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    LINDANE     JMPR 1977

    Explanation

    Lindane was evaluated by the Joint Meeting in 1966, 1967, 1968, 1969,
    1973, 1974 and 1975 (FAO/WHO 1967, 1968, 1969, 1973, 1974, 1975). The
    ADI and recommended Maximum Residue Limits were temporary and a
    lone-term carcinogenioity study was required by 1977 before a firm ADI
    could be allocated.

    Further information was also listed as desirable by the 1973 and 1974
    Meetings, especially on residues on fruit and vegetables, on raw
    grains and in their milling fractions, and in animal feedstuffs in
    relation to residues in milk, etc. (FAO/WHO 1974, 1975).

    The required carcinogenicity study has now become available, together
    with further information on absorption, distribution, excretion and
    metabolism. Further residue data from supervised trials were also
    provided. The new data are evaluated in the following monograph
    addendum.

    EVALUATION FOR ACCEPTABLE DAILY INTAKE

    BIOCHEMICAL ASPECTS

    Absorption, distribution and excretion

    The effect of dietary fibre on the metabolism of lindane has been
    studied (Chadwick at al., 1977a). Absorption was evidently most
    complete on a diet of lab cow, and least on a synthetic low residue
    diet (LRD) plus 10% pectin. The metabolic pattern was altered in that
    the rats on lab chow excreted more conjugated chlorophenole than those
    on LRD or LBD + 10% peoting agar or cellulose. All animals receiving
    fibre had a higher hepatic dechlorinase activities.

    The metabolism of lindane is summarized by pointing out that it leads
    to the formation of two alcoholat 3 triohlorophenolog 2
    tetrachlorophenole, and their conjugates (Chadwick at al., 1977b).
    Full microsomal induction requires the presence of EFA in the diet,
    consequently the amount of 2,3,4,5,6-pentachlorocyclohexene-[2]-ol
    (0L-metabolite) formed varies with the diet, being highest on menhaden
    plus linseed oils, lowest on coconut (of the oils) and still lower on
    a fat-free diet. In the first few days of this experiment the
    excretion of conjugated 2,3,4,6-tetrachlorophenol was greatest on the
    menhaden + linseed oil regimen.

    The OL metabolite of lindane was detected and identified as an
    intermediate in the formation of pentachlorophenol, and of
    tetrachlorocyclohexenol as an intermediate in the formation of
    tetraohlorophenol (Freal and Chadwick, 1973; Engst et al., 1976).
    After adaptation of rats to lindane they excreted half of a dose of
    14C-L in 3-4 days. The main radioactive residues were found in fat,
    kidneys and muscle, with the organs containing relatively more

    metabolites in the adapted rats (Seidler at al., 1975). There are also
    data on the accumulation of lindane in brain (Solomon at al., 1977).

    Biotransformation

    The metabolic process generally follows the pathway lindane
    (-HC1)->pentachloroeyolohexene (as in plants), then -> isomeric
    trichlorobenzenes, isomeric trichlorophenols and sulphate or
    glucuronide conjugates of the last-named. In rabbits receiving
    14C-lindane for 26 weeks, 54% of the 14C was recovered from the urine
    and 13% in the faeces. The compounds definitely identified in the
    urine were: two dischlorophenols, 3 trichlorophenols and 2
    tetrachlorophenols, but the presence of pentachlorophenol and
    pentachlorobenzene was also suspected (Karapally et al., 1973). In
    mice the main urinary excretory products identified were the sulphate
    and gluouronide conjugates of 2,4,dichlorophenol and
    2,4,6-trichlorophenol (Kurihara and Makajima, 1974). The metabolism of
    lindane is accelerated by the prior administration of DDT, or of
    lindane itself (Chadwick and Freal, 1972a). In addition to the di-,
    tri- and tetrachlorophenols mentioned above, a new metabolite was
    detected as 2,3,4,5,6-pentachlorocyolohexen (2)-ol(1) (Chadwick and
    Freal, 1972b; Freal and Chadwick, 1973). This metabolite, however, did
    not seem to arise from the established intermediate
    gamma-pentachlorocyclohexene. The direct dehydrogeneration of lindane
    giving gamma-hexachlorocyclohexene was also demonstrated (Chadwick et
    al., 1975). The metabolic pattern of this intermediate was found to be
    similar to that of lindane itself but further dehydrogenation to
    hexachlorobenzene did not occur.

