4.12 Indoxacarb (216)

TOXICOLOGY

Indoxacarb is the ISO approved name for a new oxadiazine insecticide, methyl (S)-N-[7-chloro-2,3,4a,5-tetrahydro-4a-(methoxycarbonyl)indeno[1,2-e][1,3,4]oxadiazin-2-ylcarbonyl]-4'-(trifluoromethoxy)carbanilate (IUPAC), also known as methyl (4aS)-7-chloro-2,5-dihydro-2-[[(methoxycarbonyl)[4-(trifluoromethoxy)phenyl]amino]carbonyl]indeno[1,2-e][1,3,4]oxadiazine-4a(3H)-carboxylate (CAS).

The indoxacarb racemate contains two enantiomers (S:R), designated DPX-KN128 and DPX-KN127, but only the S enantiomer has insecticidal activity. The ISO approved common name applies only to the insecticidally active S enantiomer. The indoxacarb racemate DPX-JW062 has been used in several toxicological studies. Subsequent refinements in the chemical synthesis process have enabled commercial production of a mixture enriched approximately 3:1 with the insecticidally active enantiomer. This enriched mixture has the code DPX-MP062 and is the active ingredient in all currently formulated products. The database contains a series of studies with DPX-MP062 to demonstrate its toxicological equivalence with DPX-JW062.

Indoxacarb has not previously been considered by the Meeting.

All pivotal studies were performed by GLP-certified laboratories and complied with the relevant OECD test guidelines.

Biochemical aspects

The kinetics and metabolism of racemic or enantiomer-enriched indoxacarb appeared to be very similar in rats. Indoxacarb administered by gavage at low doses (5 mg/kg bw) is extensively, albeit slowly, absorbed (69-81%), but at higher doses (150 mg/kg bw) saturation kinetics becomes evident (8-14% absorption). There was a considerable difference in the time required to achieve the maximal concentration in blood between the sexes. In males it was 5 h at a low dose and 3 h at a high dose, while in females it was 8 h and 27 h respectively. In-vitro evidence from rat hepatic microsome preparations showed that while females metabolized indoxacarb more slowly than males, they produced almost tenfold more of the toxic metabolite IN-JT333. This metabolite, which contains the chiral centre, showed evidence of stereospecific uptake into fat. Elimination (probably caused by the preferential accumulation of metabolites in fat and erythrocytes) was slow, with the half-life in plasma ranging between 92 h and 114 h in males and females respectively.

In rats, indoxacarb is biotransformed to yield the arylamine metabolite 4-trifluoromethoxyaniline. This metabolite, which does not contain a chiral centre, was present in the urine and erythrocytes. The N-hydroxy derivative of 4-trifluoromethoxyaniline, while not being detected in excreta or erythrocytes, has been implicated as the causative agent responsible for haemolytic effects observed in all repeat-dose studies because of its ability to effectively oxidize glutathione in erythrocytes in vitro. The haemolytic potential of the arylamine metabolite (4-trifluoromethoxyaniline) observed in the erythrocytes of treated rats was not tested.

The major metabolites in the faeces were formed by hydrolysis of the carboxymethyl group from the amino nitrogen of the trifluoromethoxyphenyl portion of the parent compound, and hydroxylation of the inandione ring. No parent compound was detected in bile and no single metabolite accounted for more than 4% of an administered dose. An oxadiazine ring-opened metabolite formed by hepatic microsomal enzymes is likely to be a precursor for several metabolites found in urine. The eight minor urinary metabolites in rats accounted in total for less than 5% of the administered dose.

Toxicological data

Indoxacarb (DPX-MP062) has low acute oral toxicity (LD₅₀ = 1730 mg/kg bw) in male rats and moderate oral toxicity (LD₅₀ = 268 mg/kg bw) in female rats, and low dermal (LD₅₀ > 5000 mg/kg bw) and inhalation toxicity (DPX-JW062; LC₅₀ = 4200 mg/m³ (4.2 mg/L) in rats. The difference in oral toxicity between the sexes is thought to arise from the more efficient biotransformation of indoxacarb to an acutely toxic metabolite IN-JT333 in females (LD₅₀ = 52 mg/kg bw and 39 mg/kg bw in males and females respectively). Purified indoxacarb (DPX-KN128) and its insecticidally-inactive enantiomer (DPX-KN127) are almost equally toxic by the oral route. Although DPX-KN128, like DPX-MP062, showed a difference in oral toxicity between the sexes (i.e. LD₅₀ = 843 mg/kg bw and 179 mg/kg bw in males and females respectively), the absence of a sex difference for DPX-KN127 (LD₅₀ = 444 mg/kg bw and 480 mg/kg bw in males and females respectively) may be attributable to the dose selection.

Indoxacarb (DPX-MP062) was a moderate eye irritant in rabbits, was not a skin irritant in rabbits, but was a skin sensitizing agent in the maximization test in guinea-pigs.

Although indoxacarb has been shown to block neuronal sodium channels in insects, clear evidence of neurotoxicity in mammals occurred only at high acute doses (200 mg/kg bw) at which ataxia, reduced motor activity, forelimb grip strength and decreased foot splay were observed in male rats. Clinical signs suggestive of neurotoxicity were noted in short-term repeat-dose dietary studies in mice and included abnormal gait/mobility and head tilt at high doses (30 mg/kg bw per day and greater). Long-term exposure to indoxacarb at doses of 22 mg/kg bw or greater in mice caused neuronal degeneration in the piriform cortex and hippocampus. Higher doses resulted in death. In contrast, a repeat-dose study of neurotoxicity in rats showed no effects on motor activity or functional observational battery assessments, and no histological evidence of neurotoxicity at doses of up to 12 mg/kg bw per day in males and 6 mg/kg bw per day in females.

In studies in mice, rats and dogs, the two main toxicological findings after repeated dosing with indoxacarb were mild haemolysis and reduced body-weight gain. Both effects occurred at similar doses in short-term repeat-dose studies, irrespective of the ratio of enantiomers. The reduction in body-weight gain was usually associated with a concomitant decrease in food consumption and food efficiency. In long-term studies in dogs and rats, the effect levels were similar (NOAELs were approximately 1-2 mg/kg bw per day respectively, and LOAELs were approximately 3-4 mg/kg bw per day). In a long-term study, mice were found to be insensitive to haematological effects and slightly less sensitive to reductions in body-weight gain (the NOAEL was 2.6 mg/kg bw per day, and the LOAEL was 13.8 mg/kg bw per day). The mild haemolysis observed in rats and dogs was characterized by reduced erythrocyte count, erythrocyte volume fraction, haemoglobin concentration, and a secondary physiological response involving increased haemopoiesis and deposition of haemosiderin in the spleen and liver. While the reductions in erythrocyte numbers through oxidative damage of haemoglobin occurred with a rather shallow dose-response curve, they achieved statistical significance relative to concurrent controls. In rats, early mortalities in groups receiving the highest dose and necropsy at 2 years revealed haemosiderin pigment in renal tubule cells and/or lumens, suggesting that haemolysis may have been a factor; these animals showed atrophy of the spleen, thymus and/or bone marrow, which was attributable to loss of lymphoid and haemopoietic cells. In mice (short-term exposure only) and dogs, haemoglobin within erythrocytes was oxidized/denatured (Heinz bodies). At high doses (> 17 mg/kg bw per day), morphological changes (Howell-Jolly bodies, polychromasia and hypochromasia) of the erythrocytes were observed in dogs.

There was no evidence of carcinogenicity at dietary concentrations of up to 125 ppm (22-30 mg/kg bw per day) in mice and up to 125 ppm (females only) and 250 ppm (8 mg/kg bw per day) in rats.

Indoxacarb (DPX-MP062) and two of its major metabolites, IN-JT333 and IN-KG433, gave negative results in an adequate battery of studies of genotoxicity in vitro and in vivo.

In view of the absence of any carcinogenic potential in rodents and the lack of genotoxic potential in vitro and in vivo, the Meeting concluded that indoxacarb is unlikely to pose a carcinogenic risk to humans.

In a two-generation study of reproductive toxicity in rats, adults given indoxacarb at a dose of 3.8 mg/kg bw per day had reduced body-weight gain and food consumption while the pups had lower body-weight gain during lactation. The NOAEL for effects in the parents and pups was 1.3 mg/kg bw per day. There were no effects on reproductive performance.

In studies of developmental toxicity in rats and rabbits, indoxacarb was not teratogenic but caused reduced fetal body weight when dams also showed reduced body weight and food consumption. The NOAEL for these effects was 2 mg/kg bw per day in rats and 1 mg/kg bw per day in rabbits.

The Meeting concluded that the existing database on indoxacarb was adequate to characterize the potential hazards to fetuses, infants and children.

In a study of acute neurotoxicity in rats, reduced body-weight gain and food consumption occurred at doses of 50 mg/kg bw and above in females and 200 mg/kg bw in males. The NOAEL was 12.5 mg/kg bw. In females, evidence of neurotoxicity, such as slightly reduced motor activity, was observed at 100 mg/kg bw. In males, a reduced forelimb grip strength and decreased foot splay was observed at 200 mg/kg bw.

In-vitro data indicated that glucose-6-phosphate dehydrogenase-deficient individuals were slightly more sensitive (the concentration of agonist that elicits a response that is 50% of the possible maximum, EC₅₀ = 55.5 µmol/L relative to 75.5 µmol/L for controls) to the oxidative effects of N-hydroxy-4-trifluoromethoxyaniline. The Meeting considered that the application of the normal tenfold safety factor for intraspecies variability would also be protective for glucose-6-phosphate dehydrogenase-deficient individuals.

Toxicological evaluation

It should be recognized that the ADI and ARfD applies to indoxacarb (S enantiomer) and its R enantiomer. The Meeting established an ADI of 0-0.01 mg/kg bw per day based on a NOAEL of 1.1 mg/kg bw per day for erythrocyte damage and the secondary increase in haematopoiesis in the spleen and liver in a 1-year dietary study in dogs and using a 100-fold safety factor. This NOAEL is supported by a similar value (1.3 mg/kg bw per day) in a two-generation study of reproduction in rats in which reduced body weight and food consumption in dams was observed. The pups lost body weight during lactation at this dose.

The Meeting established an ARfD of 0.1 mg/kg bw based on the NOAEL of 12.5 mg/kg bw for reduction in body-weight gain and food intake after a single administration of indoxacarb in a study of neurotoxicity in rats, and using 100-fold safety factor.

A toxicological monograph was prepared.

