4.10 Fenitrothion (037)(R)**

R-residue and analytical aspects

** Evaluated within the Periodic Review Programme of the Codex Committee on Pesticide Residues

RESIDUE AND ANALYTICAL ASPECTS

Fenitrothion, a contact insecticide which was first evaluated by the JMPR in 1969 and re-evaluated for residues several times up to 1989, is included under the CCPR Periodic Review Programme. At the 30th Session of the CCPR (ALINORM 99/24) fenitrothion was originally scheduled for periodic residue review by the 2001 JMPR but this was postponed until 2003.

The basic manufacturer supplied information on identity, metabolism and environmental fate, use patterns, residue analysis, residues from supervised trials on cereals, and the fate of residues during storage and processing. In addition information on GAP and/or national MRLs was reported by the governments of Australia, Germany, The Netherlands and the USA.

Animal metabolism

The Meeting received information on the fate of fenitrothion in orally-dosed lactating goats and in laying quail and hens.

Metabolism in laboratory mice, rats, guinea pigs, rabbits and dogs was evaluated by the WHO panel of the 2000 JMPR. It was concluded that orally-administered fenitrothion is rapidly and extensively absorbed from the mammalian intestinal tract (about 90-100% of the dose) and eliminated within 24 h. It is rapidly metabolized by mixed-function oxidases to the highly reactive fenitro-oxon by oxidative desulfuration. The oxon is then further metabolized by demethylation and hydrolysis to 3-methyl-4-nitrophenol and dimethyl hydrogen phosphate. A minor metabolic pathway involves further oxidation to 5-hydroxy-2-nitrobenzoic acid (3-carboxy-4-nitrophenol).

Six female Japanese Saanen goats were fed [phenyl-¹⁴C]fenitrothion mixed with 200 g of crushed hay for 7 days (0.5 mg ai/kg bw, corresponding to 7.6 ppm in the feed). The goats were milked twice daily and the evening milk samples were combined with the milk collected on the following morning. Whole milk was separated into cream and skimmed milk. Two goats were killed 1, 7 or 18 days after the last dose. The administered radiocarbon was almost quantitatively excreted during the 7-day post-treatment period; 50% of the dose was excreted in the urine, 44% in faeces and 0.1% eliminated in milk.

In whole milk a plateau of 0.011 mg/kg fenitrothion equivalents (mg/kg eq) was reached on the second day of dosing, with a maximum of 0.012 mg/kg eq on the 5th day. The residues in whole milk decreased to 0.003 mg/kg eq within 7 days of treatment. The four radioactive components detected in milk were acetylaminofenitro-oxon (5% of the TRR), sulfoaminofenitrothion (39% of the TRR), sulfoaminofenitro-oxon (22% of the TRR), and 4-acetylamino-3-methylphenyl methyl hydrogen phosphate (15% of the TRR). No parent, fenitro-oxon or 3-methyl-4-nitrophenol were detected. No radioactive residues could be detected in cream.

One day after the last dose liver contained the highest content of radiocarbon (0.85-1.5 mg/kg eq), with lower concentrations in kidneys (0.025 -0.031 mg/kg eq), muscle (0.002 to 0.005 mg/kg eq) and fat (0.008-0.012 mg/kg eq). After 18 days the radiocarbon was below 0.005 mg/kg eq in all tissues analysed except liver (0.1 mg/kg eq). The parent compound was not found (<0.001 mg/kg eq) and metabolites were not investigated.

[Phenyl-¹⁴C]fenitrothion was administered orally in gelatin capsules to 15 Japanese female quail as single doses of 5 mg/kg bw (about 20 mg/kg feed) and to six White Leghorn hens daily for 7 consecutive days at 2 mg/kg bw/day (about 35 mg/kg feed) and eggs were collected daily. The quail were killed 1 h, 1 or 7 days after their single doses, and the hens 1 or 7 days after their last doses. Radioactivity was very rapidly excreted by both: 93-94% of the applied radioactivity (AR) was excreted in the urine and faeces 6 h after dosing. The maximum radioactivity in the eggs was 0.2% of the AR.