    The fate of lindane consumed by cows as a contaminant on feed was
    studied. (Note that this is of particular interest since aerobic and
    anaerobic bacteria metabolize lindane differently; vide infra.)
    Incubation of 36Cl lindane with the microflora of cow's rumen
    resulted in a cleavage of 90% of the 36Cl in 4-5 days, while the C of
    14C-lindane was rapidly converted to volatile compounds. The
    "primary" metabolite (only 1%) was tetra-chlorocyclohexane (Haider et
    al., 1976).

    Application of lindane directly to plants, to soil, or to the nutrient
    medium leads to the formation of gamma-pentachlorcyclohexene and some
    isomeric trichlorobenzenes. Various publications of the Korte and
    Klein groups have demonstrated that up to 80% of the pesticide applied
    to plants may be recovered as unchanged lindane, along with small
    amounts of penta-, tetra-and trichlorphenols, in both free and
    conjugated forms. Still smaller amounts of non-polar compounds
    (chlorobenzenes) and pentachlorocyclohexene and hexachlorocyclohexene
    were found. The rate of metabolism of lindane on plants is very low
    (Stückigt and Rise, 1976). On various crops treated with lindane under
    practical conditions, at 10 times the recommended dosage rate, only
    traces (ca 0.04 mg/kg) of the degradation product
    gamma-pentachlorocyclohexene were detected.

    TOXICOLOGICAL STUDIES

    Special studies in carcinogenicity

    Three groups of 50 male and 50 female Chbi: NMRI (SPF) mice were fed
    12.5, 25 or 50 ppm lindane (equivalent to 2.1, 4.1 or 8.2 mg/kg/day in
    males and 2.0, 3.9 and 7.8 mg/kg/day in females) from 34 days of age
    for 80 weeks. One hundred mice of each sex served as convenient
    controls. A complete autopsy, light microscopic examination of brain,
    heart, lungs, liver, spleen, kidneys. suprarenal glandol gonads,
    bladder and all-detected tumours was performed on all survivors.
    Electron microscopy of liver was performed on 10-15 samples from each
    of 4 male and 4 female mice from each group, Animals dying during the
    study were examined grossly post mortem. Survival data were not
    available for individual groups. Combined data indicated an 84.2%
    overall survival. In animals dying during the study, 22.8% of the dead
    mice reported died owing to the presence of tumours (mainly lymphocyte
    leukaemia). In 19% (80 mice) of the survivors tumours were observed. 
    In 6 of these animals two primary tumours were present in each
    animals. A breakdown of a total of 106 tumours recorded during the
    experiment by group and tumour type does not indicate either a
    site-specific or compound-related increase of tumour incidence in any
    group. The common eat tumours in survivors were lymphooyte leukaemia
    and primary lung tumours. Electron microscopy did not reveal
    differences between treated and control groups. (Weisse and Herbst,
    1977).

    Additional unpublished data m the above study indicate that mortality
    ranged from 14 to 19% of each group (Kollmer et al., 1975).

    Two groups of 35 day old 50 male and 50 female B6C3 F1 mice were fed
    80 to 160 ppm lindane In a diet containing 2% corn oil for 80 weeks
    followed by a 10 week period on a diet containing 2% corn oil without
    lindane. Controls comprised 10 male and 10 female mice fed 2% corn oil
    for 90 weeks. Non-concurrent controls from other experiments (pooled
    controls) comprised 50 males and 50 females. Body weights of females
    receiving 80 ppm lindane were constantly reduced. During the second
    year of the study, treated females were excitable and 6 treated males
    aggressive. During the last 6 weeks of the study, all treated animals
    were in poor physical condition. At least 88% of male mice and 80% of
    female mice survived to termination of the study, Random neoplastic,
    proliferative, degenerative and inflammatory lesions occurred in all
    groups. Neoplastic liver lesions occurred in 20% of control males, 29%
    of low dose males and 20% of high dose males. In females, 0, 4% and 7%
    neoplastic liver lesions occurred at 0, 80 and 160 ppm. Statistical
    analysis of the incidence of hepatocellular carcinoma showed that it
    was not significant for any group, on the basis of the contemporary
    control comparisons. Among pooled controls a significant increase was
    noted in low dose males as compared to pooled controls (NCI, 1977),
    Two groups of 50 male Osborne Mendel rats (35 days old) were fed 320
    or 640 ppm lindane in the diet for 38 weeks followed by 160 or 320 ppm

    for a further 42 weeks. A 30 week withdrawal period preceded killing.
    Two groups of female Osborne Mendel rats (35 days old) were fed 320 or
    640 ppm lindane in the diet for 2 weeks, followed by 49 weeks on 160
    or 320 ppm, and then 29 weeks at 80 or 160 ppm. A 30 week withdrawal
    period preceded killing. Controls comprised 10 males and 10 females
    maintained for 109 weeks. Body weight varied but was generally
    comparable between groups. Clinical signs were noted with increasing
    frequency in all treated groups as the study progressed, Mortality was
    52%, 50% and 40% in highs low and control male rate and less than 40%
    in high and low dose females but 60% in female controls (NCI, 1977).