Levels relevant to risk assessment

^a Dietary administration
^b Gavage administration

Estimate of acceptable daily intake for humans

0-0.01 mg/kg bw

Estimate of acute reference dose

0.1 mg/kg bw

Information that would be useful for the continued evaluation of the compound

Results from epidemiological, occupational health and other such observational studies of human exposure

Critical end-points for setting guidance values for exposure to indoxacarb

RESIDUE AND ANALYTICAL ASPECTS

Indoxacarb was considered for the first time by the present Meeting. It is an indeno-oxadiazine insecticide that is used for control of lepidoptera and other pests.

Indoxacarb, chemical name (IUPAC) (S)-7-chloro-3-[methoxycarbonyl-(4-trifluoromethoxy-phenyl)-carbamoyl]-2,5-dihydro-indeno[1,2-e][1,3,4]oxadiazine-4a(3H)-carboxylic acid methyl ester, is a new insecticidal active ingredient.

Indoxacarb was originally marketed as a racemic mixture of indoxacarb with its R enantiomer. Subsequently, a commercial technical material was developed that contained 3 parts indoxacarb and 1 part R enantiomer. For the purposes of this report the original material will be described as "racemic indoxacarb" and the later material will be described as "indoxacarb 3S+1R". Residues, where the two enantiomers are not in a defined ratio, will be described as "indoxacarb + R enantiomer".

Animal metabolism

The Meeting received the results of animal metabolism studies in rats, lactating dairy cows and laying hens.

When rats were orally dosed with indoxacarb it was readily absorbed followed by extensive metabolism and excretion. Loss of a methoxycarbonyl group produced IN-JT333 (methyl 7-chloro-2,5-dihydro-2-[[[4-(trifluoromethoxy)phenyl]amino]carbonyl]indeno[1,2-e][1,3,4]oxadiazine-4a(3H)-carboxylate) a major metabolite in the fat (see the toxicology report for more details of laboratory animal metabolism.)

When lactating dairy cows were orally dosed with labelled racemic indoxacarb (labelled in the indanone ring or the trifluoromethoxyphenyl ring) for 5 consecutive days at 200 mg/animal/day, equivalent to 10 ppm in the feed, most of the administered ¹⁴C was excreted in the faeces (53-60%) and urine (19-20%). ¹⁴C recovery was adequate (74% and 82% for the two labels). Residues in milk and tissues accounted for 0.7-0.8% and 0.79-0.84% of the dose respectively.

Parent compound was the major identified component of the residue in milk and each of the tissues. Chiral HPLC analysis of parent compound in milk (day 5 and pooled) and kidneys showed S:R enantiomer ratios of 2:1 and 2-2.5:1 respectively, a change from the starting ratio of 1:1.

The concentration of parent compound was substantially higher in the perirenal fat than in the other tissues suggesting that indoxacarb is a fat-soluble compound.

Metabolite IN-JT333 was present in perirenal fat at levels equivalent to 7% and 11% of parent compound levels. A number of other metabolites were identified in the liver.

When laying hens were orally dosed with labelled racemic indoxacarb (labelled in the indanone ring or the trifluoromethoxyphenyl ring) for 5 consecutive days at 1.2 mg/bird/day, equivalent to 10 ppm in the feed, most of the administered ¹⁴C was excreted in the faeces (87-88%). ¹⁴C recovery was 89% and 90%. Residues in eggs and tissues accounted for 0.28-0.4% and 1.3-1.4% of the dose respectively.

More residue appeared in the egg yolk than in the egg white, suggesting a tendency for fat solubility of the residue components. Parent compound constituted 3-4% of the total ¹⁴C in egg yolk. Major metabolites in egg yolk were IN-KG433 + IN-KT319 ((E)- and (Z)-methyl 5-chloro-2,3-dihydro-2-hydroxy-1-[[[(methoxycarbonyl)[4-(trifluoromethoxy)phenyl]amino]carbonyl]hydrazono]-1H-indene-2-carboxylate) at 18-26% of total ¹⁴C and Metabolite F (proposed identification as 1-(3-(6-chloro-1-hydroxy-2-methoxycarbonylindene)-4-(4-trifluoromethoxyphenyl)-1,2,4-triazole-2,3,4,5-tetrahydro-3,5-dione) at 7-14% of total ¹⁴C.

Fat contained the highest concentration of residue, where the main component, Metabolite F constituted 45 and 38% of the total ¹⁴C in the fat. Parent compound constituted 5 and 6% of the total ¹⁴C in the fat. Metabolite IN-JT333 constituted 16 and 18% of the total ¹⁴C in the fat. Residues in breast muscle and thigh muscle were generally too low for metabolite identification. Parent compound accounted for approximately 4-5% of the total ¹⁴C in liver.

The residue in hens was fat-soluble but the residue composition in poultry fat was somewhat different from the residue composition in dairy cow fat.

Although there were similarities in the metabolic pathways in dairy cows and in poultry, there were also notable differences, e.g. a major metabolite, metabolite F in chicken fat, was not identified in dairy cow fat. In dairy cow fat, parent compound comprised 65-80% of the total residue with IN-JT333 the only identifiable metabolite at 5-7% of the total residue. In poultry fat, parent compound comprised 4-6% of the total residue with metabolite IN-JT333 at 17% of total residue. Other identified metabolites comprised 69-76% of the total residue.

Plant metabolism

The Meeting received plant metabolism studies with racemic indoxacarb on cotton, lettuce, grapes and tomatoes.

In each crop tested, parent compound mostly represented more than 90% of the total ¹⁴C residue and was essentially the only compound detected. In grapes and tomatoes the residue was found to be mostly a surface residue. Chiral HPLC analysis of the residues in tomatoes showed that the enantiomers remained in a 1:1 ratio.

When cotton plants were treated with a single application of formulated [¹⁴C]racemic indoxacarb, labelled in the indanone ring or the trifluoromethoxyphenyl ring, parent compound mostly represented more than 90% of the total ¹⁴C residue in plant samples taken 7, 14, 30, 59 and 90 days after treatment. Chiral analysis of parent compound demonstrated that it remained racemic.

When lettuce plants were treated with a single application of formulated [¹⁴C]racemic indoxacarb, labelled in the indanone ring or the trifluoromethoxyphenyl ring, parent compound mostly represented more than 95% of the total ¹⁴C residue in plant samples taken 0, 7, 14, 21, 28 and 35 days after treatment. Even on day 0 less than half of the residue was on the leaf surface and the percentage on the surface decreased further with time after treatment.

Grape vines at the early fruit development stage were treated with a single foliar application of formulated [¹⁴C] racemic indoxacarb, labelled in the indanone ring or the trifluoromethoxyphenyl ring. Most of the residue associated with fruit sampled on days 0, 14, 46 and 66 days (mature) post-treatment was surface residue, with 52% and 75% still surface residues 66 days after treatment. Parent compound was essentially the only component of the residue at all times.

When tomato vines were treated with 4 foliar applications, approximately 6-10 days apart, of formulated [¹⁴C]racemic indoxacarb, labelled in the trifluoromethoxyphenyl ring, the majority of the residue associated with the fruit sampled 3, 7 and 14 days after the final application was surface residue, mostly around 90% of the residue. Parent compound was essentially the only component of the residue at all times. Parent compound isolated from leaf extracts from the samples collected before the second application and at harvest, 14 days after final application, were subjected to chiral HPLC analysis, which demonstrated that the two enantiomers remained in a 1:1 ratio.

Environmental fate in soil

The Meeting received information on the environmental fate of indoxacarb in soil, including studies on aerobic soil metabolism, field dissipation and crop rotational studies.

When [¹⁴C]racemic indoxacarb labelled in the indanone ring or the trifluoromethoxyphenyl ring was incubated with a silt loam soil under aerobic conditions in the dark at 25°C, indoxacarb degraded quickly (half-life approximately 2-3 days). Identifiable metabolites were a minor part of the residue and mostly also degraded relatively quickly. IN-JT333 and IN-KG433 were the main metabolites in the first few days. IN-MK643 (1,2-dihydro-5-(trifluoromethoxy)-2H-benzimidazol-2-one) was identified as a longer term metabolite. The indanone ring was mineralized more quickly (26% in 120 days) than the trifluoromethoxyphenyl ring (5.4% in 120 days). The non-extractable ¹⁴C had begun to decline within 90 days.

Very little of the applied indoxacarb moved below the top 15 cm of the soil during field dissipation trials of duration up to 18 months with [¹⁴C]labelled racemic indoxacarb applied to 4 different soils. Indoxacarb (+ R enantiomer) concentrations declined to half of their initial values in seven days to six months.

In a field persistence and mobility study at two sites with racemic indoxacarb, residues of indoxacarb + R enantiomer disappeared from the top 15 cm of soil with half-lives of 55 and 60 days. Residues did not occur at lower depths except occasionally and intermittently. Metabolite IN-JT333 reached its peak concentration on days 14 and 100 at the 2 sites. Metabolite KG-433 was detected at a low concentration at one site.

In a confined rotational crop study in USA, soil was treated directly with [¹⁴C]racemic indoxacarb labelled in the indanone ring or the trifluoromethoxyphenyl ring. Crops of carrots, lettuce, wheat and soybeans were sown into the treated soil at intervals of 36, 90 and 125 days after treatment and were grown to maturity and harvested for analysis. No parent compound or potential metabolite (IN-JT333) was detected. Low levels (£ 0.05 mg/kg) of unidentifiable components were observed, with different patterns for the two different label positions suggesting that the parent compound was fragmented.

Methods of analysis

The Meeting received descriptions and validation data for analytical methods for residues of indoxacarb in raw agricultural commodities, processed commodities, feed commodities, animal tissues, milk and eggs.

Methods rely on HPLC-UV, GC-ECD and GC-MSD for analysis of indoxacarb in the various matrices. Indoxacarb and its R enantiomer are determined and reported together in all these methods. Signal enhancement by extracts of some matrices may require the preparation of standards in matrix extracts for measurement at low concentrations. A method with LOQ values of 0.2-0.3 mg/kg and not requiring that standards are prepared in control matrix solutions was provided as suitable for enforcement. A method suitable for enforcement for animal commodities (LOQ values 0.01-0.03 mg/kg) was adapted from existing method DFSG S19.

Numerous recovery data on a wide range of substrates were provided from validation testing of the methods, which showed that the methods were valid over the relevant concentration ranges.

Extraction efficiency has been proven with various solvent mixtures on [¹⁴C]indoxacarb incorporated into or incurred in crop and animal commodities. Extraction procedures used either ethyl acetate - water or acetonitrile - hexane.

