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    FAO/PL:1968/M/9/1

    WHO/FOOD ADD./69.35

    1968 EVALUATIONS OF SOME PESTICIDE RESIDUES IN FOOD

    THE MONOGRAPHS

    Issued jointly by FAO and WHO

    The content of this document is the result of the deliberations of the
    Joint Meeting of the FAO Working Party of Experts and the WHO Expert
    Committee on Pesticide Residues, which met in Geneva, 9-16 December,
    1968.

    FOOD AND AGRICULTURE ORGANIZATION OF THE UNITED NATIONS

    WORLD HEALTH ORGANIZATION

    Geneva, 1969

    TOXAPHENE

    IDENTITY

    Chemical name

    Chlorinated camphene containing 67-69 per cent chlorine.

    Synonyms

    3956, octachlorocamphene, Toxaphene(R) (Toxaphene is a common name
    in some countries and a tradename in others).

    Formula

    The average empirical formula is C10H10Cl8

    Other information on identity and properties

    Chlorinated camphene (67-69 per cent chlorine) is a complex mixture
    of polychloro bicyclic terpenses, with chlorinated camphenes
    predominating. The source of terpene and the degree of chlorination
    outside the 67-69 per cent range alter the insecticidal activity and
    the mammalian toxicity. Toxaphene, which is a registered trademark in
    most countries, is chlorinated camphene. Toxaphene is a complex
    mixture. Ninety per cent pure camphene is chlorinated to between 67
    and 69 per cent by weight which results in a general rearrangement of
    camphene to form a large group of related compounds each with about
    eight chlorines. The number of individual chemicals formed and their
    structure is unknown. The investigations reviewed here have been
    conducted on toxaphene.

    EVALUATION FOR ACCEPTABLE DAILY INTAKE

    Biochemical aspects

    Toxaphene is absorbed through the skin and the intestinal tract, the
    degree of absorption and its toxicity depending on the vehicle.
    Studies on the tissue distribution and storage of toxaphene in the
    body have demonstrated that the fat is the only organ of significant
    storage and that the degree of storage is relatively low - one fourth
    to one eighth of the feeding level for rats (Patterson and Lehman,
    1953). Although most of the data on tissue distribution and storage
    have been obtained by non-specific organochlorine determinations after
    controlled exposures, more recent studies applying thin-layer
    chromatography have confirmed the validity of the older data and of
    the fact that the toxaphene present in tissues is unchanged (Dalton,
    1966). After termination of exposure to toxaphene, elimination is
    prompt and toxaphene residues in fat disappear rapidly (Lehman, 1952a;
    Claborn, 1956).

    Excretion of toxaphene in milk closely parallels the level of storage
    in fat tissue. Cows fed 20, 60, 100 and 140 ppm toxaphene in the diet
    excreted 0.37, 0.74, 1.15 and 1.88 ppm respectively in the milk (USDA,
    1956).

    As is the case with other chlorinated hydrocarbons, toxaphene induces
    activity of liver microsomal enzymes. Feeding toxaphene for 13 weeks
    to rats at dietary levels of 25 and 50 ppm produced marked induction
    of N-demethylase, O-demethylase and EPN for detoxification enzymes.
    Four weeks after termination of toxaphene feeding the enzyme activity
    had returned almost to control level. Minimum induction occurred at 5
    ppm feeding level of toxaphene, compared to a similar induction at 1
    ppm with DDT (Kinoshita et al., 1966).

    Acute toxicity

                                                                              
                           LD50 mg/kg
    Animal        Route    body-weight    Vehicle        Reference
                                                                          

    Mouse         Oral         112        Maize oil      Negherbon, 1959

    Rat           Oral          60        Maize oil      Lehman, 1948

    Rat (M)       Oral          90        Peanut oil     Gaines, 1960

    Rat           Oral         120        Maize oil      Shelanski, 1947

    Rat           i.v.          13        Peanut oil     Gellhorn, 1947

    Guinea-pig    Oral         290        Maize oil      Shelanski, 1947

    Guinea-pig    Oral         365        Kerosene       Shelanski, 1947

    Dog           Oral          25        Maize oil      Lackey, 1949

    Dog           i.v.        5-10        Peanut oil     Gellhorn, 1947

    Goat          Oral         200        Xylene         Radeleff and
                                                         Bushland, 1952