    COMMENTS

    In view of the currently very low intake of lindane from a wide
    variety of sources, the relative rapidity with which it is degraded in
    mammalian organisms and in the environment to much less acutely toxic
    compounds, and the relatively high levels required to produce adverse
    effects (especially carcinogenesis), in humans and laboratory animals
    there appear to be no further toxicological objections to the
    continued maintenance of the previously established ADI for humans.

    Neither of the new mouse studies reported here nor the new rat study
    both undertaken with lindane of much greater purity than previously
    tested provide any evidence of tumour or cancer induction following
    exposure to lindane. Since the information required by the 1974
    meeting has now been satisfied, the present Meeting decided that the
    previously allocated ADI for humans is no longer temporary.

    TOXICOLOGICAL EVALUATION

    Level causing no toxicological effect

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

         Dog: 1.6 mg/kg bw/day

    ESTIMATE OF ACCEPTABLE DAILY INTAKE FOR HUMANS

         0-0.01 mg/kg bw

    RESIDUES IN FOOD AND THEIR EVALUATION

    RESIDUES RESULTING PROM SUPERVISED TRIALS

    Results of a number of trials in the Federal Republic of Germany on a
    variety of crops were available. As the residue levels found were
    below those previously recommended for the crops concerned, only an
    abridged summary in given in Table 1.

    Detailed data from carefully controlled trials with lindane on lettuce
    and spinach grown under glass wore available from the Netherlands (Ad

    Hoc Working Group, Codex Committee on Pesticide Residues, 1971). These
    showed an exponential rate of decay of residues during a period of 3
    weeks from sowing, with a half-life between about 3 and 3´ days on
    both crops. Results of outdoor trials with lindane in spinach (De Raig
    and Werdmuller, 1974) were also available: in this case the rate of
    decrease in residue level was higher than exponential during the first
    7 days and exponential from days 7-14. After 7-8 days residues in
    glasshouse spinach ranged from 0.8 to 1.2 mg/kg, in glasshouse lettuce
    from 0.44 to 0.67 mg/kg and in outdoor spinach from 0.05 to 0.6 mg/kg.
    Results are shown in Table 2.

    Results of residue trials with potatoes (Wit, 1973) and tomatoes grown
    under glass (ten Broeke and Dornseiffen, 1973) are also given in Table
    2. Although the data on tomatoes were from only two trials, they were
    particularly detailed and the Meeting concluded that they provided
    sufficient grounds for proposing a maximum residue limit.

    The carry-over of residues into successive crops an a consequence of
    granular application to the soil (both outdoors and under glass) was
    studied (Boehringer, 1975), A granular formulation of lindane was
    applied to the soil at a rate of 1.5 or 1.9 kg a.i./ha and potatoes
    and carrots were sown in the following one or two years. Results are
    in Table 3. The residues found in potatoes were invariably about or
    below the limit of determination (0.005 mg/kg) and no metabolites were
    detectable. Carrots grown in the year after treatment however
    contained mean residues ranging from 0.04 to 0,22 mg/kg and some
    samples also showed traces of metabolites
    (gamma-pentachlorocyclohexene and possibly also 1,2,4-trichlorobenzene
    and 1,2,3,4-tetrachlorolbenzene) at levels of < 0.02 mg/kg. Residues
    in carrots grown two years after the soil treatment were below the
    limit of determination, 0.005 mg/kg.

    RESIDUES IN FOOD IN COMMERCE OR AT CONSUMPTION

    Extensive information on residues of lindane in many home-produced and
    imported commodities was available from the Netherlands (Food
    Inspection Services, 1976). Of a total of 3381 samples of vegetables,
    fruity meaty poultry and meat and dairy products, 40 samples contained
    residues above the national limit for the commodity. Details are given
    in Tables 4 a-c.

    Data on residues in random samples at retail level found in New
    Zealand are reproduced in Table. 5 In addition, a sample of carrots
    known to have been treated with lindane contained 0.06 mg/kg.

