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    PESTICIDE RESIDUES IN FOOD - 1979


    Sponsored jointly by FAO and WHO






    EVALUATIONS 1979





    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, 3-12 December 1979



    CHLOROTHALONIL

    Explanation

    Chlorothalonil was evaluated in 1974.  In 1977 it was reviewed in the
    light of information received in response to needs recorded in 1974,
    also in response to requests for clarification of the past
    recommendations received from the 9th Session of CCPR.

    In 1977, temporary MRLs for whole and pulp of bananas were suggested
    on a basis of a minimum of acceptable data.  Since then the results
    from field trials involving revised patterns of use have been
    available.

    The 1977 Meeting also recorded requirements for additional information
    (i) to resolve the lower dose limits for kidney effects in rats, and
    (ii) to define the growth reduction after administration of
    chlorothalonil or its metabolite,
    4-hydroxy-2,5,6-trichloro-isophthalonitrile (DAC-3701) in pups
    relative to ingestion or secretion into milk.

    Information was also considered to be desirable on (i) observations in
    humans, (ii) the extent of metabolism to
    4-hydroxy-2,5,6-trichloroisophthalonitrile (DAC-3701) in mammals, and
    (iii) the effects of cooking on residues.

    The further information received is reviewed in this monograph
    addendum.

    EVALUATION FOR ACCEPTABLE DAILY INTAKE

    BIOCHEMICAL ASPECTS

    Two groups of 4 male Sprague-Dawley rats, 9 weeks of age, were
    intubated (following overnight fasting) with polyethylene glycol 400
    solutions of <99 percent pure
    14C-hydroxy-2,5,6-trichloroisophthalonitrile (DAC-3701) at dosage
    levels of 4.3 or 42.6 mg/kg body weight.  The 14C label was believed
    to be evenly distributed in the phenyl ring.  Following dosing, rats
    were maintained individually in metabolism cages.  Urine, faeces and
    cage washings were obtained every 24 hours until execution for tissue
    analysis at 96 hours post-dosing.  Cumulative percentage recovery of
    administered 14C in faeces and urine was unaffected by dose level.
    However, faecal levels were approximately 10 times greater than
    urinary levels.  At 96 hours, approximately 78% of the administered
    dose had been recovered in feces (about 70 percent) and urine (about 8
    percent).  Excretory half-life was about 48 hours.  Residues of
    14C/gm of tissue was highest in the large intestine (27 and 384 ppm
    14C-4-hydroxy-2,5,6-trichloroisophthalonitrile (DAC-3701)
    equivalents), followed by small intestine (14 and 161 ppm), liver (17
    and 139 ppm), and blood (4 and 41 ppm) following 4.3 and 42.6 mg/kg
    doses.  Low levels were found in all other tissues analyzed.  Total
    accountability of 14C was approximately 1O2% at both does levels.

    The data are suggestive of hepatic conjugation and biliary excretion
    of the 14C-labelled test material (Jarrett, et al., 1978).

    TOXICOLOGICAL STUDIES

    Special Studies on Carcinogenicity

    Mice

    Groups of 50 male B6C3F1 mice were fed chlorothalonil (98 percent
    purity technical material) at either 10,000 ppm for 2 weeks followed
    by 2,500 ppm for 78 weeks, and a pre-sacrifice withdrawal period of
    11-12 weeks (time-weighted average dose 2,688 ppm) or 20,000 ppm for 2
    weeks followed by 5,000 ppm for 78 weeks and a 12 week pre-sacrifice
    withdrawal period (time-weighted average dose 5,375 ppm).  Similar
    groups of female mice were fed either 10,000 ppm for 2 weeks, 5,000
    ppm for 10 weeks, and 2,500 ppm for 68 weeks, with an 11 week
    presacrifice withdrawal period (time-weighted average dose, 3,000
    ppm), or 20,000 ppm for 2 weeks, 10,000 ppm for 10 weeks, and 5,000
    ppm for 68 weeks, with a 12 week presacrifice withdrawal period
    (time-weighted average dose, 6,000 ppm).  Matched controls comprised
    10 male and 10 female mice were maintained for 91 weeks.

