4.3 Carbosulfan (145)/carbofuran (096)(R)

R-residue and analytical aspects

TOXICOLOGY

Carbosulfan is a carbamate insecticide that acts by inhibiting the activity of acetylcholinesterase. It was evaluated by JMPR in 1984 and 1986. A toxicological monograph was prepared by the Joint Meeting in 1984 and a monograph addendum was prepared in 1986. In 1986, an ADI of 0-0.01 mg/kg bw was established on the basis of a NOAEL of 1.3 mg/kg bw per day in a 2-year study in mice, a NOAEL of 1.0 mg/kg bw per day in a 2-year study in rats, and a NOAEL of 1.3 mg/kg bw per day in a 6-month study in dogs. One of the metabolites of carbosulfan is carbofuran, which is itself used as a pesticide and which was evaluated by JMPR in 1976, 1979, 1980, 1982, 1996 and 2002. The 1996 JMPR established an ADI of 0-0.002 mg/kg bw and the 2002 JMPR established an acute reference dose (RfD) of 0.009 mg/kg bw for carbofuran.

Carbosulfan was re-evaluated by the present Meeting within the periodic review programme of the Codex Committee on Pesticide Residues. The Meeting reviewed new data on carbosulfan that had not been considered previously and relevant data from the previous evaluation. Conclusions of studies evaluated for the 1984 JMPR that were not available for the present evaluation are included.

After oral administration to male and female rats, absorption of radiolabelled carbosulfan is rapid and almost complete. Elimination is also relatively rapid, with most (80-90%) of the absorbed radioactivity being excreted in the urine within 48-72 h, depending on dose. After repeated dosing of rats with carbosulfan, the rate of excretion appeared to be increased (80-87% within 24 h), which may indicate that induction of metabolism had occurred.

Carbosulfan is metabolized by hydrolysis to the 7-phenol or to carbofuran and dibutylamine, and is subsequently further metabolized via hydrolysis, oxidation and conjugation to a variety of metabolites. Metabolites of the dibutylamino moiety may enter the carbon pool and be incorporated into natural constituents of the body. No marked sex-specific differences were observed in rats with regard to the excretion pattern, tissue distribution and metabolite profile of carbosulfan.

Carbosulfan (technical material) is highly toxic when administered orally, with LD₅₀s ranging from 90-250 mg/kg bw in rats. The LD₅₀ for carbosulfan was >2000 mg/kg bw in rabbits treated dermally and the LC₅₀ was 0.61 mg/l in rats treated by inhalation.

Carbosulfan is minimally irritating to the eye, slightly irritating to the skin and is a dermal sensitizer.

In general, in short-term and long-term studies of toxicity, the most sensitive effect of the oral administration of carbosulfan was the inhibition of cholinesterase activity, accompanied at the same or higher doses by clinical signs indicative of cholinesterase inhibition (e.g. salivation, lacrimation, ataxia, tremors, anogenital staining, diarrhoea). In a study of acute oral neurotoxicity in rats, the NOAEL was 0.5 mg/kg bw, on the basis of effects on brain cholinesterase activity as measured 4 h after dosing. In a 90-day study in rats, the NOAEL was 20 ppm, equivalent to 1 mg/kg bw per day, on the basis of inhibition of brain and erythrocyte cholinesterase activity. In a second 90-day study of rats fed with carbosulfan, the NOAEL was 20 ppm, equal to 1.2 mg/kg bw per day, on the basis of clinical signs, observations in a functional observational battery (FOB) and effects on body weight, body-weight gain and food consumption at a dose of 62 mg/kg bw per day. In this study, cholinesterase activity was not determined.

In a 6-month study in dogs, the NOAEL reported was 50 ppm, equivalent to 1.3 mg/kg bw per day, on the basis of effects on blood chemistry parameters and occasional reductions in food consumption and body-weight gain.

