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    PESTICIDE RESIDUES IN FOOD - 1981


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    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).

    FIGURE 1

         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)