The radioactive residues in hens' eggs did not reach a plateau during the 7-day dosing period, reaching maxima of 0.02 mg/kg eq on the 8th day in the whites and 0.1 mg/kg eq on the 7th day in the yolks (73% of the TRR in the yolks and 27% in the whites). In whole eggs, fenitrothion constituted 8% of the TRR (0.005 mg/kg eq). The main metabolite was 3-methyl-4-nitrophenyl sulfate (40% of the TRR), and others identified were 3-methyl-4-nitrophenol (22% of the TRR), the glucuronide of 5-hydroxy-2-nitrobenzyl alcohol (7% of the TRR), demethylfenitro-oxon (5% of the TRR) and demethylfenitrothion (2% of the TRR).

In the hens killed one day after treatment, residues were 0.098 mg/kg eq in liver, 0.1 mg/kg eq in kidney, <0.005 mg/kg eq in muscle and 0.016 mg/kg eq in fat.

In a quail killed one h after treatment 0.81 mg/kg eq radioactive residue was found in the liver (15% parent compound, 32% 3-methyl-4-nitrophenol, 4.4% fenitro-oxon, 1.6% fenitro-oxon-3-CH₂OH and 40% unextracted), 2.2 mg/kg eq in the kidney (5% parent, 10% 3-methyl-4-nitrophenol, 0.9% fenitro-oxon-3-CH₂OH, 64% unextracted and 18% unidentified), and 0.16 mg/kg eq in muscle (34% parent, 4.4% 3-methyl-4-nitrophenol and 61% unextracted). Fat was not investigated.

The metabolism of fenitrothion in laboratory animals was qualitatively similar to that in farm animals.

Plant metabolism

The Meeting received information on the fate of fenitrothion in grapes and tomatoes after spray application and in rice during storage.

Two Thompson Seedless grape vines were sprayed three times at 14-day intervals in the field (Madera County, California, USA) with an EC 500 formulation of [phenyl-¹⁴C]fenitrothion at a rate of 0.82 kg ai/ha and a spray volume of 1000 l/ha. Bunches of grapes were collected at mature harvest 35 days after the last treatment. Of the total recovered radioactive residue (TRR) in the grapes 97% was extractable (0.72 mg/kg eq). The main metabolites were a 3-methyl-4-nitrophenol conjugate (26% of the TRR) and 3-methyl-4-nitrophenol b-glucuronide (21%); the parent was not detected. 3-methyl-4-nitrophenol conjugates 2 to 6 constituted 23.5%, demethylfenitrothion 7.2% and 3-methyl-4-nitrophenol 0.97% of the TRR.

The foliage and fruit of F1 Shirley tomato plants were sprayed twice at a 14-day interval at normal and threefold rates in a greenhouse with a solution of [phenyl-¹⁴C]fenitrothion. The first application was at growth stage BBCH 85 (ripe fruit present). The application rates were 0.69 kg ai/ha with a spray volume of 4000 l/ha for the normal application and 2.1 kg ai/ha for the threefold application. Mature fruit, immature fruit and foliage were collected at harvest 15 days after the last treatment.

Of the total recovered radioactive residue 63%-70% was recovered in rinses and initial extracts of fruits and foliage. The parent was found at 13% of the TRR, 3-methyl-4-nitrophenol b-glucuronide at 7.3% and 3-methyl-4-nitrophenol at 7% in the mature fruit. When the remaining solids from mature fruit were further extracted with acetonitrile (ACN) followed by 1 M HCl and finally with 6 M NaOH, a further 19% of the TRR was extracted. The main metabolite in the extracts (24% of the TRR) did not correspond to any of the reference compounds available but could be hydrolysed with cellulase, resulting in the formation of both 3-methyl-4-nitrophenol (28%) and 3-methyl-4-nitrophenol b-glucuronide (44%) with 27% remaining as the unaltered metabolite. The main metabolite is considered to be a further conjugate of 3-methyl-4-nitrophenol b-glucuronide.

An emulsion of [a-methyl-¹⁴C]fenitrothion was applied to unpolished Nishikaze rice grain at rates of 6 and 15 g ai/t and samples were stored at 15° or 30°C in the dark for 12 months for analysis at intervals. Residues of fenitrothion gradually decreased with half-lives of about 4 and over 12 months at 30°C and 15°C respectively. The main metabolites were demethylfenitrothion and 3-methyl-4-nitrophenol. Demethylfenitrothion was formed in the early stages of degradation but the concentration remained fairly constant after 3 months. The concentration of 3-methyl-4-nitrophenol increased throughout the storage period. After 12 months at 15°C, 65% of the applied radioactivity was recovered as the parent compound, 10% as demethylfenitrothion and 16% as 3-methyl-4-nitrophenol, and after 12 months at 30°C 24% as parent, 18% as demethylfenitrothion and 38% as 3-methyl-4-nitrophenol.

