4. Evaluation of data for acceptable daily intake (ADI) for humans, maximum residue levels and supervised trials median residues (STMRs)

4.1 Acephate (095)(R)**

R-residue and analytical aspects

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

RESIDUE AND ANALYTICAL ASPECTS

Acephate has been evaluated several times, first in 1976 and most recently in 1996. It was listed under the Periodic Review Programme by the 28th Session of the CCPR for residue review by the 2003 JMPR (ALINORM 97/24). The 2002 JMPR established an ADI and acute RfD for acephate of 0-0.01 mg/kg bw and 0.05 mg/kg bw respectively. The present Meeting received information on the metabolism and environmental fate of acephate, methods of residue analysis, freezer storage stability, national registered use patterns, supervised residue trials and national MRLs.

Some information on GAP, national MRLs and residue data was reported by the governments of Australia, Germany and The Netherlands.

Acephate is a broad-spectrum organophosphorus insecticide with uses on many crops.

The following abbreviations are used for the metabolites discussed below.

DMPT: O,S-dimethyl O-hydrogen phosphorothioate
SMPT: S-methyl O-hydrogen acetylphosphoramidothioate
OMAPAA: methyl hydrogen acetylphosphoramidate
SMPAA: S-methyl O-hydrogen phosphoramidothioate

Animal metabolism

Studies on lactating goats, quail and laying hens were reported to the present Meeting.

In the three goat studies when [S-methyl-¹⁴C]acephate either alone or in combination with [S-methyl-¹⁴C]methamidophos and/or with [carbonyl-¹⁴C]acephate was used, most of the ¹⁴C in the tissues was incorporated into natural products: proteins and amino acids in liver, kidney, muscle and milk, lipids in fat and milk, and lactose in milk. Acephate constituted a maximum of 47% of the ¹⁴C in the milk. 18-20 h after the last dose of [S-methyl-¹⁴C]acephate or [carbonyl-¹⁴C]acephate, the parent compound accounted for 4.2-4.8%, 14-26% and 22-26% of the ¹⁴C in the liver, kidney and muscle respectively but was not detected in the fat.

Only traces of acephate were detected in the tissues of quail 3 days after dosing with [S-methyl-¹⁴C]acephate, which is consistent with other observations that the metabolism of acephate is rapid. Acephate was a major component of the residue in egg whites and yolks, muscle and fat (maximum of 64% of the radiolabel in muscle, 62% in egg whites, 33% in yolks and 26% in the fat from laying hens dosed with [S-methyl-¹⁴C]- and [carbonyl-¹⁴C]acephate. Incorporation into lipids and proteins accounted for most of the ¹⁴C in yolk, liver and fat.

The metabolism of acephate proceeds by the hydrolysis of the ester/thioester and amide moieties to form SMPT, OMAPAA and methamidophos. Liberated carbon fragments enter the metabolic pool and are incorporated into natural products, principally proteins and lipids and, in the case of milk, lactose.

Plant metabolism

Studies on bean, cabbage and tomato seedlings, and on lettuce, cotton and bean plants were reported.

Acephate was the major component of the extracted ¹⁴C residue in bean, cabbage and tomato seedlings treated by either foliar application or stem injection with [S-methyl-¹⁴C]acephate. Small amounts of methamidophos were also detected. Residues of acephate are translocated and the pesticide is considered to be systemic.

20 days after the third foliar application to lettuce of [S-methyl-¹⁴C]acephate and [carbonyl-¹⁴C]acephate, the parent compound was the main identified component (45-53%) of the extracted ¹⁴C residue, and the metabolites were methamidophos (11%), SMPT (11-15%) and a metabolite tentatively identified as OMAPAA (29%). Similar results were obtained with beans harvested 14 days after three foliar applications of acephate with the same labels: acephate accounted for 62-74% of the ¹⁴C in the forage and 14-15% in the beans, and the metabolites were methamidophos (7.3-7.7% of the TRR), SMPT (6.5-14%) and OMAPAA (23-57%). Most of the remaining ¹⁴C was distributed in natural products (starch, protein, pectin, hemicellulose, cellulose).

In cotton harvested 21 days after three foliar applications of the same labels as above, ¹⁴C residues in the trash were predominantly acephate (40-41%) with smaller amounts of SMPT (17-29%) and OMAPAA (1-27%). Methamidophos was only a minor metabolite (<2% of the TRR). In contrast, acephate represented a relatively small fraction of the ¹⁴C in cotton seed meal and hulls (0.8-7.3%). OMAPAA (1-24% in hulls, 1-22% in meal) was the main metabolite with smaller amounts of SMPT (1-4.2%). Most of the ¹⁴C in cotton seed was incorporated into natural products.

In plants, acephate is metabolized by ester/thioester and amide hydrolysis reactions to form methamidophos, SMPT and OMAPAA as the main metabolites. Further metabolism results in the incorporation of acephate-derived fragments into natural plant products.

Environmental fate in soil

Information was provided on the soil adsorption of acephate and on its behaviour or fate during soil and solution photolysis, aerobic and anaerobic degradation in soil, column leaching of aged residues and field dissipation.

Acephate does not undergo significant direct photolysis on soil surfaces. In aqueous solution it is stable to hydrolysis except at high pH. At pH 9 about 40% of the initial ¹⁴C was present as acephate after 23 days.

The aerobic soil degradation of acephate was rapid with half-lives of £7 days. The main route of degradation appears to be microbial metabolism as only minimal degradation occurred in sterile soils and the degradation rate generally increased with both soil organic matter and moisture contents. The major degradation products were methamidophos, OMAPAA, DMPT, SMPT and SMPAA.

In field dissipation, the residues of acephate did not move down the soil profile and dissipation was rapid with half-lives of less than 3 days for both acephate and methamidophos.

In summary, acephate is not significantly degraded by hydrolysis, except in waters having high pH values. Photochemical transformation is expected to be a minor route of degradation. Degradation in field and in aquatic environments is rapid and acephate is not expected to persist in the environment.

Analytical methods

Samples in the field trials were analysed for acephate and methamidophos by solvent extraction (ethyl acetate or in the case of oily crops and fats acetonitrile/hexane), clean-up by solvent partition and/or silica column or gel permeation chromatography followed by GLC measurement with an FPD (phosphorus mode), NPD (nitrogen mode), thermionic or ion-selective MS detection. LOQs of 0.01-0.02 mg/kg for acephate and 0.01 mg/kg for methamidophos were reported for numerous commodities.

Stability of pesticide residues in stored analytical samples

The available data indicate that the combined residues of acephate and methamidophos are stable during frozen storage at -20°C in or on eggs for 6 months; cattle meat and milk for 7 months, or cattle kidney for 6 months; goat liver for 3 months; apple for 16 months; apple sauce and juice for 55 days; pinto beans for 15 months; snap beans for 15 months; Brussels sprouts for 9 months; celery for 12 months; maize grain and silage for 7 months; maize meal, flour and presscake for 2 months; cotton seed for 48 days; Bermuda grass forage and hay for 2 months; pasture grass for 9 months; lettuce for 17 months; pigeon peas for 14 months; bell peppers for 13 months; rice grain and straw for 17 months, and spearmint fresh and spent hay for 2 months.

Field-incurred residues were stable in tomato juice and purée and canned tomatoes when stored at ambient temperature (not specified) for up to 3 months.

Definition of the residue

A main metabolite of acephate in or on crops is methamidophos, which is a pesticide in its own right with its own MRLs. Analytical methods used for acephate can distinguish between acephate and methamidophos (i.e. they are not common moiety methods). Residues of methamidophos arising from the use of acephate must be reconciled with an MRL for compliance purposes. This could be achieved either by defining the residue of acephate as the sum of acephate and methamidophos or by establishing specific methamidophos MRLs for methamidophos residues arising from the use of acephate. In national systems the definition of the residue for acephate is generally acephate per se, and methamidophos residues resulting from the use of acephate are accounted for by separate MRLs.