    A dose related decrease in body weight gain in males was observed.
    Survival, gross, and histopathology were comparable in all groups.
    Total incidence of male mice with tumors was 30, 18, and 2 percent at
    control, low, and high dose levels.  Malignant tumor incidence was 20,
    4, and 2 percent and benign tumors incidence was 10, 12.5, and 0
    percent.  Comparable percentages in females are total tumors, 30, 12,
    and 17 percent, malignant tumors, 0, 6, and 8 percent, and benign
    tumors, 30, 6, and 8 percent in control, low, and high dose levels,
    respectively.  There was no evidence of change in tumor incidence in
    specific organs or organ systems (NCI, 1978).

    Rats

    Groups of 50 male and 50 female Osborne-Mendel rats were dosed with
    chlorothalonil (technical 98 percent purity, technical 98.5 percent
    purity, or analytical grade, pure material) at dose levels of either
    10,000 ppm for 1 week, followed by 5,000 ppm for 79 weeks and a 30
    week presacrifice withdrawal period (time-weighted average dose, 5,063
    ppm) or 20,000 ppm for 1 week followed by 10,000 ppm for 79 weeks and
    a 31 week presacrifice withdrawal period (time-weighted average dose,
    10,126 ppm).  Contemporary control groups comprised of 10 male and 10
    female rats were maintained for 110 weeks.

    Body weight data showed a dose-related decrease in weight gain in both
    sexes.  During the second year of the study, treated rats showed
    ataxia, tachypnea hematuria, hyperactivity, vaginal bleeding, a high
    incidence of abscess formation and bright yellow urine.  Survival was
    decreased in both male test groups.  The report indicates the only
    non-spontaneous pathological lesions noted were a dose-related
    increase in renal tubular epithelial tumors in both sexes.

    (Unfortunately, the test and tabular data in the report differ with
    regard to the incidence of renal tubular epithelial tumors, rendering
    an evaluation impossible.)  The tabular data does not indicate any
    cause for concern regarding renal tumor incidence (NCI, 1978).

    A detailed review of the available data on the NCI bioassay indicates
    that the tabular data on incidence of renal tubular epithelial
    neoplasms appears to be correct.  No reported tumors were noted in the
    pituitary, where the incidence of adenomas was, in males 0/8, 5/45,
    and 0/49, and in females 0/10, 3/47, and 3/42 in control, low, and
    high dose groups.  Similar errors were found in the reported incidence
    of adrenal adenomas, where in the females, the original report
    indicated 1/10, 0/47, and 0/47, the corrected data indicating 1/10,
    9/47, and 9/47 (Weinberg, 1979).

    Short Term Studies

    Rat

    Seven groups of 15 male and 15 female young adult Wister rats were fed
    1, 2, 4, 15, 30, 60, or 120 ppm chlorothalonil in the diet for 17
    weeks.  A concurrent control group of 30 male and 30 female rats were
    fed normal laboratory chow.

    All rats were elated to present a healthy appearance throughout the
    study.  Body weight, food consumption, and survival were comparable in
    all groups.  At termination of the study, all rats were sacrificed.
    Kidney, liver, and thyroid from each animal was removed and grossly
    examined.  Most kidneys had fat-like nodules on them, and a number of
    livers were mottled and discoloured (Hastings and Jessop, 1975).
    Histopathology of the kidney has been reported in detail, and although
    interstitial nephritis and regenerative epithelium were noted, no dose
    or compound related effects were observed (Busey, 1975).  A second
    examination of the slides of kidney tissue confirmed the absence of
    dose or compound related effects (Newberne, 1975).

    COMMENTS

    A previous Meeting requested additional data which, in part, were made
    available and reviewed by this Meeting.  A detailed histopathology
    review of the previous study, by two independent pathologists,
    alleviated the concerns of the previous Meeting on potential kidney
    effects.  Information on pup growth reduction requested by a previous
    meeting is still lacking, but information was available to indicate
    that a new 3-generation study is underway.  The conflicting data
    available from the rat carcinogenicity bioassay, especially with
    regard to the incidence of renal tubular epithelial tumors, and of
    adrenal adenomas precluded a full evaluation of these data.  The
    Meeting agreed to extend the temporary ADI for two years.

    TOXICOLOGICAL EVALUATION

    Level Causing No Toxicological Effect

    Rat:   60 ppm in the diet equivalent to 3 mg/kg body weight.
    Dog:  120 ppm in the diet equivalent to 3 mg/kg body weight.