Minor metabolites, found particularly at the end of the storage period, were fenitro-oxon, demethylfenitro-oxon, S-methyl-fenitrothion, demethylfenitrothion S-isomer, 1-methoxy-3-methyl-4-nitrobenzene, 3-hydroxymethyl-4-nitrophenol, 1,2-dihydroxy-4-methyl-5-nitrobenzene and 1,2-dimethoxy-4-methyl-5-nitrobenzene. These constituted together about 4% of the applied radioactivity at 15°C, and at 30°C 1-methoxy-3-methyl-4-nitrobenzene constituted about 8%, 1,2-dihydroxy-4-methyl-5-nitrobenzene about 3%, and the remaining minor metabolites about 6%. One reference compound (1-methoxy-3-hydroxymethyl-4-nitrobenzene) was not detected. No radiolabelled carbon dioxide was present.

Autoradiography showed that the radioactivity was principally in the aleurone (part of the seed coat) but penetrated into the endosperm during storage. The concentration of fenitrothion in endosperm decreased from 4.5 to 3.3 mg/kg at 15°C and to 1.2 mg/kg at 30°C. The amount of fenitrothion in bran (seed coat plus germ) was approximately 40 times that in endosperm at all sampled intervals.

Although the main metabolites found in plants were also found in animals, some minor ones were not (S-methyl-fenitrothion, demethylfenitrothion S-isomer, 1-methoxy-3-methyl-4-nitrobenzene, 1,2-dihydroxy-4-methyl-5-nitrobenzene and 1,2-dimethoxy-4-methyl-5-nitrobenzene).

Environmental fate in soil

The Meeting received information on aerobic degradation in soil.

The aerobic degradation of [phenyl-14C]fenitrothion was studied in a US sandy loam soil for 365 days and in four European soils (two sandy loams, a silt loam and a clay loam) for 90 days.

In the first study, the parent decreased from 88% initially to 0.05% of the total applied radioactivity (TAR) at 365 days. At the end of the study accumulated volatile radioactivity was 71% of the TAR, most of which was present as ¹⁴CO₂ (67.3% of the TAR). Six degradation products were identified: fenitro-oxon, 3-methyl-4-nitrophenol, demethylfenitrothion, demethylfenitro-oxon, formylaminofenitrothion and 1-methoxy-3-methyl-4-nitrobenzene. 3-methyl-4-nitrophenol, the main product, amounted to 20% of the TAR at day 3, but decreased to <1% of the TAR at day 30. Other products were below 1% of the TAR. Unextractable residues increased to 35% of the TAR at day 21, but then decreased to 20% of the TAR at day 365. A number of fractions were not identified, but the sum of these did not exceed 4.4% of the TAR. Calculated half-lives were 2.0 days and 3.3 days for parent and 3-methyl-4-nitrophenol respectively.

In the second study, unextracted radioactivity increased to 37%-54% of the TAR after 7 days, decreasing to 23%-43% after 90 days, and trapped ¹⁴C as ¹⁴CO₂ to 51%-69% by the end of the study. Fenitrothion was detected at 91%-96% of the TAR immediately after application, but decreased rapidly to 2.4%-5.4% of the TAR after 7 days. The two products identified were 3-methyl-4-nitrophenol (17%-45% of the TAR at 1 day, decreasing rapidly to below 7% of the TAR after 7 days) and 1-methoxy-3-methyl-4-nitrobenzene at quantities below 0.5% of the TAR. A further unidentified compound was detected at a maximum of 3.2% of the TAR, and other unknowns and unresolved background occurred at maxima of 0.7% and 0.6% of the TAR respectively. Calculated half-lives ranged from 1 to 33 h for the parent compound, and from 42 to 68 h for 3-methyl-4-nitrophenol.