For the estimation of dietary intake it is necessary to account for the residues of both acephate and methamidophos, and their relative toxicity must be taken into account. A conservative approach is to sum the residues after scaling the methamidophos residues for "potency" based on the ratio of the acephate to methamidophos maximum ADIs for STMR estimates and acute RfDs for HR estimates. The ratios are based on mass and do not require correction for molecular weight.

For acephate STMR estimation, residue = acephate + (2.5 × methamidophos)

For acephate HR estimation, residue = acephate + (5 × methamidophos)

The FAO Manual (page 51) states that "preferably no compound, metabolite or analyte should appear in more than one residue definition". The Meeting agreed that the acephate residue should be defined as acephate.

The log P_ow for acephate is -0.9 and this together with the animal metabolism and feeding studies indicates that acephate should not be classified as fat-soluble.

Definition of acephate residue

for compliance with MRLs: acephate
for estimation of dietary intake: acephate and methamidophos

The definitions apply to both plant and animal commodities.

Supervised trials

When evaluation of the supervised trial data leads to an estimated maximum residue level for acephate, it is also necessary to ensure that residues of methamidophos arising from the use of acephate are covered by a maximum residue level for methamidophos. As methamidophos is also under periodic review by the current Meeting residues of methamidophos arising from the use of acephate will be considered together with those from uses of methamidophos per se in the methamidophos sections of the report and the evaluations.

Supervised trials were reported on alfalfa, apples, artichokes, beans, broccoli, Brussels sprouts, cabbage, cauliflower, citrus fruits (grapefruit, lemons, oranges, mandarins), cotton, cucumbers, egg plants, hops, leeks, lettuce, peaches, pears, peppers, plums, potatoes, soya beans, sugar beet and tomatoes.

No information on trials or GAP was reported for tree tomatoes (current CXL 0.5 mg/kg) and the Meeting recommended withdrawal of the CXL.

As acephate residues in crops decrease relatively slowly the number of applications has a significant influence on the final residue. To account for the influence of multiple sprays, the Meeting decided that when an upper limit on the number of sprays was not specified by GAP, 2-3 applications would be the minimum number acceptable for estimating a maximum residue level.

In some cases untreated control samples contained residues of acephate and methamidophos. Trials were considered acceptable providing the residues in control samples were less than 10% of the residues in the treated crop.

Citrus fruits

Trials on citrus fruits were conducted in Argentina (no GAP), Brazil (GAP 0.039 kg ai/hl, PHI 21 days), Greece (no GAP), Japan (GAP 0.5-2.5 kg ai/ha, 0.03-0.06 kg ai/hl, PHI 30 days), New Zealand (GAP 0.078 kg ai/hl, PHI 14 days), South Africa (no GAP) and the USA (GAP 0.56-0.84 kg ai/ha to non-bearing trees).

Data were reported from supervised trials on grapefruit, lemons, mandarins, Natsudaidai and oranges, but only those on mandarins and Natsudaidai were conducted according to GAP.

In two trials in Japan on Natsudaidai residues of acephate were 0.1 and 3.0 mg/kg (0.01 and 0.33 mg/kg for methamidophos). The Meeting decided that this was not sufficient to estimate a maximum residue level. Fourteen trials in Japan on mandarins that approximated Japanese GAP showed acephate residues of 0.38, 0.4, 0.49, 0.68, 0.78, 0.85, 0.88, 0.98, 1.7, 1.7, 1.8, 1.8, 2.6 and 5.2 mg/kg, and methamidophos residues of 0.02, 0.03, 0.04, 0.05, 0.06, 0.08, 0.08, 0.09, 0.09, 0.1, 0.14, 0.15, 0.25 and 0.26 mg/kg. In a single trial in New Zealand on mandarins conducted according to GAP in that country the residue of acephate was 3.3 mg/kg and of methamidophos 0.29 mg/kg.

The residues of acephate and methamidophos, combined as explained above, for the purpose of estimating the STMR were 0.43, 0.48, 0.64, 0.78, 0.91, 1.1, 1.1, 1.2, 1.9, 2.1, 2.1, 2.2, 3.2 and 5.9 mg/kg on a whole fruit basis. The HR for dietary intake purposes is estimated to be 6.5 mg/kg.

The Meeting estimated a maximum residue level, STMR and HR for acephate in mandarins of 7, 1.15 and 6.5 mg/kg, all based on whole fruit as insufficient information was available to estimate residues in the edible portion.

Methamidophos residues in mandarins (0.02, 0.03, 0.04, 0.05, 0.06, 0.08, 0.08, 0.09, 0.09, 0.13, 0.14, 0.15, 0.25 and 0.26 mg/kg) are considered in the appraisal of methamidophos for the estimation of maximum residue levels.

Pome fruits

Trials on apples were conducted in Denmark (no GAP), France (GAP 0.06 kg ai/hl, PHI 21 days), Germany (no GAP), Greece (GAP 0.075 kg ai/hl, PHI 15 days), Italy (GAP 0.034-0.064 kg ai/hl, PHI 30 days), The Netherlands (no GAP), Spain (GAP apples 1.1 kg ai/ha, 0.075 kg ai/hl, PHI 14 days, pome fruit 0.038-0.11 kg ai/hl, PHI 21 days), Switzerland (no GAP), the USA (no GAP) and Yugoslavia (no GAP). Trials in The Netherlands and Germany were evaluated according to GAP in France.

In two trials in France which approximated French GAP residues of acephate were 3.7 and 4.2 mg/kg (methamidophos 0.22 and 0.28 mg/kg), and in two trials in The Netherlands and three in Germany, all matching French GAP, residues of acephate were 0.65, 1.5, 2.8, 3.2 and 3.6 mg/kg (methamidophos 0.04, 0.06, 0.13, 0.14 and 0.16 mg/kg). One trial in Italy (0.56 mg/kg, methamidophos <0.1 mg/kg) and two in Greece (0.35, 0.39 mg/kg, methamidophos 0.03, 0.04 mg/kg) complied with the GAP of the respective countries.

The Meeting considered that the residues of acephate on apples were all from the same population and that the data should be combined for estimating a maximum residue level and STMR. The residues of acephate in apples from trials according to GAP (n=10) were 0.35, 0.39, 0.56, 0.65, 1.5, 2.8, 3.2, 3.6, 3.7 and 4.2 mg/kg.

Trials on pears were conducted in France (GAP 0.06 kg ai/hl, PHI 21 days), Italy (GAP 0.034-0.064 kg ai/hl, PHI 30 days), South Africa (GAP 0.038 kg ai/hl, PHI 30 days) and Spain (GAP pears 1.2 kg ai/ha, 0.075 kg ai/hl, PHI 21 days, pome fruit 0.038-0.11 kg ai/hl, PHI 21 days).

In one trial in Italy and two in Spain conducted according to the GAP of those countries acephate residues were 0.26, 0.28 and 0.55 mg/kg, with methamidophos residues of 0.03, 0.06 and <0.1 mg/kg.

The Meeting agreed to combine the data for the residues of acephate on apples and pears to estimate a maximum residue level and STMR. The residues from trials according to GAP (n=13) were 0.26, 0.28, 0.35, 0.39, 0.55, 0.56, 0.65, 1.5, 2.8, 3.2, 3.6, 3.7 and 4.2 mg/kg.

The appropriately scaled and totalled residues of acephate and methamidophos for estimating the STMR (median underlined) were 0.34, 0.44, 0.45, 0.53, 0.7, 0.75, 0.81, 1.7, 3.1, 3.6, 4.1, 4.3 and 4.8 mg/kg. The HR is estimated to be 5.4 mg/kg.

The Meeting estimated a maximum residue level, STMR and HR for acephate in pome fruits of 7, 0.81 and 5.4 mg/kg.