Stability of pesticide residues in stored analytical samples

The Meeting received information on the freezer storage stability of residues of racemic indoxacarb and indoxacarb 3S+1R in alfalfa, apple juice, apple pomace, apples, fat, grape pomace, grapes, lettuce, liver, milk, muscle, peanut hay, peanut kernels, peanut meal, peanut oil, sweet corn, sweet corn forage, sweet corn stover, tomatoes and wine.

Residues were stable (less than 30% disappearance) during the storage intervals tested, mostly 6 months, 12 months or 18 months. Storage data was available for some animal commodities for only shorter intervals, 2-3 months, but which were suitable for the purpose of demonstrating stability of the residues in samples from the studies.

Definition of the residue

The composition of the residue in the metabolism studies, the available residue data in the supervised trials, the toxicological significance of metabolites, the capabilities of enforcement analytical methods and the national residue definitions already operating all influence the decision on residue definition. [Check the significance of metabolites with WHO Group].

Residues of indoxacarb are described as the sum of indoxacarb and its R enantiomer in national residue definitions.

In crop residue situations, parent compound comprises most of the residue and, at least in some situations, its enantiomer composition is unchanged.

In dairy cows, particularly in the fat, milk and kidney, parent compound is the major part of the residue. In liver, parent is the major identified compound in the residue. The parent residue becomes more enriched in S enantiomer (indoxacarb) in some animal commodities. Metabolite IN-JT333 was present in fat at levels of 7-11% of parent compound levels. Because of its toxicity, it should be included in the residue definition for risk assessment for animal commodities.

In poultry tissues and eggs, parent compound is a minor component of the residue and no single metabolite would be a good indicator of the residue level. Under the present dietary burden, even the total residues in poultry are estimated to be very low and unlikely to be detectable.

Available analytical methods and supervised trial data suggest that "indoxacarb and its R enantiomer" is a practical residue definition.

In the animal metabolism studies, the concentration of residue was clearly higher in the fat than in other tissues. In milk the residue partitioned into the lipid phase. The octanol-water partition coefficient (log P_OW = 4.65) also suggests that indoxacarb is a fat-soluble compound.

The Meeting recommended a residue definition for indoxacarb for plants and animals.

Definition of the residue (for compliance with the MRL for all commodities and for estimation of dietary intake for plant commodities): sum of indoxacarb and its R enantiomer. The residue is fat soluble.

Definition of the residue (for estimation of dietary intake for animal commodities): sum of indoxacarb, its R enantiomer and methyl 7-chloro-2,5-dihydro-2-[[[4- (trifluoromethoxy) phenyl] amino] carbonyl] indeno[1,2-e][1,3,4]oxadiazine-4a(3H)-carboxylate, expressed as indoxacarb.

Results of supervised trials on crops

The Meeting received supervised trials data for indoxacarb uses on apples, pears, stone fruits, grapes, cabbages, cauliflowers, broccoli, Brussels sprouts, lettuce, cucumbers, courgettes, melons, tomatoes, peppers, sweet corn, pulses (adzuki beans, chickpeas mung beans), soybeans, potato, peanuts, cotton seed, sweet corn forage, legume animal feeds, alfalfa and cotton gin trash.

In most trials, duplicate field samples from an unreplicated plot were taken at each sampling time and were analysed separately. For the purposes of the evaluation, the mean of the two results was taken as the best estimate of the residue from the plot.

In some trials the formulation was based on racemic indoxacarb and in others indoxacarb 3S+1R was used. In all situations, the application rate and spray concentration were expressed in terms of the active ingredient, indoxacarb. In all cases residues were measured and expressed as indoxacarb + R enantiomer.

Parallel trials (same place, same application rate, same operator, etc) between products based on racemic indoxacarb and products based on indoxacarb 3S+1R compared the resulting residues on apple, broccoli, cabbage, cauliflower, cotton, lettuce and tomato. Residue levels from the 3S+1R treatments were approximately 50% of those with the racemic treatments. Therefore, supervised residue trials with racemic indoxacarb were not used as GAP trials for MRL evaluation, except for cases like sweet corn where residues were below LOQ.

The Meeting was informed that racemic indoxacarb is currently registered in only one country.

Processing trials with racemic material were considered valid because the processing factors should not be influenced by higher residues than achieved by GAP. It is common practice to apply a pesticide at exaggerated rates in processing trials to achieve measurable levels in processed commodities.

In some trials residues were measured on samples taken just prior to the final application as well as just after it (the "zero day" residue). The residue just prior expressed as a % of zero day residue provides a measure of the contribution of previous applications to the final residue in the use pattern followed in the trial.

For apples, the average carryover of residue was 45% (Europe, n = 12). For peaches, the average carryover of residue was 38% (Europe, n = 6). For grapes, the average carryover of residue was 41% (Australia, n = 12) and 44% (Europe, n = 20). For cabbages, the average carryover of residue was 44% (Europe, n = 6) and 25% (South Africa, n = 4). For cauliflower, the average carryover of residue was 27% (Europe, n = 7). For broccoli, the average carryover of residue was 23% (Europe, n = 6). For lettuce, the average carryover of residue was 26% (Europe, n = 6). For melons-peel, the average carryover of residue was 36% (Europe, n = 10). For tomatoes, the average carryover of residue was 48% (Europe, n = 12). For peppers, the average carryover of residue was 49% (Europe, n = 9).

The final 3 applications would be expected to influence the final residue level where the carryover is approximately 50%, which means that if GAP specified a maximum of 4 applications, trials with only 1 or 2 applications would not be maximum GAP. The final 2 applications would be expected to influence the final residue level for a carryover of approximately 30-40%. Earlier applications should not have a significant influence.

Residue data was evaluated only where labels (or translations of labels) describing the relevant GAP were available to the Meeting.

Apples

Residue trials on apples were available from Australia, Belgium, France, Germany, Greece, Hungary, Italy, South Africa and USA with racemic indoxacarb or indoxacarb 3S+1R. The trials from Hungary could not be evaluated because the PHI in the trials did not match the label PHI.

Indoxacarb is registered in Australia for use on apple trees at a spray concentration of 0.0075 kg ai/hL with a PHI of 14 days. In four Australian trials in 1996 and 1998 approximating GAP (0.0075-0.009 kg ai/hL and PHI 14-15 days) residues of indoxacarb + R enantiomer were: 0.28, 0.45, 0.50 and 0.85 mg/kg.

In Belgium, indoxacarb may be used on apple trees at 0.075 kg ai/ha with harvest 7 days after the final application. In three apple trials in Belgium with application rates of 0.075 ± 30%, i.e. 0.053 to 0.098 kg ai/ha and 7 days PHI, indoxacarb + R enantiomer residues were 0.06, 0.07 and 0.09 mg/kg. In five trials in France within ± 30% of the Belgian application rate and a PHI of 7 days, the indoxacarb + R enantiomer residues were: 0.05, 0.08, 0.11, 0.13 and 0.14 mg/kg.

In Germany, indoxacarb may be used on pome fruit at 0.077 kg ai/ha with a PHI of 7 days. In three apple trials in Germany with application rates of 0.077 ± 30%, i.e. 0.054-0.100 kg ai/ha and 7 days PHI, indoxacarb + R enantiomer residues were 0.10, 0.16 and 0.24 mg/kg.

Indoxacarb is allowed for use on apples in Greece at 0.1 kg ai/ha with a PHI of 7 days. In four trials in Greece with application rates of 0.10 ± 30%, i.e. 0.070-0.13 kg ai/ha and 7 days PHI, indoxacarb + R enantiomer residues were 0.03, 0.06, 0.10 and 0.23 mg/kg.

In Italy, indoxacarb may be used on apple trees at 0.075 kg ai/ha with harvest 7 days after the final application. In 3 apple trials in Italy with application rates of 0.075 ± 30%, i.e. 0.053 to 0.098 kg ai/ha and 7 days PHI, indoxacarb + R enantiomer residues were 0.07, 0.07 and 0.21 mg/kg.

In summary, the European data for 18 trials in rank order, median underlined, were: 0.03, 0.05, 0.06, 0.06, 0.07, 0.07, 0.07, 0.08, 0.09, 0.10, 0.10, 0.11, 0.13, 0.14, 0.16, 0.21, 0.23 and 0.24 mg/kg.

Indoxacarb is registered for use on apples in South Africa with a spray concentration of 0.0075 kg ai/hL with a PHI of 28 days. In a trial at 0.0068 kg ai/hL and PHI of 28 days indoxacarb + R enantiomer residues were 1.1 mg/kg.

Indoxacarb is registered for use in USA on apples at 0.12 kg ai/ha with a PHI of 14 days. In 14 trials in USA with application rates of 0.12 ± 30%, i.e. 0.085-0.156 kg ai/ha, residues of indoxacarb + R enantiomer in rank order, median underlined, were: 0.087, 0.11, 0.12, 0.13, 0.15, 0.20, 0.21, 0.21, 0.21, 0.22, 0.23, 0.23, 0.26 and 0.30 mg/kg.

The Meeting decided that the data from Australia and South Africa were insufficient to use on their own. The Australian data was significantly different from the USA data on a Mann-Whitney test. The USA data was also significantly different from the European data (Mann-Whitney test) and so could not be combined.

The Meeting estimated a maximum residue level and STMR and HR values for indoxacarb in apples, based on the USA data, of 0.5, 0.21 and 0.30 mg/kg respectively.

Pears

Indoxacarb residue trials on pears were available from Australia, South Africa and USA. The South African trials could not be evaluated because the spray concentrations used in the trials were too high compared with GAP concentrations.

Indoxacarb is registered for use on pears in Australia at a spray concentration of 0.0075 kg ai/hL with a PHI of 14 days. In one trial in Australia matching those conditions, residues of indoxacarb + R enantiomer were 0.30 mg/kg, but one trial is insufficient.

Indoxacarb is registered for use in USA on pears at 0.12 kg ai/ha with a PHI of 28 days. In 6 trials in USA with application rates of 0.12 ± 30%, i.e. 0.085-0.156 kg ai/ha, and with PHIs of 24 and 28 days, residues of indoxacarb + R enantiomer in rank order, median underlined, were: 0.042, 0.051, 0.051, 0.065, 0.067 and 0.11 mg/kg.

The Meeting estimated a maximum residue level and STMR and HR values for indoxacarb in pears, based on the USA data, of 0.2, 0.051 and 0.11 mg/kg respectively.

Stone fruits

Indoxacarb residue trials on apricots, nectarines and peaches were available from Australia, France, Greece, Italy and Spain.