    Estimate Of Temporary Acceptable Daily Intake For Man

    0-0.03 mg/kg body weight

    RESIDUES IN FOOD AND THEIR EVALUATION

    USE PATTERN

    Pre-harvest treatments

    Bananas

    Chlorothalonil is proposed for use to control foliar diseases of
    bananas and plantains, primarily by low volume aerial applications of
    a flowable formulation containing 54% a.i. or a wettable powder
    containing 75% a.i.  This use pattern will result in some applications
    being made to fruiting plants, however it is common practice to place
    plastic bags over the developing stems to protect the fruit until
    harvest.  Since this agricultural practice is established in 80% or
    more of the commercial banana growing areas of the world it will be
    described in some detail as follows.

    In 1977, two experiments on bananas were carried out in the
    Philippines and one in Honduras.  In the first Philippine experiment,
    banana trees received three applications a month for five months
    followed by two applications per month for six months for a total of
    twenty seven applications at a rate of 1.75 kg (1.31 kg a.i.) Daconil
    2787 W-75/ha/application.  On or about April 2, the banana fruit were
    covered by plastic bags as is the cultural practice in the area of the
    field tests.  The last six applications were made after the bananas
    were bagged.  On June 18, following that day's spray application,
    fruit for residue determination were collected.

    In the second Philippine experiment, banana trees received nine
    applications of Daconil 2787 W-75 at a rate of 1.5 kg
    a.i./ha/application.  The test period lasted 191 days and some banana
    fruit stems were covered with plastic bags and some left uncovered.
    Samples for analysis were taken on the day of the final spray
    application from both bagged and unbagged stems.

    In the Honduras experiment banana trees received twelve applications
    of BRAVO 6F at a rate of 1.5 pounds a.i./acre/application over the 103
    day test period for a total of 18 lbs. a.i./acre.  In the test, some
    of the banana fruits were covered with plastic bags according to the
    cultural practice in the area.  On the day of the twelfth application

    replicates consisting of four stems of bagged and four stems of
    unbagged green bananas were harvested for analysis.

    Uses on various crops in New Zealand

    New information on use pattern was received from New Zealand which
    replaces that previously published in 1974 and 1977 (New Zealand,
    1979).


    Table 1.  Uses of Chlorothalonil in New Zealand

                                                                     
    Crop/Disease              Application Rate            Preharvest
                                                          Interval
                                                                     

    Potatoes/early blight     0.8-1.3 kg ai/ha             7 days
    Potatoes/late blight
    Beans/anthracnose         1.2-1.7 kg ai/ha             7 days
    Brassicas/rust            1.2-1.7 kg ai/ha             7 days
    Celery/downy mildew       150-200 g ai/100 litres      7 days
    Cucurbits/leaf spots      150-200 g ai/100 litres      1 day
    Lettuce                   150-200 g ai/100 litres     14 days
                                                                     


    Use on peanuts in South Africa

    The Republic of South Africa supplied information on the registered
    use (Oct. 36/1947) of chlorothalonil on groundnuts (peanuts) for the
    control of leaf diseases of great economic importance (S. Africa,
    1979).  The information used is WP 75% at 1125 g/ai/ha with a
    withholding period of 56 days for peanut foliage as fodder.

    Use on potatoes in Sweden

    Information was received from Sweden that chlorothalonil is used in
    that country mainly against potato blight (Phytophtera) (Sweden,
    1979).  Since the pre-harvest interval for the bisdithiocarbomates was
    extended from 1 to 4 weeks, chlorothalonil with a withholding period
    of only 1 week has come to be used for the last fungicide application
    before potato haulm desiccation and harvest.  Chlorothalonil is also
    used against disease (Alternaria and Erysiphe) on cucumber
    (withholding period 2 days), and Botrytis on ornamentals in
    glasshouses.  Formulations: WP 75% (in glasshouses, however, as a 20%
    fumigant) at a rate of application of 1.2-1.5 kg/ha.

    RESIDUES RESULTING FROM SUPERVISED TRIALS

    Bananas

    Some of the bananas obtained during the experiments referred to under
    `Use Pattern' were analysed green as harvested, others after ripening
    with ethylene in the laboratory.  They were also examined before and
    after placement in a washing tank and treatment for 15 minutes with
    400 ppm a.i. thiabendazole flowable and 1% alum according to common
    commercial practice.  Whole fruit, edible pulp and surface extractions
    were examined from each handling and treatment level and 6 to 8
    replicate analyses were undertaken on each sample of treated bananas.

