LINDANE      JMPR 1973


         Lindane was evaluated by the Joint Meeting in 1965 (FAO/WHO,
    1965b), 1966 as gamma-BHC (FAO/WHO, 1967b), 1967 (FAO/WHO, 1968b),
    1968 (FAO/WHO, 1969b), 1969 (FAO/WHO, 70b) and in 1970 (FAO/WHO,
    1972b). Further information has since become available and is
    summarized in the following monograph addendum.


    Biochemical aspects


         The metabolic fate of lindane in mammals has been examined by
    several authors who conclude that the metabolic pathway is probably
    more complex than previously described. Previously unidentified
    metabolites from rat urine have been identified as 3,4-dichlorophenol,
    2,4,6-trichlorophonol, 2,3,4,5 -and 2,3,4,1,6-tetrachlorophenol,
    2,3,4,5,6-pentachloro -2- cyclohexen -1 - ol. These investigators
    suggest that dehydrochlorination may not be a significant pathway in
    mammals. (Chadwick and Freal, 1972; Karapally et al., 1973).

         One author did not find the cyclohexenol metabolite in rabbit but
    isolated the chlorophenols and chlorobenzones mentioned above as well
    as several other organosoluble products (Karapally et al., 1973).

    Effects on enzymes and other biochemical parameters

         A study was carried out on the effect of lindane on lactate
    dehydrogenase and its isoenzymatic spectrum in blood serum and liver
    of rats (Alekbina and Khaikina, 1972). Lindane was administered at 1.7
    mg/kg for over 180 days. A decrease in the total LDH in the serum
    accompanied by a simultaneous change in the isoenzyme spectrum, e.g.
    declining LHD1 and rising LDH4. The changes in the isoenzyme
    spectrum of the liver were as follows: an increase in the activity of
    LDH1, LDH2, LDH3, LDH4 and a decrease in LDH5 with reduced total
    LDH activity in the liver. The effect of lindane on hexobarbital
    sleeping time in rats was investigated by Koldomin-Hedman et al.,
    1972. Pre-treatment with lindane shortened the sleeping time both from
    a single intraperitoneal or from short-term feeding tests. The lowest
    effective single dose was 15 mg/kg i.p. and 0.5 ppm lindane in the
    diet for one month. 100 ppm in the diet for one month increased the
    liver microsomal content of cytochrome P450 25% as compared with the


    Special studies on mutagenicity

         In a host-mediated assay, lindane was administered orally (100
    mg/kg) to a group of eight male mice and intramuscularly (12 or 25
    mg/kg) to groups of 12 mice. At the same time an indicator organism
    (Salmonella typhimurium C-42) was injected intraperitoneally as an
    indicator. After three hours the animals were sacrificed and the
    micro-organism extracted from the abdominal cavity and examined for
    back mutations. The mutation quotient or the frequency of mutations in
    the treated animals as compared to the frequency in the control were
    sufficiently low to indicate that in this experiment lindane would
    produce no definite mutagenic effects. No evidence of mutagenicity has
    been reported with lindane based on host-mediated assays using
    Salmonella or Serratia species as test organisms (Propping et al.,
    1973; Buselmaier et al., 1972).

         Groups of 10 male mice were administered single doses of 0, 12.5,
    25 and 50 mg/kg of lindane by intraperitoneal administration. The day
    after administration each male was mated with three females for seven
    days in eight successive series in a "domininant lethal test".
    Although several animals in the highest dose group died there were no
    differences in the number of pregnant females, the number of embryos
    per mother and the mutation indices. In this experiment lindane was
    found to produce no dominant mutations (Frohberg and Bauer, 1972b).

    Special studies on reproduction

         Groups of Charles River CD-rats (10 male and 20 female per group)
    were fed diets containing lindane at 0, 25, 50 and 100 ppm for 60 days
    prior to mating and the initiation of a standard two-litter,
    three-generation reproduction study. Over the course of three
    generations, there was no consistent effect of lindane on any of the
    parameters measured for the parent animals nor for the parameters
    measured with regard to the progeny. Lindane had no effect on litter
    size, breeding rate, and growth of pups in all generations. No
    deformities were observed. The liver weights of young animals of both
    sexes from the 100 ppm group were significantly increased. In the
    other two groups, both sexes showed increased relative liver weights
    which were significant only in females. Histological examination
    of the livers of these animals showed that there was a greater
    frequency of enlarged hepatocytes in the livers of animals in the two
    highest dose levels with no other histological change evident. Lindane
    at 100 ppm does not appear to affect reproduction in the rat. (Palmer
    et al., 1972).

         Lindane concentrations in tissues of the F2-A and F2-B
    generations were measured.  Lindane concentrations in fat, liver and
    brain were increased over controls at all dietary levels, Brain and
    liver concentrations in the F2A generation were related to dietary
    concentrations: 0.14. 0.40, 1.07 and 1.17 ppm for liver and 0.17,

    1.45, 1.92, and 3.30 ppm for brain for the groups fed 0, 25, 50 and
    100 ppm in the diet respectively. Fat levels for the F2A generation
    were highest in the 50 ppm group, 18.2 ppm compared to 1.2 ppm in
    controls. In the F3A generation weanlings, only fat residues exceeded
    controls at all three dietary levels, while at the 100 ppm dietary
    level residues in liver and brain were also increased (Burrows and
    Multen. 1971),

         Groups of 13 pregnant rabbits were administered lindane orally at
    doses of 0, 5, 10 and 20 mg/kg from day six to 18 of pregnancy. During
    the dosing period lindane was found to have an effect on the parent
    animals at all dosages. The pregnancy rate was unaffected although a
    statistically significant increase in pre-implantation loss occurred
    at 20 mg/kg. Litter parameters (litter size, fetal loss, litter and
    mean pup weights) were similar to the control. Incidence of
    malformations were unaffected by lindane although at 20 mg/kg there
    was a statistically significant increase in 13 ribbed pups while at 5
    mg/kg there was a significant decrease in this occurrence. Lindane
    does not appear to have a significant effect on pregnancy in the
    rabbit, (Palmer and Neuff, 1971).