        TABLE 1. Residues resulting from supervised trials (Federal Republic of Germany)
                                                                                                                                       

                              No.
                              of
    Crop           No. of     Treatment   Application*       Residue (mg/kg) at interval (days) after treatment
                   trials                 rate, a.i.
                                          (range)        0         14         21        28        35        >35
                                                                                                                                       
    Apples         6          2           0.25-0.4       0.04      0.006      0.006     0.009     0.007
                                          kg/ha          -0.29     -0.05      -0.02     -0.03     -0.013

    Plums          3          2-3         0.02% to       0.06      0.005-     <0.005    <0.005    <0.005
                                          run-off        (1        0.035      -0.018    -0.006    0.008
                                                         sample)   all        all       all

    Cherries       3          2           "                        <0.005     <0.005    <0.005
                                                         0.69      0.037                0.025     0.012

    Red currants   2          1           0.16 kg/ha     0.08      0.006      <0.005    <0.005    <0.005

    Black
    currants       1          1           0.02%          0.22      0.006                0.005     0.007

    Strawberries   2          1           0.096 kg/ha                                                       0.006-0.014
                                                                                                            (43-60 days)
    Strawberries   1          1           0.02%                                                   0.017

    Vines          2          1           0.45 g/plant
                                          (granules                                                         0.001,
                                          in soil)                                                          0.002
                                                                                                            (119 days)
                                                         0.05                 0.01      <0.005    0.006

    Cabbage        2          1           0.16 kg/ha     -0.07     0.015      -0.02     -0.01     -0.01
    red cabbage    1                      0.1% to                                                 0.04      0.02
                                          run-off                                                           (61 days)
                                          (5x normal
                                          concentration)

    TABLE 1. (Continued)
                                                                                                                                       
                              No.
                              of
    Crop           No. of     Treatment   Application*       Residue (mg/kg) at interval (days) after treatment
                   trials                 rate, a.i.
                                          (range)        0         14         21        28        35        >35
                                                                                                                                       
                   2                      1.875 kg/ha
                                          (granules on
                                          soil surface
                                          before                                                            0.03,(60  0.02(74
                                          planting)                                                         0.05 days)0-03 days)
                                                                                                            0.01(88
                                                                                                            0.03 days)
                   1                      0.0128g                                                           0.05,0.04(42,60 days)
                                          /plant
    Savoy
    cabbage        1          1           0.16 kg/ha     0.11      0.016      0.011     <0.005

    Brussels       1          1           0.0128g                                                           0.07,0.06,0.04
                                          /plant                                                            (42,60,90 days)
    sprouts        2          1           0.16 kg/ha     0.11      0.02       0.01      0.01      0.01
                                                         0.16      0.06       0.05      0.05      0.04

    Cauliflower    3          1           0.01-0.013g
                                          /plant                                                            0.01,0.01, <0.005
                                                                                                            (42, 60, 90 days)
                   2          1           0.015, 0.037
                                          g/plant
                                          (granular)                                                        <0.005, 0.02
                                                                                                            (90 days)

                   1          1           0.096 kg/ha    0.22      0.027      0.020     0.013

    Kohlrabi       3          1           0.01-0.015                                                        0.38-0.41
                                          g/plant                                                           (65 days)

    TABLE 1. (Continued)
                                                                                                                                       

                              No.
                              of
    Crop           No. of     Treatment   Application*       Residue (mg/kg) at interval (days) after treatment
                   trials                 rate, a.i.
                                          (range)        0         14         21        28        35        >35
                                                                                                                                       
    Radish         3          1           1.875                                                   0.47      0.18-0.04(9
                                          kg/ha                                                             samples,
                                          (granules                                                         40-67 days)
                                          on soil                                                 0.51
                                          surface
                                          before
                                          planting)      0.04      all        all       all
                   6          1           0.096 kg/ha    -0.14     <0.005     <0.005    <0.005
                   1          1           0.16 kg/ha     0.081     <0.005     <0.005    <0.005

    Peas           1          1           0.16 kg/ha
                                          dust                     0.005      <0.005    <0.005

    Wheat,         1 of       1                                                                             <0.005
    barley,        each                                                                                     (104-108 days)
    oats           

    Sugar          2          2           0.10 kg/ha                                                        Beets <0.005
    beets                                                                                                   (93,107 days)
                                                                                                            Leaves <0.005
                                                                                                            (93,107 days)
                                                                                                            Beets <0.005,
                                                                                                            0.025 (26-30
                                                                                                                   weeks
                   2          1           1.5 kg/ha
                                          granules                                                          Leaves 0.01-0.02
                                          before
                                          planting
                                                                                                                                       
    *Emulsion unless otherwise stated

 