    In Philippine experiment (1) no residue equal or greater than 0.02
    mg/kg was found on washed or unwashed green whole bananas, or edible
    pulp from green bananas, washed or unwashed ripe whole bananas or
    edible pulp from ripe bananas.  Treated and nontreated samples gave
    identical results.  In Philippine experiment (2), unbagged whole fruit
    from treated areas contained a maximum chlorothalonil residue of 0.11
    mg/kg (mean, 0.04 mg/kg).  Post-harvest washing reduced the mean value
    from 0.04 to 0.01 mg/kg.  Bananas protected by plastic bags during
    treatment contained no residue of chlorothalonil above 0.01 mg/kg and
    no detectable residue of DAC-3701.  The levels of chlorothalonil
    obtained by macerated extraction were comparable to those obtained by
    surface stripping.  Edible pulp from treated bananas contained no
    residues of chlorothalonil or DAC-3701 at the detection limit of 0.01
    mg/kg.  In the Honduras experiment, unwashed bananas from unbagged
    plots had a maximum residue of 0.17 mg/kg with a mean of 0.08 mg/kg
    which was reduced to 0.02 mg/kg by washing.  No DAC-3701 residues
    greater than 0.01 mg/kg were found in any samples including the edible
    pulp.  No chlorothalonil residues greater than 0.01 mg/kg were found
    in edible pulp.

    Onions (Canada)

    In Ontario, Canada, chlorothalonil (as Bravo 5F) was applied to onions
    (var. Autumn spice) at 1.6 kg ai/ha (3.25 L product in 561.1 L
    water/ha) by a 16-nozzle sprayer in a single spray with the following
    results (Canada, 1979):

    Table 2.  Residues following spraying onions (Ontario)

                                                           
    Days after
    application              chlorothalonil DAC-3701
                                                           

    0-before spray           ND (< 0.05)   ND (<0.002)
    0-after spray            13             0.24
    2                        7.7            0.15
    4                        5.8            0.03
    6                        2.7            0.01
    8*                       1.4            0.003
    10-older outer leaves    2.4            0.008
    10-all leaves*           1.5            0.01
    10-younger leaves        0.51           0.005
    14                       0.93           0.005
    15                       2.2            0.01
    22                       0.29           ND (<0.002)
                                                           


    The chlorothalonil residues decayed with a half-life of about 3 days
    while the 4-hydroxy metabolite (DAC-3701) was fairly constant at about
    0.5% of the total residue.  Selection of 10% of the initial fungicide
    as an unacceptable level suggest a 7-10 day protection period.

    Grapes (Canada)

    In two experiments in Ontario, chlorothalonil was applied to grapes at
    1.3-1.9 kg ai/ha as either 7.2 F or 500 F flowable or 75% WP
    formulations for 3-6 applications in one case or a single late season
    application of WP in the second case (Canada, 1979).  Harvest residues
    on grapes 46 days-post-spray were 0.8 mg/kg for 6 applications and 0.6
    mg/kg for 3 applications for the 75% WP.  The flowable formulations
    gave 1.0 and 3.3 mg/kg for 6 applications and 2.5 and 1.7 mg/kg for 3
    applications.  Residues of DAC-3701 were 0.006 mg/kg (6 applications)
    and 0.002 mg/kg (3 applications) for the WP whereas the flowable
    formulations gave 0.014 and 0.017 mg/kg (6 applications) and 0.008
    mg/kg (3 applications).  An August application of the WP degraded
    slowly from 7.5 to 4.9 and 3.1 mg/kg after 7 and 14 days respectively
    and remained at 1.6-2.5 mg/kg between 21 and 36 days post-spray.  The
    4-hydroxy metabolite residues declined from 0.09 mg/kg to 0.013 over
    about the same period.  Although some mild phytotoxicity was noted for
    the flowable formulations, the possible use of such grapes for wine
    indicated that the higher residue levels associated with these
    treatments should be considered for recommending maximum residue
    limits.

                   

    * mean of 2 sample replicates.

    Potatoes, Tomatoes (New Zealand)

    Information on supervised trials from New Zealand showed that potatoes
    treated 10 times at 1.7 kg ai/ha with a preharvest interval of 6 days
    had non-detectable (20-5 mg/kg) residues (New Zealand, 1979). 
    Tomatoes treated 5 times with 180 g ai/100 litres (1.5 kg ai/ha) had
    residues of 11.4, 2.8, 0.9, N.D., and N.D. at preharvest intervals of
    1, 3, 7, 10 and 14 days respectively.