    Sheep         Oral         200        Xylene         Radeleff and
                                                         Bushland, 1952
                                                                          
    

    The signs of toxicity following acute exposure to toxaphene are the
    result of diffuse stimulation of the cerebrospinal axis, and include
    salivation, spasms of the back and leg muscles, nausea, vomiting,
    hyper-excitability, tremors, shivering, clonic convulsions, then

    tetanic contractions of all skeletal muscles. With lethal doses, the
    convulsions often continue until death, which apparently is caused by
    respiratory failure. There is very little effect on the heart rate or
    blood pressure of the anaesthetized dog. Respiration is affected as a
    result of the exertion from vomiting or convulsions. It is arrested
    due to tetanic muscular contractions, then increased in both amplitude
    and rate as the muscles relax. (McGee et al., 1952; Negherbon, 1959)

    Short-term studies

    Rat

    Groups, each containing six male and six female rats, were fed 50 and
    200 ppm toxaphene in the diet. One male and one female from each group
    were sacrificed after two, four and six months. The rest were
    sacrificed after nine months. There were no clinical signs of
    toxicity, no change of food intake or body-weight gain and no increase
    in liver weights of these rats. Only the liver, kidney and spleen of
    each animal were examined histologically. There was no damage to the
    kidney or spleen. Liver changes observed consisted of centrilobular
    cell hypertrophy, peripheral migration of basophilic cytoplasmic
    granulation and presence of liposphere inclusion bodies. Three of 12
    rats fed 50 ppm showed slight changes as described above after being
    fed toxaphene for six to nine months, and it was concluded that this
    level produces possible borderline liver changes. Six of the 12 rats
    fed 200 ppm showed liver changes (Ortega et al., 1957).

    Dog

    Toxaphene was administered in capsules at a daily dose of 4 mg/kg to
    two dogs for 44 days and to two other dogs for 106 days. Occasional
    manifestations of acute toxicity (CNS stimulation) occurred for a
    short time after administration. There were no significant changes in
    the body-weight, blood picture, or gross appearance of organs.
    Histological examination of many organs revealed some damage to the
    kidney (degeneration of the tubular epithelium) and to the liver
    (generalized hydropic degenerative changes, but no destruction of the
    cells). Liver glycogen levels were normal. (Lackey, 1949)

    Toxaphene dissolved in maize oil was administered daily (five days per
    week) to dogs in gelatin capsules. A dose of 25 mg/kg was fatal. Two
    dogs were administered 10 mg/kg (equivalent to 400 ppm in the diet);
    one dog died after 33 days, but the other lived and was sacrificed
    after three-and-a-half years. Four dogs were administered 5 mg/kg; all
    survived and were sacrificed after almost four years. No information
    on the pathologic findings was reported (Lehman, 1952b).

    Toxaphene was fed daily (six days per week) for two years to three
    male and five female dogs approximately four months old. Toxaphene was
    added to the diet at levels of 10 and 50 ppm of the total wet diet,
    including their liquids, The dogs received a daily dose of 0.60-1.47
    mg/kg and 3.12-6.56 mg/kg (equivalent to approximately 40 and 200 ppm
    on a dry diet basis). Gross behaviour, body-weight, mortality,

    peripheral circulating blood elements, gross pathology, organ to
    body-weight ratios and histopathology were recorded (Treon et al.,
    1952).

    There were no effects on behaviour, body-weight, mortality or blood
    elements, but there were increases in the liver weights, liver to
    body-weight ratios and moderate liver degeneration at the higher level
    (200 ppm). At the lower level (40 ppm) one of three dogs was reported
    to have slight liver enlargement and slight granularity and
    vacuolization of the cytoplasm. Re-examination of the sections of
    these animals failed to confirm any difference from control animals.
    All other tissues were normal at both feeding levels (Brock and
    Calandra, 1964).