These results indicate that fenitrothion is mainly degraded via cleavage of the P-O-aryl linkage, and further breakdown occurs via opening of the phenyl ring with eventual mineralization to CO₂. The Meeting decided that studies on residues in succeeding crops were not necessary since the residues of fenitrothion in soil decrease rapidly.

Environmental fate in water-sediment systems

The Meeting received information on degradation in water and in water/sediment systems.

In a 30-day study at 25°C in the dark at pH 5, 7 and 9 in sterile solutions, fenitrothion (uniformly ¹⁴C-labelled in the phenyl ring) was hydrolysed faster at higher pH, with half-lives of 191-200 days at pH 5, 180-186 days at pH 7, and 100-101 days at pH 9. Demethylfenitrothion and 3-methyl-4-nitrophenol were identified as degradation products.

Fenitrothion was rapidly photolysed with a half-life of 3.3-3.6 days. Photoproducts were further degraded to CO_2. In water/sediment systems the amount of fenitrothion decreased rapidly in the water phase with a concurrent initial increase of parent in the sediment phase. Unextractable radioactivity in the sediment increased to 71%-76% of the TAR at 59 days.

Methods of analysis

Several methods for the determination of fenitrothion in cereal grains and their processed products were reported to the Meeting. Extraction with acetone, acetone/water, methanol, acetonitrile/water or acetonitrile is followed by clean-up, partitioning into a suitable organic solvent and quantification by GC-FTD, GC-ECD, GC with an FPD, or GC-MS. LOQs in grain were 0.01-0.06 mg/kg, in straw 0.04-0.06 mg/kg, in bran 0.01-0.25 mg/kg, in pollard, white and brown bread 0.01-0.1 mg/kg, in germ 0.01-0.25 mg/kg and in flour 0.01-0.05 mg/kg.

The Meeting was informed by the government of The Netherlands of a multi-residue enforcement method for fruit and vegetables, consisting of extraction by a method for non-fatty samples and GC with an ion-trap detector. LOQ is 0.05 mg/kg.

Methods to determine fenitrothion in animal commodities were not provided.

Stability of residues in stored analytical samples

The Meeting received data on the stability of residues in cereal grain and straw. Information on storage stability in animal products was not available.

Fenitrothion and demethylfenitrothion residues were stable at -20°C for the times tested: wheat grain 113 days, barley grain 105 days, rice grain 149 days and straw 71 days.

Definition of the residue

Fenitrothion was rapidly excreted by goats, quail and hens. In whole goat milk a maximum of 0.012 mg/kg eq radioactive components was found: neither the parent compound, nor fenitro-oxon nor 3-methyl-4-nitrophenol were detected. The radioactivity was attributed to 4 metabolites of which the main one constituted 39% of the TRR (0.005 mg/kg eq). No radioactive residues could be detected in cream. The parent compound could not be detected in goat liver, kidney, fat or muscle, although maximum ¹⁴C levels of 1.5 mg/kg eq were found in liver, 0.031 mg/kg eq in kidney, 0.012 mg/kg eq in fat and 0.005 mg/kg eq in muscle. The nature of these residues was not investigated.

Of the total recovered radioactivity in eggs, 73% was in the yolk and 27% in the white. In whole egg, the parent was found at 8% of the TRR (0.005 mg/kg eq) and the main metabolites were 3-methyl-4-nitrophenyl sulfate (40% of the TRR) and 3-methyl-4-nitrophenol (22% of the TRR).

In a metabolism study on hens residues were 0.098 mg/kg eq in liver, 0.1 in kidney, <0.005 in muscle and 0.016 in fat, and in a study on quail the parent made up about 15% of the residue in liver, about 5% in kidney and about 34% in muscle; the main metabolite in the tissues was 3-methyl-4-nitrophenol.

The metabolism of fenitrothion in animals has not been fully elucidated, but in general it is expected that the levels of the individual metabolites will be <0.005 mg/kg at the expected exposure levels.

On the basis of the limited information available, the Meeting agreed that fenitrothion is a suitable marker molecule for enforcement in animal commodities and is also the compound of interest for dietary risk assessment.

The log K_ow of fenitrothion is 3.32. Taking into account the results of the metabolism studies (no radioactivity in cream, but found in yolk, only slightly more in fat than in muscle), the Meeting decided that fenitrothion should not be classified as fat-soluble.