Methamidophos residues in apples and pears from the use of acephate (n=13) were <0.1, <0.1, 0.03, 0.03, 0.04, 0.04, 0.06, 0.06, 0.13, 0.14, 0.16, 0.22 and 0.28 mg/kg and are further considered in the methamidophos section of the report.

Stone fruits

Trials on peaches were conducted in France (GAP 0.06 kg ai/hl, PHI 21 days), Greece (GAP 0.038-0.075 kg ai/hl, PHI 15 days), Italy (GAP 0.034-0.064 kg ai/hl, PHI 21 days) and Spain (GAP peaches 2.8 kg ai/ha, 0.075 kg ai/hl, PHI 21 days, stone fruit 0.038-0.11 kg ai/hl, PHI 21 days).

In one trial in Italy and one in Spain conducted approximately according to Spanish GAP residues were <0.02 and 0.1 mg/kg (methamidophos 0.02 and 0.03 mg/kg).

Two peach trials each in Greece, Spain and France, conducting according to GAP in Greece, gave acephate residues of 0.46, 0.46, 0.63, 1.0, 1.4 and 1.4 mg/kg (methamidophos residues 0.09, 0.1, 0.16, 0.22, 0.28 and 0.35 mg/kg).

The appropriately adjusted and totalled residues of acephate and methamidophos for estimating the STMR (median underlined) were 0.69, 0.71, 1.0, 1.7, 2.0 and 2.3 mg/kg. The HR is 3.2 mg/kg.

The Meeting considered that the residues of acephate and methamidophos in peaches and nectarines treated at the same rate would be similar and noted that GAP in Greece was for stone fruit which includes both peaches and nectarines. The Meeting estimated maximum residue level, STMR and HR values of 2, 1.35 and 3.2 mg/kg respectively for acephate in peaches and nectarines.

Residues of methamidophos in peaches from the use of acephate were 0.09, 0.1, 0.16, 0.22, 0.28 and 0.35 mg/kg. These residues are considered in the appraisal of methamidophos for the estimation of maximum residue levels.

Trials on plums were conducted in France (no GAP), Germany (no GAP), Italy (GAP 0.034-0.064 kg ai/hl, PHI 21 days), South Africa (GAP 0.038 kg ai/hl, PHI 28 days) and the UK (no GAP).

In a single trial in South Africa conducted according to South African GAP for plums residues were 0.08 mg/kg (acephate) and <0.02 mg/kg (methamidophos).

The Meeting considered that a single trial on plums was inadequate to estimate a maximum residue level.

Leeks. Trials on leeks were conducted in France (no GAP), Germany (no GAP) and The Netherlands (no GAP). As no GAP was available the trials were not evaluated further.

Brassica vegetables

Trials on broccoli were reported from Australia (GAP 0.78-0.98 kg ai/ha, 0.075-0.098 kg ai/hl, PHI 14 days), Brazil (GAP 0.075 kg ai/hl, PHI 14 days), Canada (no GAP but cauliflower 0.56-0.83 kg ai/ha, PHI 28 days), France (no GAP), Japan (GAP 0.075-0.5 kg ai/ha, PHI 14 days), Spain (GAP 1.1 kg ai/ha, 0.11 kg ai/hl, PHI 14 days) and the USA (no GAP but cauliflower 0.56-1.3 kg ai/ha, PHI 14 days).

A single trial on broccoli in Australia complied with Australian GAP and showed a residue of 0.12 mg/kg (methamidophos 0.08 mg/kg). One trial in Brazil matched the GAP of that country, with an acephate residue of 0.2 mg/kg. Two trials in France and two in Spain assessed against the GAP of Spain showed residues of 0.05, 0.30, 0.34 and 1.2 mg/kg (methamidophos 0.03, 0.09, 0.10 and 0.33 mg/kg).

Trials on cauliflower were reported from Australia (GAP 0.78-0.98 kg ai/ha, 0.075-0.098 kg ai/hl, PHI 3 days), Brazil (GAP 0.075 kg ai/hl, PHI 14 days), France (no GAP), Germany (no GAP), Italy (GAP 0.034-0.064 kg ai/hl, PHI 21 days) and The Netherlands (GAP 0.75 kg ai/ha, PHI 14 days).

One trial conducted according to GAP for cauliflower was reported from Australia (1.4 mg/kg acephate, 0.20 mg/kg methamidophos), and one from Brazil (0.1 mg/kg acephate) matched the GAP of that country.

In eight trials in The Netherlands conducted according to GAP acephate residues were <0.01, 0.02, 0.03, 0.06, 0.07, 0.08, 0.1, and 0.11 mg/kg, with methamidophos residues <0.01 (5), 0.01 (2) and 0.03 mg/kg.

Because acephate is a systemic pesticide the Meeting decided that the residue data for broccoli and cauliflower could be used as mutual support for the estimation of a maximum residue level for flowerhead brassicas. The results of the trials on broccoli and cauliflower in rank order (n=16) were <0.01, 0.02, 0.03, 0.05, 0.06, 0.07, 0.08, 0.1, 0.1, 0.11, 0.12, 0.2, 0.3, 0.34, 1.2 and 1.4 mg/kg (methamidophos <0.01(5), 0.01(2), 0.03(2), 0.08, 0.09, 0.10, 0.2 and 0.33 mg/kg).

The calculated total residues of acephate and methamidophos for estimating the STMR (median underlined) were <0.05, <0.06, <0.09, <0.1, 0.11, 0.13, 0.13, 0.19, 0.32, 0.53, 0.59, 1.9, 1.9 and 2.0 mg/kg. The HR is 2.85 mg/kg. The Meeting estimated a maximum residue level, STMR and HR of 2, 0.16 and 2.85 mg/kg respectively for flowerhead brassicas.

Residues of methamidophos in broccoli and cauliflower arising from the use of acephate (n=14) were <0.01 (5), 0.01 (2), 0.03 (2), 0.08, 0.09, 0.10, 0.2 and 0.33 mg/kg. They are considered in the appraisal of methamidophos for the estimation of a maximum residue level.

Trials on Brussels sprouts were reported from Australia (GAP 0.75-0.98 kg ai/ha, 0.075-0.098 kg ai/hl, PHI 3 days), Belgium (no GAP), Germany (no GAP), The Netherlands (GAP 0.75 kg ai/ha, PHI 28 days), South Africa (no GAP), the UK (no GAP) and the USA (GAP 0.56-1.3 kg ai/ha, maximum 2.2 kg ai/ha/season, PHI 14 days).

Two trials on Brussels sprouts in Australia matched GAP with residues of 1.5 and 12 mg/kg (methamidophos 0.11 and 1.0 mg/kg).

Trials on head cabbage were reported from Australia (GAP 0.78-0.98 kg ai/ha, 0.075-0.098 kg ai/hl, PHI 3 days), Brazil (GAP 0.075 kg ai/hl, PHI 14 days), Canada (GAP 0.56-0.83 kg ai/ha, PHI 28 days), France (GAP 0.075 kg ai/hl, PHI 7 days), Germany (no GAP), Japan (GAP 0.3-1 kg ai/ha, 0.03-0.05 kg ai/hl, PHI 7 days), The Netherlands (GAP 0.75 kg ai/ha, PHI 14 days), South Africa (GAP 0.23-0.38 kg ai/ha, PHI 3 days), the UK (no GAP) and the USA (no GAP).

One trial according to GAP for cabbage was conducted in Australia (22 and 1.5 mg/kg for acephate and methamidophos respectively). In two trials in France complying with GAP residues of acephate were 0.06 and 0.87 mg/kg (methamidophos <0.01 and 0.09 mg/kg).

The Meeting considered the number of trials on Brussels sprouts and cabbage that complied with GAP were inadequate for estimating a maximum residue level and recommended withdrawal of the existing CXL of 2 mg/kg for head cabbage.