Indoxacarb is registered for use on apricots, nectarines and peaches in Australia at a spray concentration of 0.0075 kg ai/hL with a PHI of 7 days. In an apricot trial in Australia matching those conditions, residues of indoxacarb + R enantiomer were 1.5 mg/kg. In two nectarine trials in Australia matching those conditions, residues of indoxacarb + R enantiomer were 0.20 and 0.29 mg/kg. In one peach trial matching GAP, residues of indoxacarb + R enantiomer were 0.86 mg/kg.

In Greece, indoxacarb may be used on peach trees at 0.1 kg ai/ha with a PHI of 7 days. In three trials in Greece with application rates of 0.1 ± 30%, i.e. 0.07-0.13 kg ai/ha, residue of indoxacarb + R enantiomer were 0.12, 0.13 and 0.18 mg/kg.

In Italy, indoxacarb may be used on peach trees at 0.075 kg ai/ha with a PHI of 7 days. In four trials in Italy with application rates of 0.075 ± 30%, i.e. 0.053-0.098 kg ai/ha, residues of indoxacarb + R enantiomer were 0.06, 0.07, 0.11 and 0.16 mg/kg. In a peach trial in Spain matching Italian GAP, residues of indoxacarb + R enantiomer were 0.05 mg/kg. In a peach trial in France matching Italian GAP, residues of indoxacarb + R enantiomer were 0.10 mg/kg.

In summary, residues of indoxacarb + R enantiomer in peaches from the nine European trials in rank order, median underlined, were: 0.05, 0.060, 0.070, 0.10, 0.11, 0.12, 0.13, 0.16 and 0.18 mg/kg.

The Australian data was insufficient to support a recommendation.

The Meeting estimated a maximum residue level and STMR and HR values for indoxacarb in peaches, based on the European data, of 0.3, 0.11 and 0.18 mg/kg respectively.

Grapes

Indoxacarb residue trials on grapes were available from Australia, France, Germany, Greece, Hungary, Italy, Spain and USA.

In Australia, indoxacarb may be sprayed on grapes at a concentration of 0.0051 kg ai/hL with harvest 56 days after the final treatment. In three grape trials in Australia with application concentrations of 0.0051 ± 30%, i.e. 0.0036-0.0066 kg ai/hL, and PHIs of 60 and 61 days, residues of indoxacarb + R enantiomer were 0.04, 0.18 and 0.33 mg/kg.

In France, indoxacarb may be used on grapes at 0.038 kg ai/ha with harvest 10 days after the final application. In 15 grape trials in France with application rates of 0.038 ± 30%, i.e. 0.027-0.049 kg ai/ha and a PHI of 10 days, residues of indoxacarb + R enantiomer in rank order were: 0.02, 0.02, 0.02, 0.03, 0.03, 0.03, 0.04, 0.04, 0.04, 0.04, 0.04, 0.04, 0.05, 0.05 and 0.07 mg/kg. In one German trial matching French GAP, residues were 0.03 mg/kg.

In Germany, indoxacarb may be used on wine grapes at 0.056 kg ai/ha with harvest 14 days after the final application. In three grape trials in Germany with application rates of 0.056 ± 30%, i.e. 0.039-0.073 kg ai/ha and 14 days PHI, residues of indoxacarb + R enantiomer in rank order were: 0.04, 0.06 and 0.11 mg/kg.

Indoxacarb is registered in Greece for use on grapes at 0.068 kg ai/ha with a PHI of 10 days. In a Greek trial where indoxacarb was used at 0.052 kg ai/ha with a PHI of 9 days, residues of indoxacarb + R enantiomer were 0.12 mg/kg. In a Spanish trial in line with Greek GAP, residues of indoxacarb + R enantiomer were 0.13 mg/kg. In three Italian trials at 0.56-0.58 kg ai/ha, comparable to Greek GAP, residues 10-11 days after the final application were 0.13, 0.17 and 0.22 mg/kg.

Indoxacarb is registered in Hungary for use on grapes at 0.038 kg ai/ha with a PHI of 3 days. In two trials in Hungary with application rates of 0.045 kg ai/ha (18% above label rate) and a PHI of 3 days, residues of indoxacarb + R enantiomer were 0.12 and 0.46 mg/kg.

Indoxacarb is registered in Italy for use on grapes at 0.038 kg ai/ha with a PHI of 10 days. In four trials in Italy with application rates of 0.038 ± 30%, i.e. 0.027-0.049 kg ai/ha and PHIs of 10-11 days, residues of indoxacarb + R enantiomer were 0.06, 0.11 and 0.13 mg/kg. In 2 Spanish trials in line with Italian GAP, residues of indoxacarb + R enantiomer were 0.14 and 0.19 mg/kg.

In summary, residues in the 32 European grape trials in rank order, median underlined, were: 0.02, 0.02, 0.02, 0.03, 0.03, 0.03, 0.03, 0.04, 0.04, 0.04, 0.04, 0.04, 0.04, 0.04, 0.05, 0.05, 0.06, 0.06, 0.07, 0.11, 0.11, 0.12, 0.13, 0.13, 0.13, 0.14, 0.14, 0.17, 0.19, 0.22, 0.22 and 0.46 mg/kg.

In USA, indoxacarb may be used on grapes at 0.12 kg ai/ha with harvest 7 days after the final application. In 13 grape trials in USA matching GAP conditions, residues of indoxacarb + R enantiomer in rank order, median underlined, were: 0.09, 0.16, 0.17, 0.18, 0.26, 0.28, 0.32, 0.39, 0.42, 0.44, 0.75, 1.4 and 1.5 mg/kg.

The USA grape data and the European grape data was significantly different populations (Mann-Whitney test) and could not be combined. The USA grape data and the Australian grape data was not significantly different populations (Mann-Whitney test) and could be combined. In summary, the combined USA and Australian data set for grapes is 0.04, 0.09, 0.16, 0.17, 0.18, 0.18, 0.26, 0.28, 0.32, 0.33, 0.39, 0.42, 0.44, 0.75, 1.4 and 1.5 mg/kg.

The Meeting estimated a maximum residue level and STMR and HR values for indoxacarb in grapes, based on the USA data, of 2, 0.30 and 1.5 mg/kg respectively.

Cabbages

The Meeting received information on supervised residue trials on cabbages in Australia, Belgium, Denmark, France, Germany, Greece, India, Netherlands, Portugal, Italy, South Africa, Spain, UK and USA.

In Australia, indoxacarb is registered for use on cabbages with an application rate of 0.075 kg ai/ha and a PHI of 7 days. In two Australian trials matching GAP, residues of indoxacarb + R enantiomer were < 0.02 and 0.21 mg/kg.

Indoxacarb may be used in India on cabbages at 0.04 kg ai/ha with a PHI of 7 days. In three trials in India matching GAP, residues of indoxacarb + R enantiomer were < 0.01 (2) and 0.02 mg/kg.

In South Africa, indoxacarb may be used on cabbage at 0.045 kg ai/ha with harvest 3 days after the final treatment. In four South African trials with application rates at 0.053 kg ai/ha and a PHI of 3 days, residues of indoxacarb + R enantiomer were 0.40, 0.47, 0.83 and 2.0 mg/kg.

In France, indoxacarb is registered for use on cabbages with an application rate of 0.026 kg ai/ha and a PHI of 3 days. In seven trials in France with conditions aligned with GAP, residues of indoxacarb + R enantiomer were: < 0.02 (4), 0.02, 0.05 and 0.08 mg/kg. In three trials in The Netherlands with conditions aligned with French GAP, residues were < 0.02 (2) and 0.09 mg/kg. In three trials in Belgium, Denmark and UK with conditions aligned with French GAP, residues were < 0.02 (3) mg/kg.

In Germany, indoxacarb is registered for use on cabbages with an application rate of 0.026 kg ai/ha and a PHI of 3 days. In three trials in Germany matching GAP, residues of indoxacarb + R enantiomer were < 0.02 (3) mg/kg.

In Italy, indoxacarb is registered for use on cabbages with an application rate of 0.026 kg ai/ha and a PHI of 3 days. In three trials in Italy matching GAP, residues of indoxacarb + R enantiomer were < 0.02 (3) mg/kg. In a trial in Greece with conditions matching Italian GAP, residues were < 0.02 mg/kg.

In Spain, indoxacarb is registered for use on cabbages with an application rate of 0.025 kg ai/ha and a PHI of 3 days. In a trial in Spain matching GAP, residues of indoxacarb + R enantiomer were < 0.02 mg/kg. In a trial in Portugal under conditions matching Spanish GAP, residues were < 0.02 mg/kg.

In summary, the residues in the 22 cabbage trials from Europe, in rank order, were: < 0.02 (18), 0.03, 0.05, 0.08 and 0.09 mg/kg.

In USA, indoxacarb may be used on cabbage at 0.073 kg ai/ha with harvest 3 days after the final application. In four USA trials matching GAP, residues of indoxacarb + R enantiomer in cabbages with wrapper leaves were: 0.21, 0.34, 0.38 and 2.7 mg/kg.

The USA and South African cabbage data appeared to be similar populations and were combined. The European data and the combined USA and South African data was significantly different populations (Mann-Whitney test). In summary, the combined USA and South African data set for cabbage was 0.21, 0.34, 0.38, 0.40, 0.47,0.83, 2.0 and 2.7 mg/kg.

The Meeting estimated a maximum residue level and STMR and HR values for indoxacarb in head cabbages of 3, 0.435 and 2.7 mg/kg respectively, based on the USA and South African data.

Broccoli

The Meeting received information on supervised residue trials on broccoli in Australia, France, Italy, South Africa, UK and USA.

Indoxacarb is registered for use on broccoli in Australia at 0.075 kg ai/ha with a PHI of 7 days. In three trials on broccoli with conditions in line with GAP, residues of indoxacarb + R enantiomer were 0.08, 0.12 and 0.23 mg/kg.

Indoxacarb is registered for use on broccoli in France at 0.026 kg ai/ha with a PHI of 3 days. In three trials on broccoli in France under conditions of GAP, residues of indoxacarb + R enantiomer were: < 0.02, 0.04 and 0.08 mg/kg. In a UK trial on broccoli in line with French GAP, residues were 0.05 mg/kg.

Indoxacarb may be used on broccoli in Spain at 0.025 kg ai/ha with harvest 3 days after the final treatment. In four indoxacarb trials on broccoli in Italy under conditions of Spanish GAP, residues were 0.03, 0.06, 0.10, and 0.14 mg/kg.