         Lindane fed to female rats for 90 days at 5 mg/kg had no effect
    on reproduction. When fed at 10 mg/kg for 138 days a reduction of
    litter size and fecundity was observed and residues were found in the
    embryo. No teratogenic effects were noted (Trifonova et al., 1970).

    Special studies on teratogenicity

         Groups of pregnant mice (25 mice/group were orally administered
    lindane suspended in aqueous CMC daily from day six to 15 of gestation
    at dosage levels of 0, 12, 30 and 60 mg/kg. A similar series of
    animals were treated with lindane from day 11 to 13 of gestation.
    Lindane at 60 mg/kg was found to be toxic to the adult mice with a
    significant number of mice in the group dying before term. In the high
    treatment groups the number of abortions was significantly increased
    compared to the control group and the mean number of fetuses as well
    as the mean fetal weight was reduced. There was no apparent
    relationship between the administration of lindane and malformations
    observed in the study. It was concluded that lindane did not show any
    teratogenic effects following oral administration although there was
    considerable adult toxicity in the higher groups (Frohberg and Bauer,

         Groups of pregnant mice (25 mice/group) were administered lindane
    in daily doses of 6 mg/kg from day 6 to 15 of gestation by
    subcutaneous injection. A similar grouping was treated from day 11 to
    13 of gestation. No deformed fetuses were observed and the mean number
    of implantations and living embryos and the rate of abortions and
    resorptions were within the normal biological limits. In that group
    treated for 10 days the number of runts were significantly increased
    compared to the control and to the group treated for three days.
    Under the present test conditions lindane did not appear to show any

    teratogenic or toxic effects in mice at a subcutaneous dosage level of
    6 mg/kg per day (Frohberg and Bauer, 1972b).

         Groups of 20 female CFY-rats were orally administered lindane at
    dosage rates of 0, 5, 10 and 20 mg/kg from day 6 to 15 of pregnancy.
    Females treated at 10 and 20 mg/kg showed decreased food consumption
    and weight gain during the dosing period. Mortality was evident at 20
    mg/kg. Pregnancy rate, as assessed by the number of pregnant animals
    and pre-implantation loss, was unaffected by lindane. Litter size,
    fetal loss and number and mean weight of pups was not adversely
    affected by lindane at any of the dosage levels. There were no major
    abnormalities in any of the animals receiving lindane. although
    statistically significant differences in minor skeletal abnormalities
    (an extra rib) was evident at 20 mg/kg. Supplementary ribs was the
    only significant feature of this test resulting from the
    administration of lindane. The teratogenic potential of lindane is not
    great as the incidence of this skeletal abnormality falls within the
    normal biological variation in this strain of rat. In this experiment,
    lindane did not have a significant effect on pregnancy in rats (Palmer
    and Lovell, 1971).

    Short-term studies

    Mouse. Groups of 20 male mice (ICR/JCL, strain) were fed HCH and the
    isomers of HCH (alpha, beta, gamma, delta, epsilon,) and chlorsphenols
    for six months at 600 ppm in the diet. (Goto et al., 1972a and b).
    Enlarged livers were observed in all groups. Tumours were evident with
    alpha, beta, delta, epsilon and gamma-BHC. Hepatoma O-1 was found in
    all groups with a high incidence of malignant hepatomas observed in
    those animals for the isomers only. HCH did not induce malignancies.

    Rat. Administration of lindane to rats in the drinking-water for
    2-12 months at 1 ppm resulted in ultra-structural changes in the liver
    (Watari, 1973).

    Rat and mouse. Nagasaki et al. (1972a and b) reported that
    (gamma-BHC) lindane was carcinogenic in the liver of rats and less so
    in mice. In mice isomers of HCH were fed for 24 weeks at 100, 250 and
    500 ppm in the diet. Increased liver weight was observed in all
    groups. Hepatoma was seen only in lindane-treated mice at 250 and 500
    ppm. Rats were fed identical diet at 250, 500 and 1000 ppm for 24 and
    48 weeks. At 24 weeks only enlarged livers were noted while at 48
    weeks 1 of 7 rats showed hepatoma at 1000 ppm with gamma-BHC, 3/7
    showed hypertrophic nodules without malignancy. Other isomers also
    induced nodular formation.

    Rabbit. Lindane was administered orally to rabbits twice weekly at
    6.25 mg/kg for six months (Takahama et al.t 1972). Liver weight
    increases were observed but not kidney weight as observed with DOT and
    endrin in a similar test. No effects were noted on growth.

    Dog. Two groups of dogs (four males and four females, three of each
    sex were controls) were fed 200 ppm lindane in their diet for 32
    weeks. One animal died after a fit of convulsions on the ninety-fourth
    day while another animal had a short lasting convulsion on day 54.
    Electroencephalograms (EEG) were recorded at the conclusion of the
    study. Changes were observed in the sleeping patterns of the dosed
    dogs. In general the dosed animals had more activity (higher aptitude)
    and a larger low frequency (2-4 cycles) second component than the
    control animals. The sleeping EEG in the treated animals showed an
    increased delta-activity in comparison with control whereas the awake
    EEG activities did not differ from normal. There was 11 increased
    liver weight in animals on 200 ppm and the liver appeared to be
    enlarged and friable on gross autopsy, No morphological change was
    observed when histological examination was performed. There were no
    significant changes in urinalysis or haematological values although
    SAP levels were significantly increased throughout the test and SGPT
    and SGOT were increased at 11 weeks but normal at the end of the
    study. Several changes observed at 10 weeks were not evident at the
    end of the study, i.e, serum sodium level reduced and urinary reducing
    substances (Noel et al., 1971).