Cucumbers. Trials were reported from France (no GAP), Italy (GAP 0.034-0.064 kg ai/hl, PHI 21 days), Puerto Rico (no GAP), Spain (GAP 1.7 kg ai/ha, 0.038-0.11, PHI 21 days) and the USA (no GAP).

Acephate residues in 2 indoor trials in Italy matching the GAP (± 30%) of Spain were 0.14 and 0.31 mg/kg (methamidophos <0.05 and 0.07 mg/kg). One field trial in Spain (acephate 1.9 mg/kg, methamidophos 0.19 mg/kg) also matched GAP in that country. The Meeting considered the number of trials inadequate to estimate a maximum residue level for cucumber.

Egg plant. Trials were reported from France (no GAP), Italy (GAP 0.034-0.064 kg ai/hl, PHI 21 days) and Spain (GAP 0.038-0.11 kg ai/hl, PHI 14 days).

Acephate residues in 3 trials in France and Spain matching the GAP (± 30%) of Spain were 0.09, 0.22 and 0.51 mg/kg (methamidophos 0.01, 0.05 and 0.07 mg/kg). The Meeting considered the number of trials inadequate to estimate a maximum residue level for egg plant.

Tomatoes. Trials were reported from Australia (GAP 0.75-0.98 kg ai/ha, 0.075-0.098 kg ai/hl, PHI 3 days), Brazil (GAP 0.075 kg ai/hl, PHI 7 days), Canada (seedling drench), France (GAP 0.075 kg ai/hl, PHI 3 days), Italy (GAP 0.034-0.064 kg ai/hl, PHI 21 days), Japan (GAP 0.5-1.0 kg ai/ha, 0.025-0.05 kg ai/hl, PHI 1 day), Spain (GAP 0.038-0.11 kg ai/hl, PHI 14 days) and the USA (no GAP).

Acephate is registered in Spain for use on tomatoes at 0.11 kg ai/hl with harvest permitted 14 days after the last application. In three trials in Spain matching GAP acephate residues were 0.05, 0.08 and 0.18 mg/kg (0.03, 0.05 and 0.11 mg/kg for methamidophos); in one trial in France and two in Italy also matching Spanish GAP ± 30% residues were 0.08, 0.14 and 0.33 mg/kg (methamidophos 0.03, 0.05 and 0.15 mg/kg), in a single trial in Brazil according to GAP <0.05 mg/kg and in a single trial in Australia also according to GAP 1.8 mg/kg (0.5 mg/kg methamidophos). The Meeting considered that the trials in Brazil and Australia were in different residue populations from those in France, Italy and Spain and should not be combined to estimate a maximum residue level. Residues of acephate in tomatoes in rank order (n=6) were 0.05, 0.08, 0.08, 0.14, 0.18 and 0.33 mg/kg. The Meeting considered the database to be insufficient to estimate a maximum residue level for tomatoes and recommended withdrawal of the existing CXL of 1 mg/kg.

Peppers. Trials were reported from Canada (GAP sweet peppers, 0.83 kg ai/ha, PHI 7 days), France (no GAP), Italy (GAP 0.034-0.064 kg ai/hl, PHI 21 days), Spain (GAP 2.25 kg ai/ha, 0.038-0.11 kg ai/hl, PHI 14 days) and the USA (GAP bell peppers 0.28-1.3 kg ai/ha, maximum 2.2 kg ai/ha/season, PHI 7 days; non-bell, 0.56 kg ai/ha, maximum 1.1 kg ai/ha/season, PHI 7 days).

In one trial in Canada on sweet peppers according to Canadian GAP acephate residues were 3.7 mg/kg (methamidophos 1.6 mg/kg). Acephate residues in two trials in Italy and one in Spain (indoor crop) approximating the GAP of Spain were 0.84, 1.1 and 2.9 mg/kg (methamidophos 0.25, 0.25 and 0.29 mg/kg), in three trials in Spain approximating the GAP of Italy 0.03, 1.5 and 2.2 mg/kg (0.05, 0.24 and 0.34 mg/kg for methamidophos) in crops grown indoors, and in two trials in France (one indoor) according to GAP in Italy 0.34 mg/kg indoor (0.22 mg/kg methamidophos) and 1.0 mg/kg in the field (0.35 mg/kg methamidophos).

Residues of acephate in indoor-grown sweet peppers (n=5) were 0.03, 0.34, 1.5, 2.2 and 2.9 mg/kg (methamidophos 0.05, 0.22, 0.24, 0.25 and 0.34 mg/kg), and in field-grown (n=4) 0.84, 1.0, 1.1 and 3.7 mg/kg (methamidophos 0.25, 0.29, 0.35 and 1.6 mg/kg).

The Meeting considered the residues in indoor and field sweet peppers could be combined for the purposes of estimating a maximum residue level. Residues in sweet peppers in rank order, median underlined, (n=9) were 0.03, 0.34, 0.84, 1.0, 1.1, 1.5, 2.2, 2.9 and 3.7 mg/kg. The appropriately scaled and totalled residues of acephate and methamidophos for estimating the STMR (median underlined) were 0.16, 0.89, 1.6, 1.7, 1.9, 2.1, 3.1, 3.5 and 7.7 mg/kg. The HR is 11.7 mg/kg. The Meeting estimated a maximum residue level, STMR and HR for acephate in peppers of 5 mg/kg, 1.9 mg/kg and 11.7 mg/kg respectively.

Methamidophos residues were 0.05, 0.22, 0.24, 0.25, 0.25, 0.29, 0.34, 0.35 and 1.6 mg/kg and are considered in the appraisal of methamidophos for the estimation of maximum residue levels.

Lettuce. Trials were reported from Belgium (no GAP), Canada (GAP head lettuce, 0.56-0.83 kg ai/ha, PHI 7 days), France (GAP 0.075 kg ai/hl, PHI 14 days) and Germany (no GAP).

In one trial in Canada and two in France approximating national GAP acephate residues in head lettuce were 0.28, 0.67 and 1.1 mg/kg respectively (methamidophos 0.03, 0.06 and 0.09 mg/kg). The Meeting considered the number of trials inadequate to estimate a maximum residue level and recommended withdrawal of the existing CXL of 5 mg/kg for head lettuce.

Beans. Field trials on common beans (snap, green and French) were reported from Canada (no GAP), France (no GAP), Germany (no GAP), Italy (GAP green beans 0.034-0.064 kg ai/hl, PHI 21 days), Spain (GAP 1.1 kg ai/ha, 0.11 kg ai/hl, maximum 2 sprays, PHI 14 days) and the USA (GAP 0.28-1.3 kg ai/ha, maximum 2.2 kg ai/ha/season, PHI 14 days).

Acephate residues in green (French) beans in 2 trials in Italy (0.92 and 0.96 mg/kg) and five in Spain (0.06, 0.07, 0.72, 1.2 and 2.9 mg/kg) approximating the GAP of Spain were 0.06, 0.07, 0.72, 0.92, 0.96, 1.2 and 2.9 mg/kg (methamidophos 0.01, 0.04, 0.15, 0.19, 0.34, 0.45 and 0.54 mg/kg).

Acephate residues in green (snap) beans in a single trial in the USA approximating US GAP were 0.39 mg/kg (methamidophos 0.15 mg/kg).

Residues of acephate in green beans in rank order (n=8) were 0.06, 0.07, 0.39, 0.72, 0.92, 0.96, 1.2 and 2.9 mg/kg. The appropriately scaled and totalled residues of acephate and methamidophos for estimating the STMR (median underlined) were 0.1, 0.11, 0.77, 1.3, 1.4, 1.8, 2.1 and 4.3 mg/kg. The calculated HR is 5.6 mg/kg. The Meeting estimated a maximum residue level, STMR and HR for acephate in beans, except broad bean and soya bean, of 5 mg/kg, 1.35 mg/kg and 5.6 mg/kg respectively.