    Peanuts (South Africa)

    Information from South Africa on residues on peanut foliage (leaves)
    following treatment by 4 applications at 10 day intervals at a rate of
    1125 g ai/ha is shown in the following table (South Africa, 1979).

    Table 3.  Residues on peanut foliage (South Africa)

                                                       
    Days after          chlorothalonil      DAC-3701
    last treatment      mg/kg               mg/kg
                                                       

     0-1                57.5:55.0           0.5:0.5
     0                  77.5:80.0           0.7:0.8
     1                  68.0:74.0           0.6:0.6
     7                  39.0:47.0           0.3:0.4
    14                  20.5:25.0           0.3:0.2
    28                   7.0:8.5            0.2:0.3
                                                       

    Recovery at 5 mg/kg = 80% for chlorothalonil and 70% for DAC-3801.
    Limit of detection = 0.1 mg/kg.


    FATE OF RESIDUES

    General

    Since hexachlorobenzene (HCB) can and does occur as a manufacturing
    impurity in chlorothalonil, the question arises as to the extent of
    its occurrence in the residue spectrum of chlorothalonil.  Information
    from the manufacturer indicates that specifications permit no more
    than 0.02% in W-75 wettable powder.  At a typical application rate of
    1.5 kg a.i./ha this would result in approximately 0.3 g of HCB per
    hectare per application.  Since the agricultural practice on bananas
    could result in as many as twenty-seven applications, a total
    calculated HCB residue of 8.1 g/ha is theoretically possible assuming
    no losses by volatilization or rain wash-off.  However, since HCB is
    not systemic, any traces of residue would occur on the peel where it
    could be largely removed by the usual washing process and would not
    occur in the edible pulp.  The situation with respect to other
    commodities requiring a multiplicity of applications merits
    investigation.

    In storage and processing

    The effects of cooking on chlorothalonil and DAC-3701 were
    investigated using plain water, green beans, and tomatoes in four
    cooking techniques.  Fifty gram samples of water, chopped green beans,
    and tomatoes were each fortified with 14C-chlorothalonil and cooked
    for 10 minutes in a vessel containing 20 ml of boiling water.  The
    cooking methods were: (1) in a 600 ml beaker without a cover, (2) in a
    500 ml flat bottomed flask fitted with a reflux condenser, (3) in a
    500 ml flat bottomed flask fitted with a distillation column and an
    acetone trap cooled in dry ice/acetone, (4) in a 6 qt. pressure cooker
    with and without a tightly sealed cover.  A similar group of test
    samples were also fortified with 14C-DAC-3701 and subjected to
    cooking methods (1) and (4).  After using appropriate extraction and
    cleanup procedures, the residues were quantitated by liquid
    scintillation counting and characterized by thin layer chromatography
    and autoradiography.  Separate tests without cooking gave complete
    recovery of the fortified 14C-radioactivity under all test conditions
    indicating that the extraction and partition procedures were reliable.
    The results of the cooking experiments are shown in Tables 4, 5 and 6.

    For all three test samples, cooking under open conditions resulted in
    volatilization of chlorothalonil (94-98% loss) whereas cooking under
    closed conditions resulted in partial hydrolysis to DAC-3701 and
    either 3-cyano-2,4,5,6-tetrachlorobenzamide (water) or unidentified
    residues (tomatoes and beans).  Only chlorothalonil was found in the
    distillate.  Pressure cooking without a cover resulted in loss of a
    major portion of the chlorothalonil through volatilization.  However,
    with the cover tightly sealed (15 Psi), the major portion of the
    chlorothalonil remained unchanged and no significant amounts of
    DAC-3701 were detected.  The later result is postulated to be due to
    instant sublimation which prevented hydrolysis.  The parallel
    experiments with 14C-DAC-3701 indicated that DAC-3701 is stable and
    neither chemical change nor loss will occur during cooking.

    Grape juice

    In the previously described experiments in Canada (see "Residues from
    Supervised Trials"), the effect of 3- and 6-spray programmes of 3
    formulations of chlorothalonil on carry-over of residues into grape
    juice are shown in table 7 (Canada, 1979).