In long-term studies in mice and rats, carbosulfan was not carcinogenic at concentrations in the diet of up to and including the highest dose tested of 2500 ppm, equal to 320 and 153 mg/kg bw per day for mouse and rat, respectively. In the study in mice, the NOAEL was 20 ppm, equal to 2.5 mg/kg bw per day, on the basis of reductions in body weight, inhibition of brain and erythrocyte cholinesterase activity and reductions in absolute and relative spleen weight. In the study in rats, the NOAEL was 20 ppm, equal to 1 mg/kg bw per day, on the basis of inhibition of brain and erythrocyte cholinesterase activity and pathological changes in the eye, i.e. focal iris atrophy, iris coloboma and absence of iris tissue. The mechanism by which these pathological changes in the eye were induced is not clear.

The genotoxic potential of carbosulfan was investigated in a wide range of tests. Primarily negative results were obtained in a number of tests in vitro and in vivo. Positive effects were observed in a few tests, however these tests were confounded by the use of very high doses in vivo, the occurrence of marked cytotoxicity in vitro and the lack of information on the purity of the test compound. The Meeting concluded that carbosulfan is unlikely to be genotoxic.

In view of the lack of genotoxicity and the absence of carcinogenicity in rats and mice the Meeting concluded that carbosulfan is unlikely to pose a carcinogenic risk to humans.

In a three-generation study of reproductive toxicity, carbosulfan was administered at doses of 10, 20 and 250 ppm. No effects on mating index, gestation index and number of viable fetuses were observed. At a dose of 250 ppm, pup weight, litter size and pup survival were decreased, as were the body weights of parental males and females at this dose. In parental animals, the NOAEL was 20 ppm, equivalent to 1.3 mg/kg bw per day, on the basis of the decreases in body weight. The NOAEL for pup toxicity was 20 ppm on the basis of the reductions in litter size, pup body weight and pup body-weight gain. The NOAEL for reproductive toxicity was 250 ppm, equivalent to 17 mg/kg bw per day, the highest dose tested.

In studies of developmental toxicity in rats and rabbits, carbosulfan was not teratogenic. The NOAEL for maternal toxicity was 2 mg/kg bw per day in the study in rats, on the basis of clinical signs and reduction in body weight. The NOAEL for toxicity in offspring was 2 mg/kg bw per day, on the basis of the reduction in fetal body weight. In the study in rabbits, the NOAEL for maternal and offspring toxicity was 10 mg/kg bw per day, the highest dose tested.

When tested in hens, carbosulfan did not induce delayed polyneuropathy after a single exposure.

No new human data were available.

The Meeting concluded that the present database is sufficient to characterize the potential hazard of carbosulfan to fetuses, infants and children.

Toxicological evaluation

The Meeting established an ADI of 0-0.01 mg/kg bw per day based on a NOAEL of 1 mg/kg bw per day, on the basis of pathological changes in the eye, inhibition of brain and erythrocyte cholinesterase activity and body-weight reduction in the 2-year study in rats, with a safety factor of 100. This safety factor was used because the pathological changes in the eye could not definitely be attributed to inhibition of cholinesterase.

After considering the data available to the present Meeting, as well as the previous evaluations, the Meeting established an acute RfD of 0.02 mg/kg bw. This was based on the NOAEL of 0.5 mg/kg bw per day for inhibition of brain cholinesterase activity in a study of acute neurotoxicity in rats, and a safety factor of 25, as the relevant toxic effects of carbosulfan are dependent on the C_max (Annex 5, reference 95).

A toxicological monograph was prepared.

Levels relevant to risk assessment

a Diet
b Gavage
c Highest dose tested

Estimate of acceptable daily intake for humans

0-0.01 mg/kg bw

Estimate of acute reference dose

0.02 mg/kg bw

Studies that would provide information useful for continued evaluation of the compound

Further observations in humans

Summary of critical end-points for carbosulfan

RESIDUE AND ANALYTICAL ASPECTS

Carbosulfan is a broad-spectrum carbamate pesticide used to control insects, mites and nematodes by soil, foliar and seed treatment applications, mainly on potatoes, sugar beet, rice, maize and citrus. Carbofuran is the main metabolite of carbosulfan in plants and is itself a pesticide.