In summary, residues in broccoli in nine European trials were < 0.02, 0.03, 0.04, 0.05, 0.06, 0.08, 0.10, 0.13 and 0.14 mg/kg.

Indoxacarb may be used in South Africa at 0.045 kg ai/ha on broccoli, with a PHI of 3 days. In two broccoli trials in South Africa in line with GAP conditions, residues of indoxacarb + R enantiomer were 0.22 and 0.31 mg/kg.

Indoxacarb is registered for use on broccoli in USA at 0.073 kg ai/ha with a 3 days PHI. In two trials in the USA in line with the registered use, residues of indoxacarb + R enantiomer were: 0.25, and 0.39 mg/kg.

The numbers of trials from Australia, South Africa and USA were too small, so the evaluation was based on the European data with the lower residue values. In summary, the European residue data for broccoli are: < 0.02, 0.03, 0.04, 0.05, 0.06, 0.08, 0.10 and 0.14 mg/kg.

The Meeting estimated a maximum residue level and STMR and HR values for indoxacarb in broccoli, based on the European data, of 0.2, 0.055 and 0.14 mg/kg respectively.

Cauliflower

The Meeting received information on supervised residue trials on cauliflowers in Australia, Denmark, France, Germany, Greece, Italy, Netherlands, South Africa and Spain.

Indoxacarb is registered for use on cauliflowers in Australia at 0.075 kg ai/ha with a PHI of 7 days. In a trial on cauliflower with conditions in line with GAP, residues of indoxacarb + R enantiomer were < 0.01 mg/kg.

Indoxacarb is registered for use on cauliflowers in France at 0.026 kg ai/ha with a PHI of 3 days. In seven trials on cauliflowers in France under conditions of GAP, residues of indoxacarb + R enantiomer were: < 0.02 (4), 0.01, 0.05 and 0.14 mg/kg. In a cauliflower trial in Denmark under conditions of French GAP, residues were 0.03 mg/kg. In 2 cauliflower trials in The Netherlands under conditions of French GAP, residues were < 0.02 and 0.09 mg/kg.

Indoxacarb is registered for use on cauliflowers in Germany at 0.026 kg ai/ha with a PHI of 3 days. In three trials on cauliflowers in Germany under conditions of GAP, residues of indoxacarb + R enantiomer were < 0.02, 0.03 and 0.07 mg/kg.

Indoxacarb may be used on cauliflowers in Italy at 0.026 kg ai/ha with harvest 3 days after the final treatment. In a trial in Italy in line with GAP, residues of indoxacarb + R enantiomer were 0.02 mg/kg. In a cauliflower trial in Greece in line with Italian GAP, residues were < 0.02 mg/kg.

Indoxacarb may be used on cauliflowers in Spain at 0.025 kg ai/ha with harvest 3 days after the final treatment. In a trial in Spain on cauliflowers according to GAP conditions, residues of indoxacarb + R enantiomer were < 0.02 mg/kg.

In summary, residues in cauliflowers in 16 European trials, in rank order, median underlined, were: 0.01, < 0.02 (8), 0.02, 0.03, 0.03, 0.05, 0.07, 0.09 and 0.14 mg/kg.

Indoxacarb may be used in South Africa at 0.045 kg ai/ha on cauliflowers, with a PHI of 3 days. In two cauliflower trials in South Africa in line with GAP conditions, residues of indoxacarb + R enantiomer were < 0.01 and 0.04 mg/kg.

The data from the cauliflower trials from Australia (1) and South Africa (2) appear to be of the same population as the European data and may be combined: < 0.01 (2), 0.01, < 0.02 (8), 0.02, 0.03, 0.03, 0.04, 0.05, 0.07, 0.09 and 0.14 mg/kg.

The Meeting estimated a maximum residue level and STMR and HR values for indoxacarb in cauliflowers, based on the European, South African and Australian data, of 0.2, 0.02 and 0.14 mg/kg respectively.

Brussels sprouts

The Meeting received information on supervised residue trials on Brussels sprouts in Australia.

Indoxacarb is registered in Australia for use on Brussels sprouts at 0.075 kg ai/ha with a PHI of 7 days. In two trials in Australia where the use was in line with GAP, residues of indoxacarb + R enantiomer were 0.03 and 0.07 mg/kg.

Because two trials are insufficient, the Meeting was unable to recommend a maximum residue level for indoxacarb on Brussels sprouts.

Cucumbers and summer squash

The Meeting received information on supervised residue trials on cucumbers in France, Greece, Italy and Spain. The Meeting also received information on 2 supervised trials on courgettes (summer squash) from Italy.

Indoxacarb is registered in Spain for field or greenhouse use on cucurbits at 0.038 kg ai/ha with a 1-day PHI. In two field trials on cucumbers in Spain under conditions matching GAP, residues of indoxacarb + R enantiomer were < 0.02 and < 0.02 mg/kg. In four greenhouse trials on cucumbers in Spain with conditions matching GAP (one trial with application rate of 0.047 kg ai/ha), residues were < 0.02 (2), 0.02 and 0.10 mg/kg. In two field trials on cucumbers in Italy under conditions matching Spanish GAP, residues were < 0.02 and < 0.02 mg/kg. In four greenhouse trials on cucumbers in France under conditions matching Spanish GAP, residues were < 0.02 (2), 0.02 and 0.03 mg/kg.

Indoxacarb is registered in Greece for field or greenhouse use on cucumbers at 0.038 kg ai/ha with a 1-day PHI. In two greenhouse trials on cucumbers in Greece with conditions matching GAP, residues of indoxacarb + R enantiomer were < 0.02 and < 0.02 mg/kg.

Indoxacarb may be used in Hungary for field or greenhouse use on cucumbers at 0.051 kg ai/ha with a 1-day PHI. In two greenhouse trials in France and one in Spain on cucumbers under conditions in line with Hungarian GAP, residues in indoxacarb + R enantiomer were 0.03, 0.03 and 0.05 mg/kg.

In summary, residues in cucumbers in four field trials from Europe were < 0.02 (4), and residues from 13 greenhouse trials in rank order, median underlined, were < 0.02 (6), 0.02, 0.02, 0.03, 0.03, 0.03, 0.05 and 0.10 mg/kg.

The Meeting agreed to use the greenhouse data set to support the MRL.

The Meeting estimated a maximum residue level and STMR and HR values for indoxacarb in cucumbers, based on the European greenhouse data, of 0.2, 0.02 and 0.10 mg/kg respectively.

Residues in the courgettes (summer squash) from the 2 field trials (0.07 and 0.09 mg/kg) were apparently different from the residues in cucumbers (< 0.02 (4)) in the field trials, so the data could not be combined to support a summer squash recommendation.

Melons

The Meeting received information on supervised residue trials on melons in France, Greece, Italy and Spain. Residues were measured on peel and pulp separately and the residue levels for whole fruit were calculated from the measured residues and the weights of peel and pulp.

Indoxacarb is registered in Spain for field or greenhouse use on cucurbits at 0.038 kg ai/ha with a 1-day PHI. In one field trial and 3 greenhouse trials on melons in Spain under conditions matching GAP, residues of indoxacarb + R enantiomer were 0.04 mg/kg (field) and 0.02, 0.03 and 0.04 mg/kg (greenhouse).

In four field trials and 3 greenhouse trials on melons in France with conditions matching Spanish GAP, residues of indoxacarb + R enantiomer were 0.02, 0.03, 0.03 and 0.05 mg/kg (field) and 0.02, 0.024 and 0.03 mg/kg (greenhouse).

In two field trials and 1 greenhouse trial on melons in Greece with conditions matching Spanish GAP, residues of indoxacarb + R enantiomer were 0.03 and 0.04 mg/kg (field) and 0.085 mg/kg (greenhouse).

In two field trials and two greenhouse trials on melons in Italy with conditions matching Spanish GAP, residues of indoxacarb + R enantiomer were 0.03 and 0.03 mg/kg (field) and 0.03 and 0.04 mg/kg (greenhouse).

In summary, the 9 field trials on melons produced residues of 0.02, 0.03 (5), 0.04, 0.04 and 0.05 mg/kg and the 9 greenhouse trials produced residues of 0.02, 0.02, 0.024, 0.03 (3), 0.04, 0.04 and 0.085 mg/kg.

The two data populations, field and greenhouse, are not significantly different (Mann-Whitney test) and can be combined for evaluation: 0.02 (3), 0.024, 0.03 (8), 0.04 (4), 0.05 and 0.085 mg/kg.

The Meeting estimated a maximum residue level for indoxacarb in melons, except watermelon, of 0.1 mg/kg.

Indoxacarb residues were below LOQ (0.02 mg/kg) in every sample of pulp in all the trials, so residues are unlikely to occur. In the absence of additional evidence that residues do not occur in the pulp, the Meeting estimated STMR and HR values of 0.02 mg/kg for melons.

Tomatoes

The Meeting received information on supervised residue trials on tomatoes in Australia, France, Greece, Italy, Spain and USA.

In Australia, indoxacarb may be applied to tomatoes at 0.075 kg ai/ha with a 3-days PHI. In two trials from Australia matching GAP conditions, residues of indoxacarb + R enantiomer were 0.09 and 0.12 mg/kg.

In France, indoxacarb may be applied to tomatoes in the field at 0.038 kg ai/ha with a 3-days PHI. In six trials on tomatoes in France matching GAP conditions, residues of indoxacarb + R enantiomer were < 0.02 (3), 0.03, 0.05 and 0.05 mg/kg.

In Greece, indoxacarb may be applied to tomatoes in the field or greenhouse at 0.038 kg ai/ha with a 1-day PHI. In one field trial and two greenhouse trials on tomatoes in Greece with conditions matching GAP, residues of indoxacarb + R enantiomer were 0.03 mg/kg (field) and 0.02 and 0.04 mg/kg (greenhouse).

In Spain, indoxacarb may be applied to tomatoes in the field or greenhouse at 0.038 kg ai/ha with a 1-day PHI. In three greenhouse trials on tomatoes in Spain with conditions matching GAP, residues of indoxacarb + R enantiomer were < 0.02, 0.03 and 0.03 mg/kg. In four field trials on tomatoes in Italy with conditions matching Spanish GAP, residues were 0.03, 0.03, 0.04 and 0.07 mg/kg. In one field trial and four greenhouse trials on tomatoes in France with conditions matching Spanish GAP, residues were < 0.02 mg/kg (field) and 0.02, 0.02, 0.065 and 0.065 mg/kg (greenhouse).

