PESTICIDE RESIDUES IN FOOD - 1981 Sponsored jointly by FAO and WHO EVALUATIONS 1981 Food and Agriculture Organization of the United Nations Rome FAO PLANT PRODUCTION AND PROTECTION PAPER 42 pesticide residues in food: 1981 evaluations the monographs data and recommendations of the joint meeting of the FAO panel of experts on pesticide residues in food and the environment and the WHO expert group on pesticide residues Geneva, 23 November-2 December 1981 FOOD AND AGRICULTURE ORGANIZATION OF THE UNITED NATIONS Rome 1982 CHINOMETHIONAT Explanation Under the name of oxythioquinox, chinomethionat was first evaluated by the JMPR in 1968.* At that time, no ADI was established as a no-effect level could not be deduced from the long-term studies performed in rats. Animals at the lowest level of treatment (10 ppm) (in the 1974 monograph this dose was misleadingly stated to be 10 mg/kg) showed liver hypertrophy. On the basis of additional information reviewed by the JMPR in 1974, a temporary ADI of 0.003 mg/kg bw was allocated (no-effect level in a long-term study in rats: 12 ppm). At that meeting, the submission, by 1977, of the results of studies to identify and evaluate the toxicity of metabolites was requested. Furthermore, the presentation of the following information was considered desirable: 1. Results of studies on the relationship between observed liver enlargement and reduced microsomal enzyme activity. 2. Results of studies on metabolism in non-rodent species. 3. Observations in humans. For the 1977 JMPR, only some new metabolic data were submitted. The temporary ADI, established in 1974, was extended and the submissions before July 1981, of the results of the following investigations was requested: 1. studies on the identity and relative toxicity of metabolites. 2. An additional carcinogenicity study in another species, in view of the hepatic toxicity observed in rodents. As in 1974, observations on humans were declared desirable. The requested studies were not available for evaluation by the 1981 JMPR, but the Meeting was informed that a long-term study in mice was in progress and should be available by 1985. A 12-month dog study is also in progress. Chinomethionat was evaluated by the 1968, 1974 and 1977 Joint Meetings and a number of temporary maximum residue limits were recommended. * See Annex II for FAO and WHO documentation. Some additional data on residues in treated and rotational crops on the fate of residues in animals and on environmental behaviour have been provided to the Joint Meeting for evaluation. The results of experiments are discussed in the present evaluation. DATA FOR THE ESTIMATION OF ACCEPTABLE DAILY INTAKE TOXICOLOGICAL STUDIES Special studies on mutagenicity in bacteria Chinomethionat was tested with Bacillus subtilis (strains M45 and H17) over the range of 20 to 2 000 µg/plate in the rec-assay, as well as with Escherichia coli (strain WP2 hcr) and Salmonella typhimurium (strains TA 1535, 100, 1537, 1538 and 98) over the range of 1 to 5 000 µg/plate for reverse mutations. The latter studies were performed both in the presence and absence of appropriate activation systems derived from rats following induction by Arochlor 1254. In none of these assays were signs of mutagenicity detected. In one study performed with strains TA 100, 1537 and 98 (3.15 to 315 µg/plate), it was noted that the test substance precipitated in the culture medium. It is therefore questionable whether the negative results of these tests can be interpreted in a dose-related manner. The lack of mutagenicity in bacteria appears to be proven only for the dissolved fraction of chinomethionat and for its soluble impurities. Special studies on embryotoxicity and teratogenicity Three groups of 15 rabbits (Himalayan strain) each received 13 daily oral doses of 10, 20 or 100 mg/kg of chinomethionat between days 6 and 18 of gestation. A group