Carbosulfan was evaluated for residues under the Periodic Review Programme by the JMPR in 1997. The present evaluation of carbosulfan includes estimates for carbofuran resulting from the use of carbosulfan. The current definition of the carbosulfan residue for compliance with MRLs and for dietary risk assessment is "carbosulfan".

The carbofuran residue is defined as carbofuran + 3-hydroxycarbofuran for compliance with MRLs and carbofuran + 3-hydroxycarbofuran + conjugated 3-hydroxycarbofuran for dietary risk assessment.

The Meeting received information on metabolism in hens, methods of analysis, supervised trials conducted on potatoes, sugar beet, cotton, maize and rice, residues in food in commerce, and national MRLs

Animal metabolism

One metabolism study in hens was reported. The hens were dosed with either phenyl- or dibutylamine-labelled carbosulfan for 14 days at levels corresponding to approximately 0.5, 1.5 or 5 ppm in the diet. At each treatment level, a plateau of ¹⁴C residues in eggs was reached at day 5. For both labelled compounds the yolk contained higher ¹⁴C residues than the white.

The maximum ¹⁴C residues observed in egg yolk and white were 1.87 mg/kg and 0.119 mg/kg respectively at the dose of 5 ppm, and 0.18 mg/kg and 0.014 mg/kg at 0.5 ppm. Only dibutylamine was detected in yolk at 0.023 mg/kg after 9-12 days (4.3% of the TRR). Carbosulfan was less than 0.02 mg/kg.

The highest radioactive tissue residue from both labels was observed in liver. After seven days of depuration, all radioactive tissue residues were below 0.002 mg/kg.

With the phenyl-labelled compound, the major extractable residue found in the thigh muscle at day 0 was 3-hydroxycarbofuran. The 3-hydroxy-7-phenol was the major metabolite in liver. There were no detectable residues (<0.002 mg/kg equivalents) of carbosulfan or carbofuran in any tissue analysed.

A significant amount of radioactivity was found in the fat from the dibutylamine label. High ¹⁴C residues were observed in the liver (1.35 mg/kg equivalents) and fat (0.30 mg/kg equivalents). After 14 days of depuration all residues had decreased to less than 0.05 mg/kg except in fat (0.37 mg/kg) and skin.

Dibutylamine was the main metabolite in the extractable fraction of the thigh muscle (22.5 % of the TRR) and liver (39.6% of the TRR) at day 0. Essentially all the radioactive residue (>95% of the TRR) in the 14-day fat sample was isolated as fatty acid. Derivatization of this fraction with bromoacetophenone and isolation of the derivatised fatty acids indicated that the radiocarbon had been mainly incorporated into palmitic (33.3% of the TRR), oleic (37.0%), stearic (7.7%) and linoleic (6.2%) acids.

The metabolism of carbosulfan in hens begins with hydrolysis to the 7-phenol, carbofuran and dibutylamine. Further hydrolysis and oxidation give 3-hydroxycarbofuran, the 3-hydroxy-7-phenol, 3-keto-7-phenol, 3-ketocarbofuran, butylamine, substituted butanols and 5-hydroxycarbofuran. Metabolism studies in rats and goats evaluated by the 1997 JMPR show a common metabolic pathway.

Residue analysis

Analytical methods are available for the determination of carbosulfan, carbofuran, 3-hydroxycarbofuran, dibutylamine and phenolic metabolites in plant and animal products. Carbosulfan and carbofuran in vegetables are extracted with hexane/2-propanol or hexane/acetone and the partitioned extract is cleaned up on a Florisil or aminopropyl SPE cartridge. The compounds are determined by GC with NPD, GC/MS or GC/MS/MS detection. The LOQ ranges from 0.01 to 0.05 mg/kg.