         Groups of beagle dogs (four males and four females per group)
    were fed lindane in the diet at levels of 0, 25, 50 and 100 ppm for
    two years. Isolated convulsive episodes were observed in one control
    animal and two animals receiving the low dose of lindane. One of the
    two animals at 25 ppm died on day 613 probably preceded by a
    convulsive episode. There were no convulsions observed at higher
    levels of exposure. EEG examination with awake animals showed no
    differences from those of the controls while EEGs from the sleeping
    animals showed slight evidence of irregular slow waves superimposed on
    the normal sleep pattern, At the conclusion of this study, SAP
    activity was slightly increased in animals at 100 ppm. No adverse
    effects were observed with regard to weight gain, urinalysis,
    haematology, and ophthalmological examinations. Liver function tests
    (BSP retention) showed no functional disturbance. At autopsy no
    irregularities were found in the high dosed animals except for
    somewhat darker coloration and a friable consistency of the liver.
    Histological examination showed no morphological irregularity
    corresponding to the gross observations.

         The measured mean daily dosages and the tissue concentrations of
    lindane determined in two dogs at the termination of the study were as
    Diet                Daily intake                Tissue Levels (ppm)      
    (ppm)               (mg/kg)              Fat        Liver      Brain

    0 (control)         -                    0.05       0.05       0.09
    25                  0.83                 12.1       0.90       0.38
    50                  1.60                 23.4       0.63       0.41
    100                 2.92                 66.8       2.9        1.35

         The apparent no-effect level in this study based upon gross
    morphological changes in the liver and SAP elevations correspond to 50
    ppm in the diet which was calculated to be 1.6 mg/kg per day based
    upon actual food consumption data (Rivett et al., 1971).

    Long-term studies

    Mouse. Groups of mice (30 male and 30 female per group) were fed
    lindane in the diet at levels of 0 and 400 ppm. (Beta BHC was also fed
    at 200 ppm to another group) for two years. During the first three
    months 10% of the males and 20% of the females died (12% of the males
    and 25% of the females fed beta-BHC died). Liver enlargement with
    nodular surfaces were described with both isomers as hyperplastic
    nodules and in some cases neoplasms. There were no incidents of
    neoplasms in nun hepatic tissues (Thorpe and Walker, 1973).

    Observations in man

         Milby and Samuels (1971) reported the results of clinical
    biochemistry measurements on individuals occupationally exposed to
    lindane and on individuals without occupational exposure. The mean
    blood lindane levels of the exposed group was 11.9 parts per billion
    (ppb) compared with 0.1 ppb for the unexposed group. With the
    exception of the blood lindane values for the exposed groups, all
    values were within the normal range for the general population.
    However, statistically significant differences (P<0.01) were detected
    between the two groups. These were: higher reticulocyte, total white
    blood cells and polymorphonuclear counts and lower blood creatinine
    levels for the lindane exposed group. No significant differences were
    noted in: blood uric acid levels, alkaline phosphatase levels,
    platelets, haematocrit, haemoglobin, lymphocytes, eosinophils, or
    monocytes. The authors concluded that under conditions of their study
    lindane did not produce haematologic disorders on the basis of a toxic
    suppression of haematopoesis, and that the health significance of the
    differences observed is unclear. They did not rule out the possibility
    that lindane might produce impaired haematopoosis on an idiosyncratic
    basis, which would not likely be detected with a study of this type.

         Selby et al. (1969) reported a comparison of chlorinated
    hydrocarbon pesticide residues in maternal blood and placental
    tissues. Fifty-three hospitalized women in Louisiana were studied.
    Detectable levels of lindane were found in 89% of the placenta samples
    and 88% of the maternal blood. The mean concentration in maternal
    blood was 0.39 ppb (range 0.1-6.0 ppb) and in placentas was 1.10 ppb
    (range 0.1-6.0). The placenta/blood ratio for the paired samples was
    2.8. In the placenta a concentration of 0.97 ppb in the fresh tissue
    was equivalent to 295.9 ppb on a lipid basis.

         Individuals occupationally exposed to lindane in Sweden were
    examined for liver function and blood abnormalities. There were no
    adverse effects attributable to lindane which was present in levels up
    to 87 ng/ml plasma (Kolomodin-Hedman, 1973).

         Thirty-five male workers having an occupational exposure to
    lindane have been examined for neurological status (EEG) and lindane
    level in the blood (GLC). The duration of the exposure varied from a
    half to two years. In half of the subjects under study the blood level
    of lindane did not exceed that of the controls (0.003-0.017 ppm).
    Slight changes in the EEG and the neurological status of 15 subjects
    were associated with a blood level of 0.02-0.34 ppm. The frequency of
    clinical symptoms and changes in the EEG increase in subjects with a
    lindane blood level above 0.02 ppm. (Czegledi-Janko and Avar, 1970).

         The level of lindane in the fat tissue of the general population
    in Bulgaria was found to be 0.24 ppm, while that of ß BHC was 0.52 ppm
    (Kaloyanova et al., 1972).


