ALDRIN/DIELDRIN         JMPR 1977


    Dieldrin was reevaluated at the Joint FAO/WHO Meeting in 1970 (FAO/WHO
    1971) and additional information on the significance of the hepatic
    lesions observed in mice after dieldrin treatment was thought
    desirable. Moreover further data on long term studies of industrial
    workers, on teratogenicity, on comparative metabolism studies in
    humans, monkey rat and mouse and data an possible photo-dieldrin
    residues in foodstuff should become available for evaluation.

    Since that last reevaluation results of several studies have been
    presented and are summarized in the following monograph addendum,
    together with data on the teratogenicity and carcinogenicity of



    Absorption, distribution, excretion and biotransformation

    Dieldrin has been reported to produce hepatoma in certain mice strains
    not however in other laboratory animals so far studied. Different
    metabolic pathways and differences in excretion could be the reason
    for this possible species-specific reaction of mouse liver on the
    ingestion of dieldrin.

    A comparative metabolism study in mice (strain Swiss White), rats,
    rabbits, rhesus monkeys and chimpanzees showed that there are two main
    metabolic pathways in mammals. The first involves direct oxidation,
    supposedly by cytochrome oxidases, resulting in 12-hydroxydieldrin,
    the second involves the opening of the epoxide ring by epoxide
    hydrases resulting in aldrin-4,5-trans-dihydrodiol. Single oral
    doses of 0.5 mg/kg of 14C labelled dieldrin were administered to the
    test animals. Faeces and urine were collected separately for 10 days
    following administration. The major metabolites in the excreta of all
    five species under study were 12-hydroxydieldrin and
    4,5-aldrin-transdiol. In all species the faecal excretion of unchanged
    dieldrin was high in the first 48 h after administration and declined
    rapidly thereafter. The urine contained no unchanged dieldrin.
    Regarding the ratios of the two major metabolites, the rats and
    primates seemed to metabolize dieldrin mainly by direct oxidation
    resulting in 12-OH-dieldrin, whereas the common main metabolic pathway
    of mice and rabbits seemed to be the opening of the epoxide ring to
    the diol. The highest rate of metabolism was found in the mouse with
    33% of the administered dieldrin being metabolized within 10 days,
    compared to about 9% in rats, 2% in rabbits, 11% in rhesus monkeys and
    3% in chimpanzees. The high rate in mice may result in relatively high
    diol concentrations in the mouse liver. About 23% of the administered

    dose was excreted as aldrin-trans-diol by mice compared with only 1-2%
    in the other species examined (Müller at al., 1975a). Similar results
    were also obtained by Bedford and Hutson (1976).

    14C labelled dieldrin was administered to rhesus monkeys either as a
    single i.v. injection of 2.5 mg/kg or as a single oral dose of 0.36 or
    0.5 mg/kg. The excreta were separately collected for 75 days following
    administration. After administration by injection there was a short
    period of relatively high excretion; 13% of the administered dose was
    eliminated within the first 5 days. The excretion rate decreased to
    about 0.05% per day after 20 days. A total of 20% was excreted over
    the whole period. Only 10% of the excreted radio-carbon was eliminated
    with the urine during the initial excretion phase, after day 20 the
    urinary excretion rate increased to 30-40%. The three identified
    metabolites found in the excreta were 12-hydroxydieldrin,
    4,5-aldrin-trans-dihydrodiol and the last one was assumed to be a
    glucuronic acid conjugate of the diol. After oral administration 17%
    and 25% of the administered dose respectively were eliminated within
    10 days at the 0.36 and 0.5 mg/kg dose level. The faeces contained
    predominantly dieldrin for the first two days. From the third day
    urine and faeces contained the same metabolites found in the injection
    study. 7% and 11% respectively were excreted as unchanged dieldrin, 8%
    and 12% respectively as 12-hydroxydieldrin in the monkeys treated with
    0.36 mg/kg and 0.5 mg/kg (Müller et al., 1975b).