In a method developed in 2000, carbosulfan and carbofuran are determined by HPLC using two post-column reactors, one with H₂SO₄ to hydrolyse carbosulfan to carbofuran and the other with o-phthalaldehyde + N,N-dimethyl-2-mercaptoethylamine to form a chromophore for fluorescence detection. The LOQ was 0.05 mg/kg.

The extraction of 3-hydroxycarbofuran in vegetables was with acid hydrolysis, and was followed by partition with dichloromethane and further clean-up on a Florisil cartridge. In another method, with an alumina clean-up, carbosulfan, carbofuran and hydroxycarbofuran were determined without acid hydrolysis.

Phenolic fractions are derivatized with pentafluorobenzyl bromide (PFBBr), and 3-hydroxy-7-phenols also by ethylation, before analysis. Dibutylamine fractions are derivatized with dansyl chloride. Both the phenolic and dibutylamine derivatives are determined by GC-MS with single ion monitoring.

Validations were provided for tobacco, potatoes, a leafy vegetable and cotton seed (LOQ 0.05 mg/kg).

Results from supervised residue trials

Potatoes. Ten trials were conducted in France with soil application of carbosulfan at the GAP rate (1.25 kg ai/ha). Residues were <0.01 (3), <0.03 (4), <0.05 and 0.02 (2) mg/kg carbosulfan. Six trials were conducted at 1.85 kg ai/ha

In 4 trials in Italy according to GAP (0.75 kg ai/ha soil treatment), carbosulfan residues were <0.05 mg/kg.

In 2 trials conducted in Japan at the GAP rate (1.8 kg ai/ha, soil treatment), residues were <0.005 mg/kg. Two other trials conducted in Japan at a higher rate gave the same results.

One trial conducted in the Philippines with foliar application at 0.3 kg/ha (GAP 0.2 kg ai/ha) gave residues of <0.05 mg/kg. One trial in Brazil according to GAP (0.24 kg ai/ha and 21 days PHI) also gave residues of <0.05 mg/kg, as did two trials at 0.48 kg ai/ha.

Sixteen trials complying with GAP using soil application gave residues of <0.005 (2), <0.01 (3), <0.03 (4), <0.05 (5) and 0.02 (2) mg/kg. Samples were also analysed for residues of carbofuran and 3-hydroxycarbofuran. No residues of 3-hydroxycarbofuran were found (<0.005, <0.01 or <0.05 mg/kg).

The Meeting estimated a maximum residue level of 0.05 mg/kg and an STMR of 0.03 mg/kg for carbosulfan in potato.

Residues of carbofuran + 3-hydroxycarbofuran were <0.005 (2), <0.01 (4), <0.05 (5), 0.02, 0.03, 0.06, 0.07 and 0.11 mg/kg.

The Meeting estimated a maximum residue level of 0.2 mg/kg, an STMR of 0.05 mg/kg and an HR of 0.11 mg/kg for carbofuran in potato.

Sugar beet. Field trials on sugar beet were reported from France (GAP 0.75-1 kg ai/ha, soil treatment), Belgium (GAP 0.75 kg ai/ha, soil treatment), Spain and Italy (0.6 kg ai/ha, soil treatment).

Thirteen trials conducted in France with soil treatment according to GAP gave carbosulfan residues of <0.05 (9), 0.06 (2), 0.15 and 0.18 mg/kg.

In two trials in Belgium according to GAP for soil treatment residues were <0.02 mg/kg. Four trials in Spain and Italy with soil application according to GAP gave residues of <0.05 mg/kg

Six trials in France, 2 in Switzerland and 1 in Hungary were conducted above the GAP rate.

Nineteen trials according to GAP with soil application gave carbosulfan residues of <0.02 (2), <0.05 (13), 0.06 (2), 0.15 and 0.18 mg/kg.