After the pre-harvest treatment of grapes, the main metabolites were 3-methyl-4-nitrophenol conjugate 1 (26% of the TRR) and 3-methyl-4-nitrophenol b-glucuronide (21%); the parent was not detected. The main metabolite in tomatoes (24%) is considered to be a further conjugate of 3-methyl-4-nitrophenol b -glucuronide. The parent constituted 13% of the TRR. Information on residues in cereal grains after pre-harvest treatments was not reported.

After the post-harvest treatment of cereal grains, the residue consisted mainly of parent, demethylfenitrothion and 3-methyl-4-nitrophenol. The key effect that determines the ADI and the acute RfD for fenitrothion is inhibition of brain and/or red cell acetylcholinesterase. The Meeting concluded that 3-methyl-4-nitrophenol does not need to be considered for dietary risk assessment since it does not inhibit cholinesterase. Demethylfenitrothion was also not considered to be relevant for dietary risk assessment since it is not metabolized to a more potent oxon, and structure-activity considerations indicate that it is likely to be only a weak cholinesterase inhibitor.

The metabolism of fenitrothion in plants has also not been fully characterized. The supported uses of fenitrothion are pre-harvest applications on cereals and post-harvest on stored cereal grains. The Meeting concluded that the available studies were adequate only for the post-harvest uses on stored cereal grains. To support the pre-harvest uses on cereals, relevant metabolism studies are required.

Definition of the residue (for compliance with MRLs and for estimations of dietary intake):

fenitrothion, for both plant and animal commodities.

Results of supervised trials on crops

The Meeting received information on supervised trials on cereal grains (rice, wheat, barley, triticale) with pre-harvest treatments in Japan and Australia. In some trials pre-harvest treatments were combined with a seed treatment before planting. However, as data on metabolism in cereal grains after pre-harvest treatment were lacking the trials could not be evaluated.

No trials were reported on apples, head cabbages, cacao beans, cauliflower, cherries, citrus fruits, cucumbers, egg plants, grapes, leeks, head lettuce, bulb onions, peaches, pears, peas, peppers, potatoes, radishes, soya beans, strawberries, tea or tomatoes. The Meeting therefore recommended the withdrawal of the existing CXLs for these commodities.

Cereal grains (group 020)

Five trials on stored wheat were carried out in Australia and Argentina. The trial in Australia complied with Australian GAP for post-harvest use on wheat (912 g ai/t with a waiting period of 3 months) and the residue was 7.6 mg/kg. In Argentina the trials complied with Argentinean GAP for post-harvest use on cereals (6 g ai/t with a waiting period of 1 day) and residues were 3.1, 3.5, 5.0 and 5.6 mg/kg.

The Meeting estimated a maximum residue level for cereals based on the post-harvest use confirming the current CXL for cereal grains of 10 mg/kg (Po) and estimated an HR of 7.6 mg/kg and an STMR of 5.0 mg/kg.

Straw, fodder and forage of cereal grains and grasses (group 051)

The Meeting received details of supervised trials on cereal grains (rice, wheat, barley, triticale) with pre-harvest treatments in Japan and Australia. However, because details of metabolism were not provided the trials could not be evaluated.

Fate of residues in storage and processing

In storage

Hard red spring Neepawa wheat grains were evenly sprayed with fenitrothion at a rate of 12 g ai/t, and samples stored in screw-capped jars (240 ml) in the dark at 20°C for analysis after 0, 1, 3, 6 and 12 months. The concentration of fenitrothion in the stored samples decreased to about 5.5 mg/kg after 3 months and to about 2.5 mg/kg after 12 months. The main metabolites were demethylfenitrothion, 3-methyl-4-nitrophenol and dimethyl phosphorothioic acid. Residues of the first and the last increased to 2.0 and 0.55 mg/kg after 6 months, and decreased to 0.98 mg/kg and 0.21 mg/kg respectively after 12 months. 3-Methyl-4-nitrophenol increased from 0.38 mg/kg at 1 month to 0.96 mg/kg after 12 months. Neither fenitro-oxon nor S-methyl-fenitrothion was detected at any time point.

In processing

The Meeting received information on the fate of fenitrothion during simulated processing, in stored rice during polishing and cooking and in stored wheat during milling and baking.

