) Recovery of 65 organophosphorus pesticides from Florisil with a new solvent elution system. J. Ass. Offic. Anal. Chem. 52:286-93 Bowman, M.C. and Beroza, M. (1965) Extraction p-values of pesticides and related compounds in six binary solvent systems. J. Ass. Offic. Agr. Chem. 48:943-52 Bowman, M.C. and Beroza, M. (1969) Determination of Accothion, its oxygen analog, and its cresol in corn, grass and milk by gas chromatography. J. Agr. Food Chem. 17:271-6 Bowman, M.C. (1969) Private communication Braid, P.E. and Nix, M. (1968) Potentiation of toxicity of Sumithion by phosphamidon in the rat. Canad. J. Physiol. Pharmacol. 46:145-9 Carshalton (1962) WHO insecticide evaluation and testing programme - stage I. Mammalian toxicity report OMS 43=S5660, Test for neurotoxic effects in hens. Unpub. Rept. from the Toxicology Research Unit, Charshalton. Submitted by Farbenfabriken Bayer AG. Carshalton. (1964) OMS 43. Summary. OMS 43. Mammalian toxicity. Unpub. Rept. of the Toxicology Research Unit, Carshalton. Submitted by Farbenfabriken Bayer AG. Coffin, D.E. and Savary, G. (1964) Procedure for extraction and cleanup of plant material prior to determination of organophosphate residues. J. Ass. Offic. Agr. Chem. 47:875-81 Cooper. (1966) Toxicity of Sumithion. Unpub. Rept. of the Cooper Technical Bureau. Submitted by Sumitomo Chemical Co., Ltd. Osaka Cooper. (1968) Technical Bureau. Sumithion as a grain protectant. Technical report by William Cooper and Nephews, Australia. Cited by Sumitomo, 1969 Dawson, J.A., Donegan, L. and Thain, E.M. (1964) The determination of parathion and related insecticides by gas-liquid chromatography with special reference to fenitrothion residues in cocoa. Analyst, 89:495-6 Douch, P.G.C., Hook, C.E.R. and Smith, J.N. (1968) Metabolism of Folithion (dimethyl-4-nitro-3-methylphenyl phosphorothionate). Australasian J. Pharm., 49: No.584. Suppl. Nr.66, 2.S. DuBois, K.P. and Puchala, E. (1960) The acute toxicity and anticholinesterase action of Bayer 41831. Unpub. Rept. from the Department of Pharmacology, University or Chicago. Submitted by Farbenfabriken Bayer AG. DuBois, K.P. and Kinoshita, F. (1963) The acute toxicity of Bayer 41831 in combination with other anticholinesterase insecticides. Unpub. Rept. from the Department of Pharmacology, University of Chicago. Submitted by Farbenfabriken Bayer AG. Fischer, R. (1968) Nachweis und quantitative Bestimmung von Phosphor-Insektiziden in biologischem Material. III. Arch. Toxicol., 23:129-35 Franz, J. and Kovac, J. (1965) Bestimmung toxischer Rückstände von O,O-Dimethyl-O-(3-methyl-4-nitrophenyl)-thiophosphat in Milch. Z. Anal. Chem. 210:354-8 Frehse, H. and Möllhoff, E. (1969) Organophosphorus insecticide residue analysis. Evaluation. (A) Metabolic products. In report of IUPAC Commission on the development, improvement, and standardization of methods of pesticide residue analysis. Egan, H. J. Ass. Offic. Anal. Chem. 52:306-9 Gaines, T.B. (1969) Acute toxicity of pesticides. Toxicol. appl. Pharmacol., 14:515-34 Green, A.A. and Tyler, P.S. (1966) A field comparison of malathion, dichlorvos and fenitrothion for the control of Oryzaephilus surinamensis (L) infesting stored barley. J. Stored Prod. Res. 1:273-85 Hais, K. and Franz, J. (1965) On the problem of Metathione residues in milk after disinfestation. Cesk. Hyg. 10.205-8 Hladká, A. and Nosál, M. (1967) The determination of the exposition to Metathion fenitrothion) on the basis of excreting its metabolite p-nitro-m-cresol through urine in rats. Internat. Arch. Gewerbepath. Gewerbehyg. 