    Groups each of 12 dogs (six male and six female) were fed toxaphene at
    dietary levels of 5, 10 and 20 ppm along with control groups. Two male
    and two female animals were sacrificed after six, 12 and 24 months.
    None of the feeding levels produced any change revealed by organ
    weights, gross or histological examination, or any of the clinical or
    organ function tests at any time, (Industrial Bio-Test Laboratories,
    Inc., 1965).

    Monkey

    Two adult, female monkeys were given toxaphene in their food six days
    per week at a daily dose of 0.64 to 0.78 mg/kg for two years. A third
    animal served as a control. There were no signs of intoxication and no
    evidence of tissue or organ damage as evaluated by growth rate, ratios
    of liver to body-weight, spleen to body-weight or by histological
    examination of the tissues (Treon et al., 1952).

    Long-term studies

    Rat

    Four groups each of 40 rats (20 males and 20 females) were fed 10,
    100, 1000 and 1500 ppm toxaphene in the diet. Effects were determined
    by gross observation, mortality, body-weight, blood tests, liver
    weight, liver to body-weight ratio, gross autopsy and histological
    examination of the tissues. After seven-and-a-half to 10 months of
    feeding some of the rats fed 1500 ppm and a few of the rats fed 1000
    ppm showed occasional convulsions. The body-weight gain of the rats
    fed the highest feeding level (1500 ppm) for the first 20 weeks was
    less than those of the controls, probably due to decreased food intake
    because of the unpalatability of the diet. As the rats became
    accustomed to the diet, their growth rate was essentially the same as
    that of the controls. There were no significant effects on mortality
    or the haematopoietic system. The liver weight and liver to
    body-weight ratio was significantly increased only in the 1000 and
    1500 ppm groups. Liver changes consisted of swelling and homogeneity
    of the cytoplasm with a peripheral arrangement of the granules in the
    cytoplasm of the centrilobular hepatic cells. These changes occurred

    to a moderate degree in the 1500 ppm group and to a slight degree in
    the 1000 ppm group (Treon et al., 1952).

    Groups of rats were fed 25, 100 and 400 ppm in the diet. The only
    organ which showed significant histological change was the liver and
    occurred at the 100 ppm and 400 ppm levels. There were centrilobular
    hepatic cell enlargement with increased oxyphilia, peripheral
    margination of basophilic granules and a tendency to hyalinization of
    the remainder of the cytoplasm. The effects at the various feeding
    levels were summarized by Lehman as follows: 400 ppm was the lowest
    level producing a gross effect of liver enlargement; 100 ppm the
    highest level not producing gross effects; 100 ppm the lowest level
    producing tissue damage; and 25 ppm the highest level not producing
    tissue damage (Fitzhugh and Nelson, 1951; Lehman, 1952b).

    Special studies

    Reproduction

    Rat. A three-generation, six-litter reproduction study was conducted
    with toxaphene. Groups of weanling rats were fed 25 ppm and 100 ppm
    for 79 days before mating. All animals were continued on their
    respective dietary concentration of toxaphene during the mating,
    gestation, weaning of two generations, or for a period of 36 to 39
    weeks. Weanlings from the second litter were selected as parents for
    the second generation and continued on their respective diets until
    after weaning of 4 second litter. A third generation was selected in
    the same manner. Complete gross and histological examination was
    performed on all three parental generations after 36 weeks of
    toxaphene administration. The only pathologic changes found were
    slight alterations in the livers of the 100 ppm group similar to those
    changes seen in long term studies. Reproductive performance, fertility
    and lactation were normal. The progeny were viable, normal in size and
    anatomical structure. Findings among all test animals, three parental
    generations and six litters of progeny were comparable to control
    animals for all parameters (Kennedy et al., 1968).

    Pheasant. Pheasants were fed 100 or 300 ppm toxaphene in the diet.
    In the 300 ppm group, egg-laying and hatchability were significantly
    depressed, food consumption and weight gain were reduced. Both dose
    levels caused a significantly greater total mortality of the young
    pheasants than that of controls over the period from hatching to the
    thirteenth day. Relative reproductive success was: for controls, 70
    per cent; for the 100 ppm group, 62 per cent; and for the 300 ppm
    group, 46 per cent (Genelly et al., 1956).