    Determination of the faecal and urinary radioactivity during the 7
    days following a single oral dose of 14C-dieldrin to different rat
    and mouse strains showed that the major route of excretion is via the
    faeces. The nature of the excreted metabolites and the excretion rates
    of individual metabolic products depended on species, strain and sex.
    The major faecal metabolite in rat and mouse was
    syn-12-hydroxydieldrin, the excretion rate of this metabolite being
    much higher in rats than in mice. On the other hand the production of
    the trans-diol was higher in mice than in rats. Similar amounts of the
    tricyclic diacid were excreted in both species. Unchanged dieldrin was
    also excreted via the faeces in rats and mice. Most of the urinary
    label in the male rat (CFE strain) was dieldrin pentachloroketone;
    this metabolite was found only in traces in the urine of female rats
    or mice. Unchanged dieldrin and the diacid were excreted in the urine
    of both rat and mouse.

    The investigation of the metabolites in organs and tissues of rats
    showed that dieldrin was present in all organs and tissues, the
    adipose tissue being the major site of deposition. Dieldrin
    pentachloroketone was also present in most tissues and organs, notably
    in the kidney of male animals. No other metabolites were detected.

    The monohydroxylated metabolite of dieldrin, syn-12-hydroxydieldrin is
    formed after incubation of dieldrin with rat liver microsomes. Since
    the production can be inhibited in vitro by the addition of
    mono-oxygenase inhibitors such as sesamex, syn-12-hydroxydieldrin is
    obviously formed by liver microsomal monooxygenase action. The bridged

    pentachloroketone is also a sesamex-inhibited product of dieldrin
    incubation with liver microsomes and seems to be formed also by
    monooxygenase activity. It has been assumed that the trans-diol is
    formed by the action of epoxide hydratase upon dieldrin. The formed
    cis-diol is converted into the ketol by oxidation and the reduction of
    the latter would lead to the trans-diol. Based on the results of
    recent studies a novel pathway of the trans-diol formation is proposed
    involving direct oxidative formation of the ketol from dieldrin,
    reduction of which yields the cis- as well as the trans-diol.
    In vitro experiments with cis- and trans-diols indicated that the
    cis-diol was convertible into the trans-diol, but that the reverse
    reaction did not occur (Bedford and Hutson, 1976).


    Special studies on mutagenicity

    The compound did not produce any mutagenic response when tested
    in vitro with or without microsomal activation against five
    indicator organisms of histidine auxotroph tester strains of
    Salmonella typhimurium. Tester strains that revert due to base
    analogue and frameshift mutation in repair deficient as well as repair
    competent strains had been utilized. Additionally two strains were
    examined that are deficient in their lipo-polysaccharide coat which
    allows for penetration of lipophilic compounds (Bidwell et al., 1975).

    Preliminary results of a microbial mutagenicity study showed that also
    metabolites of dieldrin, i.e. syn-12-hydroxydieldrin, aldrin
    dicarboxylic acid, cis-aldrin diol, trans-aldrin diol and
    pentachloroketone did not significantly increase the incidence of
    reverse mutations of six histidine auxotroph tester strains of
    Salmonella typhimurium (Dean and Brooks, 1977).

    For the evaluation of possible host-activated mutagenic metabolites of
    dieldrin, host-mediated assays and blood-and urine recovery studies
    were performed in mice. The animals were treated daily for 5 days with
    an oral dose of 20 mg/kg and then received injections of tester
    bacteria. Mutation frequencies showed no significant increase in
    mutation in the dieldrin-treated animals (Bidwell et al., 1975).

    No mutagenic activity could be found in a further host-mediated assay.
    Mice were treated with a single oral dose of 25 and 50 mg/kg dieldrin
    (HEOD) or with repeated doses of 5 and 10 mg/kg on five consecutive
    days. The indicator organism, injected after the fifth dose into the
    peritoneal cavity, was a strain of the yeast
    Saccharomyces cerevisiae (Dean at al., 1975).

    The examination of blood and urine samples of mice treated with a
    single oral dose of 20 mg/kg by spot test revealed no mutagenic
    substances in blood or urine treated animals (Bidwell et al., 1975).