        Table 4.  Effect of cooking on 14C-chlorothalonil with water

                                                                                                                       

                   14C-Chlorothalonil      Recovery of 14C-radioactivity (dpm)
                        Fortified             Organic           Aqueous
    Sample                (dpm)                Phase             Phase          Distillate       Total       Loss, %
                                                                                                                       
    Open beaker        1,000,000               29,400            2,700              -            32,100       96.8
    Reflux             1,000,000              987,160            7,335              -            994,495       0.6
    Distillation       1,000,000              800,400           10,500           200,500       1,011,400       0.0
                                                                                                                       

    Table 5.  Effects of cooking on 14C-chlorothalonil with tomatoes

                                                                                                                       

                     14C-Chlorothalonil     Recovery of 14C-radioactivity (dpm)
                          Fortified             Organic            Aqueous
    Sample                  (dpm)               Phase              Phase          Distillate       Total       Loss, %
                                                                                                                       
    Open beaker      1,400,000                  20,500               7,065            -             27,565     98.0
    Reflux           1,000,000                  797,100            346,430            -          1,041,160      0.0
    Distillation     1,000,000                  805,600             14,600         107,100         927,300      7.3
                                                                                                                       

    Table 6.  Effects of cooking on 14C-chlorothalonil with green beans.

                                                                                                                       

                     14C-Chlorothalonil         Recovery of 14C-radioactivity (dpm)
                          Fortified             Organic            Aqueous
    Sample                  (dpm)               Phase              Phase          Distillate       Total       Loss, %
                                                                                                                       

    Open beaker           1,400,000              59,000             27,420            -             86.420     93.8
    Reflux                1,000,000             772,080            269,080            -          1,041,100     0.0
    Distillation          1,000,000             786,000              7,200         160,000         953,200     4.7
                                                                                                                       
    


    Table 7.  Residues in Grapes and Juice (Canada)

                                                                           
    Formulation      Grape berries, mg/kg          Grape juice, mg/kg
    and program    chlorothalonil   DAC-3701    chlorothalonil   DAC-3701
                                                                           

    Full season: 6 applications

    75 W.P.            0.3          <0.002           0.3          0.0005
    7.2 F              0.8           0.006           0.7          0.0005
    500 F              1.6           0.008           0.9          0.002

    Late season: 3 applications

    75 W.P.             0.2         <0.002           0.3         <0.0005
    7.2 F               0.7          0.011           0.8         <0.0005
    500 F               0.6          0.006           0.2          0.004

    Check              <0.002       <0.002          <0.001      
    <0.0005
                                                                           


    EVIDENCE OF RESIDUES IN FOOD IN COMMERCE OR AT CONSUMPTION

    Chlorothalonil is detectable by the analytical methods employed for
    the Total Diet Study conducted in the United States by the Food and
    Drug Administration.  During the 1976 and 1977 periods, no residues of
    chlorothalonil were detected at a sensitivity of slightly less than
    0.01 mg/kg (Weasel, 1979).

    Finland and Sweden

    In the course of monitoring of imported produce during 1978 (Finland,
    1979), several lots of imported fruits, vegetables, and rootcrops were
    analysed with detectable residues only in the following cases:
    strawberries, 3 samples, 0.02-0.15 mg/kg; chinese lettuce, 6 samples,
    0.01-0.86 mg/kg; peaches, 2 samples, 0.12-1.2 mg/kg.  In Sweden,
    thirty-four samples of Swedish potatoes were analysed during 1979
    (Sweden 1979).  No sample contained detectable levels (0.005 mg/kg) of
    chlorothalonil.

    METHODS OF RESIDUE ANALYSIS

    A specific GLC method for chlorothalonil and its major metabolite,
    4-hydroxy-2,5,6-trichloroisophthalonitrile (DAC-3701) in soil, water,
    green leafy vegetables, tomatoes, and dry oily crops such as soybeans,

    dry beans, and peanuts has been developed and published (Ballee,
    1976).  Recoveries ranged from 85-100% for both compounds at a
    sensitivity level of 0.01 mg/kg.