    Observations in man

    A nine-month-old girl was poisoned acutely by a dust containing 13.8
    per cent toxaphene and 7.04 per cent DDT. Convulsions, respiratory
    arrest and death followed. Cerebral oedema was found. Analysis of the
    brain, liver and kidney indicated that toxaphene is stored to a
    greater extent than DDT (Haun and Cueto, 1967).

    Twenty-five human volunteers were exposed in a closed chamber to an
    aerosol of toxaphene for 30 minutes a day for 10 consecutive days at
    an average concentration of 500 mg/m3 of air. After three weeks,
    they received the same exposure on three consecutive days. Based on an
    assumed retention of 50 per cent of the inhaled toxaphene, each
    individual received a dosage of 75 mg of toxaphene daily - or slightly
    more than 1 mg/kg/day. Complete physical examinations, including
    fluoroscopic, blood and urine tests, failed to reveal any toxic
    manifestations (Shelanski, 1947).

    Comments

    Long-term toxicity studies on toxaphene have been conducted in the rat
    only, and several short-term studies in dogs and monkeys. Very little
    difference in species susceptibility had been observed. No toxic
    effect was observed at dietary levels of 25 ppm for the rat, 40 ppm
    for the dog and 15 ppm for the monkey (only level studied). The toxic
    manifestations of toxaphene at higher levels are primarily those of
    liver enlargement and other hepatic alterations observed with most
    chlorinated hydrocarbons. Microsomal stimulation has been measured and
    demonstrated to be reversible. Toxaphene is stored in fat tissue at a
    low level compared to most chlorinated hydrocarbons, and is more
    rapidly eliminated after exposure is terminated. Reproduction is not
    affected at the 100 ppm dietary level in the rat, but liver damage
    occurs above 25 ppm.

    Although adequate work has been done on the original compound of known
    composition, the substance at present in agricultural use does not
    necessarily conform to the specifications of the original material
    tested biologically. Before an evaluation can be made, the identity of
    the compounds presently in use must be established, and future
    toxicological work must be related to them.

    RESIDUES IN FOOD AND THEIR EVALUATION

    Use pattern

    Toxaphene is reported to be a widely used pesticide in many parts of
    the world and particularly in the United States of America, both in
    quantity used and in number of uses.

    Pre-harvest treatments

    Toxaphene is used in many countries for control of armyworms,
    cutworms, earworms, budworms, thrips, beetles, weevils, grasshoppers
    and many other insects. Crops treated include a wide variety of
    agronomic, vegetable and fruit crops. Most treatments are foliar
    applications except those for cutworms. Toxaphene is also used for
    ectoparasite control on cattle, sheep and swine.

    On crops the usual rates of application are 1.26 to 3.78 kg/ha.
    Toxaphene is frequently applied in mixture with other insecticides
    such as methyl parathion, parathion, DDT, naled and others.

    Post-harvest treatment

    Toxaphene is not used for post-harvest treatments.

    Residues resulting from supervised trials

    There have been many analyses made for toxaphene in treated crops.
    Generally these show residues likely to occur with a specific
    treatment or set of multiple treatments used in the production of that
    crop. A compilation of published and unpublished data (Hercules, Inc.)
    is held at FAO headquarters in Rome. Table I summarizes selective data
    which indicate the levels of residues that result from usual
    agricultural practice on representative types of crops. The residue
    level is controlled by proper application restrictions such as
    pre-harvest intervals, application prior to formation of edible parts
    or application to crops where the harvested portion is protected from
    the spray by pods, husks, outer leaves or other coverings.