of equal size, given the vehicle only without the test substance, served as control. On day 29 of gestation the dams were sacrificed and the foetuses removed by caesarean section. Examination of the offspring by standard methods and the evaluation of the results gave no indication of teratogenicity. On the other hand, in the group treated with 100 mg/kg of chinomethionat, a significant decrease in both the number and size of foetuses was found. In this group, pronounced signs of maternal toxicity (e.g. diarrhoea, reduced feed intake, loss of weight) were also observed, No difference could, however, be detected between the two lower dose groups (10 and 30 mg/kg) and the controls. It is concluded that embryotoxicity at the 100 mg/kg dose level is only secondary and merely the consequence of the toxicity of chinomethionat to the dams. Eye and dermal irritancy of chinomethionat The left eye of 9 New Zealand white rabbits was treated with 100 mg chinomethionat per animal. After forty-five seconds, the treated eyes of 3 rabbits were rinsed with 200 ml lukewarm water each. No ocular changes were detected in these animals. The eyes of the remaining 6 rabbits were not washed. As appraised by the method of Draize, 2 of the 6 animals showed symptoms of severe eye irritation. Four shaven test sites (on the size and the back), 2 of which were abraded per animal, were exposed for 24 h to 0.5 mg of chinomethional (moistened with physiological saline). Appraisal 24 h and 72 h following the application of the test substance revealed no signs of dermal irritation. RESIDUES IN FOOD USE PATTERN In addition to the use patterns given in previous evaluations, the registered use on cucumber in Japan was provided. Chinomethionat is used up to 0.0125% against mildew and 0.025% against spider mites on cucumber, which is equivalent to 0.25 mg a.i./ha and 0.5 mg a.i./ha respectively. RESIDUES RESULTING FROM SUPERVISED TRIALS Almond Supervised trials were carried out in California by applying chinomethionat as a foliar spray to almond trees at a rate of 1.7 kg/ha. In one experiment the samples were taken 57 days post-treatment. Kernel, shells and hulls were analysed, and they contained residues of <0.02 mg/kg, <0.02 mg/kg and 0.21-0.28 mg/kg, respectively. In the other study hulls taken from various positions on the trees at day 0 contained 2.7 mg/kg, 3.8 mg/kg and 8 mg/kg chinomethionat in the top, middle and bottom portions, respectively. Cucumber Supervised trials were carried out on different varieties of cucumber in the Federal Republic of Germany (Bayer 1975) and in Japan (Nikon Tokushu Noyaku Seizo KK 1971). Chinomethionat was applied at a rate of 0.075 to 0.75 kg/ha 1 to 10 times, most frequently at intervals of 5 to 7 days. The results are summarized in Table 1. TABLE 1. Residues of chinomethionat in cucumber Application Residues (mg/kg) at intervals (days) after Country Year No. Rate last application (kg a.i./ha) Formulation 0 1 3 4 to 5 7 10 Federal 1976 8 0.075 25 WP <0.02 <0.02 Republic 1976 8 0.075 25 WP <0.02 <0.02 of Germany 1975 8 2x0.075+2x 0.125+4x 25 WP 0.07 0.05 <0.02 0.25 3 to 5 days apart 1975 8 4x0.075+0.125 +3x0.25 25 WP 0.025 0.011 0.012 0.007 3 to 5 days apart 1976 8 0.125 6 to 7 days apart 25 WP 0.07 0.04 0.08 0.15 1976 8 0.15 1 25 WF 0.02 0.06 0.04 5 to 8 days apart Japan 1971 5 0.23-0.46 25 WP 0.07 0.04 <0.02 5 days apart 10 0.23-0.46 25 WP 0.1 0.03 <0.02 5 days apart 1 0.38 25 WP 0.063 2 0.38)5 days 25 WP 0.046 3 0.38)apart 25 WP 0.064 0.036 0.015 1 0.5 25 WP 0.11 2 0.5)5 days 25 WP 0.13 3 0.5)apart 25 WP 0.18 0.1 0.02 1 0.75 25 WP 0.48 2 0.75)5 days 25 WP 0.37 3 0.75) apart 25 WP 0.61 0.34 0.11 5 0.25 7 days apart 25 WP 0.17 0.09 0.04 0.02 1 The seventh treatment was 12 days before the last application. Currant Chinomethionat was applied two times, 13 days apart, at a rate of 0.15 kg/ha. Samples were taken 7, 14, 21 and 28 days