23:209-14 Hollingworth, R.M., Fukuto, T.R. and Metcalf, R.L. (1967) Selectivity of Sumithion Compared with Methyl Parathion. Influence of structure on anticholinesterase activity. Metabolism in the white mouse. J. Agric. Food Chem., 15:235-49 Horler, D.F. (1966) Determination of fenitrothion on stored barley. J. Stored Prod. Res. 1:287-90 Horler, D.F. (1968) Gel filtration on Sephadex LH-20. A general clean-up method for pesticides extracted from grain. J. Sci. Food Agr. 19:229-31 Kane, J. and Green, A.A. (1968) The protection of bagged grain from insect infestation using fenitrothion. J. Stored Prod. Res. 4 59. Kimmerle, G. (1962a) Toxikologische Untersuchungen mit dem Wirkstoff S 5660. Unpub. Rept. from Toxilkolisches und Gewerbehygienisches Laboratorium. Submitted by Farbenfabriken Bayer AG. Kimmerle, G. (1962b) S 5660. Unpub. Rept. on the neurotoxic effect on hens from Toxikologisches und Gewerbehygienisches Laboratorium. Submitted by Farbenfabriken Bayer AG. Klimmer, O.R. (1961) Opinion on the toxicity of the compound "S 5660" of Farbenfabriken Bayer AG., Leverkusen. Unpub. Rept. from Pharmakologisches Institut der Rheinischen Friedrich-Wilhelms-Universität, Bonn. Submitted by Farbenfabriken Bayer AG. Kovac, J. (1963) Bestimmung von O,O-Dimethyl-O-(3-methyl-4-nitrophenyl)-thiophosphat in technischen Produkten nach vorhergehender Abtrennung der Begleitstoffe mittels Dünnschichtchromatographie. J. Chromatogr. 11:412-3 Kovac, J. and Sohler, E. (1965) Bestimmung von O,O-Dimethyl-O-(3-methyl-4-nitrophenyl)-thiophosphat-Rückständen in Obst und Gemüse nach vorangegangener Abtrennung der mitextrahierten Farbstoffe durch Dünnschichtchromatographie. Z. Anal. Chem. 208.201-4 Mendoza, C.E., Wales, P.J., McLeod, H.A. and McKinley, W.P. (1968) Thin-layer chromatographic-enzyme inhibition procedure to screen for organophosphorus pesticides in plant extracts without elaborate clean-up. Analyst 93:173-7 Misu, Y., Segawa, T., Kuruma, I., Kojima, M. and Takagi, H. (1966) Subacute toxicity of O,O-dimethyl-O-(3-methyl-4-nitrophenyl) phosphorothioate (Sumithion) in the rat. Toxicol. appl. Pharmacol., 9:17-26 Miyamoto, J., Sato, Y., Kadota, T., Fujinami, A. and Endo, M. (1963a) Studies on the mode of action of organophosphorus compounds. Part I. Metabolic Fate of p32 labeled Sumithion and Methylparathion in guinea-pig and white rat. Agric. Biol. Chem. (Tokyo), 27:381-9 Miyamoto, J., Sato, Y., Kadota, T. and Fujinami, A. (1963b) Studies on the mode of action of organophosphorus compounds. Part II. Inhibition of mammalian cholinesterase in vivo following the administration of Sumithion and Methylparathion. Agric. Biol. Chem. (Tokyo), 27:669-76 Miyamoto, J. (1964a) Studies on the mode of action of organophosphorus compounds. Part III. Activation and degradation of Sumithion and Methylparathion in vivo. Agric. Biol. Chem. (Tokyo), 28:411-21 Miyamoto, J. (1964b) Studies on the mode of action of organophosphorus compounds. Part IV. Penetration of Sumithion, Methylparathion and their oxygen analogs into guinea pig brain and inhibition of cholinesterase in vivo. Agric. Biol. Chem. Tokyo), 28:422-30 Miyamoto, J. and Sato, Y. (1965) Determination of insecticide residue in animal and plant tissues. II. Metabolic fate of Sumithion in rice plant applied at the preheading stage and its residue in harvested grains. Botyu-Kagaku, 30:45-9 Miyamoto, J., Kawaguchi, Y. and Sato, Y. (1965a) Determination of insecticide residue in animal and plant tissues. I. Determination of Sumithion residues in bananas grown in Formosa. Botyu-Kagaku, 30:9-12 Miyamoto, J., Sato, Y. and Fujikawa, K. (1965b) Determination of insecticide residue in animal and plant tissues. III. Determination of residual amount of Sumithion in cocoa beans grown in Nigeria. Botyu-Kagaku 30:49-51 Miyamoto, J., Kitagawa, K. and Sato, Y. (1966) Metabolism of organophosphorus insecticides by Bacillus subtilis, with special emphasis on Sumithion. Jap. J. Exp. Med. 36:211-25 Miyamoto, J., Sato, Y. and Suzuki, S. (1967) Determination of insecticide residue in animal and plant tissues. IV. Determination of residual amount of Sumithion and some of its metabolites in fresh milk. Botyu-Kagaku. 