    Toxaphene residues resulting from a foliar application generally
    exhibit a half-life of 5-10 days on growing crops. The half-life
    varies with weathering conditions, plant or fruit type, and plant
    growth rate, and for different formulations. Residues from wettable
    powders or dusts are lost more rapidly than from emulsifiable
    concentrates. Brett and Bowery (1951) show the declining rates of
    toxaphene on three kinds of vegetables: snapbeans, tomatoes and
    collards. On snapbeans, with no rain, a steady decline from 8.1 ppm to
    1.5 ppm occurred in 12 days. Rain markedly hastened the disappearance
    of residues in the other crops. Tomatoes with a small surface area in
    comparison to total volume had a residue which declined from 4 ppm to
    0.15 ppm in 12 days. In contrast, collards with a large surface area
    in relation to total volume had a residue which decreased from 168 ppm
    to 5.0 ppm in 12 days.

    Nash and Woolson (1967) reported that when toxaphene was applied and
    thoroughly mixed with soil, 45 per cent of the original application
    remained after 14 years. This extreme persistence would not be
    expected when toxaphene is used as a topical soil application for the
    control of cutworms. Residue loss by volatilization and weathering
    from a surface soil treatment would probably more closely resemble the
    decline pattern on crops from foliar application. Because foliar
    application is the major use of toxaphene, residues in the soil would
    be primarily from this use.

    In a soil monitoring study conducted in the Mississippi Delta by USDA
    (1966) involving agricultural areas in which general use of toxaphene
    had been made (but not known to have been used specifically on each
    sample site), soil residues of 0.88 to 3.78 ppm were found. Muns et
    al. (1970) found that residues of toxaphene in potatoes, table beets,
    sugar beet roots and tops, and radishes grown in soil treated with

    toxaphene were less than 0.4 ppm. There is no positive evidence to
    indicate an excessive buildup in the soil from normal use or that
    residues in the soil are absorbed by plants and concentrated to any
    degree.

    Toxaphene accumulates in fat of animals after ingestion or after
    spraying or dipping for insect control. The research of Claborn and
    associates (1960) established two important residue characteristics of
    toxaphene: (1) with any given rate of subacute intake a certain
    storage level is attained with no buildup above this level; and (2)
    when the source of toxaphene is removed the residue is rapidly
    reduced. The level of storage is lower and elimination more rapid than
    with most other chlorinated hydrocarbons. As a rule storage level in
    the fat of cattle and sheep will be one fourth to one half the level
    in the food. Storage concentration in hogs is somewhat less than in
    other livestock probably because of the greater fat content.

    The work of Claborn et al. (1960) and Zweig et al. (1963) shows the
    amount of residue that would occur in milk of cows fed toxaphene in
    their diet. Both studies indicate that the ratio of toxaphene in the
    milk to that in the feed is about 1:100. Uncontaminated milk was
    produced in 14 days or less after feeding levels up to 10 ppm were
    stopped. Spraying dairy cows for insect control causes residues in the
    milk. For this reason dermal application of toxaphene is not permitted
    on dairy animals.

    Fate of residues

    Toxaphene can be altered chemically by dechlorination or by
    hydroxylation.

    Non-specific organochlorine methods have been used to measure the
    residues in supervised trials. The identity of the individual
    components in the complex technical mixture is not known, nor has
    isolation of the individual components which comprise the residue in
    plants and animals been reported. Thin-layer, paper and gas
    chromatography patterns can be used to identify the residue. Ives
    (1967) by gas chromatography of toxaphene saw evidence of at least 25
    different components.

    Because of the complex nature of the parent chemical mixtures, it is
    impossible to define the nature of the residue with any degree of
    specificity.

    Ihde and Taft (1954) have shown that insecticidal activity is
    characteristic only of the parent material with chlorine content of
    67-69 per cent. Slight alteration in the chlorine content either above
    or below this level markedly decreases insecticidal activity. Carter
    et al. (1950) extracted aged toxaphene residues from treated alfalfa
    and compared the insecticidal activity of this residue with that of
    standard toxaphene. They found very close agreement in insecticidal
    activity of the alfalfa hay residue and the standard. They also
    assayed the residue from beef fat and again found the insecticidal


                                                                                                        
    TABLE I.  TOXAPHENE RESIDUES RESULTING FROM SUPERVISED TRIALS

                     Rate of                   Pre-harvest*     Residue
         Crop      application     No. of        interval      at harvest        Comments
                     (kg/ha)      treatment       (days)         (ppm)
                                                                                                    