A study with radiolabelled fenitrothion in sterile buffer solutions showed that fenitrothion is relatively stable during simulated pasteurisation (90ºC for 20 min; 82% of the TAR left as parent, 12% demethylfenitrothion and 0.7% 3-methyl-4-nitrophenol formed) but is readily degraded to demethylfenitrothion during simulated baking/brewing/boiling (100ºC for 60 min; 35% of the TAR left as parent, 62% demethylfenitrothion and 0.8% 3-methyl-4-nitrophenol formed) and sterilization (120ºC for 20 min; 15% of the TAR left as parent, 82% demethylfenitrothion and 1.3% 3-methyl-4-nitrophenol formed).

When unpolished rice grains, treated post-harvest with 15 g ai/t [a-methyl-¹⁴C]fenitrothion and stored at 30°C, were cooked immediately after treatment, the amount of fenitrothion decreased to about 60%, with the formation of demethylfenitrothion and 3-methyl-4-nitrophenol. When cooked after storage about 40% of the fenitrothion was lost, and residues of demethylfenitro-oxon and 3-methyl-4-nitrophenol increased. Other metabolites, such as 1-methoxy-3-methyl-4-nitrobenzene and 1,2-dihydroxy-4-methyl-5-nitrobenzene, decreased.

When cooked after polishing and washing, 80% of the applied radioactivity remained in the bran and rinses. The combination of washing and boiling decreased the contents of fenitrothion, demethylfenitrothion and 3-methyl-4-nitrophenol by about a factor of 2. Processing factors could not be calculated since actual residue levels were not reported. The Meeting recommended the withdrawal of the existing CXLs for rice, polished (1 mg/kg PoP) and rice bran, unprocessed (20 mg/kg PoP).

Wheat stored for up to 3 months after post-harvest treatment with 12 g ai/t fenitrothion was milled and baked into white and brown bread. The parent compound was determined in all processed products. Processing factors from wheat stored for 1 and 3 months were comparable. Calculated processing factors were 4.0 and 3.9 for bran (mean 3.95), 1.7 for pollard, 3.7 and 3.2 for germ (mean 3.45), 0.21 and 0.26 for flour (mean 0.235), 0.60 for gluten, 0.089 and 0.11 for white bread (mean 0.010) and 0.43 and 0.33 for brown bread (mean 0.38).

From the highest residue and STMR for wheat (7.6 mg/kg and 5 mg/kg respectively) and the processing factors for wheat bran, flour, and white and brown bread, the Meeting estimated a maximum residue level of 30 mg/kg in bran, and STMR-Ps of 19.75 mg/kg in bran, 1.175 mg/kg in flour, 0.05 mg/kg in white bread and 1.9 mg/kg in brown bread.

Farm animal dietary burden

The Meeting estimated the dietary burden of diflubenzuron residues in farm animals from the diets listed in Appendix IX of the FAO Manual (FAO, 2002). One feed commodity only from each Codex Commodity Group was used, so the calculation includes wheat grain but no other cereals. Calculation from the MRL for wheat provides the concentrations in feed for estimating MRLs, while calculation from the STMR gives feed levels for estimating STMRs, for animal commodities. In the case of processed commodities, the STMR-P value would be used for both intake calculations.

Maximum farm animal dietary burden

Mean farm animal dietary burden

Farm animal feeding studies

The Meeting received information on residues in the tissues cattle after grazing on fenitrothion-treated grass and in cattle fed with fenitrothion-treated maize.

Fenitrothion was applied as an EC formulation to two pastures at rates of 0.125 and 0.375 kg ai/ha. Ten cows were confined to each pasture immediately after spraying. Four animals, two from each field, were slaughtered after 1, 3, 7 or 10 days and breast muscle and omental fat only were analysed. Residues were found in the muscle and fat samples taken 1 day after spraying from cows from both pastures (0.007-0.014 mg/kg in muscle, <0.001-0.014 mg/kg in fat), at day 3 residues were found only in samples from the cows grazing on the pasture treated with 0.375 kg ai/ha (<0.001-0.001 mg/kg in muscle, 0.004-0.007 mg/kg in fat), and after day 3 no residues could be detected.