Residues of methamidophos in beans in rank order, median underlined, (n=8) were 0.01, 0.04, 0.15, 0.15, 0.19, 0.34, 0.45 and 0.54 mg/kg. These residues are considered in the appraisal of methamidophos for the estimation of maximum residue levels.

Beans (dry). Field trials were reported from the USA on dry beans, including lima beans, red kidney beans and Navy beans but none of these were conducted according to GAP and the trials were not considered further.

Soya beans. Field trials were reported from the USA and assessed against the GAP of Mexico (0.5-1.1 kg ai/ha, PHI 14 days). Acephate residues in seven trials approximating GAP were <0.02, <0.02, 0.03, 0.03, 0.03, 0.14 and 0.17 mg/kg (methamidophos <0.01, <0.01, <0.01, <0.01, 0.02, 0.06 and 0.06 mg/kg).

Residues of acephate and methamidophos adjusted and totalled for estimating the STMR and HR (median underlined) were 0.045, 0.045, 0.055, 0.055, 0.08, 0.29 and 0.32 mg/kg. The HR is 0.47 mg/kg. The Meeting estimated a maximum residue level, STMR and HR for acephate in soya bean (dry) of 0.3 mg/kg, 0.055 mg/kg and 0.47 mg/kg respectively. The maximum residue level is recommended to replace the existing CXL of 0.5 mg/kg for soya bean (dry).

Residues of methamidophos in soya beans in rank order, median underlined, (n=7) were <0.01, <0.01, <0.01, <0.01, 0.02, 0.06 and 0.06 mg/kg. These residues are considered in the appraisal of methamidophos for the estimation of maximum residue levels.

Potatoes. Field trials were reported from Canada (GAP 0.56-0.83 kg ai/ha, PHI 21 days), France (no GAP), Italy (GAP 0.34-0.63 kg ai/ha, PHI 21 days), the UK (no GAP) and the USA (no GAP).

In one trial in France approximating the GAP of Italy acephate residues in potatoes were <0.02 mg/kg (methamidophos <0.01 mg/kg). The Meeting considered that one trial was inadequate to estimate a maximum residue level for potatoes and recommended the withdrawal of the existing CXL (0.5 mg/kg).

Sugar beet. Field trials were reported from France (GAP 0.5 kg ai/ha, PHI 21 days), Italy (GAP 0.34-0.63 kg ai/ha, PHI 21 days) and the UK (no GAP). As none of the trials matched GAP they were not evaluated further. The Meeting recommended the withdrawal of the existing CXLs for sugar beet (0.1 mg/kg) and sugar beet leaves or tops (10 mg/kg).

Globe artichokes. Trials conducted in France (GAP 0.075 kg ai/hl, PHI 14 days) and Italy (GAP 0.034-0.064 kg ai/hl, PHI 21 days) were reported.

In three French trials approximating French GAP acephate residues were 0.54, 1.3 and 1.6 mg/kg (methamidophos 0.08, 0.12 and 0.13 mg/kg), and in four trials according to GAP in Italy 0.08, 0.08, 0.08 and <0.1 mg/kg (methamidophos 0.02, 0.02, 0.04 and 0.08 mg/kg).

The Meeting decided that the residues in the trials in France and Italy were from different populations and should not be combined to estimate a maximum residue level, HR or STMR. The Meeting considered the number of trials in France inadequate for the purpose and decided to use the trials in Italy to estimate a maximum residue level. Residues of acephate and methamidophos, adjusted and totalled for estimating the STMR and HR (median underlined) were 0.13, 0.13, 0.18 and 0.3 mg/kg. The HR is 0.5 mg/kg.

The Meeting estimated a maximum residue level, STMR and HR for acephate in globe artichokes of 0.3 mg/kg, 0.155 mg/kg and 0.5 mg/kg.

The residues of methamidophos were 0.02, 0.02, 0.04 and 0.08 mg/kg. These residues are considered in the appraisal of methamidophos for the estimation of maximum residue levels.

Alfalfa. Trials in the USA (no GAP) were reported. As none of the trials matched GAP they were not evaluated further. The Meeting recommended the withdrawal of the existing CXL of 10 mg/kg for alfalfa forage (green).

Hops. Trials conducted in France (no GAP), Germany (no GAP), the UK (no GAP) and the USA (no GAP) were reported. As none of the trials matched GAP they were not evaluated further.

Processing

The Meeting received reports of processing studies for acephate in citrus fruits (oranges, lemons and grapefruit), apples, tomatoes, beans, potatoes and soya beans, investigating the effects of washing and further processing on incurred residues of acephate and methamidophos in a range of processed fractions.

No data were provided on the processing of mandarins. In the three citrus studies from field trials in the USA the data were sufficient for the Meeting to derive mean citrus processing factors of 0.34 (juice) and 0.61 (dry pulp) for acephate and 0.4 (juice) and 1.66 (dry pulp) for methamidophos.

Processing factors for apple juice, sauce, and wet pomace were derived from two field trials in the USA where initial acephate residues in the fruit were 0.46-1.0 mg/kg. For juice, processing factors were 1.0 for acephate and for methamidophos, and for wet pomace 0.98 and 1.35 respectively. The Meeting noted that washing did not significantly reduce residues of either compound in fruit treated 118-day before harvest and that residues of acephate in apple sauce were about half those in the raw fruit.

Studies on the effects of washing, cooking and/or canning on residues of acephate and methamidophos in common beans in the USA and France were evaluated, and the Meeting noted a slight reduction in residues in washed beans. Cooking resulted in a reduction of acephate (mean processing factor of 0.5) and methamidophos (mean processing factor of 0.83).

The results of processing trials in the USA in 1978 with the production of soya bean meal, hulls and crude oil were reported in summary form. Residues in the crude oil were below the reported limits of quantification except in one analysis, where acephate residues (0.03 mg/kg) were half those measured in the fresh beans. Processing factors estimated by the Meeting for acephate were 0.69 for meal, 7.15 for hulls, and <0.425 for crude oil, and for methamidophos 2.0, 4.5 and <0.5 respectively.

The Meeting noted that in a study on globe artichokes reported in summary, there was a significant reduction in residues in cooked artichokes.

Farm animal dietary burdens

The Meeting estimated the farm animal dietary burdens of acephate residues using the diets in Appendix IX of the FAO Manual. The calculation from the maximum residue levels and STMRs in the feed provides the dietary burdens suitable for estimating maximum residue levels and STMRs respectively in animal commodities. In the case of acephate, the animal diet consists of commodities that are blended and the dietary burden is therefore calculated only from STMRs. This results in the same dietary burden for both maximum residue level and STMR estimation in animal commodities. The dry matter (DM) content is taken as 100% where maximum residue levels and STMRs are already expressed on the dry weight. The figures in parentheses are for methamidophos.

The acephate and (methamidophos) dietary burdens for animal commodity maximum residue level and STMR estimation (residue levels in animal feeds expressed on a dry weight basis) are beef cattle 2.2 (0.083) ppm, dairy cattle 1.1 (0.0422) ppm and poultry 0.0067 (0.0022) ppm.

Farm animal feeding studies

The Meeting received information on residues in animal tissues and milk when dairy cows were dosed after the morning milking by capsule with mixtures of acephate and methamidophos in a ratio of 5:1, specifically chosen to reflect typical ratios observed in crop field trials, for 30 days, equivalent to 3:0.6, 10:2 and 30:6 ppm in the diet. Residues in the milk reached a plateau within 7 days and were always higher in the evening sample. Average residues of the parent compound in morning and evening milk collected from day 7 through to day 30 for the 10:2 ppm dose group were 0.062 and 0.19 mg/kg respectively, and returned to below the LOQ within two days of the end of dosing. Tissue residues in single animals slaughtered after 21 days of dosing were <0.02 (<0.01) mg/kg in liver, 0.03 (<0.01) mg/kg in heart, 0.03 (<0.01) mg/kg in kidney, 0.03 (<0.01) mg/kg in muscle and <0.02 (<0.01) mg/kg in fat for the 3:0.6 ppm dose group, and respectively <0.02 (<0.01) mg/kg, 0.10 (0.01) mg/kg, 0.21 (0.01) mg/kg 0.08 (<0.01) mg/kg) and 0.03 (<0.01) mg/kg for the 10:2 ppm dose group, and 0.08 (<0.01) mg/kg, 0.32 (0.06) mg/kg, 0.57 (0.05) mg/kg, 0.28 (0.04) mg/kg) and 0.13 (0.02) mg/kg for the 30:6 ppm dose group. Within 6 days of dosing ceasing, residues in the tissues were all below the LOQ.