In summary, residues on tomatoes from 13 field trials in Europe were < 0.02, (4), 0.025, 0.03, 0.03, 0.033, 0.04, 0.045, 0.045, 0.050 and 0.070 mg/kg, and from 9 greenhouse trials < 0.02, 0.02, 0.02, 0.02, 0.03, 0.035, 0.04, 0.065 and 0.065 mg/kg. The two populations were not significantly different and could be combined: < 0.02, < 0.02, < 0.02, < 0.02, < 0.02, 0.02, 0.02, 0.02, 0.025, 0.03, 0.03, 0.03, 0.033, 0.035, 0.04, 0.04, 0.045, 0.045, 0.050, 0.065, 0.065 and 0.070 mg/kg.

In USA, indoxacarb is registered for use on tomatoes at 0.073 kg ai/ha with harvest 3 days after the final application. In six trials on tomatoes in USA under conditions matching GAP, but with intervals after treatment longer than PHI when residues were greater, residues of indoxacarb + R enantiomer in rank order, median underlined, were: 0.02, 0.05, 0.06, 0.13, 0.13 and 0.30 mg/kg.

The tomato residue data populations from Europe and US were significantly different (Mann-Whitney test) and could not be combined. The residue data from the Australian trials and the USA trials appeared to be similar populations and were combined resulting in an eight trial data-set: 0.02, 0.05, 0.06, 0.09, 0.12, 0.13, 0.13 and 0.30 mg/kg.

The Meeting estimated a maximum residue level and STMR and HR values for indoxacarb in tomatoes, based on the USA and Australian data, of 0.5, 0.11 and 0.30 mg/kg respectively.

Peppers

The Meeting received information on supervised residue trials on peppers in Australia, France, Greece, Italy, Portugal, Spain and USA.

In Australia, indoxacarb is registered for application to peppers at 0.075 kg ai/ha with harvest permitted 3 days after the final application. In three trials on sweet peppers with conditions matching GAP, residues of indoxacarb + R enantiomer were 0.03, 0.06 and 0.41 mg/kg.

In Greece, indoxacarb may be applied to peppers in the field or in greenhouses at 0.038 kg ai/ha with harvest 1 day after the final application. In two peppers trials in the field and two in greenhouses in Greece with conditions matching GAP, residues of indoxacarb + R enantiomer were 0.03 and 0.05 mg/kg (field) and 0.06 and 0.21 mg/kg (greenhouse).

In two peppers trials in the field and three in greenhouses in France with conditions matching GAP in Greece, residues of indoxacarb + R enantiomer were < 0.02 and < 0.02 mg/kg (field) and < 0.02 (2) and 0.02 mg/kg (greenhouse).

In three peppers trials in the field in Italy with conditions matching GAP in Greece, residues of indoxacarb + R enantiomer were < 0.02, 0.045 and 0.05 mg/kg.

In one peppers trial in the field in Portugal with conditions matching GAP in Greece, residues of indoxacarb + R enantiomer were 0.035 mg/kg.

In four peppers trials in the field and four in greenhouses in Spain with conditions matching GAP in Greece, residues of indoxacarb + R enantiomer were 0.03, 0.06, 0.075 and 0.19 mg/kg (field) and 0.035, 0.04, 0.085 and 0.09 mg/kg (greenhouse).

In summary, residues in peppers from 12 field trials in Europe were < 0.02 (3), 0.03, 0.03, 0.035, 0.045, 0.05, 0.05, 0.06, 0.075 and 0.19 mg/kg, and in 9 greenhouse trials < 0.02 (2) 0.02, 0.035, 0.04, 0.06, 0.085, 0.09 and 0.21 mg/kg.

In USA, indoxacarb is registered for use on peppers at 0.073 kg ai/ha with harvest 3 days after the final application. In nine trials with both bell peppers and non-bell peppers in USA with conditions matching GAP, residues of indoxacarb + R enantiomer in rank order, median underlined, were < 0.02 (3), 0.02, 0.02, 0.04, 0.067, 0.076 and 0.096 mg/kg.

The residue data populations from the European field trials and greenhouse trials are not significantly different (Mann-Whitney test) and may be combined. The populations of the European data set and the USA field trial data are not significantly different (Mann-Whitney test) and may all be combined for evaluation. A single value from three trials in Australia was higher than all the 30 values from USA and Europe suggesting a different data population. Combined European and USA data in rank order, median underlined: < 0.02 (8), 0.02, 0.02, 0.02, 0.03, 0.03, 0.035, 0.035, 0.04, 0.04, 0.045, 0.05, 0.05, 0.06, 0.06, 0.067, 0.075, 0.076, 0.085, 0.09, 0.096, 0.19 and 0.21 mg/kg.

The Meeting estimated a maximum residue level and STMR and HR values for indoxacarb in peppers, based on the combined data, of 0.3, 0.038 and 0.21 mg/kg respectively.

Egg plant

In USA, indoxacarb is registered for use on egg plant at 0.073 kg ai/ha with harvest 3 days after the final application, the same use pattern as on tomatoes and peppers. The Meeting decided to extrapolate the tomato recommendations to egg plant.

The Meeting estimated a maximum residue level and STMR and HR values for indoxacarb in egg plant of 0.5, 0.11 and 0.30 mg/kg respectively.

Sweet corn

The Meeting received information on supervised residue trials on sweet corn in USA.

Indoxacarb is registered for use on sweet corn in the USA with an application rate of 0.073 kg ai/ha and harvest 3 days after the final application. In six sweet corn trials in USA in line with GAP, residues of indoxacarb + R enantiomer in kernel + cob with husk removed were below LOQ (0.01 mg/kg). The six trials are supported with data from 12 USA trials with racemic indoxacarb. In 12 sweet corn trials with racemic indoxacarb, which is expected to give higher residues than the 3S+1R indoxacarb, residues were below LOQ (0.01 mg/kg) in 11 trials and close to LOQ in the remaining one (0.012 mg/kg).

The Meeting estimated a maximum residue level and STMR and HR values for indoxacarb in sweet corn (corn-on-the-cob) of 0.02, 0.01 and 0.012 mg/kg respectively.

Lettuce

The Meeting received information on supervised residue trials on lettuce in France, Greece, Italy, Spain and USA.

In Spain, indoxacarb may be applied to lettuce in field or greenhouse at 0.038 kg ai/ha with harvest permitted 1 day after the final application. In four field trials in Spain in line with GAP, residues of indoxacarb + R enantiomer in the head lettuce were 0.19, 0.25, 0.39 and 0.52 mg/kg.

In two field trials on head lettuce in Italy under conditions in line with Spanish GAP, residues of indoxacarb + R enantiomer were 0.16 and 0.88 mg/kg.

In three field trials on lettuce in France with conditions matching Spanish GAP, residues of indoxacarb + R enantiomer were 0.54 mg/kg for head lettuce and 0.52 and 0.86 mg/kg for leaf lettuce.

In a field trial on lettuce in Greece with conditions matching GAP (same as for Spain), residues of indoxacarb + R enantiomer were 1.65 mg/kg for leaf lettuce.

In summary, the residues on head lettuce from the European trials were 0.16, 0.19, 0.25, 0.39, 0.52, 0.54 and 0.88 mg/kg, while the residues on leaf lettuce were 0.52, 0.86 and 1.65 mg/kg.

In the USA, indoxacarb is registered for application to lettuce at 0.12 kg ai/ha with harvest 3 days after the final application. In nine field trials with head lettuce where conditions matched GAP conditions, residues of indoxacarb + R enantiomer were in rank order, median underlined, 0.61, 2.1, 2.5, 2.7, 2.8, 3.2, 3.8, 4.0 and 4.3 mg/kg and for nine field trials on leaf lettuce, residues were 2.8, 3.6, 4.1, 6.1, 6.6, 7.2, 7.4, 8.2 and 8.4 mg/kg.

The USA and European residue data populations for head lettuce were significantly different (Mann-Whitney test) and should not be combined. The same conclusion was reached for the leaf lettuce.

The Meeting estimated a maximum residue level and STMR and HR values for indoxacarb in head lettuce, based on the USA data, of 7, 2.8 and 4.3 mg/kg respectively.

The Meeting estimated a maximum residue level and STMR and HR values for indoxacarb in leaf lettuce, based on the USA data, of 15, 6.6 and 8.4 mg/kg respectively.

Pulses - adzuki beans, chickpeas and mungbeans

The Meeting received information on supervised residue trials on adzuki beans, chickpeas, mungbeans and soybeans from Australia. The adzuki bean data could not be evaluated because there is no registered indoxacarb use on adzuki beans.

In Australia, indoxacarb is registered for a single application to chickpeas at 0.045 kg ai/ha 28 days before harvest. In four chickpea trials in Australia with conditions matching GAP, residues of indoxacarb + R enantiomer in the chickpea grain were < 0.01, 0.02, 0.02 and 0.13 mg/kg.

In Australia, indoxacarb is registered for a single application to mungbeans at 0.060 kg ai/ha 28 days before harvest. In three mungbean trials in Australia with conditions matching GAP, residues of indoxacarb + R enantiomer in the mungbean grain were < 0.01 (2) and 0.02 mg/kg.

The Meeting combined the data from the three pulse crops for mutual support. Residues in the seven trials in rank order, median underlined, were: < 0.01 (3), 0.02 (3) and 0.13 mg/kg.

The Meeting estimated a maximum residue level and an STMR value for indoxacarb in chickpeas and mungbeans, based on the Australian data, of 0.2 and 0.02 mg/kg respectively.

Soybeans

The Meeting received information on supervised residue trials on soybeans from USA and Australia.

In Australia, indoxacarb is registered for a single application to soybeans at 0.060 kg ai/ha 28 days before harvest. In three soybean trials in Australia with conditions matching GAP, residues of indoxacarb + R enantiomer in the soybean grain were < 0.01 (2) and 0.06 mg/kg.

In the USA, indoxacarb is registered for use on soybeans at an application rate of 0.12 kg ai/ha with harvest 21 days after the final application. In 20 supervised trials in USA with a use pattern matching GAP, residues of indoxacarb + R enantiomer in rank order, with median underlined, were: 0.008, 0.009, 0.010, 0.010, 0.010, 0.011, 0.012, 0.014, 0.020, 0.024, 0.030, 0.032, 0.032, 0.039, 0.17, 0.24, 0.25, 0.29, 0.29 and 0.45 mg/kg.

The Australian data appear to be a different population from the USA data. The Meeting estimated a maximum residue level and an STMR value for indoxacarb in soybeans, based on the USA data, of 0.5 and 0.027 mg/kg respectively.