         Lindane was evaluated at the 1970 Joint Meeting and an ADI of
    0.0125 was reconfirmed. Information reported to be in progress at that
    time has been completed and was reviewed. In a two-year study in dogs,
    hepatic lesions were evident at 100 ppm. A no-effect level was
    considered to be 50 ppm in the diet corresponding to an intake of 1.6
    mg/kg per day. Epileptiform convulsions seen in the control and one
    test group were thought to be examples of hereditary canine epilepsy
    and not due to lindane. Lindane at 100 ppm in the diet did not affect
    reproduction in the rat although at 50 ppm and above hepatic lesions
    were observed in the F3B generation. Lindane had no effect upon
    maintenance of pregnancy in the rabbit, rat or mouse and two tests
    currently used to evaluate the mutagenic potential were negative. No
    further data have become available concerning the occurrence of blood
    dyscrasias in humans exposed to lindane. It was noted that with mice
    at high dietary intake, liver enlargement and nodular formation was
    evident. Since the no-effect level for this effect on mouse liver has
    not been established and since neither of the two long-term studies in
    rats is fully adequate, the Meeting considered that a further
    long-term carcinogenicity study was now required.


    Level causing no toxicological effect

         Rat:      25 ppm in the diet equivalent to 1.25 mg/kg bw

         Dog:      1.6 mg/kg bw/day

    Estimate of temporary acceptable daily intake for man

         0-0.01 mg/kg bw


    Use pattern

         In 1973, a book entitled "LINDANE, Monograph of an Insecticide"
    was published (Ulmann, 1972) (in German, French, and English) which
    summarizes the use patterns, tolerances (if any), and regulatory
    procedures for lindane of virtually every country in the world. Prom
    these summaries, and also data received from the governments of Canada
    and France, it is clear that, in addition to its uses on agricultural
    crops, lindane is needed and used for ectoparasite control on animals
    by direct application (sprays, dips, oilers, back rubbers, smears, and

    Residues resulting from supervised trials

         When pigs were sprayed twice with 0.5% solution of lindane,
    residues in backfat averaged 5.2 ppm (range 4.2-6.0 ppm). This spray
    treatment was 10 times the legally permitted dose and last treatment
    was 10 days prior to slaughter instead of the required 30 days. Since
    fat accumulation of most organochlorine pesticides is linearly dose
    related, it can be calculated that fat residues under good
    agricultural practice would not exceed 0.5 ppm (Davy et al., 1969).

         Lindane (0.1 ppm) was added to the ration of laying hens and fed
    for six weeks. Residues in eggs (yolks) reached a maximum of 0.056 ppm
    after seven weeks, then fell to less than 0.001 ppm within five weeks
    after feeding ceased. Charcoal in the diet had no effect on residues
    and the residues had no effect on eggshell thickness or quality.
    Lindane residues reached a maximum of 0.074 ppm in the abdominal fat
    of the hens after six weeks on the treated diet, then fell to below
    detectable levels in three weeks after the pesticide was removed from
    the diet (Foster, et al., 1972).

         Residues of lindane in whole milk and milk products from cows fed
    either 1.4 mg/day or 4.2 mg/day in their ration were reported by Smart
    et al., 1972. Unfortunately, the residue data were not corrected to a
    standard butterfat content (usually 4%) or reported on a fat basis and
    therefore cannot be used for estimating regulatory levels.

         In field trials in Japan, rice and Chinese cabbage were treated
    with various dosages (sometimes excessive) and numbers of applications
    of lindane and samples of raw rice grains and cabbage were analysed at
    various time intervals after application (Kanazawa, 1973). In rice
    grains residues averaged 0.032 ppm (range 0.007-0.286 ppm); in cabbage
    the average was 1.02 ppm (range 0.01-7.8 ppm). Since details of the
    relation between applied dosage and residues found were omitted, these
    data should not be regarded as typical of good agricultural practice.

         Studies carried out by CELAMERCK (1972) on residues in sugarbeets
    and in wine from treated grapes gave the results shown in Table 1.

         Data was received from the Netherlands on results of supervised
    trials on apples, pears, and head lettuce. When sprayed on apple and
    pear trees at rates of 0.56, 0.7, or 1.4 g. a.i/tree, lindane residues
    in fruit at 14 days post-treatment (recommended interval) ranged from
    "not detectable" (<0.1 ppm) to 0.1 ppm (Schuddeboom, 1973).

         When glasshouse lettuce was treated via a lindane smoke generator
    at a rate of 3 g/100m2, lindane residues at seven days post-treatment
    averaged 1.2 ppm (range 1.0-1.6 ppm) in one trial and 1.0 ppm (range
    0.8-1.3 ppm) in a second trial.

    Fate of residues

    In animals

         Five previously unreported metabolites from the urine of rats fed
    lindane have been identified as 3,4-dichlorophenol,
    2,4,6-trichlorophenol, 2,3,4,5-tetrachlorophenol,
    2,3,4,6-tetrachlorophenol, and 2,3,4,5,6-pentachloro-2-cyclohexen-1-ol
    by Chadwick and Freal (1972).

         When lindane 14C was fed to rabbits for 26 weeks, 54% of the
    dose was excreted in urine and 13% in faeces. Urinary metabolites
    identified were 2,3,5-, 2,4,5-, and 2,4,6-trichlorophenol;
    2,3,4,6-tetrachlorophenol, 2,3-, and 2,4-dichlorophenol, and
    2,3,4,5-tetrachlorophonol. Seven more chlorophenols and six
    chlorobenzones were tentatively identified (Karapally et al., 1973).