post-treatment; the residue content was found to be 0.03, 0.015, 0.008 and 0.005 mg/kg, respectively (Bayer 1974). Melon Supervised trials were carried out at various locations in the USA and in Japan and Mexico on different varieties. Chinomethionat was applied at a dose rate of 0.15 to 0.5 kg/ha 4 to 10 times at intervals of 5 to 10 days. Samples were taken at 0 to 8 days post-treatment. The pulp and the rind or peel were analysed separately. The weight of different portions was measured at the time of analysis and the residue was calculated on a whole fruit basis. The results are summarized in Table 2 (Mobay 1979; Nikon Tokushu Noyaku Seizo KK 1976). The residue in the pulp was generally lower than the limit of determination (< 0.005 to 0.01 mg/kg); however, in few cases, 0.02 and on one occasion 0.03 mg/kg were detected, while the rind contained < 0.01 - 0.06 mg/kg chinomethionat. In one sample 0.9 mg/kg was measured at day 0. Kaki persimmon Chinomethionat was applied at a rate of 0.5 - 0.75 kg/ha to kaki persimmon 3 to 5 times in four experiments. The last application followed the previous ones 15 or more days later. Eight samples were taken 12 to 57 days after the last application. The residue ranged from 0.005 to 0.036 mg/kg at the 12 to 39-day interval, while it was undetectable (<0.005 mg/kg) later (Nikon Tokushu Noyaku Seizo KK 1973). Orange Supervised trials were carried out in California in 1977-1978 and in Japan in 1974 (Mobay 1978; Nikon Tokushu Noyaku Seizo KK 1974). Chinomethionat was applied 1 to 3 times at intervals of 1 month or longer at a dose rate of 0.15 to 7 kg/ha. In California the same orchards were treated in spring, when samples were taken from 0 to 6 days post-treatment, and in autumn, when fields were sampled 14 to 35 days after the last application. Peel and pulp were analysed separately and the residue was calculated on a whole fruit basis. The results are summarized in Table 3. TABLE 2. Residues of dhinomethionat in melons Application Residues in whole fruit (mg/kg) at Crop Country Year No. Rate intervals (days) after application (kg a.i./ha) Formulation 0 1 2 7-8 Cantaloupe Mexico 1979 6 0.15 5x7 27 25 WP 0.03 days apart Honeydew Mexico 1979 9 0.5 7 to 9 days 25 WP <0.01 <0.01 apart USA Arizona 1979 6 0.42 8 to 10 25 WP 0.43 0.35 0.11 days apart Missouri 1977 5 0.42 6 to 7 25 WP 0.01 <0.01 0.01 days apart Florida 1977 6 0.42 9 to 10 25 WP 0.43 0.01 0.01 days apart Texas 1976 6 0.42 9 to 10 25 WP 0.09 0.02 0.01 days apart Muskmelon Arizona 1977 6 0.42 7 days 25 WP 0.01 <0.01 0.01 apart Florida 1977 6 0.42 10 days 25 WP 0.01 0.03 0.01 apart Japan 1976 4) 0.25 to 0.63 25 WP <0.0051 <0.0051 <0.0051 8) 6 days apart 25 WP <0.0051 <0.0051 <0.0051 Japan 1976 5) 0.37 25 WP <0.0051 <0.0051 <0.0051 10) 5 to 6 days apart 25 WP <0.0051 <0.0051 <0.0051 TABLE 2 (con't) Application Residues in whole fruit (mg/kg) at Crop Country Year No. Rate intervals (days) after application (kg a.i./ha) Formulation 0 1 2 7-8 USA Watermelon Texas 1976 6 0.42 t0 to 12 25 WP <0.01 <0.01 days apart Florida 1977 6 0.42 10 days 25 WP 0.04 0.02 0.01 apart Arizona 1977 6 0.42 2x10+13+ 5+4 days apart 25 WP 0.03 0.02 0.02 1 Pulp only. TABLE 3. Residues resulting from supervised trials on orange Application Residues (mg/kg) at intervals (days) after last application Country Year No. Rate Portion (kg a.i./ha) Formulation analysed 0 3 6 14 21 28 35 >46 USA California 1977 1 1.4 25 WP whole 0.15 0.23 0.05 1978 pulp 0.06 0.1 0.02 1 1.4 25 WP whole 0.12 0.08 0.08 0.05 pulp 0.03 0.02 0.01 0.01 1 1.4 25 WP whole 0.13 0.09 0.18 pulp 0.03 0.03 0.05 1 1.4 25 WP whole 0.05 0.03 0.03 0.03 pulp 0.02 0.01 0.01 0.01 1 1.4 25 WP whole 0.12 0.14 0.08 pulp 0.04 0.07 0.03 1 1.4 25 WP whole 0.05 0.02 0.03 0.02 pulp 0.02 0.01 0.01 0.01 1 7 25 WP whole 0.14 0.07 0.09 pulp 0.03 0.01 0.03 1 7 25 WP whole 0.21 0.06 0.07 0.05 pulp 0.09 0.01 0.01 <0.01 1 7 25 WP whole 