The Meeting estimated a maximum residue level of 0.3 mg/kg and an STMR of 0.05 mg/kg for carbosulfan in sugar beet.

Samples from the same trials were analysed for carbofuran and 3-hydroxycarbofuran. All residues were below the LOQ, except in one trial where the residue of 3-hydroxycarbofuran was 0.06 mg/kg. Residues of carbofuran + hydroxy-carbofuran were <0.05 (18) and 0.11 mg/kg.

The Meeting estimated a maximum residue level of 0.2 mg/kg and an STMR of 0.05 mg/kg for carbofuran in sugar beet.

Maize. Field trials with soil treatment on maize were reported from Belgium (GAP 0.6 kg ai/ha, 2 trials), France (GAP 0.5 to 0.75 kg ai/ha, 9 trials), Germany (no GAP for soil application, 3 trials) and Italy (0.5 kg ai/ha, 2 trials). In the eight trials according to GAP residues were <0.05 mg/kg. Residues in four other trials conducted at a higher rate (1.5 kg ai/ha) were at the same level. No residues of carbofuran or 3-hydroxycarbofuran were found in any of the trials (<0.05 mg/kg).

Field trials were conducted with seed treatment in the Philippines (GAP 5g ai/kg seed, 1 trial) and Brazil (GAP 0.5 to 0.7 kg ai/100 kg seed, 14 trials). Residues in grain from 9 trials according to GAP and in 6 trials at a higher rate in Brazil and the one in the Philippines below maximum GAP gave residues <0.01 or <0.05 mg/kg.

The Meeting agreed that soil application is the critical use and estimated a maximum residue level of 0.05* mg/kg and an STMR of 0 for both carbosulfan and carbofuran in maize grain.

Rice. Three trials with soil application in India complying with GAP (1 kg ai/ha, 37 days PHI) gave residues of <0.01 (2) and 0.02 mg/kg carbosulfan in grain. 3 other trials at a double rate gave residues of <0.01 to 0.03 mg/kg.

Of 4 trials in Korea with soil application, only one was according to GAP, giving residues of <0.02 mg/kg in husked rice.

In 8 trials in Japan with seedling treatment, 4 were according to GAP, giving carbosulfan residues in husked rice of <0.005 mg/kg. Four trials conducted at half or twice the rate gave the same results.

8 trials were carried out in China (GAP 0.75 kg ai/ha, 30 days PHI, foliar application) but the PHI was ³69 days. The residues were <0.002 mg/kg.

In 7 trials in Brazil with seed treatment within GAP (5g ai/kg seed), no residues occurred in grain (<0.01 or <0.05 mg/kg). 11 trials at a higher rate gave the same results.

In 7 trials in China above the GAP for seed treatment residues were also <0.01 mg/kg in husked rice.

Trials using soil application according to GAP were too few to support a recommendation.

Residues from the seed treatment trials according to GAP in Brazil were <0.01 (2) and <0.05 mg/kg (5).

With the support of the trials conducted at a higher rate in Brazil, the Meeting estimated a maximum residue level of 0.05* mg/kg and an STMR of 0 for carbosulfan in rice grain.

Two field trials according to GAP in Brazil gave residues of carbofuran and 3-hydroxycarbofuran of <0.01 mg/kg in grain. Residues in husked rice in 35 trials in China, Korea and Japan at a higher rate than the recommended GAP were all below the LOQs.

The residues resulting from the uses of carbosulfan gave residues covered by the uses of carbofuran in husked rice.

The Meeting recommended maintaining the recommendation of the 2002 JMPR for carbofuran of 0.1 mg/kg in husked rice.

Cotton seed. Twelve trials were carried out in Greece and Spain according to GAP (0.375 kg ai/ha, 2 applications, 28 days PHI, foliar application). The residues of carbosulfan, carbofuran and 3-hydroxycarbofuran were all <0.05 mg/kg.

