RESIDUE AND ANALYTICAL ASPECTS
Residue aspects of folpet were most recently reviewed in 1993 and 1994. The Meeting received information on metabolism, analytical methods, stability of samples during freezer storage, registered uses, data from supervised trials on fruit and vegetable crops, and processing studies.
The Meeting noted that folpet was scheduled for periodic review by the FAO Panel in 1998.
When the roots of tomato plants were treated with [carbonyl-14C] folpet the 14C was rapidly absorbed into the plants (85% within 1 day). After 11 days 90% of the absorbed 14C was in the tops. Folpet itself was a very minor constituent (<0.1-0.2%) of the residue within the plant. The main identified components were phthalimide, phthalamic acid and phthalic acid. Unidentified polar metabolites, possibly ring-hydroxylated phthalamic acid derivatives, accounted for 15-30% of the 14C in the tops.
When wheat was treated with [phenylene-14C] folpet at a rate equivalent to 1.6 kg ai/ha and harvested 43 and 54 days after the second treatment the levels of 14C were lower in the roots than in the straw or grain. Folpet was the major component of the residue in the straw (4.7 mg/kg) and grain (9.3 mg/kg) with the metabolites phthalic acid (4.3 mg/kg in straw and 6.4 mg/kg in grain) and phthalimide (1.5 mg/kg in straw and 3.1 mg/kg in grain) also significant constituents.
When Thomson Seedless grape vines were treated 3 times with [phenylene-14C] folpet at a rate equivalent to 1.5 kg ai/ha and the grapes harvested 25 days after the final treatment, surface rinsing removed 26% of the grape residue. Folpet itself constituted 27% of the residue in or on the grapes, and phthalic acid and phthalimide 5.8% and 11% respectively. An unidentified compound in the water-soluble fraction accounted for 41% of the residue. It was very polar and yielded phthalic acid on hydrolysis, so was likely to be a conjugate or conjugates of phthalic acid.
A small avocado tree was treated with 3 foliar applications equivalent to 3.4 kg ai/ha of [phenylene-14C] folpet and fruit were harvested at maturity 97 days after the final application. Very little residue was removed by rinsing the fruit, but most of it was extractable with ethyl acetate from the peel and pulp. The residues in or on the fruit were folpet 0.026 mg/kg, phthalimide 0.22 mg/kg and phthalic acid 4.5 mg/kg. Polar and other unidentified residues accounted for about 0.7 mg/kg. Folpet and phthalimide residues were mainly on the peel, but most of the phthalic acid residue was in the pulp.
The 1993 JMPR reviewed the Schlesinger analytical method for residues of folpet and phthalimide. The methods used in the supervised trials on apples, lettuce, melons, onions, strawberries and tomatoes were developed from the Schlesinger method. Folpet was determined in the cleaned up extract by GLC with an BCD. The recovery of folpet from various fortified commodities was commonly 70-100%, but with some excursions outside this range. In a total of 340 tests the mean and median recoveries were 87% and 86% respectively. The LOD was 0.05 mg/kg.
Folpet residues were shown to be stable during freezer storage for the intervals tested in apple juice (30 days), wet apple pomace (35 days), apples (149 days), cranberries (176 days), cucumbers (29 days), grape juice (36 days), lettuce (90 days), onions (41 days), tomato paste (30 days), tomato puree (31 days) and tomatoes (136 days).
Information was made available to the Meeting on registered uses of folpet and on supervised trials on apples, grapes, strawberries, onions, cucumbers, melons, tomatoes and lettuce. Relevant data evaluated in 1993 and 1994 were also reviewed where possible.
Folpet is registered in Argentina for use on apples with 3 applications of 3.6 kg ai/ha and harvest 10 days after the final application. Folpet residues in apples from 2 trials according to GAP were 1.4 and 2.6 mg/kg.
Canadian GAP permits folpet to be applied 8 times to apples at 0.8 kg ai/ha with harvest 7 days after the final application. In 4 trials where the use pattern corresponded to GAP the residues were 0.43, 0.65, 1.1 and 1.4 mg/kg.
Folpet residues from 2 trials on apples in Chile where the trial conditions corresponded to the registered use (2.0 kg ai/ha, 3 applications, 7 days PHI) were 2.0 and 3.7 mg/kg.
In a Hungarian trial which complied with GAP (8 applications of 1.6 kg ai/ha and a PHI of 10 days), a Swiss trial according to GAP (4 applications of 2.0 kg ai/ha and a PHI of 21 days), and a Spanish trial complying with GAP (10 applications of 1.9 kg ai/ha and a PHI of 10 days), the folpet residues were 8.0, 3.4, and 3.1 mg/kg respectively.