0.13 0.11 0.13 pulp 0.07 0.02 0.03 TABLE 3 (con't) Application Residues (mg/kg) at intervals (days) after last application Country Year No. Rate Portion (kg a.i./ha) Formulation analysed 0 3 6 14 21 28 35 >46 1 7 25 WP whole 0.07 0.02 0.04 0.03 pulp 0.01 0.01 0.01 <0.01 2 7 3 months 25 WP whole 0.08 0.15 0.08 apart pulp 0.03 0.05 0.03 1 7 25 WP whole 0.14 0.03 0.06 0.06 pulp 0.04 0.01 0.02 0.01 1 4.2 25 WP whole 0.1 0.09 0.03 pulp 0.05 0.04 0.01 1 4.2 25 WP whole 0.06 0.02 0.02 <0.01 pulp 0.05 0.01 0.01 <0.01 1 0.15 25 WP whole 0.12 0.02 0.07 pulp 0.02 0.01 0.02 1 0.15 25 WP whole 0.03 0.02 0.03 0.03 pulp 0.02 0.01 0.02 0.02 1 0.15 25 WP whole 0.05 0.13 0.04 pulp 0.02 0.02 0.01 whole 0.04 0.02 0.03 0.02 pulp 0.01 0.01 0.01 0.01 TABLE 3 (con't) Application Residues (mg/kg) at intervals (days) after last application Country Year No. Rate Portion (kg a.i./ha) Formulation analysed 0 3 6 14 21 28 35 \>46 Japan 1 0.88 25 WP whole1 <0.02 3 0.88 1 month 25 WP pulp 1 <0.02 <0.02 apart 1 Two sets of experiments. Residue in the pulp was always below 0.1 mg/kg and <0.05 mg/kg 6 days after last application, independently of the dosage. The peel contained residue in the range of 0.15 to 0.51 mg/kg at 0 to 6 day intervals and the residue decreased in the peel. The residue was always below 0.2 mg/kg on whole fruit basis. Strawberry In England strawberries were treated two times at a 44 day- interval. Samples taken from the two plots 14 days after the last application contained 0.01 and <0.01 mg/kg residue (Bayer 1969). In Japan, the plots were treated 2 or 4 times at 5-day intervals at a rate of 0.4 kg/ha. The fruits were analysed 1, 5 and 10 days after last application, and contained residues of 0.31, 0.14 and 0.08 mg/kg after 2 treatments and 0.3, 0.21 and 0.08 mg/kg respectively after 4 treatments (Nikon Tokushu Noyaku Seizo KK 1978). Tomato Tomatoes grown in a greenhouse were treated 1 to 3 times at 5-day intervals with chinomethionat at a rate of 0.5 kg/ha (Nikon Tokushu Noyaku Seizo KK 1978). Samples taken 1 to 7 days after last application were analysed. The residues detected are summarized in Table 4. TABLE 4. Residues resulting from supervised trials on tomato Residue (mg/kg) after application (days) No. of treatments 1 3 7 1 0.05 0.24 2 0.07 0.26 3 0.12 0.1 0.12 0.38 0.26 0.18 FATE OF RESIDUES In animals Two dairy cows were fed a ration containing 20% chinomethionat- treated almond hulls, which were from almonds treated 56 days prior to harvest with Morestan 25 WP at a rate of 1.7 kg/ha, or on which (2,3-14C)-chinomethionat was applied individually in a quantity approximating the average chinomethionat residue detected on the non- radioactive chinomethionat-treated almonds. The almond hull feed contained approximately 0.08 mg/kg chinomethionat equivalent. Radioactive residues in milk reached a maximum 10 days after the feeding study began, but never exceeded 0.008 mg/kg. Radioactive residues (mg/kg) in the tissues were: liver 0.03; kidney 0.03; heart < 0.02; muscle < 0.02; brain < 0.02; and fat 0.02 (Murphy et al 1977). The results of this experiment support the conclusions drawn from studies on other commodities and animals that indicate low biological availability of plant residues. Bluegill fish, Leponis macrochirus, were continuously exposed to (2,3-14C)chinomethionat for 14 days at 1 µg/kg concentration in a continuous flow system (Lamb 1975). Fish were collected from aquaria on day 0 (15 min, 1, 2, 4 and 8 h) on days 1, 2, 4, 7 and 14 of the exposure period, and on day 1, 2, 4, 7, 14, 21, 28 and 51 of the withdrawal period. During the first 7 days, 14C residues in the fish tissue constantly increased to a maximum level of approximately 1 100 times the level in the water. No further accumulation was found after 14 days, and it appears that an accumulation factor plateau of 700 to 1,100 was established between 4 and 7 days of