    After oral treatment of male mice with 12.5, 25 and 50 mg/kg dieldrin
    (HEOD) and mating with untreated females in a dominant lethal test no
    adverse effects could be observed (Dean et al., 1975). Consistent
    results were obtained when mice were treated with 0.08, 0.8 and 8
    mg/kg dieldrin for 5 consecutive days before mating with untreated
    females (Bidwell et al., 1975).

    The oral administration of single doses of 30 and 60 mg/kg dieldrin
    (HEOD) to Chinese hamsters did not cause any demonstrable chromosome
    damage in bone marrow cells (Dean et al., 1975).

    Standard metaphase analysis and micronuclei test after oral treatment
    of mice with 0.8 and 8 mg/kg dieldrin for 5 days revealed no
    cytogenetic abnormalities (Bidwell at al., 1975).

    The heritable translocation test was carried out with male mice that
    sired low numbers of pups after oral intake of 0.008, 0.08 and 0.2
    mg/kg over a period of 6 weeks. The cytogenetic determination of
    somatic cells utilizing the micronuclei test and the usual analysis of
    spermatocytes did not reveal an increase in the number of
    trans-locations that could have led to sterility or semisterility
    (Bidwell et al., 1975).

    Special Study on Teratogenicity

    Foetotoxic and teratogenic effects were found after administration of
    aldrin and dieldrin as single oral doses to hamsters and mice.
    Hamsters were treated with 30 mg/kg of dieldrin and 50 mg/kg aldrin on
    gestation day 7, 8 or 9, mice were treated with 15 mg/kg dieldrin and
    25 mg/kg aldrin on day 9 of gestation. Foetotoxicity in hamsters
    resulted in an increase of foetal death and foetal growth retardation.
    High incidences of congenital anomalies such as cleft palate, open eye
    and webbed foot were found as teratogenic defects. In treated mice
    similar anomalies were found but without increase of foetal mortality
    and growth retardation (Ottolenghi at al., 1974).

    After daily oral administration of 1.5, 3 and 6 mg/kg dieldrin and
    0.15, 0.3 and 0.6 mg/kg photodieldrin to mice and rats on gestation
    days 6 through 16 no teratogenic effects were observed even at the
    highest dose levels. The administration of 6 mg/kg dieldrin resulted
    in a reduction of the average body weight gain in mice and rats, an
    increase of the relative liver weights in mice and a 41% mortality in
    rats. The highest dose of photodieldrin resulted in increased liver
    weights in mice and a 15% mortality in rats (Chernoff et al., 1975).

    No teratogenic activity of the compound could be found when dieldrin
    (HEOD) was orally administered at dose levels of 1.5 and 4 mg/kg in
    corn oil or 1.25, 0.5 and 1 mg/kg in DMSO to mice on days 6 through 14
    of gestation. The only adverse effects such as reduced body weight
    gains of the pregnant mice, some maternal deaths, lower foetal body
    weights and increased incidence of delayed ossification of the foetal
    bones were observed in the control and treatment groups when DMSO was
    used as vehicle (Dix et al., 1975).

    Special Study on Carcinogenicity


    Groups of 50 mice of each sex were maintained on a diet containing
    dieldrin at doses of 2.5 and 5 ppm for a period of 80 weeks followed
    by an observation period of 10-13 weeks. Matched controls consisted of
    groups of 20 untreated male and 10 untreated female mice. Pooled
    controls used for statistical evaluation consisted of the animals in
    the matched control group combined with 92 male and 79 female
    untreated animals from similar bioassays with other chemicals. All
    surviving mice were killed at weeks 90-93. The treatment did not
    affect the mean body weights or the survival rates. During the second
    6 months of the study clinical signs such as tremors, abdominal
    distention, alopoecia, tachnypnea and hyperexcitability appeared among
    treated animals and increased in frequency during the second year of
    study, together with pale mucous membranes and rough hair coat. In
    male mice there was a marked dose-related increase in hepatocellular
    carcinomas showing frequencies of 17/92 (18.5%) in the pooled
    controls, 12/50 (24%) in the 2.5 ppm group and 16/45 (36%) in the 5
    ppm group. The incidence of hepatocellular carcinoma was much higher
    in male animals of the control and treated groups than in females. The
    incidence in females was not dose-related. 3.8% of the females in the
    pooled control group showed heptocellular carcinoma, 12% in the low
    and 4% in the high dose groups. There was a low incidence of other
    types of neoplasms involving various organs and tissues with no
    obvious difference between control and treated animals (NCI, 1977a).