Folpet may be applied 8 times at 1.6 kg ai/ha to apples in Portugal with harvest 21 days after the final application. In a trial meeting these conditions the residue was 3.2 mg/kg. In a trial reported in 1993 folpet was applied 10 times at 1.3 kg ai/ha, which is within the acceptable range for evaluation, and the resulting residue after 21 days was 1.8 mg/kg
In France folpet may be used up to 11 times on apples at 1.0-1.2 kg ai/ha with harvest 14 days later. In 4 trials in France complying with GAP the residues were 0.9, 1.4, 1.4 and 1.8 mg/kg.
In summary, the folpet residues in apples from trials according to GAP were 1.4 and 2.6 mg/kg in Argentina, 0.43, 0.65, 1.1 and 1.4 mg/kg in Canada, 2.0 and 3.7 mg/kg in Chile, 8.0 mg/kg in Hungary, 3.4 mg/kg in Switzerland, 3.1 mg/kg in Spain, 1.8 and 3.2 mg/kg in Portugal, and 0.9, 1.4, 1.4 and 1.8 mg/kg in France. The residues in rank order (median underlined) in the 17 trials were 0.43, 0.65, 0.9, 1.1, 1.4, 1.4, 1.4, 1.4,1.8, 1.8, 2.0, 2.6, 3.1, 3.2, 3.4, 3.7 and 8.0 mg/kg.
The Meeting estimated a maximum residue level and an STMR of 10 mg/kg and 1.8 mg/kg respectively for apples.
The folpet residue in grapes was 1.6 mg/kg in a supervised trial that complied with GAP in Argentina (4 applications of 1.0 kg ai/ha and a PHI of 7 days). The residues were 2.6 and 3.0 mg/kg in 2 supervised trials in Chile according to GAP (2.0 kg ai/ha, 3 applications and 14 days PHI), and below the LOD, <0.05 mg/kg, in a Mexican trial in accordance with GAP (1.0 kg ai/ha, 7 applications and a PHI of 10 days).
Italian GAP permits 5 applications of folpet to grapes at 1.6 kg ai/ha with harvest 10 days after the final application. In an Italian trial according to GAP in 1996 and 2 Italian trials reported in 1993 where folpet was used 7 and 10 times at 1.5 kg ai/ha with a PHI of 10 days the folpet residues were 3.3, 0.58 and 0.75 mg/kg.
Four French trials (2 reported in 1993) were evaluated in terms of Italian GAP. The application rates were 1.5 and 1.6 kg ai/ha, with 7 and 8 applications and PHIs of 8 and 10 days, conditions which were acceptably close to GAP. The residues were 1.3, 2.2, 3.7 and 8.1 mg/kg.
In summary, folpet residues in grapes from trials according to GAP were 1.6 mg/kg in Argentina, 2.6 and 3.0 mg/kg in Chile, <0.05 mg/kg in Mexico, and 0.58, 0.75, 1.3, 2.2, 3.3, 3.7 an and 8.1 mg/kg in Italy and France. The residues in rank order (median underlined) in the 11 trials were <0.05, 0.58, 0.75, 1.3, 1.6, 2.2, 2.6, 3.0, 3.3, 3.7 and 8.1 mg/kg.
The Meeting estimated maximum residue and STMR levels for grapes of 10 mg/kg and 2.2 mg/kg respectively.
GAP in Mexico permits 4 applications of folpet to strawberries at 1.3 kg ai/ha with harvest 2 days after the final application, and in The Netherlands 2 applications of 1.4 kg ai/ha and a 14-day PHI. The residues in 3 Mexican and 3 Dutch trials complying with GAP were 1.6, 1.7 and 2.2 mg/kg, and 1.4, 1.6 and 1.9 mg/kg respectively.
The Meeting noted that the results of these 6 trials were in line with the current draft MRL for strawberry of 5 mg/kg, and decided that it would be preferable to estimate an STMR when all the information on residue trials and current GAP become available for the periodic review in 1998.
GAP for onions in Chile allows 3 applications of 2 kg ai/ha and in Mexico 4 applications at 1.5 kg ai/ha, both with harvest 7 days after the final application. Folpet residues in one Chilean and two 2 Mexican trials complying with GAP were 0.36, 0.41 and 0.41 mg/kg.
Two trials in Greece and four in Hungary according to national GAP gave residues of <0.05 (3), 0.07 and 0.21 mg/kg.