exposure. On the seventh day of exposure, the nonedible portion (head, viscera and scales) accounted for 45% of the body weight and contained 93% of the extractable residues. Only 10% of the whole body 14C residue was extractable in hexane, while 90% was extracted into the polar solvent (acetonitrile). Following transfer of fish to uncontaminated water, whole body 14C residues declined at a slow rate. After 51 days of withdrawal, approximately 10% of the accumulated residues remained in the fish tissue. In plants Uptake of chinomethionat soil residues by rotational crops was studied under greenhouse conditions. (13C, 14C) chinomethionat, as 25 WP, was added to the soil in a water solution at a rate equivalent to 0.42 kg a.i./ha. The applications were made 6 times at 10-day intervals. Lettuce, red beets and oats were chosen to represent the leafy vegetable, root and grain rotational crops respectively. The plants were planted 30 days, 120 days and 1 year after the last of the 6 applications and they were harvested when their maturity was estimated to be 1/4, 1/2, 3/4 and complete. The total radioactive residue in all plants was less than 0.1 mg/kg at any time, with the exception of lettuce harvested at 1/4 maturity from soil treated 1 year before and of oat foliage, in which 0.2 mg/kg and 0.12-0.26 mg/kg were found, respectively. The soil residue ranged from 0.72 to 1.05 mg/kg dry soil during the study (Stoner 1980). The total radioactive residue found in various portions of plants at harvest are summarized in Table 5. TABLE 5. Residues in plants grown in soil treated with chinomethionat before planting Portion of plant Residue (mg/kg) 30 days 120 days 365 days Lettuce 0.015 0.007 0.011 Red beet root 0.047 0.019 0.012 tops 0.03 0.016 0.015 Oats foliage 0.077 0.261 0.122 grain 0.017 0.061 0.056 In soil The metabolism of chinomethionat was studied in sandy loam and silt loam under aerobic, anaerobic and sterile conditions after application of 14C-chinomethionat, formulated as a 25% wettable powder, at 2.46 kg a.i./ha (Shaw II 1980). The major metabolite identified in these soils was 6-methyl 1,4-dihydro 2,3-quinoxalinedione (QDOH). During a year of soil incubation, QDOH reached a maximum content of 57% of applied radioactivity in sandy loam at 180 days and 42% in silt loam by 90 days. It then decreased to 48% in sandy loam and 30% in silt loam at one year post-treatment. Minor metabolites identified and their maximum proportion, found under aerobic condition respectively in sandy loam and silt loam, were 2-hydroxy or 3-hydroxy 6-methyl 2(1H) quinoxalinethione (QDSOH) 16% and 15%; 6-methyl 1,4-dihydro 2,3-quinoxalinedithione (QDSOH) 4% and 10%; 1, 2, 3, 4-tetrahydro 2,3-dioxo 6-quinoxalinecarboxylic acid (acid QDOH) 4% and 4%; and 2,9 or 2,10 dimethyl (1,4 dithiino-)2,3-b: 5,6-b')-diquinoxaline (dimer) 1%. The structural formulas of these metabolites are shown in Figure 1. The aerobic and anaerobic conditions resulted in similar metabolites and rate of metabolite formation, except possibly in the formation of acid QDOH. Soil microorganisms, however, did appear to be involved in the degradation of chinomethionat, as its half life under sterile conditions was 52 days in sandy loam and 18 days in silt loam, in contrast to the 4 day and < 1 day half lives under nonsterile, aerobic conditions. Hydrolysis, carried out primarily by soil microbes, was the main mechanism for degradation of chinomethionat. Other than radioactive carbon dioxide (< 1%) no volatile radioactivity was detected. During the one-year study, 85% to 97% of the applied radioactivity in the sandy loam and 77% to 90% in the silt loam were identified or characterized. Runoff characteristics of chinomethionat were studied on apple trees treated once with spray containing 0.08% a.i. or four times with 0.03% a.i. spray. Simulated and natural rainfall were measured and the runoff was