    The method of analysis used in the field trials on bananas (Diamond
    Shamrock, 1979a) was essentially the same as that reported in the
    initial evaluation of chlorothalonil (FAO, 1975) differing only in
    details such as the composition of the Florisil eluting mixtures used
    - 20% dichloromethane in hexane (Eluent A) and 50% dichloromethane,
    1.5% acetonitrile, 48.5% hexane (Eluent C) instead of 5% acetone, 95%
    dichloromethane for chlorothalonil and 50% acetone, 50%
    dichloromethane for DAC-3701 - and in the use of 
    1-n-propyl-3-p-tolyltriazene to form the propyl ether of DAC-3701
    instead of diazomethane to form the methyl ether.  Although the
    propylated DAC-3701 has desirable GLC properties, its use cannot be
    recommended due to toxicological hazards associated with the
    derivitizing agent which has led to its general lack of availability.
    The original recommended procedure using diazomethane is therefore
    still the method of choice for determining DAC-3701.  As the data
    herein shows, there is no significant difference in residue results
    obtained on whole bananas either by surface stripping or by
    maceration; due to the additional cleanup required when maceration is
    used the surface stripping technique is preferred.  The mean recovery
    for whole bananas was 93% for chlorothalonil and 84% for DAC-3701; on
    macerated whole bananas the figures were 72% and 83% respectively. The
    mean recovery for edible pulp was 71% for chlorothalonil and 64% for
    DAC-3701.

    For screening purposes where only chlorothalonil and not the sum of
    the residues of chlorothalonil plus DAC-3701 is required, the
    multiresidue method described in the U.S. Food and Drug Administration
    Pesticide Analytical Manual (PAM), Vol. I, sections 212.1 plus 252 for
    nonfatty foods can be used.  The procedure yields a partial (75%)
    recovery and has a limit of 0.005 mg/kg.  Alternately PAM I, 212.2 can
    be used; also with a limit of 0.005 mg/kg.  For fatty foods PAM I,
    212.2 plus 252 can be used with a limit of 0.03 mg/kg fat.

    NATIONAL MRLs REPORTED TO THE MEETING

                                                         
       Country         Commodity                 MRL
                                                         

    United States    Banana (whole)           0.5 mg/kg
                     Banana (pulp)            0.05 " "

    New Zealand      Celery                   15   " "
                     Lettuce                  10   " "
                     Beans, brassicas,
                     cucurbits, tomatoes      5    " "

    South Africa     Shelled Ground Nuts      0.1  " " 
                                                         

    APPRAISAL

    Chlorothalonil was re-evaluated in response to information desired by
    the 1977 Joint Meeting on the effects of cooking on residues and to a
    request from the 1979 Codex Committee on Pesticide Residues to review
    the recommended temporary maximum residue limits on bananas (whole and
    pulp) in light of extensive new data available from field trials
    reflecting improved agricultural practice.

    In tests conducted in Honduras and the Philippines, repeated low
    volume aerial applications of chlorothalonil formulations were made on
    bananas for control of foliar diseases.  Although this use will result
    in some applications being made to fruiting plants it is common
    practice to place plastic bags over the developing stems to protect
    the fruit until harvest.  Samples of mature banana fruits from bagged
    and unbagged stems were analyzed for chlorothalonil and its metabolite
    DAC-3701.  No residues (<0.01 mg/kg) of chlorothalonil or DAC-3701
    were detected in edible pulp of any samples.  Commercial washing of
    the banana fruits prior to export resulted in an average of 75%
    reduction in residual chlorothalonil.  The data support a reduction in
    the recommended temporary maximum residue limits from 4 mg/kg (whole
    banana) and 0.1 mg/kg (banana pulp) to 0.2 mg/kg (whole banana) and
    0.05 mg/kg (banana pulp).

    Data on residues in onions, grapes, potatoes, and tomatoes from
    supervised trials in various countries were available.  These
    confirmed the previous recommendations for onions, potatoes, and
    tomatoes and permit the recommendation of a temporary MRL for grapes.

    Although it is theoretically possible to have a detectable residue of
    the manufacturing impurity hexachlorobenzene on whole bananas if many
    repeat applications are made, calculations based on a specification of
    not more than 0.02% HCB in a commercial formulation indicate that this
    would not be a problem in bananas since no residues should occur in
    edible pulp.  The situation for other agricultural commodities needs
    investigation and clarification.

    Chlorothalonil would be detected by the multiresidue methods of
    analysis for fatty and non-fatty foods described in the FDA Pesticide
    Analytical Manual, Vol. I, and equivalent procedures utilized in other
    countries but DAC-3701 would not.  Therefore the multiresidue methods
    are useful for screening purposes, but if the presence of
    chlorothalonil is indicated, need to be followed by the more specific
    methods developed for chlorothalonil and DAC-3701 for regulatory
    compliance.