    Vegetables

    Lettuce            5.5           1-4             10         5.8-7.9        whole head
    Kale               5.0             4             36         3.3-7.2
    Cabbage            1.9-12        2-6           9-38         0.8-6.6        on outer leaves
    Spinach            5.0             4             30         16.7-18.8
    Celery             1.1-1.6         9             13         1.8 stalks     washed
                                                                6.5 leaves
    Cauliflower        3.8             1              8         1.1            (processed commercially
    Broccoli          10               1              8         3.4            (and frozen before
                                                                               (before analysis
    Tomatoes           1.3-2.5       8-9            5-7         2.0-4.3
    Greenbeans         7.5             1              7         1.3            unwashed
    Lima beans         3.9             1             14         0.3            shelled beans
    Carrots           25             2-4                        0.9-3.3        soil applic. (1 yr)
    Potatoes           0.95-2.5        6             21         0 detected
    Field peas         2.5             3              4         1.8

    Oil seeds

    Cotton (seed)      3.9-5.0        15              6         3.6-5.2        lint bearing seed
    Soybeans           3.8             3             60         0.5
    Peanuts
     (shelled)         25-50           1                        0 detected     soil treat.

    Fruit

    Oranges            5.7             2           7-70         0-10.9 skins
                                                                0-0.3 pulp
    Bananas            3.8             1              1         0.3-1.3        whole fruit
    Pineapple          2.8             2          84-96         1.3-2.7        whole fruit

                                                                                                    
    TABLE I.  (continued)

                     Rate of                   Pre-harvest*     Residue
         Crop      application     No. of        interval      at harvest        Comments
                     (kg/ha)      treatment       (days)         (ppm)
                                                                                                    

    Cereal grains

    Wheat              1.9-3.8         1          14-21         0.5-1.8
    Barley             1.9-3.8         1           7-28         0.7-14.2
    Oats               1.9-3.8         1              7         1.0-2.6
    Rice               1.9-3.8         1           7-28         1.5-5.6        unfinished grain
    Sorghum            2.5             1             28         2.5-3.1
    Corn (maize)       2.5             1             12         0.08 kernels

    Fat of meat animals

    Beef               0.5%           12             28         5.0            12 weekly sprays
    Swine              0.5%            2             28         0-0.6          2 sprays

    Shelled nuts

    Almonds            4.0             3            135         1.5
                                                                                                    
    * Interval from last application if multiple applications were made.
    

    activity from the beef fat residue to be equal to the standard
    toxaphene.

    Klein and Link (1967) reported field weathering of toxaphene on kale
    for a 28-day period. One foliar application was made at a rate of 2.52
    kg/ha using a water suspension of a 40 per cent wettable powder.
    Electron capture and microcoulometric gas chromatography and the
    colorimetric method of Graupner and Dunn (1960) were used for the
    analyses. An initial residue of 155 ppm was reduced to essentially
    zero in 28 days. At the seventh day only about 8 per cent of the
    initial residue was present. Its composition remained fairly constant
    although some of the more volatile fractions were lost as evidenced by
    GLC. However, at 14 days with only about 1 per cent of the pesticide
    remaining, its composition had altered. Even at low levels the
    remaining components appeared to be organic chlorine compounds.

    Evidence of residues in food in commerce or at consumption

    The United States Food and Drug Administration has conducted residue
    studies in foods and total diet samples since 1962. Duggan (1967,
    1968b) shows the frequency and magnitude of pesticides in different
    classes of foods and in individual diet samples.

    Toxaphene was not among the 15 pesticide chemicals most frequently
    found in the 888 total diet composites examined from 1964 to 1967.
    When toxaphene is found in total diet composites, it is usually in
    either the leafy vegetable or garden fruit composite. For the period
    June 1964 to April 1967 toxaphene was found in 1.4 per cent of the
    leafy vegetable composites at an average level of 0.005 ppm and in 2.7
    per cent of the garden fruit composites at an average level of
    <0.001 ppm.