collected in buckets from a ditch dug just outside the periphery of the foliage. Runoff on the soil surface was tested on three soil types, by collecting runoff water from the area treated at 3.36 kg a.i./ha after the water had traversed 1.5, 3 and 6 m of untreated soil. The runoff water under the apple tree collected after 3.8 mm rain on the day of application contained less than 1% of the applied material. Following 2mm of rain 2 days post-treatment, the runoff water from silt loam soil on an 8.5% slope contained 0.185, 0.079 and 0.031% of applied chinomethionat at the end of test soil plots of 1.5, 3 and 6 m length respectively (Flint and Shaw 1970). The low mobility of chinomethionat was also indicated by adsorption and soil column leaching experiments. Adsorption coefficients of chinomethionat (kd) in soil/water systems at 0.05, 0.2 and 1 mg/kg concentration in water were 52.5 g/ml in sandy loam, 45 g/ml in silt loam and 90 in high organic silt loam (Flint and Shaw 1970). Shaw (1979) found the adsorption coefficients (Ka) determined by the Freudlich equation to be 37 for sandy loam and 41 for silt loam over the concentration range of 0.5 to 12.1 mg/kg. After leaching in a soil column, the chinomethionat remained in the upper layer of soil (Flint and Shaw 1970). Column leaching of chinomethionat on three different soils (organic carbon content 0.51%, 0.69% and 2.89%) resulted in non-detectable residue in the leachates (Bayer 1976).Leaching characteristics of aged chinomethionat soil residues were studied in two sets of experiments. Sandy loam soil was fortified at 7.05 mg/kg with (13C, 14C)-chinomethionat, followed by incubation at room temperature for 30 days. Of the original applied activity, 12% was lost during the ageing process, probably due to volatilization. In three replicates, the aged soil was placed on top of sandy loam soil columns, which were 30 cm high and 4.3 cm in internal diameter. Leaching was effected by passing water, equivalent to 1.25 cm of rainfall daily, through the columns for 45 days. Only 4% of the applied radioactivity was found in the water leaching gradually over the 45-day period, with no apparent peak, while nearly 90% of the activity was retained in the upper 1.25 cm of the column. The residue in soil contained primarily QDOH (39%), QDSH (13%), QDSOH (6%) and chinomethionat (4%). About 1.5+1.1% of applied activity was associated with the insoluble humin fraction of soil, and the remainder of the activity distributed into the fluvic (98 ± 1.1%) and humic (4.3%) acid fractions (Obrist 1979). The residues in the leachate were identified in the other experiments carried out with standard and modified soil columns type 2.1 (Vogeler 1981). The water collected under the modified soil column contained 6.8 and 6.9% of applied activity. Two metabolites, identified in water, were QDOH and a small amount of QDSH. In water Technical chinomethionat was dissolved in phosphate buffers of pH 5 and pH 7, with the final concentration being approximately 0.05 mg/kg. The solutions were placed in capped amber bottles and maintained in constant temperature water baths at 30 and 50°C. The concentration of chinomethionat decreased to half of the initial value within 109 hours at 30°C and 27 hours at 50°C. An increase of pH from 5 to 7 decreased the water stability of chinomethionat three and five fold, respectively. In the outdoor experiment, conducted in a mini-pond containing 5 cm silt and 25 cm of surface water of pH 7, 100 mg/kg of chinomethionat decomposed rapidly, showing a half life of 3.4 h in a 7-hour experiment during which the temperature of water increased from 27°C to 37°C (Flint and Shaw 1970). Photodegradation In a laboratory experiment, 14C-chinomethionat applied to a thin layer of soil on a glass plate was irradiated with light from a high intensity, mercury vapour lamp. Soil samples were analysed