    Groups of 50 mice of each sex were administered aldrin at time-
    weighted dietary average doses of 4 and 8 ppm for males and 3 and 6
    ppm for females. The diet was administered over a period of 80 weeks,
    then the animals were observed for 10-13 weeks. The control groups
    included the matched control animals and the 92 male and 79 female
    untreated mice from the pooled control group. All surviving mice were
    killed at 90-93 weeks.

    The treatment did not affect the mean body weights. During the second
    year of the study, clinical signs including rough hair coat, alopecia
    and abdominal distention appeared with increasing frequency. No
    dose-related increase in mortality in the male mice was found, whereas
    in female mice there was a dose-related trend in mortality represented
    by early deaths in the high-dose group. A dose-related increase of
    hepatocellular carcinomas in the treated male mice was seen with
    incidences of 10.8% in pooled control group, 33% in the low dose group
    and 54% in the high dose group, whereas the frequency of this neoplasm
    in the female mice was much lower and not dose-related with incidences
    of 2.3% in pooled controls, 10% in the low dose and 5% in the high
    dose group.

    The low incidences of other types of neoplasms in various organs and
    tissues were not considered to present a difference between treated
    and control groups (NCI, 1977a).

    Groups of 50 rats of each sex were administered dieldrin at time-
    weighted average dietary dose levels of 29 ppm for a period of 80
    weeks followed by an observation period of 30-31 weeks and 65 ppm for
    59 weeks, followed by 51-52 weeks of observation. Matched controls
    consisted of groups of 10 untreated rats of each sex. Pooled controls
    used for statistical evaluation, consisted of the matched-control
    groups combined with untreated animals from similar bioassays of other
    chemicals, 58 male and 60 female rats. All surviving rats were killed
    at 110-111 weeks.

    Mean body weights showed no difference compared with those of the
    controls during the first year of the study; however during the second
    year the treated animals showed lower weights than the control. During
    the first 6 months of treatment the treated animals were comparable to
    the controls with respect to behaviour and appearance with the
    exception of high-dosed animals having convulsions. During the second
    6 months of the study clinical signs including diarrhoea, alopoecia, 
    epistaxis, haematuria, discoloured hair coats, tremors and weight loss
    appeared and increased in frequency during the second year of study,
    together with pale mucous membranes, vaginal bleeding, dermatitis,
    dyspnoea, ataxia, tachypnea, abdominal distention, rough hair coats
    and discoloured urine.

    There was a marked increase in the mortality rate of rats during the
    first 90 weeks of the study. However because of the high rates of
    mortality in the control groups during the remaining study period,
    mortality did not appear to be treatment-related. A significant
    increase was found in the combined incidence of adrenal cortical
    adenoma and carcinoma in the low-dosed females (6/45) compared with
    the pooled controls (0/55). No dose-relationship could be seen.

    There were instances where neoplasms occured only in treated animals
    (adrenal cortical adenoma, spleen haemangiosarcoma) or with increased
    frequency when compared to control groups (pituitary
    chromophobe-adenoma). Incidence and severity of the lesions were not
    considered to provide clear evidence of a carcinogenic effect of
    dieldrin on rat (NCI, 1977).