    From 1963 to 1966, 26 326 domestic raw agricultural samples (not
    including animal tissues) were found to contain pesticide residues.
    Toxaphene was present in 754 of these samples and ranked tenth in
    incidence among the 11 pesticides which contributed 95 per cent of
    all residues found during that period. Toxaphene ranks third in
    incidence in animal tissues.

    Table II shows the percentage of domestic samples from 1964 to 1967
    which contained toxaphene and the average level found for various raw
    agricultural products.

    TABLE II
                                                        

    Raw agricultural product     Indicence    Average
                                 per cent.     ppm
                                                        

    Leaf and stem vegetables       6.4         0.18
    Vine and ear vegetables        1.4         0.01
    Root vegetables                1.1        <0.005

    TABLE II (continued)
                                                        

    Raw agricultural product     Indicence    Average
                                 per cent.     ppm
                                                        

    Small fruit                    1.0        <0.005
    Beans                          0.9        <0.005
    Large fruit                    0.3        <0.005
    Cereal grains                  0.3        <0.005
    Nuts                           0.3        <0.005
    Eggs                           0.2        <0.005
    Animal food grains             0.1        <0.005
                                                        

    Among the domestic samples of canned and frozen products examined from
    1964 to 1967 toxaphene ranked sixth in incidence with 5.0 per cent of
    the samples containing residues at an average level of 0.45 ppm, the
    highest average level found among the 17 most frequently encountered
    pesticide residues.

    Duggan (1968a) showed that toxaphene was frequently found in oil seed
    products. Table III gives the per cent of samples containing
    toxaphene and the average level found in 1544 samples analysed from
    1964 to 1966.

    TABLE III
                                                                     

                  Raw product    Crude oil      Meal     Refined oil
                                                                     

    Soybeans       8.0*           4.1             -        4.3
                  (0.004)**      (0.024)                 (<0.001)

    Peanuts        1.7            2.8             -         -
                  (0.006)        (0.008)

    Cottonseed    30.4            1.3           1.1       12.2
                  (0.023)        (0.010)       (0.003)    (0.140)
                                                                     

    *  Incidence in per cent.
    ** Average residue found (ppm).

    Methods of residue analysis

    In the past, several total chloride methods have been used for residue
    studies. These methods are accurate for known residues. Where mixtures
    with other organic chlorine insecticides were encountered such as DDT,
    a specific method for that compound was employed and the toxaphene was
    determined by difference. The toxaphene was then identified by

    thin-layer or paper chromatography. While these methods are accurate,
    they are somewhat difficult to use in surveillance work.

    A specific residue method is now available. A gas chromatographic
    electron capture system has been applied to toxaphene residue analyses
    (Eastman, 1968). Toxaphene residues are dehydrohalogenated with
    potassium hydroxide and measured by gas chromatography. The clean-up
    procedures and dehydrohalogenation remove all possible interfering
    residues except chlordane.

    National tolerances

                                                                               
                                                               Tolerance
    Country                        Crop                          (ppm)
                                                                           

    Canada*           Oats, pineapple, wheat                       3
                      Barley, grain sorghum, rice                  5
                      Beans, blackeyed peas, broccoli,
                      Brussel sprouts, cabbage,
                      cauliflower, celery, citrus fruit,
                      egg-plant, fat of meat from cattle,
                      sheep, goats and hogs, kohlrabi,
                      lettuce, okra, onions, pears, peas,
                      strawberries, tomatoes                       7

    Germany           Pears, strawberries, raspberries,
                      cherries, plums                              0.4
                      Other plant products                         0.04

    Netherlands       Fruit, vegetables, except potatoes           0.4

    United States     Soybeans                                     2
    of America*       Pineapples, bananas (0.3 ppm in pulp)        3
                      Wheat, barley, rye, rice, cottonseed,
                      stone and pome fruit, cane fruit,
                      corn, leafy, fleshy and fruit
                      vegetables, nuts, beans, peanuts, peas,
                      strawberries and fat of beef, sheep,
                      goats, swine and horses                      7
                                                                           

    * Tolerances are under review in Canada and the United States of America.
    