The folpet residues in onions in trials in Portugal (5.0 mg/kg) and Spain (2.5 mg/kg) were somewhat higher than in other European countries (<0.05-0.21 mg/kg), and probably related to the drip irrigation system used in Portugal and Spain, whereas sprinkler irrigation is used elsewhere.
In the trials in Greece, Hungary, Portugal and Spain the field sample was described as at least 2 kg consisting of 12 or more onions. The soil was removed mechanically by hand and the whole plant, including roots and foliage, was analysed. The Meeting was informed that this sampling procedure was based on a draft EU guideline, which is unfortunately in conflict with a long-established Codex procedure. Because the correct sample for bulb onions does not include roots or foliage the Meeting could not use the data, and the 3 trials in Chile and Mexico were insufficient to estimate a maximum residue level.
The folpet residue in cucumbers was 0.07 mg/kg in a Canadian trial according to Canadian GAP (8 applications of 1,0 kg ai/ha with a PHI of 7 days), and 0.11, 0.36, 0.56 and 0.70 mg/kg in four Mexican trials complying with national GAP (1.8 kg ai/ha with harvest after the last of 4 applications).
The Meeting noted that the current draft MRL for cucumbers is 0.5 mg/kg and concluded that it would be preferable to evaluate all the residue data in terms of relevant GAP at the periodic review in 1998.
In Greece folpet is registered for use on melons at 0.49 kg ai/ha with harvest 20 days after the final application (maximum 4). Folpet residues were below the LOD (<0.05 mg/kg) in melons in 4 Greek trials according to GAP and in 2 others where folpet was applied at twice the GAP rate.
Mexican GAP permits 6 applications at 1.8 kg ai/ha and harvest 7 days after the final application. The residues in 3 Mexican trials complying with GAP were 0.40, 0.89 and 2.2 mg/kg.
In two trials in Honduras according to GAP (4 applications of 0.64 kg ai/ha and a PHI of 3 days), the residues were 0.32 and 0.41 mg/kg, and in a Guatemalan trial according to GAP (6 applications of 0.48 kg ai/ha and a PHI of 3 days), the residue was 0.23 mg/kg.
In summary, folpet residues in melons from trials effectively according to GAP were <0.05 (6) in Greece, 0.40, 0.89 and 2.2 mg/kg in Mexico, 0.32 and 0.41 mg/kg in Honduras and 0.23 mg/kg in Guatemala. The residues in rank order in the 12 trials were <0.05 (6), 0.23, 0.32, 0.40, 0.41, 0.89 and 2.2 mg/kg.
As the residues in the Greek trials appear to belong to a different population from the others, the 6 trials in Mexico, Honduras and Guatemala were used to estimate an STMR.
The Meeting estimated maximum residue and STMR levels for folpet in melons of 3 mg/kg and 0.41 mg/kg respectively. The STMR in this case is for the whole melon because data were not available on residues in the edible portion.
GAP for tomatoes in Chile allows 7 applications of 1.7 kg ai/ha with a 7-day PHI, and in Mexico 5 applications at 2.0 kg ai/ha with a 2-day PHI. Folpet residues in one Chilean and 5 Mexican trials complying with GAP were 2.4 mg/kg and 0.45, 1.0, 1.3, 1.6 and 1.8 mg/kg respectively.
In Hungary folpet is registered for use on tomatoes at an application rate of 0.65 kg ai/ha with harvest 14 days after the final application (maximum of 3). In 4 Hungarian trials according to GAP and in 1 trial reported in 1993 with 5 applications at the GAP rate and PHI the residues were all below the LOD (<0.02 and <0.05 (4) mg/kg).
In one Italian and two Portuguese trials in compliance with Portuguese GAP (4 applications of 1.3 kg ai/ha and 7 days PHI) the residues were 0.34, 0.55 and 0.58 mg/kg. In a Spanish trial according to GAP (6 applications of 1.6 kg ai/ha and a 10-day PHI) the residue was 1.3 mg/kg.
In summary, folpet residues in tomatoes from trials according to GAP were 2.4 mg/kg in Chile, 0.45, 1.0, 1.3, 1.6 and 1.8 mg/kg in Mexico, 0.02 and 0.05 (4) mg/kg in Hungary, 0.55, 0.34 and 0.58 mg/kg in Portugal and Italy, and 1.3 mg/kg in Spain. The residues in rank order in the 15 trials were <0.02, <0.05 (4), 0.34, 0.45, 0.55, 0.58, 1.0, 1.3 (2), 1.6, 1.8 and 2.4 mg/kg.