    TABLE 2. Residues of lindane resulting from supervised trials on spinach, lettuce, potatoes and tomatoes (Netherlands)
                                                                                                                                             
                                                      Application
    Responsible        Crop or      Year of     Number       Rate per     Formulation                                               Ref.
    body               situation     trial      of           treatment
                                                treatments   kg a.i./ha                       days after     mean      range
                                                                                              (last)         residue,  (five
                                                                                                                       composite
                                                                                              application    mg/kg     samples)
                                                                                                                                             
    Inspector general  spinach       1970       1            0.15         emulsiflable        0              4.35      3.99-4.71
    of Public Health   (glasshouse)                                       liquid (applied     2              3.00      2.44-3.49
    in charge of Food                                                     together with       5              1.64      1.45-1.84
    stuffs Division                                                       25% parathion       8              0.96      0.81-1.15    1
                                                                          w.p.                11             0.37      0.35-0.39
                                                                                              14             0.38      0.32-0.45
                                                                                              17             0.10      0.08-0.11
                                                                                              21             0.05      0.04-0.06
                       lettuce         "        "            "            "                   0              3.04      2.66-4.05
                       (glasshouse)                                                           2              1.89      1.68-2.12
                                                                                              5              1.06      0.96-1.19    1
                                                                                              8              0.52      0.44-0.67
                                                                                              11             0.32      0.29-0.35
                                                                                              14             0.20      0.18-0.24
                                                                                              17             0.062     0.054-0.070
                                                                                              21             0.028     0.026-0.033

    Rijkszuivel-       spinach       1971       1            0.21(+0.38   emulsifiable        0              2.6       2.3 -2.8
    station            (outdoor)     June                    parathion)   liquid 21%          2              1.1       1.0 -1.2
                                                                          lindane in          4              0.20      0.19-0.21
                                                                          combination         7              o.063     0.05-0.08    3
                                                                          25% parathion       9              0.045     0.03-0.06

                                                                                              11             0.030     0.03-0.03
                                                                                              14             0.013     0.01-0.02

    Rijkszuivel-       spinach       1971       1            "            "                   0              8.1       4.6 -14
    station            (outdoor)   September                                                  2              2.0       1.3 -2.8
                                                                                              4              1.5       1.0 -1.7

    TABLE 2. (Continued)
                                                                                                                                             
                                                      Application
    Responsible        Crop or      Year of     Number       Rate per     Formulation                                               Ref.
    body               situation     trial      of           treatment
                                                treatments   kg a.i./ha                       days after     mean      range
                                                                                              (last)         residue,  (five
                                                                                                                       composite
                                                                                              application    mg/kg     samples)
                                                                                                                                             
     Rijkszuivel-       spinach       1971                                                    7              0.40      0.33-0.59    3
     station            (outdoor)   September                                                 9              0.31      0.30-0.33
                                                                                              11             0.25      0.21-0.29
                                                                                              14             0.16      0.16-0.16

    National
    Institute          potatoes      1971       2            0.15         e.c.,210g/l         30             0.01*                  2
    of Public          (Bintje)
    Health
                       potatoes
    "                  (Gineke)        "        "            "            "                   30             0.01*                  2

    Food Inspection    tomatoes      1973       1            fumigation   smoke               3              0.43      0.34-0.50    4
    Service,           (glasshouse)   (2                     2.4 g/100m3  Tablet              3              0.003     0.002-0.004  4
    Amsterdam                        trails)                              10%
                                                                                                                                             

    References

    1. Ad Hoc Working Group, Codex Committee on Pesticide Residues, 1971

    2. Wit, 1973

    3. de Ruig and Werdmuller, 1974

    4. ten Broeke and Dornseiffen, 1973
    * Limit of determination


    TABLE 3. Uptake of lindane by potatoes and carrots sown in rotation after soil treatment

                                                                                                                   

    Treatment           Crop grown     Sampled        Date of                       Residue, mg/kg
    and date            at             crop           sampling
                        treatment
                                                                          Lindane                  Metabolites
                                                                                                                   

    1.875 kg a.i.       Radish,        Potatoes       2.10.73             <0.005                   n.d.
    /ha                 cole           (3 plots)                          <0.005                   n.d.
                        crop                                              <0.005                   n.d.