after 1, 2, 2.2, 3.5, 5, 7, 11 and 12 days exposure. Several minor products were detected. Chinomethionat was the major residue component at each sampling time, although several minor photolysis products were detected. The "dimer" and QDOH were tentatively identified. Disappearance of chinomethionat was influenced by several factors. It decreased by approximately 50% during the first day but declined more slowly subsequently. After 12 days, about 25% of the initial concentration was still detectable on the plates (Mulkey et al 1980). EVALUATION COMMENTS AND APPRAISAL Additional data evaluated by this Meeting further extend the basis for the toxicological characterization of chinomethionat. The outcome of studies on mutagenicity in bacteria and in mice, as well as on embryotoxicity and teratogenicity in rabbits, supports earlier evaluations. It was noted that a long-term study performed on an additional species is still outstanding. However, the Meeting was informed that a long-term study in mice and a 1-year study in dogs were in progress. On this basis, the Meeting decided to extend the temporary ADI of 0.003 mg/kg until 1984. Chinomethionat was last evaluated by the 1977 Joint Meeting. Since then, some additional data have been made available for evaluation of residues. Results of supervised trials on almond and currant showed a residue pattern similar to that of the previous experiments, while in orange the residue was lower and did not exceed 0.2 mg/kg on a whole product basis. The residue in orange pulp was always below 0.1 mg/kg and <0.05 mg/kg at 6 days after last application. The peel contained residue in the range of 0.15 to 0.51 mg/kg at 0 to 6 days interval. The residue in cucumber, treated at the recommended rates up to 0.5 mg a.i./ha, did not exceed 0.1 mg/kg, which is the present TMRL. The results of these supervised trials support the maximum residue levels recommended by the 1974 Joint Meeting. Residues in melon, kaki persimmon, strawberry and tomato were evaluated for the first time. In melon and kaki persimmon, chinomethionat residue was low, i.e. less than 0.1 and 0.05 mg/kg at the time of harvest, and concentrated in the peel or rind. The residues in strawberry were less than 0.5 mg/kg at day 1 post-treatment even after 4 applications and declined to under 0.1 mg/kg 9 days later. Tomatoes treated in a greenhouse contained residue in the range of 0.05 to 0.38 mg/kg at 1 to 3 days after last application. A feeding study was carried out on dairy cows kept on a diet consisting of 20% chinomethionat-treated almond hulls containing 0.08 mg/kg chinomethionat equivalent. Radioactive residues in milk reached a maximum 10 days after the feeding study began, but never exceeded 0.008 mg/kg chinomethionat equivalent. Radioactive residues were 0.03 mg/kg in liver and kidney and <0.02 mg/kg in other tissues. These results confirmed the low biological availability of plant residues found in previous experiments. A plateau of the accumulation factor in bluegill fish was observed in the range of 700 to 1 100 after 4 to 7 days of exposure. Approximately 10% of the accumulated residue remained in the fish 51 days after withdrawal. The metabolism of chinomethionat was studied in sandy loam and silt loam under aerobic, anaerobic and sterile conditions. The major metabolite identified in these soils was 6-methyl 1,4-dihydro 2,3-quinoxalinedione (QDOH). Its maximum concentration ranged between 42 and 57% of applied radioactivity. Minor metabolites identified and their maximum concentrations found under aerobic conditions were 2-hydroxy or 3-hydroxy 6-methyl 2 (1H) quinoxalinethione (QDSOH) 15 to 16%; 6-methyl 1,4-dihydro-2,3-quinoxalinedithione (QDSH) 4 to 10%; 1, 2, 3, 4-tetrahydro 2,3-dioxo 6-quinoxaline carboxylic acid (acid QDOH) 4%, and 2, 9-or 2,10-dimethyl (1,4)-dithiino (2,3-b:5,6-b'- diquinoxaline (dimer) 1%. Aerobic and anaerobic