For the feeding trial, maize was sprayed in the field with 1.1, 2.2 or 3.4 kg ai/ha fenitrothion as an EC formulation, cut the next day and aged for 76 days. Groups of four lactating Jersey cows were fed treated or control silage ad libitum for 56 days. Cows fed silage from corn treated with 1.1, 2.2 and 3.4 kg ai/ha ingested averages of 0.21, 0.41 and 0.66 mg/kg bw/day of fenitrothion and its metabolites. Animals were milked twice daily and at the end of each week a composite sample was prepared by combining the milk from 2 consecutive morning and evening milkings.

In the milk of cows fed silage from maize treated at 3.4 kg ai/ha aminofenitrothion was the only compound detected, at levels ranging from 0.001 to 0.005 mg/kg equivalents. No residues (<0.001 mg/kg eq) were found in the milk of cows consuming silage from maize treated at lower levels. Tissues were not analysed.

Animal commodity maximum residue levels

In a metabolism study when goats were dosed at 7.6 mg/kg eq in the feed, the parent compound was undetected in tissues and milk, so no residues are to be expected at the calculated dietary burden of 5.6 mg/kg feed for beef cattle and 4.5 mg/kg for dairy cattle.

The dietary burden for poultry was 9 mg/kg, lower than the feeding level in the metabolism study on hens (approximately 35 mg/kg feed); the resulting residues in eggs and poultry tissues were therefore calculated by applying the respective transfer factors (Transfer factor = residue level in egg or tissue ÷ residue level in diet) at this feeding level.

Since in the metabolism study only one residue was reported per tissue, this value was used in conjunction with the maximum dietary burden to calculate the highest likely poultry commodity residue levels, and it was used in conjunction with the STMR dietary burden to estimate the poultry commodity STMRs.

Calculation of MRLs and STMRs for poultry tissues and eggs

¹ Residue values in parentheses in italics are extrapolated from residues found at the feeding level in the hen metabolism study

² Italics show the estimated dietary burdens. Normal font shows the feeding level in the hen metabolism study

³ High is the residue found in the feeding study combined with the maximum dietary burden

⁴ Mean is the residue found in the feeding study combined with the STMR dietary burden

The Meeting concluded that residues above the LOQ are unlikely to arise in poultry commodities, since the calculations were based on total radioactive residue levels. In the quail metabolism study 15% of the radioactive residue in liver was the parent, in kidney 5% and in muscle 34%.

However because a validated analytical method for the determination of fenitrothion in animal commodities was not available and no information on the storage stability of residues in analytical samples of animal commodities was reported, the Meeting decided it could not estimate maximum residue levels for animal commodities.

FURTHER WORK OR INFORMATION

Desirable

1. Metabolism in cereals (including rice) after pre-harvest treatment
2. Validated analytical method for the determination of fenitrothion in animal commodities
3. Freezer storage stability of residues in animal commodities
4. Farm animal transfer studies
5. Processing study on rice

DIETARY RISK ASSESSMENT

Long-term intake

The International Estimated Daily Intake of fenitrothion, based on the STMRs estimated for 3 commodities, was 120-640% of the maximum ADI (0.005 mg/kg bw) for the GEMS/Food diets. The information provided to the Meeting precludes an estimate that the dietary intake would be below the ADI.

The Meeting noted that the intake calculations were conservative, since they did not take into account the reduction of the residue obtained by the processing of cereal grains, except the processing of wheat. Especially processing information on rice would be useful to refine the intake calculations.

Short-term intake

The International Estimated Short Term Intake (IESTI) for fenitrothion was calculated for the food commodities (and their processed fractions) for which maximum residue levels were estimated and for which consumption data were available. The results are shown in Annex 4.

The IESTI represented 1-150% of the acute RfD (0.04 mg/kg bw) for the general population and 2-240% of the acute RfD for children. The estimated short-term intakes from husked and polished rice were 120 and 150% respectively for the total population. The estimated short-term intakes from maize (fresh, flour, oil), husked rice and polished rice were 160, 240 and 240% respectively for children. The Meeting concluded that the short-term intake of residues of fenitrothion from uses, other than on these 3 commodities, that have been considered by the JMPR is unlikely to present a public health concern.

The Meeting noted that the intake calculations were conservative, since they did not take into account the reduction of the residue obtained by the processing cereal grains, except the processing of wheat. Especially processing information on rice would be useful to refine the intake calculations.