    Granular
    27.7.72                            Carrots        2.8.73              0.40                     0.02
                                       (3 Plots)                          0.22                     <0.02
                                                                          0.23                     0.02
                                       Soil           6.4.73              0.12                     0.02
                                       Soil           16.11.73            0.02                     <0.02
                                       Potatoes       26.8.74             <0.005                   n.d.
                                       Carrots        11.9.74             <0.005                   n.d.
                                       soil           11.9.74             0.06                     n.d.
    1.5 kg a.i.         Sugar          Potatoes       9.9.74              I <0.005                 n.d.
    /ha                 beet                                              II 0.005                 n.d.
                        summer
    Granular            wheat,         Carrots        9.9.74              I 0.1                    0.02
    23.3.73             maize                                             II 0.1                   <0.02
    Two separate                       Soil           19.9.76             II 0.13                  0.02
    trials, I and II

    1.5 kg a.i.         Vegetables     Potatoes       10.7.74             0.006                    <0.02
    /ha granular                       Carrots        14.8.74             0.04                     <0.02
    24.4.73                            Soil           31.7.74             0.09                     <0.02
    (under glass)
                                                                                                                   


    TABLE 4a. Residues of lindane in commodities moving in Commerce (Netherlands, 1976)

                                                                                                                                    

                          endive   lettuce  parsley  purslane  turnip-tops  celery  spinach   corn-salad   cauliflower  chinese
                                                                                              (lamb's                   cabbage
                                                                                              lettuce)
    Range of residues,
    mg/kg
                                                                                                                                    

    0 - 0.05              73       159      9        6         24           21      47        0            21           1
    0.051 - 0.10          13       93       1        2         5            5       12        2            0            1
    0.101 - 0.50          34       147      4        1         5            17      4                      2            1
    0.501 - 1.00          13       62       1                  3            1       0                                   
    1.001 - 2.00          8        31       1                  3            0       1                                   
    2.01 - 3.00           2        10                                       1                                           
    3.01 - 5.00                    4                                                                                    
    > 5.00                1                                                 1

    total                 144      506      16       9         40           46      64        2            23           3

    No. of
    samples
    exceeding
    Netherlands           3        14       -        -         -            2       -         -            -            -
    MRL (2 mg/kg)

    Residues found
    over 5 mg/kg                                                            13.0
                                                                            mg/
                                                                            kg
                          7.78
                          mg/
                          kg
                                                                                                                                    

        proposed limit


    Table 4a.(2) Residues of lindane in commodities moving in Commerce ( Netherlands, 1976)

                                                                                                                                 

                          red      savoy    Brussels butter    French       brown   pea       asparagus    chicory      leek
    Range of              cabbage  cabbage  Sprouts  -bean     bean         bean
    residues,
    mg/kg
                                                                                                                                 

    0 - 0.05              4        1        13       35        79           2       3         1            18           5
    0.051 - 0.10                            1                  2                                           2            1
    0.101 - 0.50                            3                  3                                           5            6
    0.501 - 1.00                            1                                                                           0
    1.001 - 2.00                                                                                                        5
    2.01 - 3.00                                                                                                         2
    3.01 - 5.00                                                                                                         1
    > 5.00                                                                                                              1

    total                 4        1        18       35        84           2       3         1            25           22

    No. of
    samples
    exceeding
    Netherlands           -        -        -        -         -            -       -         -            -            4

    MRL (2 mg/kg

    Residues found over 5 mg/kg                                                                                         5.2
                                                                                                                        mg/
                                                                                                                        kg
                                                                                                                                 

       proposed limit

    Table 4a.(3) Residues of lindane in commodities
    moving in Commerce ( Netherlands, 1976)

                                                                   

                          cucumber  melon   eggplant   paprika
    Range of
    residue,
    mg/kg
                                                                   

    0 - 0.05              99        47      1          53
    0.051 - 0.10          1                            1
    0.101 - 0.50                                       2
    0.501 - 1.00                                       
    1.001 - 2.00                                      
    2.01 - 3.00
    3.01 - 5.00
    > 5.00

    total                 100       47      1          56

    No. of
    samples
    exceeding
    Netherlands           -         -       -          -

    Residues found
    over 5 mg/kg
                                                                   

       proposed limit

    TABLE 4b.(1) Residues of lindane in commodities moving in Commerce (Netherlands, 1976)

                                                                                                                                     

    mg/kg             tomato   celeriac   Swedish  beet root  radish   apple   pear    strawberry   mushroom       meat  meat of
                                          turnip                                                                         pig
                                                                                                                                     

    0.051 - 0.10      38       3          0        4          18       75      9       9            3              121   5
    0.101 - 0.50      3                   1                            4               3            2              53    1
    0.501 - 1.00                                                                       1            3              23
    1.001 - 2.00                                                                                    1              3
    2.01 - 3.00                                                                                                    2
    3.01 - 5.00
    > 5.00                                                                                                        1

    total             41       3          1        4          18       79      9       13           9              203   6