    RECOMMENDATIONS FOR TOLERANCES AND PRACTICAL RESIDUE LIMITS

    Appraisal

    Because of the many questions related to this compound, outlined in
    detail below, no recommendations can be made at this time.

    Further work or information

    Required (before an acceptable daily intake or tolerance can be
              established)

    1.   Data relating to the uniformity of the technical product:

    (a)  variability in biological activity (e.g., LD50 variation in
         mammals or in insects) from batch to batch;

    (b)  variability in the chemical composition as determined by gas
         chromatography, thin-layer chromatography or other analytical
         methods;

    (c)  variability in the starting product and in the final product from
         different sources;

    (d)  criteria for control of the degree of chlorination.

    2.   Information on the chemical nature of terminal residues in
         plants, animals, and their products, as determined by modern
         analytical methods, including the possibility of formation of
         photo-oxidation products.

    3.   Further residue data from supervised trials on a variety of
         crops.

    4.   Residue data in:

    (a)  poultry, cattle, sheep and swine;

    (b)  unprocessed and processed vegetable oils;

    (c)  cereals, after processing into flour, bread, etc.

    5.   Development and comparative evaluation of methods of analysis for
         regulatory purposes.

    6.   Complete toxicological studies based upon a standardized
         technical product, the constituents of which have been
         identified.

    REFERENCES

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    vegetables. J. Econ. Entomol., 51: 818-821

    Brock, D. and Calandra, J. C. (1964) Re-evaluation of microscopic
    sections from chronic oral toxaphene study. Industrial Bio-Test
    Laboratories, Inc., unpublished report

    Carter, R. H., Nelson, R. H. and Gersdorff, W. A. (1950) Organic
    chlorine determination as a measure of insecticide residues in
    agricultural products. Advances in Chem. Series, 1: 271-3

    Claborn, H. V. (1956) Insecticide residues in meat and milk. United
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    Claborn, H. V., Radeleff, R. D. and Bushland, R. C. (1960) Pesticide
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    Dalton, C. J. Toxaphene residue in dog tissues. (1966) Two-year
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    Duggan, R. E. (1967) Pesticide residues in foods. Presented at the
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    Duggan, R. E. (1968a) Pesticide residues in vegetable oil seed, oils
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    Duggan, R. E. (1968b) Pesticide residue levels in foods in the United
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    Eastman, G. E. (1968) Toxaphene determination by electron capture gas
    chromatography. Hercules, Inc., Wilmington, Delaware, unpublished
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    Fitzhugh, O. G. and Nelson, A. A. (1951) Comparison of chronic effects
    produced in rats by several chlorinated hydrocarbon insecticides.
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    Gaines, T. B. (1960) The acute toxicity of pesticides to rats.
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    Gellhorn, A. (1947) Toxicological and pharmacological observations on
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    Genelly, R. E. and Rudd, R. L. (1956) Effects of DDT, toxaphene and
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    Graupner, A. J. and Dunn, C. (1960) Determination of toxaphene by a
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    Ives, N. F. (1967) United States Food and Drug Administration. Private
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    Kinoshita, F. K., Frawley, J. P. and DuBois, K. P. (1966) Quantitative
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    Klein, A. K. and Link, J. D. (1967) Field weathering of toxaphene and
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    Lehman, A. J. (1948) The toxicology of the newer agricultural
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    Lehman, A. J. (1952a) Chemicals in foods: a report to the Association
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    Lehman, A. J. (1952b) Chemicals in food: a report to the Association
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    McGee, L. C., Reed, H. L. and Fleming, J. P. (1952) Accidental
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    Ortega, P., Hayes, W. J. and Durham, W. F. (1957) Pathologic changes
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    Shelanski, H. A. (1947) Smyth Laboratories, Philadelphia, Penn.
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    J. Agr. Food Chem., 11: 70-72

    


    See Also:
       Toxicological Abbreviations
       Toxaphene  (IARC Summary & Evaluation, Volume 79, 2001)