32:95-100 Miyamoto, J. (1969) Mechanism of low toxicity of Sumithion toward mammals. Residue Reviews, 25:251-64 Miyamoto, J. and Sato, Y. (1969) Determination of insecticide residue in animal and plant tissues. VI. Determination of Sumithion residue in cattle tissues. Botyu Kagaku 34:3-6 Möllhoff, E. (1967) Gas chromatographic determination of residues of E605 products and Agritox in plants and soil samples. Pflanzenschutz-Nachrichten Bayer 20:557-74 Möllhoff, E. (1968) Beitrag zur Frage der Rückstände und ihrer Bestimmung in Pflanzen nach Anwendung von Präparaten der E 605 - und Agritox - Reihe. Pflanzenschutz-Nachrichten Bayer 21:331-58 Muramoto, N. (1967) Unpub. observations, cited by Sumitomo, 1969 Nishizawa, Y., Fujii, K., Kadota, T., Miyamoto, J. and Sakamoto, H. (1961) Studies on the organophosphorus insecticides. Part VII. Chemical and biological properties of new low toxic organophosphorus insecticide. O,o-Dimethyl-O-(3-methyl-4-nitrophenyl) phosphorothioate. Agric. Biol. Chem. (Japan), 25:605-10 Nosäl, M. and Hladkä, A. (1968) Determination of the exposure to fenitrothion [O,O-dimethyl-O-(3-methyl-4-nitrophenyl) thiophosphate] on the basis of the excretion of p-nitro-m-cresol by the urine of the persons tested. Internat. Arch. Gewerbepath. Gewerbehyg. 25:28-38 Republic of Argentina (1968) - Unpub. Rept. prepared for Codex Committee on Pesticide Residues Ruzicka, J.H., Thomson, J., Wheals, B.B. and Wood, N.F. (1968) The application of gel chromatography to the separation of pesticides. I. Organophosphorus pesticides. J. Chromatogr. 34:14-20 Sato, Y., Miyamoto, J., and Suzuki, S. (1968) Determination of insecticide residue in animal and plant tissues. V. A device to increase the sensitivity of the gas chromatography detector to organophosphorus insecticides. 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(1964) Comparative metabolism of O, O-dimethyl-O-p-nitrophenyl phosphorothioate (Methylparathion and O, O-dimethyl-O-(3-methyl-1-nitrophenyl) phosphorothioate (Sumithion) J. Econ. Entomol. 57:136-9 Vandekar, M. (1965) Observations on the toxicity of carbaryl, Folithion and 3-isopropropyl-phenyl N-methylcarbamate in a village-scale trial in Southern Nigeria. Bull. Wld. Hlth Org. 33.107-15 Wilford, K., Lietaert, P.E.A. and Foll, C.V. (1965) Toxicological observations during large scale field trial of OMS-43 in Northern Nigeria (preliminary report). WHO working paper 65/TOX/1 prepared for an informal meeting on toxicology of insecticides. Geneva, 18-24 February 1965 Winterlin, W., Walker, G. and Frank, H. (1968) Detection of cholinesterase-inhibiting pesticides following separation on thin-layer chromatograms. J. Agr. Food Chem. 16:808-12 Yasuno, M., Hirakoshi, S. Sasa, M. and Uchida, M. (1965) Inactivation of some organophosphorus insecticides by bacteria in polluted water. Jap. J. Exp. Med. 35:545 Yuen, S.H. (1966) Absorptiometric determination of fenitrothion residues in cocoa beans. Analyst 91:811-3
See Also: Toxicological Abbreviations Fenitrothion (EHC 133, 1992) Fenitrothion (HSG 65, 1991) Fenitrothion (ICSC) Fenitrothion (WHO Pesticide Residues Series 4) Fenitrothion (Pesticide residues in food: 1976 evaluations) Fenitrothion (Pesticide residues in food: 1977 evaluations) Fenitrothion (Pesticide residues in food: 1979 evaluations) Fenitrothion (Pesticide residues in food: 1982 evaluations) Fenitrothion (Pesticide residues in food: 1983 evaluations) Fenitrothion (Pesticide residues in food: 1984 evaluations) Fenitrothion (Pesticide residues in food: 1986 evaluations Part II Toxicology) Fenitrothion (Pesticide residues in food: 1988 evaluations Part II Toxicology) Fenitrothion (JMPR Evaluations 2000 Part II Toxicological)