conditions resulted in similar metabolites. Microbial degradation is of primary importance, as the hydrolysis carried out by soil microbes appeared to be the main mechanism for degradation of chinomethionat. The concentration of chinomethionat declined rapidly in soils and was about 6 to 10% of the applied dose 30 days after soil treatment. At harvest, the total radioactive residue in lettuce, red beet and oats planted 30 to 65 days after soil treatment with radioactive chinomethionat were in the range of 0.03 to 0.06 mg/kg. Although rotational crops can take up soil residues, owing to the rapid decomposition of chinomethionat, no intact parent compound can be expected in detectable amounts in mature crops planted 30 days or later post-treatment. Studies on the runoff characteristics of chinomethionat from treated trees or from a soil surface revealed that less than 1% of the applied dose could be washed off by rain, even on the day of application. The low mobility of chinomethionat and its soil metabolites was also indicated by adsorption, desorption and soil column leaching experiments. The concentration of chinomethionat decreased to half of initial value within 109 hours at 30°C in phosphate buffer of pH 5. At pH 7 the rate of degradation increased three fold. Level causing no toxicological effect Rat : 12 ppm in the diet equivalent to 0.6 mg/kg bw/day, Estimate of temporary acceptable daily intake for man 0 to 0.003 mg/kg bw. RECOMMENDATIONS OF RESIDUE LIMITS On the basis of new data, the Meeting recommends the following additional residue limits: PHI on which Commodity Limits recommendations are based (days) Melon 0.1 3 Watermelon 0.02 3 Strawberry 0.2 7 Kaki persimmon 0.05 14 FURTHER WORK OR INFORMATION Required (by 1984) 1. The submission of the studies known to be in progress. Desirable 1. Information on use pattern on tomato and additional residue data deriving from supervised trials. REFERENCES Bayer Residue Reports, Nos. 322-323/69. 1969 1974 Residue Report, No. 8400/74 (black currant). 1975 Residue Reports, Nos. 8400-8405/75 (cucumbers), 1976 Leaching studies. Reports Nos. 8400-8402/76. Flint, D.R. and Shaw, H.R. Soil runoff, leaching, adsorption and water 1970 stability studies with MORESTAN. Mobay Report No. 28 365. Lamb, D.W., Roney, D.J. and Jones, R.E. Accumulation and persistence 1975 of residues in bluegill fish exposed to MORESTAN-14C. Mobay Report No. 44 329. Mobay Residue Reports, Nos. 613-66621. 1978 1979 Residue Reports, Nos. 51125, 51126, 51384, 51706, 51707, 53050, 53051, 53082, 67200-67203. Mulkey, N.S., Herrera, R., Breault, G.O. and Wargo Jr., J.P. 1980 Photodegradation of 14C-MORESTAN on soil surface. Mobay Report No. 68 881. Murphy, J.J. et al. 14C MORESTAN - Almond hull - dairy cow feeding 1977 study. Mobay Report No. 53 619. Nikon Tokushu Noyaku Seizo KK. Residue Reports, Nos. 98, 268, 622, 1971 623, 795 (cucumbers). 1973 Residue Reports, Nos. 242, 243. 1974 Residue Reports, Nos. 95, 96. 1976 Residue Reports, Nos. 431, 432 1978 Residue Reports, Nos. 100, 620, 621. Obrist, J.J. Leaching Characteristics of Aged MORESTAN Soil Residues. 1979 Mobay Report No. 67 821. Shaw II, H.R. Adsorption and desorption of (13,14C)-MORESTAN by Soils. 1979 Mobay Report No. 67 484. 1980 Metabolism of MORESTAN in soil. Mobay Report No. 67 820. Stoner, J.H. MORESTAN 14C. A rotational crop study. Mobay Report No. 1980 69 199. Vogeler, K. Untersuchungen zum leachingverhalten von Chinomethionat. 1981 Bayer AG, Pflanzenschutz-Anwendungstechnik, Report RA - 194. (Unpublished)
See Also: Toxicological Abbreviations Chinomethionat (WHO Pesticide Residues Series 4) Chinomethionat (Pesticide residues in food: 1977 evaluations) Chinomethionat (Pesticide residues in food: 1983 evaluations) Chinomethionat (Pesticide residues in food: 1984 evaluations) Chinomethionat (Pesticide residues in food: 1987 evaluations Part II Toxicology)