    No. of samples
    exceeding
    Netherlands       -        -          -        -          -        -       -       -            -              1     -

    MRL (2 mg/kg)

    Residues found
    over 5 mg/kg                                                                                                   (5.8
                                                                                                                   mg/
                                                                                                                   kg
                                                                                                                                     

    ---proposed limit 

    TABLE 4b.(2) Residues of lindane in commodities moving in Commerce (Netherlands, 1976)

                                                                                                    

    mg/kg             meat-products   summer      winter        grape    banana   miscellaneous
                                      carrot      carrot
                                                                                                    

    0 - 0.05          80              21          4             3        0        19
    0.051 - 0.10      7                                         0        0        10
    0.101 - 0.50      1                                     1        0
    0.501 - 1.00                                                         1
    1.001 - 2.00
    2.01 - 3.00
    3.01 - 5.00
    > 5.00

    total             88              21          4             4        1        29

    No. of samples
    exceeding
    Netherlands       -               -           -             -        -        -

    MRL (2 mg/kg)

    Residues found
    over 5 mg/kg

                                                                                                    

    --- proposed limit

    TABLE 4c. Residues of lindane in comodities moving in Commerce (Netherlands, 1976)

                                                                                                                                        

    mg/kg            cacoa      milk   milk       meat         eggs     egg       wheat (incl.)  wheat       rice             maize
                     products          products   of poultry            products                 (before     (untreated)
                                                                                                 milling)
                                                                                                                                        

    0 - 0.05         3          922    93         90           36       1         13             1           0              0
                                                                                                                               
    0.051 - 0.10     2          194    42         32           12                 1                          1              1
    0.101 - 0.20     5          80     16         15           1                  2
                                          
    0.201 - 0.50                8      1          3            1
                                                                                    
    0.501 - 0.70                2                 2
                                                                  
    0.701 - 1.00                1
                        
    >1.00                       2

    total            10         1209   151        142          50       1         16             1           1              1

    No. of
    samples
    exceeding
    Netherlands      -          13     1          -            -        -         -              -           1              1
    MRL

                                       0.23
                                       mg/kg

    Residues found
    over 1 mg/kg                (1.42
                                3.75
                                mg/kg
                                                                                                                                        

    

   APPRAISAL

    Some of the information listed as desirable by the 1973 and 1974
    Meeting, 83 further residue data for various crops, from supervised
    trails carried out in the Federal Republic of Germany and the
    Netherlands, were considered by the present Meeting, they showed that
    the residue levels were at or below the limits recommended by the 1975
    Meeting. As no other information on these crops had become available
    for consideration, the Meeting decided not to make any alterations to
    the existing recommendations.

    Further supervised trials with spinach and tomatoes, for which
    recommendations had not previously been made, resulted in residues at
    or below 2 and 0.5 mg/kg respectively. Recommendations were therefore
    made for these products at these levels.

    Carrots absorbed about 0.1 mg lindane/kg from soil in which maize,
    sugar beets, vegetables or wheat had been treated with lindane in the
    previous year; an adequate extraneous residue limit is therefore
    necessary for this crop.

    Extensive data in residues in commodities moving in commerce were
    received.

        TABLE 5.         Residues of lindane in food moving in commerce (New Zealand, 1973 and
    1975, random sampling at retail level)
                                                                                              
    Year           crop            No. of Samples                     Residue levels
                                   containing residues                    (mg/kg)
                                                                  Highest         Average
                                                                                              
    1973     leafy vegetables      3 samples in 61                0.26            0.12
             root vegetables       1 "       "  39                                0.18
             mushrooms             5 "       "  6                 0.2             0.08

    1975     grain                 11 "      "  16                0.03            0.007
             meat                  5  "      "  16                0.03            0.01
             vegetables            1  "      "  16                                0.003
                                                                                              

    

    RECOMMENDATIONS

    1.   The maximum residue limits recommended by the 1975 Meeting and
         those of the 1972 Meeting which were not changed in 1975, are
         maintained.

    2.   Additional maximum residue limits are recommended for spinach and
         tomatoes; an extraneous residue limit, marked (E) in the table
         below, is recommended for carrots.

    Commodity      Limit, mg/kg        Pre-harvest interval
                                       (days) on which recommendation
                                       is based.
    Spinach        2                   7-14
    Tomatoes       0.5                 3-4
    Carrots        0.2 (E)

    FURTHER WORK OR INFORMATION

    DESIRABLE

    Additional residue data, especially from countries outside Europe in
    which lindane is used.