The residues in the Hungarian trials appear to be in a different population from the others. The 10 trials from Chile, Portugal, Italy and Spain were used to estimate an STMR.
The Meeting estimated maximum residue and STMR levels for folpet in tomatoes of 3 mg/kg and 1.15 mg/kg respectively.
Folpet is registered in Mexico for 4 applications of 1.3 kg ai/ha to lettuce with harvest 7 days after the final application. Folpet residues were 4.5, 9.8 and 16 mg/kg in 3 Mexican trials on head lettuce with 5 applications at the GAP rate and PHI, and 22 mg/kg in one trial on leaf lettuce under the same conditions.
Folpet residues were not detected (<0.05 mg/kg) in head or leaf lettuce in 2 trials in Greece according to Greek GAP (4 applications of 0.61 kg ai/ha and 20 days PHI), except that only 3 applications were made to head lettuce. No residue was detected (<0.05 mg/kg) in leaf lettuce in a Spanish trial according to GAP (4 applications of 0.78 kg ai/ha and 21 days PHI).
In summary, folpet residues in head lettuce were 4.5, 9.8 and 16 mg/kg in Mexico and <0.05 mg/kg in Greece, and in leaf lettuce 22 mg/kg in Mexico, <0.05 mg/kg in Greece and <0.05 mg/kg in Spain. The data populations in Mexico and Europe appear to be different. There were too few results to make a recommendation.
Field-treated apples were processed to juice and wet pomace to simulate commercial practice as closely as possible. The process included an initial washing step which removed about 40% of the residue. The processing factors for the production of wet pomace and apple juice were 2.6 and 0.035 respectively.
The STMR-Ps for the processed apple commodities calculated from the processing factors and the STMR for apples (1.8 mg/kg) are wet apple pomace 4.7 mg/kg and apple juice 0.063 mg/kg.
Grapes were treated post-harvest by dipping bunches for 30 seconds in a vat containing folpet (1.25 kg ai/hl). The grapes were allowed to dry and then processed into raisins and juice. Because folpet is a surface residue it was considered valid to treat grapes in this way.
The treated grapes were dried in the sun until the moisture level reached 12-16%. After destemming, the dried grapes were rehydrated to 18-20% moisture in an incubator at 21°C to produce raisins. Juice was produced from treated grapes by crushing, enzyme treatment, heating and filtering.
Folpet residues were not detectable (<0.05 mg/kg) in the grape juice. The calculated processing factor for juice is <0.003. Folpet residues in the dried and hydrated raisins were higher than in the original grapes, with processing factors of 3.2 and 1.9 respectively.
The Meeting estimated a maximum residue level for folpet residues in dried grapes or raisins of 40 mg/kg after rounding up, from the processing factor of 3.2 and the maximum residue level estimated for grapes (10 mg/kg).
The STMR-P levels calculated from the processing factors and the STMR for grapes (2.2 mg/kg) are grape juice 0.0066 mg/kg, dried raisins 7.0 mg/kg, and hydrated raisins 4.2 mg/kg.
In 10 trials on grapes in Germany in 1993 residues of folpet were measured in the must and wine produced from treated grapes. The processing factors for folpet transfer from grapes to must ranged from 0 to 0.97, mean 0.29. Folpet was not detected (<0.05 mg/kg) in any wine sample, hence the processing factor for wine is 0. Phthalimide, a metabolite and breakdown product of folpet, was consistently present in both must and wine.
The STMR-P for must calculated from the mean processing factor and the STMR for grapes (2.2 mg/kg) is 0.64 mg/kg.
The Meeting noted that the use of folpet on grapes consistently results in phthalimide residues in wine at levels typically 25-50% of the folpet levels in the grapes. The metabolism study on grapes had shown the formation of a water-soluble conjugate of phthalic acid in grapes which also has the potential to reach the wine.
A tomato crop was treated 5 times with folpet at 2.2 kg ai/ha and harvested 7 days after the final application for processing. The tomatoes were treated in 0.5% sodium hydroxide and then vigorously washed before being processed to juice, puree and paste. Puree was produced from juice by evaporation, adjustment of salt and water levels, heating and canning. Paste was produced similarly, but with a higher salt level.
Folpet residues were not detected (<0.05 mg/kg) in tomato puree or paste produced from tomatoes containing 1.8 mg/kg of folpet. It is quite likely that the initial vigorous cleaning of the tomatoes would remove or destroy most of the folpet residues. The calculated processing factor for the transfer of folpet from tomatoes to purée and paste is <0.028, and the STMR-P calculated from the STMR for tomatoes of 1.15 mg/kg is 0.032 mg/kg.