    Groups of 50 rats of each sex were maintained on a diet containing
    aldrin at dose levels of 30 to 60 ppm. Male rats were treated for 74
    weeks, followed by 37-38 weeks of observation, female rats were
    treated for 80 weeks, followed by an observation period of 32-33
    weeks. Matched controls consisted of groups of 10 untreated rats of
    each sex. Pooled controls consisted of the matched-control groups
    combined with 58 untreated males and 60 untreated females from other
    bioassays. All surviving rats were killed at 111-113 weeks. During the
    second year of the study mean body weights of the treated animals were
    lower than those of the control animals. Hyperexcitability was
    observed in all treated groups with increasing frequency and severity
    during the second year. The mortality was not dose-relatedly affected
    by the treatment. During the second 6 months of the study convulsions
    were observed in several high-dosed female rats. Throughout the second
    year of the study clinical signs including pale mucous membranes,
    rough hair coats, weight loss and vaginal bleeding were apparent in
    all treated groups.

    The combined incidence of follicular-cell adenoma and -carcinoma of
    the thyroid was increased in both sexes. These incidences however were
    significantly increased only in the low-dose animals compared with the
    pooled controls. Adrenal cortical adenoma incidence showed a
    significant increase compared with pooled controls in the low-dose
    females. There were instances where neoplasms occurred only in the
    treatment groups or with increased frequency compared with those in
    control groups. The incidence of tumors and the severity of lesions
    are however not considered to be dose-related (NCI, 1977a).

    Groups of 24 Fischer 344 rats of each sex were administered dieldrin
    technical grade, purified and recrystallized, at 0, 2, 10, or 50 ppm,
    for 104-105 weeks. The dose level of 50 ppm constitutes a maximum
    tolerated dose. All surviving rats were killed at 104-105 weeks. Body
    weights of the rats were essentially unaffected by the treatment, but
    typical signs of organochlorine intoxication including
    hyperexcitability, tremors and coma were observed in high-dose males
    beginning in week 76 and in high-dose females beginning in week 80.
    Survival was not adversely affected, and adequate numbers of rats were
    available for meaningful statistical analysis of the incidence of
    tumors: 67-70% of the high dose group, 75-83% of the mid-and low-dose
    group, and 88-92% of the matched control group survived to the
    termination of the study. A variety of neoplasm occurred in control
    and treated rats; however, the incidences were not related to
    treatment. Frequently interstitial-cell tumours of the testes
    (80-100%), and lymphocytic and granulocytic leukaemia (8-21%)
    occurred. It is concluded that under the conditions of this bioassay,
    dieldrin was not carcinogenic in Fischer 344 rats (NCI, 1977b).


    145 female and 147 male Syrian hamsters received dietary
    concentrations of 0, 20, 60 and 180 ppm dieldrin (purity 99%) for
    life. The survival rate at 50 weeks of age was comparable to the
    control being 66%. Among control females 12% showed tumors whereas in
    treated females 3-15% had tumors. 8% of the control males had tumors
    and between 16 and 23% of the treated males. The study showed that by
    the treatment of hamsters no significant increase in tumor incidence
    is observed (Cabral at al., 1977).

    In view of the possible species-specific reaction of mouse liver to
    ingested dieldrin several studies have been performed on the
    interactions of dieldrin with liver cells at the subcellular level in
    different mammalian species (Wright at al., 1977). The earliest
    structural change observed in the livers of rats, mice and dogs
    treated with dieldrin was the proliferation of the smooth endoplasmic
    reticulum (SER). During the initial phase of the exposure to dieldrin
    the increases in the SER in rats, dogs and mice were of the vesicular
    type. Thereafter as an effect of microsomal enzyme induction
    intracellular whorls of smooth membranes appeared in the liver cells
    of rats and dogs. None of these structures was induced in mice liver.
    All these structural changes were reversible. In contrast no
    structural changes in the livers of rhesus monkeys were observed.
    Dieldrin administered in large doses caused liver enlargement in the
    rat, mouse and dog but not in monkeys. In vitro  determinations,
    being the most sensitive criterion for the effect produced by
    dieldrin, showed that the activity of the liver microsomal
    monooxygenase system was increased after treatment. Microsomal enzyme
    induction was detected in all four species exposed to dieldrin. A
    dietary concentration of about 1 ppm was reported to be sufficient to
    produce monooxygenase induction in rat liver.