Potato

The Meeting received information on supervised residue trials on potatoes from USA.

In USA, indoxacarb is registered for use on potatoes at an application rate of 0.12 kg ai/ha with harvest 7 days after the final application. In 17 potato trials in USA with application rates of 0.15 kg ai/ha (25% above label rate) and PHI of 7 days, residues of indoxacarb + R enantiomer in rank order, median underlined, were: < 0.01 (17) mg/kg.

The Meeting estimated a maximum residue level and STMR and HR values for indoxacarb in potatoes of 0.02, 0.01 and 0.01 mg/kg respectively. Residue levels exceeded the detection limit (0.003 mg/kg) in some trials, so it is not a nil residue situation. Regulatory analytical methods for indoxacarb may not be practical for the low concentrations measured in the trials. The estimated maximum residue level of 0.02 mg/kg is based on the capabilities of the reviewed analytical methods.

Peanuts

The Meeting received information on supervised residue trials on peanuts from the USA.

In the USA, indoxacarb may be used on peanuts at 0.12 kg ai/ha with harvest 14 days after the final treatment. In 13 peanut trials in USA with conditions matching GAP, residues of indoxacarb + R enantiomer in peanut kernels were below LOQ (0.01 mg/kg) in every sample tested. Residue levels did not exceed the detection limit (0.003 mg/kg) in any trial. It should be noted that the PHI for peanuts is the interval between final treatment and digging, in this case 14 days. In the trials, peanuts were dug and allowed to dry in the field for 3 to 13 days before sampling.

The Meeting estimated a maximum residue level and STMR and HR values for indoxacarb in peanuts of 0.02*, 0.01 and 0.01 mg/kg respectively. Regulatory analytical methods for indoxacarb may not be practical for the low concentrations measured in the trials. The estimated maximum residue level of 0.02 mg/kg is based on the capabilities of the reviewed analytical methods.

Cotton

The Meeting received information on supervised residue trials on cotton from the USA.

In the USA, indoxacarb is registered for use on cotton at 0.12 kg ai/ha with harvest permitted 14 days after the final application. In seven cotton trials in USA with application rates of 0.15 kg ai/ha (25% above label rate) and PHI of 13-17 days (with intervals after treatment longer than PHI when residues were greater), residues of indoxacarb + R enantiomer in cotton seed in rank order, median underlined, were: 0.067, 0.26, 0.27, 0.36, 0.37, 0.65 and 0.92 mg/kg.

The Meeting estimated a maximum residue level and STMR and HR values for indoxacarb in cotton seed of 1, 0.36 and 0.92 mg/kg respectively.

Legume animal feeds - chickpea, mungbean and soybean fodder

The Meeting received information on residues in legume fodder from the supervised residue trials in Australia.

In Australia, the indoxacarb label instruction for fodder of chickpeas, mungbeans and soybeans is: Do not graze or cut for stock food for 28 days after application. See previous section on pulses for GAP in Australia.

In four trials in Australia in line with GAP, residues of indoxacarb + R enantiomer in "chickpea trash" were: 0.78, 0.78, 1.1 and 1.2 mg/kg. In three trials in line with Australian GAP, residues in "mungbean trash" were: 1.3, 1.7 and 5.6 mg/kg. In 3 trials in line with Australian GAP, residues in "soybean trash" were: 0.07, 0.11 and 0.20 mg/kg.

The fodder data from the three crops appear not to be of the same population and so cannot be combined. The number of trials for each crop on its own is insufficient to recommend a fodder MRL.

Peanut hay

The Meeting received information on residues in peanut hay from the supervised residue trials in USA.

See previous section on peanuts for GAP in the USA. In 12 peanut trials in the USA matching the conditions of GAP, residues of indoxacarb + R enantiomer in peanut hay in rank order, median underlined, were: 2.1, 2.5, 8.9, 9.7, 11, 11, 12, 13, 15, 18, 21 and 33 mg/kg. Moisture levels were measured on 13 samples of peanut hay (mean = 28%, range = 19-36%). Residues in peanut hay expressed on dry weight (i.e. adjusted for 28% moisture) were: 2.9, 3.5, 12, 13, 15, 15, 17, 18, 21, 25, 29 and 45 mg/kg.

The Meeting estimated a maximum residue level and STMR and highest residue values for indoxacarb in peanut fodder (= hay) of 50, 16 and 45 mg/kg respectively.

Alfalfa

The Meeting received information on residues in alfalfa from supervised residue trials in the USA.

In USA, indoxacarb is registered for use on alfalfa at 0.12 kg ai/ha, once per cutting, with cutting permitted 7 days after application. In 12 trials on alfalfa with conditions matching GAP, residues were measured in each trial after each of 3 or 4 cuttings. From each cutting, the 7 days residue (or later if it was higher) was chosen for evaluation. Residues of indoxacarb + R enantiomer in the alfalfa forage (fresh weight) from the 43 cuttings were: 0.94, 1.5, 1.6, 1.8, 1.9, 2.1, 2.2, 2.4, 2.4, 2.5, 2.5, 2.7, 2.9, 2.9, 3.1, 3.1, 3.1, 3.2, 3.3, 3.3, 3.4, 3.4, 3.8, 3.8, 3.9, 3.9, 3.9, 4, 4.2, 4.4, 4.4, 4.5, 4.8, 5.3, 5.3, 5.6, 5.7, 6, 6.2, 6.6, 7, 7.5 and 9.7 mg/kg. Residues expressed as dry weight in rank order, median underlined, were: 4.7, 6.0, 8.0, 9.4, 9.6, 10, 10, 11, 11, 12, 12, 13, 13, 13, 14, 15, 15, 15, 16, 16, 16, 16, 16, 17, 17, 17, 18, 18, 18, 18, 19, 19, 20, 21, 22, 22, 23, 24, 24, 26, 26, 27 and 28 mg/kg.

Residues of indoxacarb + R enantiomer in the alfalfa hay (fresh weight) from the 43 cuttings were: 2.4, 5.8, 6.1, 6.3, 6.7, 6.8, 7, 7.5, 7.7, 7.7, 8.2, 8.2, 8.2, 8.6, 9.1, 9.2, 9.2, 10, 10, 10, 10, 11, 12, 15, 15, 15, 16, 16, 16, 16, 17, 18, 18, 19, 20, 20, 20, 21, 23, 24, 25, 26 and 26 mg/kg. Residues expressed as dry weight in rank order, median underlined, were: 7.3, 7.5, 9.1, 10, 10, 11, 12, 12, 12, 12, 13, 13, 13, 14, 14, 14, 15, 15, 15, 16, 16, 17, 18, 19, 19, 20, 20, 20, 21, 23, 24, 25, 25, 25, 25, 26, 27, 31, 32, 33, 33, 33 and 43 mg/kg.

The Meeting estimated an STMR and a highest residue value for indoxacarb in alfalfa forage of 16 and 28 mg/kg respectively.

The Meeting estimated a maximum residue level and STMR and highest residue values for indoxacarb in alfalfa fodder (= hay) of 60, 18 and 43 mg/kg respectively.

Maize fodder

The Meeting received information on residues in sweet corn fodder (= maize fodder) from the supervised residue trials in USA.

See previous section on sweet corn for GAP in the USA. The PHI for fodder and stover is 35 days. In five sweet corn trials in the USA with application rates matching GAP, residue data on stover (mature dried stalks from which the grain or whole ear (cob + grain) have been removed) were accepted with PHIs of 28-66 days. Residues, expressed as fresh weight, of indoxacarb + R enantiomer in maize fodder were: 1.6, 1.9, 3.7, 5.3 and 9.8 mg/kg.

Moisture levels were measured on six samples of stover (3 of the 6 were in the GAP trials), giving a range and mean of 23-68% and 43% dry matter respectively. Residue levels were adjusted to dry weight in maize fodder using the measured dry matter for the 3 samples directly and the average dry matter for the other two. Residue levels in maize fodder, expressed as dry weight, in rank order, median underlined, were: 4.4, 4.8, 7.8, 8.6, and 15 mg/kg.

A set of five trials is rather a limited data set to support an MRL. However, the Meeting decided that it was best to take into account the residues occurring in the fodder from sweet corn when assessing farm animal dietary burden and therefore estimated a maximum residue level for maize fodder.

The Meeting estimated a maximum residue level and STMR and highest residue values for indoxacarb in maize fodder of 25, 7.8 and 15 mg/kg respectively.

Cotton fodder

The Meeting received information on residues in cotton gin trash (= cotton fodder) from the supervised residue trials in USA.

See previous section on cotton for GAP in USA. In seven trials on cotton in USA with an indoxacarb application rate of 0.15 kg ai/ha (25% above label rate) with harvest 13-17 days after the final application, residues of indoxacarb + R enantiomer in cotton gin trash in rank order, median underlined, were: 3.6, 6.6, 6.7, 8.0, 8.4, 8.4 and 11 mg/kg.

Moisture levels were measured on several samples of cotton gin trash from these and associated trials, giving a range and mean of 77-96% and 91% dry matter (n = 9) respectively. Because moisture levels were low (average < 10%) no adjustment was made for dry matter content.

The Meeting estimated a maximum residue level and STMR and highest residue values for indoxacarb in cotton fodder of 20, 8.0 and 11 mg/kg respectively.

Fate of residues during processing

Information on the fate of indoxacarb residues during food processing was available for apples, peaches, grapes, tomatoes, potatoes and soybeans. Processing factors for potato products could not be estimated because residues in the raw agricultural commodity were less than the LOQ.

Racemic indoxacarb was generally stable to hydrolysis under pasteurization conditions. Approximately 7-30% was lost during baking and boiling conditions. The products of hydrolysis were minor and polar.

Racemic indoxacarb was used in some of the processing studies. It is quite suitable for processing studies because it is the relative residue levels that are important.

Calculated processing factors and the mean or best estimate are summarized in the following table.

¹ Mean of 0.14, and the 3 smaller "less-than" values.

The processing factors for wet apple pomace (2.6), apple juice (0.05) and apple sauce (0.2) were applied to the estimated STMR for apples (0.21 mg/kg) to produce STMR-P values for wet apple pomace (0.55 mg/kg), apple juice (0.011 mg/kg) and apple sauce (0.042 mg/kg).

The processing factors for peach juice (0.08) and canned peaches (0.08) were applied to the estimated STMR for peaches (0.11 mg/kg) to produce STMR-P values for peach juice (0.009 mg/kg) and canned peaches (0.009 mg/kg).