In 5 trials in Australia according to GAP (0.5 to 1 kg ai/ha, foliar application), carbosulfan residues were <0.05 (4) and 0.03 mg/kg.

In 3 trials in Brazil complying with GAP (0.12 kg ai/ha, foliar application) residues of carbosulfan, carbofuran and 3-hydroxycarbofuran were all <0.01 (2) and <0.05 mg/kg.

In 2 trials carried out in Brazil using seed treatment according to GAP (7g ai/kg), residues were <0.05 (2) mg/kg.

Trials according to GAP with foliar treatment gave residues of <0.01 (2), <0.05 (17) and 0.03 mg/kg.

The Meeting estimated a maximum residue level and an STMR of 0.05 mg/kg for carbosulfan in cotton seed

Fourteen trials according to GAP gave residues of carbofuran + 3-hydroxycarbofuran of <0.01 (2) and <0.05 (12) mg/kg.

The residues resulting from the uses of carbofuran were at the same levels as those from the uses of carbosulfan in cotton seed. The Meeting confirmed the recommendation of the 2002 JMPR for carbofuran of 0.1 mg/kg in cotton seed.

Feed items

Sugar beet leaves and tops. Residues from trials according to GAP in Belgium, Spain, Italy and France were <0.02 (2) and <0.05 (17) mg/kg of carbosulfan. Trials at a double rate gave the same results.

As no residues are expected in sugar beet tops, even at higher rates, the residues, allowing for 23% dry matter (DM) (FAO Manual, 2002), would probably be below the LOQ.

The Meeting estimated a maximum residue level of 0.05* mg/kg and an STMR of 0 for carbosulfan in sugar beet leaves or tops.

Residues of carbofuran + 3-hydroxycarbofuran in the same trials were 0.05 (17), 0.10 and 0.13 mg/kg.

Allowing for 23% DM, the median and highest residues in sugar beet forage were 0.217 mg/kg and 0.56 mg/kg.

The Meeting estimated a maximum residue level of 0.7 mg/kg and an STMR of 0.217 mg/kg for carbofuran in sugar beet leaves or tops.

Maize forage (whole plant). In 2 trials in Brazil according to GAP (seed treatment) residues were <0.01 mg/kg. 13 trials conducted in Belgium, France, Germany and Italy according to GAP showed residues of <0.05 mg/kg in whole plant. In 4 trials at a higher rate the results were the same.

Residues of carbosulfan in trials according to GAP were <0.01 (2) and <0.05 (13) mg/kg.

Allowing for 40% DM, the median and the highest residue of carbosulfan in maize forage would be (<)0.13 mg/kg, but as no residues are expected in maize forage, even at higher rates, the residues allowing for 40% DM would probably be below the LOQ.

The Meeting estimated a maximum residue level of 0.05* mg/kg and an STMR of 0 for carbosulfan in maize forage on a dry weight basis.

Fifteen trials according to GAP gave residues of carbofuran + 3-hydroxycarbofuran of <0.01 (2), <0.05 (11), 0.11 and 0.14 mg/kg.

Allowing for 40% DM, the median and highest residues in maize forage were (<)0.13 mg/kg and 0.35 mg/kg respectively.

The Meeting estimated a maximum residue level of 0.5 mg/kg and an STMR of 0.13 mg/kg for carbofuran in maize forage, on a dry weight basis.

Rice straw. In 2 field trials conducted according to GAP in Brazil (seed treatment) residues were <0.01 mg/kg for carbosulfan, carbofuran and 3-hydroxycarbofuran. There were too few trials according to GAP to make a recommendation.

Processing

No information was provided.

Animal feeding studies

In one feeding study evaluated by the 1997 JMPR, dairy cows were dosed at 1, 3 and 50 ppm carbosulfan in the diet for 28 days. At 50 ppm residues were <0.05 mg/kg in kidney, liver and muscle, 0.012 mg/kg in milk and 0.076 mg/kg in fat. Except for one sample from 10 ppm (0.007 mg/kg of 3-hydroxycarbofuran), no residues were found from the lower feeding levels in any milk sample. No information was provided on the residues in fat at lower feeding levels.