         High protein diets and starvation accelerated the excretion of
    lindane from all organs of female rats according to Oshiba and
    Kawakita (1973); 70 to 90% of accumulated lindane was excreted in six

    In plants

         Bean and corn seedlings immersed in aqueous solution of lindane
    (0.05 mg/ml) for eight days took up insecticide through the roots. In
    beans, the only nonpolar metabolic products were
    gamma-pentachlorocyclohex-l-ene (gamma-PCCH) (4 ppm) and
    1,2,4-trichlorobenzene (0.36 ppm); unchanged lindane amounted to 20
    ppm. In corn, three nonpolar metabolites were found: gamma-PCCH,(5
    ppm), 1,2,4-trichlorobenzene (0.3 ppm), and 1,2,3-trichlorobenzene
    (0.14 ppm). These nonpolar metabolites accounted for 70% of the total
    metabolites in these plants (Mostafa et al., 1971).

         Studies in progress on lindane-14C metabolism in lettuce grown
    hydroponically and on soil have shown the presence (in hydroponic
    lettuce) of small mounts of trichlorobenzene,
    2,3,4,6-tetrachlorobenzene, pentachlorobenzene,
    pentachlorocyclohex-l-ene. dehydrolindane. and
    2,3,4,6-tetrachloro-phenolmethyl ether; the major residue was
    unchanged lindane (Korte, 1973).

                                   Application        Application      Days between last treatment and sampling
    Crop              Number of    concentration      rate                                                                   
                      treatments   % (preparation)    a.i.             118       178       183       193       197       198

    Wine                  1        3.75% gran.        0.45 g/stock     0.001

                          1        3.75% gran.        0.45 g/stock     0.002
    Sugar beets           1        0.5%               1 600 g/ha                                                         0.03

                          1        0.25%              800 g/ha                                                           0.06

                          1        0.33%              1 600 g/ha                                               0.10

                          1        0.167%             800 g/ha                                                 0.02

                          1        -                  2 000 g/ha                 < 0.02 
                                                                                 < 0.02
                          1        3.75% G            94 g/ha                    < 0.02
                                                      row treatment              < 0.02

                          1        3.75% G            750 g/ha                             0.07)
                          1        3.75% G            1 500 g/ha                           0.10)
                                                                                               )     control:  
                          1        0.25% G            800 g/ha                             0.11)     0.1 ppm
                                                                                               )     lindane
                          1        0.5%               1 600 g/ha                           0.12)

                          1        3.75% G            750 g/ha                                       0.04

                          1        3.75% G            1 500 g/ha                                     < 0.02

                          1        0.25%              800 g/ha                                       0.03

                          1        0.5%               1 600 g/ha                                     0.10

    In storage, processing or cooking

         Lindane was fed to dairy cows at 1 mg/kg bw/day and the milk was
    collected and processed into pasteurized whole milk, 30% fat cream,
    butter, spray-dried whole milk, condensed whole milk, and cheddar
    cheese (Li et al., 1970). The residue was very stable for ordinary
    processing operations and remained essentially unchanged (on a fat
    basis). However, spray drying reduced the lindane content by 34%.
    Similar results were obtained by Smart et al., 1972 who fed either 0.2
    ppm or 0.6 ppm to cows and prepared cheese, butter, whey, buttermilk,
    and separated milk. Maximum residues of 0.05 ppm in cheese and 0.15
    ppm in butter were reported.

         Lindane was fed to broilers at 10 ppm throughout an eight-week
    period. Tissue residues of 7.3 ppm (raw, dry) were 9.0 ppm after
    baking, 5.5 ppm after frying, 3.9 ppm after steaming, and 1.5 ppm
    after heating in a closed container for 90 minutes (Ritchey et al.,

         Polished rice containing 0.012 ppm of lindane was boiled in a
    home-type cooker with and without pressurization (Kanazawa, 1973). A
    55% reduction in residues was obtained in either case. In another
    experiment green tea containing 0.174 ppm lindane was extracted by hot
    water for three minutes and for one day. Only about 1% was lost even
    in the one-day extraction.

    Evidence of residues in food in commerce or at consumption

         In studies of residues in the total diet in Canada in 1971 (Smith
    et al., 1973) lindane residues were found at average values (mg/kg) of
    0.001 in dairy products, 0.013 in cereals, and 0.001 in oils and fats.

         In a continuation of the market-basket survey in the United
    States for the years June 1968 to April 1970, the daily intake of
    lindane was found to be 0.001 mg for 1969 and 0.001 mg for 1970
    (Duggan et al., 1972). This represents a three-four fold reduction
    from previous years. In the period June 1968 to April 1969, the daily
    intake was at trace levels (<0.001 mg) for all food classes except
    beverages and root vegetables (none) and grains and cereals (0.001
    mg). In the period June 1969 to April 1970, daily intake was less than
    0.001 mg in all food classes.

         Data from New Zealand (1973) on residue levels found in random
    sampling at retail level and in crops known to be treated with lindane
    is shown in the following table.