The processing factors for raisins (2.7), grape juice (0.007) and wine (0.06) were applied to the estimated STMR for grapes (0.30 mg/kg) to produce STMR-P values for raisins (0.81 mg/kg), grape juice (0.002 mg/kg) and wine (0.018 mg/kg). The processing factor for raisins (2.7) was applied to the HR for grapes (1.5 mg/kg) to produce an HR-P value for raisins (4.1 mg/kg).

The Meeting estimated a maximum residue level for indoxacarb in dried grapes (= currants, raisins, sultanas) of 5 mg/kg.

The processing factors for tomato puree (0.83), tomato paste (1.9) and tomato juice (0.2) were applied to the estimated STMR for tomatoes (0.11 mg/kg) to produce STMR-P values for tomato puree (0.09 mg/kg), tomato paste (0.21 mg/kg) and tomato juice (0.022 mg/kg).

The processing factors for cotton seed hulls (0.026), cotton seed meal (0.0014) and cotton seed refined oil (0.036) were applied to the estimated STMR for cotton seed (0.36 mg/kg) to produce STMR-P values for cotton seed hulls (0.0094 mg/kg), cotton seed meal (0.0005 mg/kg) and cotton seed refined oil (0.013 mg/kg). The estimated residue in cotton seed oil would be less than the highest residue in cotton seed because the processing factor is 0.036.

The Meeting agreed not to recommend a residue level suitable for establishing an MRL for cotton seed oil, because the level would not exceed the value recommended for the RAC, cotton seed.

The processing factors for peanut oil (1) and peanut meal (0.39) were applied to the estimated STMR for peanuts (0.003 mg/kg) to produce STMR-P values for peanut oil (0.003 mg/kg) and peanut meal (0.0012 mg/kg). The estimated residue in peanut oil would be the same as the highest residue in peanuts because the processing factor is 1.

The Meeting agreed not to recommend a residue level suitable for establishing an MRL for peanut oil, because the level would not exceed the value recommended for the RAC, peanuts.

The processing factors for soybean hulls (8.5), soybean meal (0.14) and soybean refined oil (0.66) were applied to the estimated STMR for soybean (0.027 mg/kg) to produce STMR-P values for soybean hulls (0.23 mg/kg), soybean meal (0.0038 mg/kg) and soybean refined oil (0.018 mg/kg). The estimated residue in soybean oil would be less than the highest residue in soybean because the processing factor is 0.66.

The Meeting agreed not to recommend a residue level suitable for establishing an MRL for soybean oil, because the level would not exceed the value recommended for the RAC, soybean.

Residues in animal commodities

Farm animal feeding

The Meeting received a lactating dairy cow feeding study, which provided information on likely residues resulting in animal tissues and milk from residues in the animal diet.

Lactating Holstein cows were dosed with indoxacarb 3S+1R at the equivalent of 7.5 (low dose), 22.5 (medium dose) and 75 (high dose) ppm in the dry-weight diet for 28 consecutive days. Milk was collected throughout and tissues were collected for residue analysis (as indoxacarb + R enantiomer) and as metabolite IN-JT333 from animals slaughtered on day 29.

Residues in milk reached a plateau within about 4 days and levels of residue were approximately proportional to the dose. Highest residues in the milk at the 3 dosing levels were: 0.021 mg/kg (low dose), 0.054 mg/kg (medium dose) and 0.19 mg/kg (high dose). Highest residues in cream were: 0.22 mg/kg (low dose), 0.60 mg/kg (medium dose) and 2.2 mg/kg (high dose).

Metabolite IN-JT333 was below LOQ (< 0.01 mg/kg) for almost all the milk samples, but was present in cream from the 3 dosing levels on day 28 at 0.018 (low dose), 0.027 (medium dose) and 0.075 (high dose) mg/kg, representing about 3-8% of the parent compound concentration.

Indoxacarb is fat-soluble. The residue concentration in cream was found to be 10.8 times the residue in the milk (regression line for 40 data points).

In the tissues, the mean residues (indoxacarb + R enantiomer) at the 3 dosing levels were: muscle (< 0.01, < 0.01, 0.066 mg/kg); fat (0.22, 0.45, 1.9 mg/kg); liver (< 0.01, 0.01, 0.018 mg/kg); kidney (< 0.01, 0.017, 0.039 mg/kg).

Metabolite IN-JT333 was below LOQ (< 0.01 mg/kg) in muscle, kidney and liver from all doses. Metabolite IN-JT333 was present in fat at approximately 4-7% of the parent compound concentration.

Residues depleted quickly from the milk of a high-dose animal after dosing was stopped, falling below LOQ (0.01 mg/kg) after 5 days. Residues depleted to 0.079 mg/kg in the fat of the animal subjected to a 75 ppm dose for 28 days and then no dose for 15 days, i.e. depletion by approximately 96% from the value at day 28.

Farm animal dietary burden

The Meeting estimated the dietary burden of indoxacarb in farm animals on the basis of the diets listed in Appendix IX of the FAO Manual. Calculation from highest residue and STMR-P values provides the levels in feed suitable for estimating MRLs, while calculation from STMR and STMR-P values for feed is suitable for estimating STMR values for animal commodities. The percentage dry matter is taken as 100% when the highest residue levels and STMRs are already expressed as dry weight.

Estimated maximum dietary burden of farm animals

Estimated mean dietary burden of farm animals

Animal commodities, MRL estimation

For MRL estimation, the high residues in the tissues were calculated by interpolating the maximum dietary burden between the relevant feeding levels from the dairy cow feeding study and using the highest tissue concentrations from individual animals within those feeding groups. The high residues for milk and cream were calculated similarly except that the mean milk and cream concentrations from the relevant groups were used instead of the highest individual values.

The STMR values for the tissues, milk and cream were calculated by interpolating the STMR dietary burdens between the relevant feeding levels from the dairy cow feeding study and using the mean tissue and milk concentrations from those feeding groups. The concentrations of Metabolite IN-JT333 in the tissues, milk and cream were expressed as indoxacarb and added to the concentrations of indoxacarb and its enantiomer, which caused a slight change in concentrations in cream and fat, but not in milk or the other tissues.

In the table, dietary burdens are shown in round brackets (), feeding levels and residue concentrations from the feeding study are shown in square brackets [] and estimated concentrations related to the dietary burdens are shown without brackets. Residue concentrations from the feeding study and estimated concentrations related to the dietary burdens include metabolite IN-JT1333.

The Meeting estimated dietary burdens for indoxacarb + R enantiomer in dairy cows to be 31.6 and 18.3 ppm (maximum and mean). By interpolation, the highest residue and STMR for milk were estimated as 0.081 and 0.048 mg/kg. Similarly, the STMR for cream was estimated 0.51 mg/kg. On the assumption of 50% milk fat in cream, these values become 1.82 and 1.02 mg/kg for milk fat. The highest residue for parent compound only in cream was 0.88 mg/kg, i.e. 1.76 mg/kg in milk fat.

The Meeting estimated a maximum residue level and an STMR value for indoxacarb in milk of 0.1 and 0.048 mg/kg, respectively.

The Meeting estimated a maximum residue level and an STMR value for indoxacarb in milk fat of 2 and 1.0 mg/kg, respectively.

The Meeting estimated dietary burdens for indoxacarb + R enantiomer in beef cattle to be 35.0 and 20.4 ppm (maximum and mean). By interpolation, the highest residues for muscle, liver, kidney and fat were estimated as 0.03, 0.014, 0.027 and 0.91 respectively, with corresponding STMR values of < 0.01, 0.01, 0.016 and 0.44 mg/kg. The highest residue of parent only in fat was 0.86 mg/kg.

The Meeting estimated maximum residue levels of 1 (fat) and 0.05 mg/kg for indoxacarb in mammalian meat and edible offal respectively.

The Meeting estimated STMR values for indoxacarb in muscle tissue, mammalian fat and edible offal of 0.01, 0.44 and 0.016 respectively, with corresponding HR values of 0.03, 0.91 and 0.027 mg/kg, respectively.

The Meeting estimated dietary burdens for indoxacarb + R enantiomer in poultry to be 0.15 and 0.006 ppm (maximum and mean). The dosing level in the laying hen metabolism study was equivalent to 10 ppm in feed. Indoxacarb (+ R enantiomer) was not a major component of the identified residue in poultry commodities so estimates were made of both the total ¹⁴C residue and the indoxacarb residue resulting from exposure to the dietary burden feed levels. Calculations were made on the assumption that residues at the dietary burden level were proportional to residues in the laying hen metabolism study, based on relative intakes.

For a dietary burden of 0.15 ppm, estimated equivalent total residues were calculated as 0.0073, 0.0005, 0.0035, 0.0020 and 0.0048 mg/kg in fat, muscle, skin + fat, liver and eggs (yolk) respectively. Estimated residues of indoxacarb + R enantiomer were: 0.0004, < 0.0002, 0.0005, 0.0002 and 0.0002 mg/kg in fat, muscle, skin + fat, liver and eggs (yolk) respectively. All of these values are below the LOQ of the analytical method (0.01 mg/kg).

The Meeting recommended maximum residue levels of 0.01*(fat), 0.01* and 0.01* for indoxacarb in poultry meat, poultry offal and eggs, respectively. The Meeting recommended STMR and HR values of 0 mg/kg for poultry fat, muscle, offal and eggs, respectively.

DIETARY RISK ASSESSMENT

Long-term intake

The evaluation of indoxacarb resulted in recommendations for MRLs and STMR values for raw and processed commodities. Data on consumption were available for 37 food commodities and were used to calculate dietary intake. The results are shown in Annex 3.

The IEDIs in the five GEMS/Food regional diets, based on estimated STMRs were 1-50 % of the maximum ADI of 0.01 mg/kg bw. The Meeting concluded that the long-term intake of residues of indoxacarb from uses that have been considered by the JMPR is unlikely to present a public health concern.

Short-term intake

The IESTI of indoxacarb calculated on the basis of the recommendations made by the JMPR represented 0-130% of the ARfD (0.1 mg/kg bw) for children and 0-50 % for the general population. The IESTI for head cabbage for children was 130% of the ARfD.

It should be noted that unit weight data are not available for leaf lettuce in the GEMS/Food data base. Availability of a realistic unit weight would improve the estimate of short-term intake.

The Meeting concluded that the short-term intake of residues of indoxacarb resulting from uses that have been considered by the JMPR, except the use on head cabbages, is unlikely to present a public health concern.

The information provided to the JMPR precludes an estimate that the dietary intake would be below the ARfD for consumption of head cabbages by children.