In another study with dairy cows the dose was split into two and administered after the morning and after the evening milking. The capsules contained mixtures of acephate and methamidophos in a ratio of 5:1 at rates nominally equivalent to 15:3, 30:6 and 60:12 ppm in the diet. Residues in the milk reached a plateau by day 4 at 0.15 (0.01), 0.33 (0.02) and 0.85 (0.06) mg/kg for the three groups. The residues in the milk were below the LOQ within two days of the end of dosing for the 15:3 and 30:6 ppm groups and 0.07 (<0.01) mg/kg for the 60:12 ppm group. Maximum residues in the tissues in three animals slaughtered after 28 days were 0.02 (<0.01) mg/kg in the liver, 0.11 (0.01) mg/kg in the heart, 0.26 (0.02) mg/kg in the kidney, 0.12 (<0.01) mg/kg in muscle and 0.10 (<0.01) mg/kg in fat for the 15:3 ppm group, 0.04 (<0.01) mg/kg, 0.16 (0.02) mg/kg, 0.40 (0.04) mg/kg, 0.21 (0.01) mg/kg and 0.15 (<0.01) mg/kg for the 30:6 ppm group, and 0.15 (0.02) mg/kg, 0.40 (0.04) mg/kg, 0.85 (0.07) mg/kg and 0.40 (0.03) mg/kg, 0.40 (<0.01) mg/kg respectively for the 60:12 ppm group. 3 days after dosing ceased, residues in all tissues were below the LOQ in all groups.

The Meeting also received information on residues in the tissues of pigs fed a ration containing acephate and methamidophos for 30 days at rates of 3:0.6, 10:2 and 30:6 ppm in the diet. Maximum residues at 3:0.6 ppm were <0.02 (<0.01) mg/kg in the liver, 0.05 (<0.01) mg/kg in the heart, 0.04 (<0.01) mg/kg in the kidney, 0.05 (<0.01) mg/kg in muscle, <0.02 (<0.01) mg/kg in fat and 0.04 (<0.01) mg/kg in brain. Residues in all tissues were below the LOQ within a day of end of dosing.

In a trial on laying hens fed a diet containing acephate at 3 ppm for up to 92 days, residues were below the LOQ in the tissues and eggs. At higher feeding levels, maximum acephate and (methamidophos) residues in eggs were 0.09 (0.006) mg/kg from a 10 ppm feeding level and 0.19 (0.016) mg/kg at 30 ppm, and in tissues were below the LOQ in fat, kidney and liver, and 0.01 (0.008) mg/kg and 0.12 (0.046) mg/kg in muscle from the 10 and 30 ppm groups respectively.

Similar results were obtained when quail were fed diets incorporating acephate at 10 and 30 ppm for up to 148 days. Maximum residues in the eggs were 0.19 (0.007) mg/kg and 0.34 (0.014) mg/kg in the 10 and 30 ppm groups respectively. In liver and kidney they were below the LOQ, in fat 0.06 (0.014) and 0.04 (<0.001) mg/kg, and in muscle 0.01 (<0.001) and 0.04 (<0.001) mg/kg at the two feeding levels.

Maximum residue levels in animal commodities

The maximum/STMR dietary burdens for beef and dairy cattle are 2.2 (0.083) and 1.1 (0.042) mg/kg respectively, so the levels of residues in tissues and milk can be obtained by extrapolation from the highest residues in tissues at the 3 ppm feeding level and the mean residue in milk at the 15 ppm level (in the second study where cows were dosed in the morning and evening). The maximum acephate and (methamidophos) residues expected are <0.02 (<0.01) mg/kg in liver, 0.022 (<0.01) mg/kg in fat, 0.022 (<0.01) mg/kg in muscle and 0.022 (<0.01) mg/kg in kidney, and the mean residue in milk is 0.011 (0.00014) mg/kg. As the dietary burden for STMR estimation is the same as for maximum residue level estimation the STMRs and HRs can be calculated from the above values. Essentially no residues of methamidophos are expected in tissues or milk so the STMRs and HRs for dietary intake estimation are the estimated acephate residues.

¹ Values in parentheses are estimated dietary burdens

² Values in square brackets are actual feeding levels in the feeding studies

³ Residue values in parentheses in italics are extrapolated from the residues and feeding levels in the feeding studies to the dietary burdens. High is the highest individual tissue residue, and mean the mean milk residue in the relevant feeding group.

The maximum dietary burden for pigs is 0.008 (0.003) ppm, based on the feeding of soya beans at 25% of the total diet. The residues of both acephate and methamidophos in all tissues are expected to be <0.01 mg/kg at this level.

The Meeting estimated maximum residue levels for meat (from mammals other than marine mammals) 0.05 mg/kg, edible offal (mammalian) 0.05 mg/kg, and milks 0.02 mg/kg. The estimates are recommended to replace the existing CXLs of 0.1 mg/kg for cattle fat and meat, pig fat and meat and milks.

The maximum dietary burden for poultry is 0.0067 (0.0022) ppm. The levels of acephate and methamidophos residues in all tissues and eggs are expected to be <0.01 mg/kg at this level.

The Meeting estimated maximum residue levels for poultry meat 0.01 (*) mg/kg, poultry offal 0.01 (*) mg/kg and eggs 0.01 (*) mg/kg. As no residues are expected at the maximum feeding level for poultry, the STMRs for poultry meat, edible offal and eggs are zero.

DIETARY RISK ASSESSMENT

The Meeting considered how best to approach the dietary risk assessment of mixed residues of acephate and methamidophos and decided that an appropriately conservative approach would be to calculate the sum of the acephate and methamidophos residues after scaling the methamidophos residues to account for the difference in toxicity. The relevant factors for chronic and short-term intake were derived from the ratios of the acephate and methamidophos maximum ADI and acute RfD values and are 2.5 and 5 respectively. Dietary intake estimates for the combined adjusted residues were compared with the acephate maximum ADI and acute RfD.

Long-term intake

The evaluation of acephate has resulted in estimates of maximum residue levels and STMRs for raw and processed commodities. Consumption data were available for 22 raw or processed food commodities and were used in the dietary intake calculation. The results are shown in Annex 3.

The International Estimated Daily Intakes for the 5 GEMS/Food regional diets, based on estimated STMRs were in the range 2-20% of the maximum ADI of 0.01 mg/kg bw (Annex 3). The Meeting concluded that the long-term intake of residues of acephate from uses that have been considered by the JMPR is unlikely to present a public health concern

Short-term intake

The international estimated short-term intake (IESTI) for acephate (including any contribution from the presence of methamidophos residues) was calculated for the raw or processed food commodities for which HRs were estimated and for which consumption data were available. Where group maximum residue levels were estimated the IESTI was calculated for all commodities within the group for which consumption data were available. The results are shown in Annex 4.

The IESTI varied from 0 to 260% of the acute RfD (0.05 mg/kg bw) for the general population, and from 0 to 630% for children aged 6 years or less. The short-term intakes from pome fruit, mandarins, cauliflower and sweet peppers were 140-260% of the acute RfD for the general population, and from pome fruit, mandarins, peaches, nectarines, beans, broccoli, cauliflower and peppers 190-630% for children. The information provided to the Meeting precluded a conclusion that the acute dietary intake from these commodities would be below the acute RfD.