    A.  Random sampling at retain level


    Year   Crop                   Frequency             Residue levels in ppm

    1966   Leaf vegetables        6 samples in 70       0.2 (max.)
    1966   Root vegetables        2 samples in 46       0.3 (max.)
    1967   Leaf vegetables        8 samples in 72       0.8 (max.)
    1967   Pipfruit               3 samples in 17       0.2 (max.)
    1967   Stonefruit             2 samples in 14       0.01 (max.)
    1968   Leaf vegetables        1 sample in 50        0.05
    1968   Root vegetables        2 samples in 44       0.1 (max.)
    1969   Leaf vegetables        1 sample in 38        0.7
    1970   Leaf vegetables        1 sample in 43        0.02
    1970   Stonefruit             2 samples in 6        0.02 (max)
    1971   Leaf vegetables        2 samples in 57       0.2
    1971   Root vegetables        5 samples in 32       0.03
    1971   Stonefruit             1 sample in 10        0.02
    1971   Potatoes               1 sample in 19        0.03

    B.  Residues in crops known to be treated with lindane

    1968   Apples                 9 samples             0.1 (max.)
    1970   Apples                 1 sample              N.D.
    1971   Apples                 4 samples             0.2 (max)

         Data from surveys on lindane residues on glasshouse lettuce
    carried out by the Central Bureau of Fruit and Vegetable Auctions in
    the Netherlands (1973) is shown in the following table.

    Lindane residues: Percentage of samples in rangesa


    ppm        1967/68    1968/69    1969/70    1970/71    1971/72    1972/73

    N.D.       57.7       53.2       52.1       47.8       44.7       80.6

    0.01-1     26.9       29.3       31.6       39.5       36.1       16.3

    1-2        10.9       11.9       10.9       8.6        12,2       2.8

    >2         4.6        5.6        5.4        4.1        6.9        0.3

    a About 1000 lettuce samples each year except 1972/73 - 2000 samples.

         In the Czechoslovak Socialist Republic in the years 1971 and
    1972, the content of chlorinated insecticide residues in some
    foodstuffs, especially butter, and in the whole-day's diet was
    followed analytically, also the daily intake of the human organism was
    calculated (Rosa, 1973). Butter samples were taken in five dairy
    plants in Sloyakia representing more than half a million hectoliters
    of milk. The whole day's diet samples were taken in six colleges
    during one week in the spring and autumn. The results are presented in
    the following table.

    A. Lindane residues in milk fat and whole day's diet, 1971/72 (mg/kg)


                      Milk fat                   Whole day's diet
                   (133 samples)                   (123 Samples)
    Residue     Min.     Max.     Med.        Min.      Max.      Med.

    gamma-BHC   0.006    0.157    0.041       0.001     0.009     0.004

    B.  Daily intake in mg/kg bw

                                                           Whole day's
    Residue     milk      butter    cheese     together       diet

    gamma-BHC   0.000005  0.000005  0.000001   0.000011    0.000146

         It was not clear whether these residues arise from the use of
    lindane or technical BHC.

         Investigations in France in 1970 and 1971 on the sources of
    organochlorine pesticide residues in milk revealed that lindane
    residues arose from three sources: animal feed (grain, cattle-cake,
    etc.), local treatment Of grain storage facilities, and treatment of
    stables (Marion, 1973 [via Demozay]). Milk residues from feed sources
    ranged from 0.01 to 0.08 ppm; from storage facility treatment, 0.01 to
    0.60 ppm; from stable treatment, 0.01 to 0.22 ppm. Milk residues fell
    rapidly when the source of contamination was removed or after
    treatment in the case of veterinary use.

         Various surveys in Japan on pesticide residues in dairy products,
    meat, fish, and imported meat (Takeda et al., 1972; Sakai et al.,
    1972; Minagawa et al., 1972; and Otsuki of al., 1972) showed gamma-BHC
    residues ranging from traces to 0.03 ppm in raw milk, 0.01 to 0.46 ppm

    in butter, N.D. to 0.048 ppm in modified milk powder, trace to 0.016
    ppm in cheese, 0.01 to 0.1 ppm in fresh-water fish, 0.001 to 0.036 ppm
    in marine fish, 0.01 to 0.042 ppm in imported beef (fat), 0.013 to
    0.024 ppm in imported chicken (fat), 0.01 ppm in imported horse (fat),
    0.011 to 0.015 ppm in imported mutton (fat), 0.015 ppm in imported
    lamb (fat), and 0.053 ppm in imported rabbit (fat). Such data,
    however, cannot be interpreted to reflect uses of lindane since all
    other BHC isomers were present in all samples and it is very probable
    that technical BHC was the main source of residue.

    Methods of residue analysis

         The multi-residue methods of analysis for organochlorine
    pesticides as published by the AOAC (Official Methods of Analysis of
    the Association of Official Analytical Chemists, 11th ed., 1970,
    29.001) for fruit, vegetables, milk, and milk products and subsequent
    changes to include fish, meat, and dry cereals (J. Assoc. Off. Anal.
    Chem., 54, 470 (1971); 55, 428 (1972)) are suitable for regulatory
    purposes for lindane. Other suitable methods are references in LINDANE

    National tolerances

         See LINDANE Monograph of an Insecticide, 1972, pp. 263-335.


         Evidence was available to show the need for direct application of
    lindane to animals for ectoparasite control. The Meeting recognized
    that direct application to lactating dairy animals occurs but does not
    consider this procedure to be good agricultural practice because it
    would likely give rise to residues in milk exceeding the recommended
    practical residue limit.

         No new information was provided on the disappearance of lindane
    residues during storage and processing of cocoa beans and derived
    products or of cereals into cereal products. Since the requirement for
    these data was introduced in 1968 and since there was no response from
    either the lindane manufacturers or countries growing these crops in
    providing the needed data, it is the consensus of this Meeting that
    these requirements should only be considered as desirable.