Farm animal dietary burden

The Meeting estimated the farm animal dietary burden of carbosulfan from the residues in animal feeds resulting from its use.

Maximum farm animal burden of carbosulfan

STMR farm animal burden of carbosulfan

Residue levels in animal commodities

Cattle. No carbosulfan was detected in liver, kidney or meat of cattle at a 50 ppm feeding level which is over 200 times the estimated burden. Carbosulfan was present in fat and in milk (0.076 and 0.012 mg/kg) at this feeding level.

The Meeting agreed that it was unlikely that residues of carbosulfan would be detected in products from animals fed with commodities treated with this compound.

The Meeting estimated a maximum residue level of 0.05* mg/kg, an STMR of 0 and an HR of 0 in for carbosulfan in meat (fat) and edible offal of mammals, and a maximum residue level of 0.03* mg/kg and an STMR and HR of 0 for carbosulfan in milks.

Poultry. In a metabolism study in hens no residues of carbosulfan or the metabolites carbofuran and 3-hydroxycarbofuran were found at a feeding level of 0.5 ppm in tissues (<0.002 mg/kg). Residues in eggs were 0.18 mg/kg eq in yolks and 0.014 mg/kg in whites at a 5 ppm feeding level. In the yolk 85% of the radioactivity was due to unknown products of high molecular weight (>500). Residues of carbosulfan were <0.002 mg/kg.

The Meeting agreed that it was unlikely that residues of carbosulfan would be detected in products from animals fed with commodities treated with this compound.

The Meeting estimated a maximum residue level at the limit of quantification, 0.05* mg/kg, and an STMR and HR of 0 for carbosulfan in eggs, meat and offal of poultry

The farm animal burden estimated by the 2002 JMPR was based on a diet containing 80% of alfalfa fodder and there are few animal feed items.

The Meeting agreed to confirm the 1997 recommendations of 0.05* mg/kg for carbofuran in a range of animal commodities.

DIETARY RISK ASSESSMENT

Carbosulfan

Long-term intake

The ADI for carbosulfan is 0- 0.01 mg/kg body weight/day. International estimated daily intake (IEDI) was calculated for commodities for human consumption for which STMRs were estimated in this evaluation. The results are shown in Annex 3.

International Estimated Daily Intakes for the five GEMS/Food regional diets, based on estimated STMRs, ranged from 0 to 1% of the ADI. The Meeting concluded that the intake of residues of carbosulfan resulting from its uses that have been considered by the JMPR is unlikely to present a public heath concern.

Short-term intake

The International estimated short-term intakes (IESTI) for carbosulfan were calculated for commodities for which STMR and HR values were estimated in this evaluation and for which data on consumption (large portion and unit weight) were available. The results are shown in Annex 4.

The acute RfD for carbosulfan is 0.02 mg/kg. The IESTI represented 0 to 4% of the acute RfD for children and 0 to 2% of the acute RfD for the general population. The Meeting concluded that the short-term intake of residues of carbosulfan from uses on the commodities that have been considered by the JMPR is unlikely to present a public health concern.

Carbofuran

Long-term intake

Estimates of carbofuran residues arising from the use of carbosulfan, made at this Meeting, do not affect the assessment carried out at the 2002 JMPR for this compound.

Short-term intake

The International estimated short-term intakes (IESTI) for carbofuran were calculated for commodities for which STMR and HR values were estimated in this evaluation and for which data on consumption (large portion and unit weight) were available. The results are shown in Annex 4.

The acute RfD for carbofuran is 0.009 mg/kg. The IESTI represented 0 to 50% of the acute RfD for children and 0 to 20% of the acute RfD for the general population. The Meeting concluded that the short-term intake of residues of carbofuran from uses on the commodities that have been considered by the JMPR is unlikely to present a public health concern.