The Meeting concluded that the short-term intake of residues of acephate from uses that have been considered by the JMPR is unlikely to present a public health concern, with the exception of those from pome fruit, mandarins, peaches, nectarines, beans except broad beans and soya beans, broccoli, cauliflower and peppers.

4.2 Carbendazim (072)/thiophanate-methyl (077)(R)

R-residue and analytical aspects

RESIDUES AND ANALYTICAL ASPECTS

Carbendazim and its related compounds benomyl and thiophanate-methyl were evaluated by the 1998 JMPR under the CCPR Periodic Review Programme. The Meeting recommended MRLs (expressed as carbendazim) for barley, barley straw and fodder, cucumber, gherkin, pome fruits, rape seed and tomato on the basis of carbendazim residue data; for beans (dry), garden peas (succulent seeds), grapes, pome fruits and wheat on the basis of thiophanate-methyl residue data; for banana, Brussels sprouts, carrot, cattle meat, chicken fat, edible offal (mammalian), eggs, milks, oranges, peach, pineapple, plums (including prunes), pome fruit, poultry meat, rice, rice straw and fodder and wheat straw and fodder on the basis of benomyl residue data.

The 1998 JMPR recommended the withdrawal of numerous MRLs, including those for apricot, asparagus, avocado, berries and other small fruits, broad bean (green pods and immature seeds), celery, cherries, coffee beans, common bean (pods and immature seeds), egg plant, hops, head lettuce, mango, melons, mushrooms, nectarine, bulb onion, peanut, peanut fodder, peppers, potato, sugar beet, sugar beet leaves or tops, tree nuts and winter squash.

The present Meeting received information on GAP and national MRLs for carbendazim and thiophanate-methyl from the governments of Germany and The Netherlands. The thiophanate-methyl manufacturer reported US GAP (with labels), analytical methods, information on the stability of residues in stored analytical samples and new US supervised residue trials on cherries, summer squash, snap beans, soya beans, sugar beet and peanuts. The government of Thailand provided information on carbendazim use patterns and reported supervised trials on asparagus, mangoes and peppers. Information on GAP, national MRLs and residues of carbendazim from post-harvest trials on mangoes was reported by the government of Australia.

Analytical methods

The Meeting received descriptions and validation data for analytical methods for thiophanate-methyl and carbendazim. The methods rely on HPLC with UV detection and LC/MS/MS, and achieve LOQs of 0.01-0.05 mg/kg in crops.

Stability of pesticide residues in stored analytical samples

The Meeting received information on the stability of thiophanate-methyl and carbendazim residues in various crops (fruits, fruiting vegetables, leafy vegetables, roots, pulses, and cereal grains). The residues were generally stable for the duration of the tests.

Definition of the residue

The 1998 JMPR defined the residues (for compliance with MRLs and dietary intake calculations) arising from the use of

- benomyl as "sum of benomyl and carbendazim, expressed as carbendazim"

- carbendazim as "carbendazim"

- thiophanate-methyl as "sum of thiophanate-methyl and carbendazim, expressed as carbendazim".

At the 34th Session of the CCPR (2002), the Committee agreed to change the definition of the residue to "sum of benomyl, carbendazim and thiophanate-methyl, expressed as carbendazim".

All the following residues are expressed as carbendazim.

Results of supervised trials on crops

Cherries. Thiophanate-methyl is registered in the USA for use on cherries 1-3 times at a rate of 0.78-1.2 kg ai/ha with a 1-day PHI. In eight trials in four states in 1996, with five applications at 1.2 kg ai/ha and 0.08-0.13 kg ai/hl for ground and 1.5-2.5 kg ai/hl for aerial application and harvest at one day, the residues (sum of thiophanate-methyl and carbendazim, expressed as carbendazim) were 0.38, 0.53, 0.60, 0.81, 1.5, 2.4, 2.7 and 9.1 mg/kg.

The Meeting estimated a maximum residue level of 10 mg/kg, an STMR of 1.16 mg/kg and an HR of 9.1 mg/kg for carbendazim residues in cherries.

Mangoes. Carbendazim is registered in Thailand for foliar use on mangoes several times at a rate of 1.5 kg ai/ha and a spray concentration of 0.03 kg ai/hl with a PHI of 7 days. In 5 trials conducted in 2001 and 2002 in Thailand in accordance with GAP (6 x 1.5 kg ai/ha, 0.03 kg ai/hl, PHI 6-7 days), the residues were 0.70, 0.71, 0.72, 0.72 and 1.1 mg/kg in fruits without stones. The results could not be evaluated because the ratio of the weight of skin and flesh to whole fruit was not reported.

Post-harvest dipping of mangoes in carbendazim is registered in Australia with a dip concentration of 0.05 kg ai/hl. Harvested fruit were dipped at a concentration of 0.05 kg ai/hl. The dip temperature was 52°C and the fruit were dipped for 5 minutes before removal and air-drying. Whole fruits were weighed and the stones then separated from skin and pulp. The peels, pulp and stones were weighed separately and their weight percentages calculated. Residues in whole fruit were 1.2, 1.3, 1.6, 1.9, 3.0 and 3.1 mg/kg and in the pulp (edible portion) 0.21, 0.29, 0.4, 0.5 and 1.7 mg/kg.

The Meeting estimated a maximum residue level of 5 mg/kg, an STMR of 0.4 mg/kg and an HR of 1.7 mg/kg for residues in mango.

Summer squash. Thiophanate-methyl is registered in the USA for use on summer squash several times at a rate of 0.2-0.39 kg ai/ha (PHI not stated). In ten trials in eight states in 1991, with eight applications at 0.38-0.40 kg ai/ha and harvest at one day, the residues (sum of thiophanate-methyl and carbendazim, expressed as carbendazim) were <0.08, <0.08, 0.08, 0.08, 0.09, 0.10, 0.12, 0.12, 0.14 and 0.32 mg/kg.

The Meeting estimated a maximum residue level of 0.5 mg/kg, an STMR of 0.095 mg/kg and an HR of 0.32 mg/kg for residues in summer squash.

Chili peppers. Carbendazim is registered in Thailand for use on vegetables at a rate of 0.25-0.50 kg ai/ha with a PHI of 5 days. In 5 trials conducted on chili peppers in 2000-2002 in Thailand in accordance with GAP (4 x 0.5 kg ai/ha, PHI 5 days), the residues were 0.55, 0.63, 0.78, 0.87 and 0.98 mg/kg.

The Meeting estimated a maximum residue level of 2 mg/kg, an STMR of 0.78 mg/kg and an HR of 0.98 mg/kg for residues in chili peppers.

Common bean (pods and/or immature seeds). Thiophanate-methyl is registered in the USA for use on beans 1-2 times at a rate of 0.78-1.6 kg ai/ha with a PHI of 14 days for snap beans and 28 days for lima beans. In eleven trials in nine states in 1990, with two applications at 1.6 kg ai/ha and harvest at 14 days, the residues (sum of thiophanate-methyl and carbendazim, expressed as carbendazim) were <0.08 (6), 0.09, 0.14, 0.16, 0.22 and 0.45 mg/kg.

The Meeting estimated a maximum residue level of 0.5 mg/kg, an STMR of 0.08 mg/kg and an HR of 0.45 mg/kg for residues in common bean (pods and/or immature seeds).

Soya bean (dry). Thiophanate-methyl is registered in the USA for use on soya beans twice at a rate of 0.39-0.78 kg ai/ha (PHI not stated). The second application must be not later than 14 days when beans become visible in the pod. In twelve trials in twelve states in 1990, with three applications at 0.64-0.85 kg ai/ha and harvest at 14 days, the residues (sum of thiophanate-methyl and carbendazim, expressed as carbendazim) were <0.08 (10), 0.25 and 0.31 mg/kg.