         Limited data was evaluated from supervised trials on pigs, laying
    hens, dairy cows (milk and milk products), rice, cabbage. sugar beets,
    grapes (wine), apples, pears, and glasshouse lettuce. The data did not
    show a need for revision of the values of any existing tolerance
    recommendation although a survey of world-wide tolerances for lindane
    on fruits and vegetables (in LINDANE, Monograph of an Insecticide)
    would appear to indicate little need for a value greater than 2 ppm on
    those commodities. On the basis of new data available, a tolerance of
    0.5 ppm is recommended on rice (rough), 0.2 ppm on sugar beets (both
    roots and foliage) and 1 ppm on apples and pears. No significant
    residues were found in wine.

         In response to a written suggestion that the tolerance on
    vegetables seems too high (at 3 ppm) and should be reduced to 2 ppm:
    the Meeting received information on new work in progress to determine
    residue levels from supervised trials in a variety of fruits and
    vegetables. This data, when available, will be used in assessing the
    need to revise the tolerance recommendation for vegetables and fruit.

         Home cooking experiments with chicken and rice show that lindane
    residues are reduced significantly (50% or greater) by steaming or
    boiling. Since reductions by boiling are equivalent whether the
    containers are closed or open, it is apparent that volatilization or
    steam distillation is not the primary pathway of loss.

         In order to be consistent with the recommendations for residue
    limits in eggs as published for other pesticides, the recommendation
    for a practical residue limit for residues of lindane is changed from
    egg (yolk) to eggs (shell-free) and the value of the limit is adjusted
    from 0.2 to 0.1 ppm to allow for the change in sample weight and
    dilution by egg white.

         Completely adequate methods suitable for regulatory purposes for
    analysis for lindane residues have been developed. However,
    considerable care is still required to confirm the qualitative
    identification since there are numerous potential interferences.


         As the ADI has been changed to temporary all previous tolerances
    and PRL's are changed to temporary. The following temporary tolerances
    are in addition to those previously recommended.

    Temporary tolerances

         Apples, pears                         1 ppm
         Rice (rough)                          0.5 ppm
         Sugarbeet roots, sugarbeet foliage    0.2  ppm


    Required (before 1977)

    1. A long-term carcinogenicity study.


    1. The results of supervised trials currently in progress to determine
    residues on a variety of fruits and vegetables.

    2. Information from governments on residues of lindane found in cocoa
    beans and cocoa products moving in commerce.

    3. Further information from governments on the occurrence of lindane
    residues on raw grains, the effect of processing on these residues,
    and the fate of the residues in the various milled cereal fractions.

    4. Further information and statistics on the occurrence of lindane
    residues in animal foodstuffs and on the uses of lindane in
    association with animals (such as stable treatments) with a view to a
    re-evaluation of the practical residue limit of 0.1 mg/kg in the fat
    of milk.


    J.A.O.A.C. (1970) Official methods of analysis of the Association of
    Official Analytical Chemists, 11th edition

    Bauer, A. and Frohberg, H. (1972) Lindane, testing for teratogenic
    effects in mice following subcutaneous injection. Unpublished report
    submitted by E. Merck

    Burrows, I.E. and Multen, L.W. Effect of lindane on the reproductive
    function of multiple generation in the rat. I. The determination of
    dietary concentrations of lindane in rat tissues. Unpublished report
    from Huntingdon Research Centre submitted by E. Merck

    Buselmaier, W., Rohrborn, G. and Propping, P. (1972) Mutagenitäts
    Untersuchengen mit pestiziden im host-mediated assay und mit dem
    dominanten lethal test an der mans. Biol. Zbl., 91: 311-325

    Celamerck. (1972) Reports of analysis. Private communication

    Chadwick, R.W. and Freal, J.J. (1972) Bull. Environ. Contan. Toxicol. 
    7, No. 2/3: 137-146

    Czegledi-Janko, G. and Avar, P. (1970) Occupational exposure to
    lindane. Clinical and laboratory findings. Brit. J. Ind. Mod.,
    27(3): 283-286

    Davey, R.J. and Gerrits, R.J.J. (1969) Anim. Sci., 28: 872

    Duggan, R.E. and Corneliusson, P.E. (1972) Pest. Monit. Jour. 5(4)

    Foster, T. S., Motley, H. V., Purkayastha, R.,Greenhaigh, R. and Hunt,
    J.R.J. (1972) Econ. Entomol. 65(4): 982-988

    Frohberg, H. and Bauer, A. (1972a) Lindane, testing for teratogenic 
    effects in mice following oral administration. Unpublished report
    submitted by E. Merck

    Frohberg, H. and Bauer, A. (1972b) Lindane testing for mutagenic
    effects Dominant Lethal Test in male mice. Unpublished report
    submitted by E. Merck

    J.A.O.A.C. (1971/72) Changes in methods, 54:.470; 55: 428

    Kaloyanova-Simeonova, F. et al. (1972) Organochlorine pesticides in
    the fat tissue of the general population in Bulgaria. Paper at the
    XVII International Congress on Occupational Hygiene, Buenos Aires

    Kanazawa, Jun. (1973) Japan Pesticide Information No. 11, pages 5-16

    Karapally, J.C., Saha, J.G. and Lee, Y.W. (1973) Metabolism of lindane
    14C in the rabbit: ether soluble urinary metabolites. J. Agr. Food
    Chem., 21: 811-118

    Klekmina, S. M. and Khaikina, B.I. (1972) The effect of lindane an the
    activity of lactate dehydrogenase and its isoenzyme spectrum. Farmazia
    i Toksikologia, 35(6): 734-737

    Kolomodin-Hedman, B.. Alexanderson, N. and Sjöqvist, F, (1971)
    Toxicol. Appl. Pharmacol. 20, 299

    Kolomodin-Hedman, B.., Palmer, L., Gotell, P. and Skerfving, S. (1973)
    Plasma levels of lindane p,p'-DDE and p,p'-DDT in occupationally
    exposed persons in Sweden. Work-environm. Hlth, 10: 100-106