    The effect of cooking upon chlorothalonil with plain water, tomatoes,
    or green beans was evaluated.  Under open cooking conditions,
    chlorothalonil was lost (94-98%) through volatilization.  Under closed
    cooking conditions, hydrolysis to 4-hydroxy-
    2,5,6-trichloroisophthalonitrile (DAC-3701) and
    3-cyano-2,4,5,6-tetrachlorobenzamide (DS-19221) occurred.  When cooked

    in a tightly sealed pressure cooker, chlorothalonil remained
    unchanged.  Under similar test conditions, neither losses nor chemical
    changes were observed, for DAC-3701.

    RECOMMENDATIONS

    A temporary maximum residue limit for grapes is recommended in
    addition to those temporary MRL's previously recommended.  The
    temporary maximum residue limits recommended in 1977 for bananas are
    amended as follows:

                                                                       
                                        Preharvest interval on which
                                        recommendations are based;
    Commodity           Limit, mg/kg               days
                                                                       

    Grapes                  5                       46
    Bananas (whole)         0.2                    none
    Bananas (pulp)          0.05                   none
                                                                       

    FURTHER WORK OR INFORMATION

    Required by 1981:

    1.  Studies to define the growth reduction after administration of
        chlorothalonil or its major metabolite (DAC-3701) in pups relative
        to ingestion or secretion into milk.

    Desirable

    1.  Experimental information on the possible occurrence of
        hexachlorobenzene residues on crops requiring multiple
        applications.
    2.  Results of on-going studies on the effects of cooking under closed
        conditions on residue levels and composition.
    3.  Elucidation of the discrepancies in the carcinogenicity studies.
    4.  Observations in occupationally exposed humans.
    5.  Information on the extent of metabolism of chlorothalonil in
        mammals.

    REFERENCES

    Ballee, D.L., Duane, W.C., Stallord, D.E.,and Wolfe, A.L.  "Analytical
    Methods for Pesticides and Plant Growth Regulators," Vol. VIII, pp.
    263-274 (1976).  Edited by Gunter Zweig and Joseph Sherma.  Academic
    Press, Inc., New York, N.Y., publishers.

    Busey, W.M.  Histopathological Incidence Data - Kidney.  (1975)
    Unpublished Report by Experimental Pathology Laboratory, Inc.
    Submitted by Diamond Shamrock Corporation.

    Canada.  Information provided by national government. (1979).

    Diamond Shamrock.  Residue Chemistry. Results of tests on the amount
    of residues remaining (on bananas), including a description of the
    analytical method. (1979a) Unpublished report.

    Diamond Shamrock.  Effect of cooking upon
    2,4,5,6-tetrachloroisophthalonitrile (chlorothalonil, DS-2787) and
    4-hydroxy-2,5,6-trichloroisophthalonitrile (DS-3701).  Report Document
    Number: 283-3EF-79-0058-001. (1979b) Unpublished report.

    Finland.  Information provided by national government.  (1979).

    Hastings, T.F. and Jessop, D.C.  4-month Dietary Toxicity Study-Rats.
    Chlorothalonil.  Final Report.  (1979) Unpublished Report by Bio/Tox
    Research Laboratories, Inc. Submitted by Diamond Shamrock Corporation.

    Jarrett, R.D., Stallard, D.E., and Bachand, R.T. Absorption, Excretion
    and Tissue Distribution of Orally Administered
    14C-4-Hydroxy-2,5,6-Trichloro-isophthalonitrile (14C-DAC 3701) in
    Male Sprague-Dawley Rats.  (1978) Unpublished Report by T.R. Evans
    Research Centre Submitted Diamond Shamrock Corporation.

    NCI.  Bioassay of Chlorothalonil for Possible Carcinogenicity.  United
    States Department of Health, Education, and Welfare, Publication No.
    (NIH) 78-841 (1978).

    Newberne, P.K.  (1975) Unpublished Report by the Department of
    Nutritional Pathology, Massachusetts Institute of Technology,
    submitted by Diamond Shamrock Corporation.

    New Zealand.  Information provided by national government. (1979).

    South Africa.  Information provided by national government. (1979).

    Sweden.  Information provided by national government. (1979).

    Weinberg, M.S.  Review of Bioassay Study of Chlorothalonil Performed
    for the National Cancer Institute by Gulf South Research Institute
    Phase 1: Rat Study.  (1979) Unpublished Report by Booz, Allen, and
    Hamilton, Inc.  Submitted by Diamond Shamrock Corporation.

    Weasel, J.R.  Private Communication. (1979).
    


    See Also:
       Toxicological Abbreviations