The Meeting estimated a maximum residue level of 0.5 mg/kg and an STMR 0.08 mg/kg for residues in soya bean (dry).

Sugar beet. Thiophanate-methyl is registered in the USA for use on sugar beet several times at a rate of 0.39-0.78 kg ai/ha with a PHI of 21 days. In eleven trials in seven states in 1997, with seed treatment and three foliar applications at 0.78-0.81 kg ai/ha and harvest at 21 days, the residues (sum of thiophanate-methyl and carbendazim, expressed as carbendazim) were <0.08 (11) mg/kg.

The Meeting estimated a maximum residue level of 0.1* mg/kg, an STMR of 0.08 mg/kg and an HR of 0.08 mg/kg for sugar beet.

Asparagus. Carbendazim is registered in Thailand for use on asparagus at a rate of 0.38 kg ai/ha with a PHI of 5 days. In 4 trials conducted in 1995-2001 in Thailand in accordance with GAP (4-5 × 0.38 kg ai/ha, PHI 5 days), the residues were <0.01, 0.05, 0.08 and 0.09 mg/kg.

The Meeting estimated a maximum residue level of 0.2 mg/kg, an STMR of 0.065 mg/kg and an HR of 0.09 mg/kg for residues of carbendazim in asparagus.

Peanuts. Thiophanate-methyl is registered in the USA for use on peanuts several times at a rate of 0.39 kg ai/ha with a PHI of 14 days. Ten trials with six applications at 0.39 kg ai/ha were carried out in five states in 1991. Peanuts were harvested according to normal commercial practices: the plants were inverted at a 14-day PHI, the remaining crops were allowed to dry for 0-7 days in the field, then separate in-shell nut and hay samples were taken. The concentrations of residues (sum of thiophanate-methyl and carbendazim, expressed as carbendazim) in the kernels were <0.08 (10) mg/kg.

The Meeting estimated a maximum residue level of 0.1* mg/kg and an STMR of 0.08 mg/kg for residues in peanut.

Soya bean fodder. The residues (sum of thiophanate-methyl and carbendazim, expressed as carbendazim) in soya bean hay in the US trials on soya beans described above were <0.3, <0.3, 0.88, 0.95, 2.1, 2.6, 3.3, 3.8, 4.4, 4.8, 5.3 and 9.5 mg/kg.

The Meeting noted a label restriction against feeding ("Do not graze or feed treated vines or hay to livestock") and did not estimate a maximum residue level. The previous recommendation (withdrawal of the Codex MRL) was confirmed.

Snap bean vines. Thiophanate-methyl is registered in the USA for use on beans once or twice at a rate of 0.78-1.6 kg ai/ha with a PHI of 14 days for snap beans. In eleven trials in nine states in 1990, with two applications at 1.6 kg ai/ha and harvest at 14 days, the residues (sum of thiophanate-methyl and carbendazim, expressed as carbendazim) in vines were <0.08, 0.62, 0.65, 2.0, 2.6, 2.7, 3.2, 4.0, 7.3, 8.1 and 11 mg/kg.

The Meeting noted that snap bean forage or fodder is not mentioned as a feed item in the FAO Manual (Appendix IX) and did not estimate a maximum residue level.

Peanut fodder. The residues (sum of thiophanate-methyl and carbendazim, expressed as carbendazim) in peanut hay in the US peanut trials described above were <0.8 (6), 0.91, 1.1, 1.6 and 2.1 mg/kg (fresh weight).

Allowing for the standard 85% dry matter content of peanut hay (FAO Manual, p. 148), the Meeting estimated a maximum residue level and an STMR (dry weight) for residues in peanut fodder of 3 and 0.94 mg/kg.

Sugar beet leaves or tops. The residues (sum of thiophanate-methyl and carbendazim, expressed as carbendazim) in the leaves and tops from the US trials on sugar beet described above were 0.13, 0.16, 0.22, 0.24, 0.31, 0.33, 0.52, 0.69, 0.72, 0.84 and 2.2 mg/kg (fresh weight).

Allowing for the standard 23% dry matter in sugar beet tops (FAO Manual, p. 147), the Meeting estimated a maximum residue level and an STMR (dry weight) of 10 and 1.4 mg/kg for residues in sugar beet leaves or tops.

Dietary burdens in farm animals

The 1998 JMPR estimated dietary burdens (calculated as benomyl) of 17, 18 and 2 mg/kg for dairy cattle, beef cattle and poultry respectively, based on residues in the feed items wet citrus pulp, wet tomato pomace, raisin culls and raisin waste (JMPR residue evaluation 1998, p. 159).

The current Meeting estimated the dietary burden of carbendazim/thiophanate-methyl residues (expressed as carbendazim) in farm animals on the basis of the diets listed in Appendix IX of the FAO Manual. Calculation from MRLs and HRs provides the levels in feed for estimating MRLs for animal commodities, while calculation from STMRs in feed is suitable for estimating STMRs for animal commodities. The dry matter is taken as 100% when MRLs and STMRs are already expressed on the dry weight. In addition to the new residue data for sugar beet leaves or tops and peanut hay the Meeting took into consideration the feed items for which maximum residue levels and STMRs were estimated by the 1998 JMPR.

Maximum dietary burden

¹ estimated by 1998 JMPR (residue evaluation p. 159): 2 mg/kg as benomyl, equivalent to 1.3 mg/kg as carbendazim

² maximum residue estimated by 1998 JMPR (residue evaluation p. 159)

³ recommendation by 1998 JMPR

⁴ estimated by 1998 JMPR (residue evaluation p. 159): 2 mg/kg as benomyl, equivalent to 8.6 mg/kg as carbendazim

STMR dietary burden

¹ basis: STMR for benomyl in pome fruit estimated by 1998 JMPR: 0.6 mg/kg expressed as carbendazim

² estimated by 1998 JMPR

³ basis: STMR for benomyl in oranges 0.325 mg/kg expressed as carbendazim estimated by 1998 JMPR. Calculation as described for MRL dietary burden in 1998 JMPR residue evaluation p. 159 (0.325 x 91/21= 1.408)

The dietary burdens on a dry weight basis for MRL and STMR estimation respectively, are 6.9 and 1.1 mg/kg for beef cattle, 6.3 and 1.2 mg/kg for dairy cattle and 1.4 and 0.04 for poultry (expressed as carbendazim) or, expressed as benomyl, 10.5 and 1.7 mg/kg for beef cattle, 9.6 and 1.8 mg/kg for dairy cattle and 2.1 and 0.06 for poultry. The new dietary burden calculation is the same order as that of the 1998 JMPR.

Because the benomyl and carbendazim feeding studies reported to the 1998 Meeting showed a "nil residue situation" in animal commodities, the 1998 JMPR recommended MRLs at the LOQ of 0.05* mg/kg and estimated STMRs of 0 for cattle meat, chicken fat, edible offal (mammalian), eggs, milks and poultry meat. The Meeting confirmed the previous recommendations.

DIETARY RISK ASSESSMENT

Long-term intake

The residues of benomyl, carbendazim and thiophanate-methyl are all expressed as carbendazim which has the lowest ADI (0-0.03 mg/kg bw/day). The International Estimated Daily Intakes (IEDI) for carbendazim, based on the STMRs estimated for 33 commodities by the 1998 and 2003 JMPRs, for the five GEMS/Food regional diets were in the range of 1-4% of the ADI (Annex 3). The Meeting concluded that the long-term intake of residues of carbendazim resulting from the uses considered by the JMPR is unlikely to present a public health concern.

Short-term intake

The International Estimated Short Term Intake (IESTI) for carbendazim was calculated for 31 food commodities for which maximum residue levels were estimated by the JMPR in 1998 and 2003 and for which consumption data were available. These results are shown in Annex 4. The Meeting concluded that an acute RfD may be necessary, but as it has not yet been established the acute risk assessment for carbendazim could not be finalized.