    Korte, F. (1973) Progress report on lindane metabolism in lettuce
    submitted to IUPAC Terminal Residues Commission

    Li, C.F., Bradley, R.L. jr., and Schultz, L.H. (1970) J.A.O.A.C.,
    53(11): 127

    Marion, R. (1973) Report for I.T.E.B. (Provided by D. Demozay, PEPRO,

    Milby, T.H. and Samuels, A.J.J. (1971) occup Med., 13: 256-258

    Minagawa, O. et al. J. Food Hyg. Soc. Japan 13(4): 317 1972

    Mostafa, I.Y., Moza, P.N. and Klein, W. (1971) Prepublication paper
    submitted to IUPAC Terminal Residues Commission

    Netherlands. (1973) Private communication

    New Zealand. (1973) Private communication

    Noel, R.B., Rivett, K.R., Sortwell, R.J., Cheshire, P.J., Street.,
    A.E., and Mawdesley-Thomas, L.E. (1971) Lindane toxicity studies in
    beagle dogs - dietary Intake (200 ppm) for 32 weeks. Unpublished
    report from Huntingdon Research Center, submitted by E. Merek

    Oshiba, K. and Kawakita, H. (1973) Osaka Shiritsu Elsei Kenkyusho
    Kenyku Hokoku, 34: 158. (1971) English abstract Health Aspects of
    Pesticides 6(4): 205

    Oshiba, K., and Kawakita, H. (1973) Shokuhin Eiseigaku Zasshi,
    13(5): 383. (1972) English abstract - Health Aspects of Pesticides,
    6(3): 152

    Otsuki, K. et al. (1972) J. Food Hyg. Soc. Japan 13(4): 338

    Palmer, A.K., Cozens, D.D., Lovell, M.R., Spicer, E.J.F. (1972) and
    Newman, A.J. Effect of lindane on reproductive function of multiple
    generations in the rat - final report. Unpublished report from
    Hungtingdon Research Centre submitted by E. Merck

    Palmer, A.K. and Lovell, M.R. (1971) Effect of lindane on pregnancy of
    the rat. Unpublished report from Huntingdon Research Centre submitted
    by E. Merck

    Palmer A.K. and Neuff, A.M. (1971) Effect of lindane on pregnancy of
    the New Zealand white rabbit. Unpublished report from Huntingdon
    Research Centre submitted by E. Merck

    Propping, P., Buselmaier, W. and Rohrborn, G. (1973) Kritische
    Betrachtung usher die intra-animale Kultur von Mikroorganismen, eine
    Methode zum Nachweis chemisch induzierter Mutationen [Critical
    considerations on the host-mediated assay, a method for detection of
    chemically induced mutations], Arzneim-Forsch., 23(6): 746-749

    Ritchey, S,J., Young, R.W, and Essary, E.O.J. (1972) Agr. Food Chem.
    20(2): 291-293

    Rivett, K.F., Sortwell, R.J., Spicer, E.J.F., Cheshire, P.J., Street,
    A.E. and Burrows, I.E. (1971) Lindane, toxicity studies in beagle dogs
    (Initial studies and dietary intake for 104 weeks). Unpublished report
    from Huntingdon Research Centre submitted by E. Merck

    Rosa, Dr Jaroslav. (1973) Private communication from the Foreign
    Department of the Federal Ministry of Agriculture and Food of the CSSR

    Sakai, K. et al. (1972) J. Food Hyg. Soc. Japan, 13(4), 310

    Schuddeboom, L.J. (1973) Inspekteur van de Volksgezondheid, Private

    Selby, L.S., Newell, K.W., Hansen, O.A. and Junker, G. (1969)
    Comparison of chlorinated hydrocarbon pesticides in maternal blood and
    placental tissues. Environ. Res., 2: 247-255

    Smart, N.A., Hill, A.R.C. and Roughan, Mrs P.A. (1972) Pestic. Sci.,
    3: 415-419

    Smith, D.C., Leduc, R. and Charbonneau, C. (1973) Pestic. Sci., 4:

    Takeda, M. et al. (1972) J. Food Hyg. Soc. Japan, 13(4): 299

    Trifonova, T.K., Gladenko, I.N. and Shulyak, V.D. (1970) Effect of
    gamma-BHC and serum on reproduction. Veterinariya, 47(6): 91-93

    Ulmann, E. (ed.) (1973) LINDANE Monograph of an Insecticide, Verlag K.
    Schillinger, Freiberg im Breisgau, Wallstr. 14

    See Also:
       Toxicological Abbreviations
       Lindane (EHC 124, 1991)
       Lindane (HSG 54, 1991)
       Lindane (ICSC)
       Lindane (PIM 859)
       Lindane (FAO Meeting Report PL/1965/10/1)
       Lindane (FAO/PL:1967/M/11/1)
       Lindane (JMPR Evaluations 2002 Part II Toxicological)
       Lindane (FAO/PL:1968/M/9/1)
       Lindane (FAO/PL:1969/M/17/1)
       Lindane (WHO Pesticide Residues Series 4)
       Lindane (WHO Pesticide Residues Series 5)
       Lindane (Pesticide residues in food: 1977 evaluations)
       Lindane (Pesticide residues in food: 1978 evaluations)
       Lindane (Pesticide residues in food: 1979 evaluations)
       Lindane (Pesticide residues in food: 1989 evaluations Part II Toxicology)
       Lindane (Pesticide residues in food: 1997 evaluations Part II Toxicological & Environmental)