    REFERENCES

    Ad. Hoc. Working Group Codex Committee on Pesticide Residues. (1971) A
    contribution to the determination of acceptable quality levels of
    pesticide residue concentrations in food. Report Cx/pr/wg 71/10 add.
    1. Unpublished.

    Boehringer (1975) Sohn Zum Rücketandeverhalten von lindan. Unpublished
    report.

    Chadwick, R.W. and Freal, J.J. (1972a) Fd. Cosmet, Toxicol. 10:789.

    Chadwick, R.W. and Freal, J.J. (1972b) Bull. Env. Contam. Toxicol*
    7:137.

    Chadwick, R.W., Chuang, L.T. and Williams, K. (1975) Pesticide
    Biochem. Physiol. 5:575.

    Chadwick, R.W., Copeland, M.F. and Chadwick, C.J. (1977d) Toxicol.
    Appl. Pharmacol. 41:161.

    Chadwick, R.W., Simmons, W.S., Bryden, C.C., Chuang, L.T., Key, L.M.
    and Chadwick, C.J. (1977b) Ibid., 39:391.

    Engst, R., Macholz, R.M., Kujawa, M., Lewerertz, H.J. and Plaas, R.
    (1975) J. Env. Sci. Health (b), 11:95.

    Freal, J.J. and Chadwick, R.W. (1973) J. Agr. Fd. Chem. 21:424.

    Haider, K., Jagnow, G. and Rohr, K, (1976) Vd. Lufa, Manheim
    (unpublished report)

    Karapally, J.C., Saha, J.G. and Lee, Y.W. (1973) J. Agr. Fd. Chem.
    21:812.

    Kurihara, N. and Nakajima, M. (1974) Pesticide Biochem. Physiol.
    4:220.

    Kollmer, H., Weisse, I. and Stolzer, H. (1975) Testing of the
    substance lindane for cancerogenic effects in mice using oral
    administration during 80 weeks. Unpublished report submitted to WHO by
    C.R. Boehringer Shon.

    NCI (1977) Bioassay of lindane for possible carcinogenicity. Report of
    the Carcinogen Bioassay and Program Resources Branch, Carcinogenesis
    Program, Division of Cancer Cause and Prevention, National Cancer
    Institute, National Institutes of Health, Bethesda, Maryland, 
    submitted to WHO by Hooker. (unpublished report)

    deRuig, W.G. and Werdmuller, G.A. (1974) Pesticidenproeven op spinazie
    en appels 1971. Statistische ver weking van de resultaten. Report 2nd
    serie no., 121. Unpublished.

    Seidler. H., Macholz, R.M., Hartig, M., Kujawa, M. and Engst, R.
    (1975) Die Nahrung 19:473

    Solomon, L.M., West, D.P., Fitzloff, J.F. and Becker, A.M. (1977) J.
    Inv. Dermatol. 68:310. 

    Stügkigt, J. and Ries, B. Internationaler Kongress für
    Arzneipflanzen-Forasch. Munich, Sept. 1976.

    ten Broeke, R. and Dornseiffen, J.W. (1973) Residuen van idcofol en
    lindane in tomaten (glasteelt) Report KvW 176/CvF/PD. Unpublished.

    Weisse I. and Herbst, M. (1977) Carcinogenicity study of lindane in
    the mouse. Toxicology, 7,233-239.

    Wit, S.L. (1973) Residuen van enige insecticiden in aardappelen.
    Report 72/73. Unpublished.

    FAO/WHO (1967) Evaluation of some pesticide residues in food.
    FAO:PL/CP/15; WHO/Food Add./67.32.

    FAO/WHO (1968) 1967 evaluation of some pesticide residues in food.
    FAO/PL:1967/M/11/1; WHO/Food Add./68.30.

    FAO/WHO (1969) 1968 evaluations of some pesticide residues in food.
    FAO/PL:1968/M/9/1; (1969) WHO/Food Add./69.35.

    FAO/WHO (1970) 1969 evaluations of some pesticide residues in food.
    FAO/PL:1969/M/17/1; WHO/Food Add./70.38.

    FAO/WHO (1974) 1973 evaluations of some pesticide residues in food.
    AGP:1973/M/9/1; WHO Pesticide Residues Series, No. 3.

    FAO/WHO (1973) 1974 evaluations of some pesticide residues in food.
    AGP:1974/M/11.
    


    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 3)
       Lindane (WHO Pesticide Residues Series 4)
       Lindane (WHO Pesticide Residues Series 5)
       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)