    The possibility that dieldrin or one of its metabolites exerts its
    tumorigenic action on mouse liver by means of a direct interaction
    with DNA has been studied measuring the extent of binding of
    14C-labelled dieldrin and/or its metabolites to liver DNA utilizing
    one rat strain and two mouse strains. CF1 mice are susceptible to
    liver tumor induction by dieldrin, whereas LACG mice represent a
    strain which is not or only very weakly susceptible. The results
    showed that the extent of binding was not correlated with
    susceptibility. Binding was highest in the rat, intermediate in the
    susceptible and lowest in the non-susceptible mouse strain. Based on
    these results on the one hand and the uniformly negative results of
    different mutagenicity tests on the other, the conclusion is drawn
    that the increased incidence of liver tumors in dieldrin-treated mice
    is not due to direct damaging effects on DNA.

    Experiments determining the rate of semi-conservative DNA synthesis in
    normal primary human fibroblasts (AH) as well as experiments
    determining repair replication in AH cells and SV-40 transformed human
    cells also gave no indication of damage to DNA or induction of repair
    replication after treatment with dieldrin (Zelle and Lohman, 1977).
    The treatment of SV-40 transformed human cells in culture with
    dieldrin resulted in increased unscheduled DNA synthesis and in
    induction of DNA repair. They reported that in these treated human
    cells long-type excision repair of DNA could be found (Ahmed et al.,

    Observations in Humans

    Previous results of a long term study of occupationally exposed
    industrial workers (Jager, 1970) were presented at the Joint FAO/WHO

    Meeting in 1970 (FAO/WHO, 1971). A follow-up survey of the study has
    been carried out (Versteeg and Jager, 1973). The figures from this
    continuing study were updated. The population under study numbered
    about 1,000 persons. Because not all of the workers had prolonged and
    severe exposure, smaller groups with exposure meaningful enough for
    carcinogenicity evaluation were taken. One group consisted of 166 men
    (including still exposed, still employed workers, and also workers who
    left the company) with a mean exposure time of 16.9 years (range 4-19)
    and more than 15 years of observation (mean observation period 17
    years, range 4-20). A sub-group of these comprised 69 men with a mean
    exposure time of 14.9 years (range 10-19) and a mean observation
    period of 17.2 years. Among these 166 workers, 51 were older than 50
    years. One man with only 5 years of comparatively mild exposure died
    because of a gastric carcinoma. A lymphosarcoma occurred in a man with
    7 years of very mild exposure. Both incidences occurred before 1964.
    No new cases were noted in the last 11 years and no undue mortality
    from other causes that could have marked a higher cancer incidence was

    The organochlorine pesticide concentrations of dieldrin, pp'DDE,
    pp'DDD, pp'DDT, gamma-HCH, ß-HCH and HCB have been determined in the
    blood from mothers and their babies as well as in mother's milk. The
    results showed no evidence that breast-feeding resulted in higher
    dieldrin concentrations in the blood of the babies than did
    bottle-feeding. There was some evidence that the placenta restricted
    the transmission of the pesticides to some extent. The daily intake of
    dieldrin by mothers was assessed at 7-20 µg/person in the diet of the
    U.K. population. Between 12 and 21% of the estimated daily intake of
    dieldrin by mothers may be eliminated by lactation during the first 3
    months after birth. Based on an average daily dieldrin intake of 10
    µg/person a baby's daily intake could increase to 1.2-2.1 µg or
    0.3-0.5 µg/kg b.w. (Van Raalte, 1977).


    The required teratogenicity studies in different animal species were
    submitted and showed dieldrin not to be a teratogen. In several
    studies where the test compounds were administered in repeated small
    doses to pregnant mice no teratogenic effect could be found. However,
    the administration of a single high dose of 15 mg/kg dieldrin to mice
    (1/2 LD50) or 30 mg/kg to hamsters resulted in minor malformations
    which were attributed to maternal toxicity.

    Results of various carcinogenicity tests in mice and other mammalian
    species indicate that there is a species-specific effect of dieldrin
    and aldrin on the mouse liver, resulting in an increased frequency of
    liver tumors only in this animal species. In all species examined
    (mouse, rat, rabbit, rhesus monkey, chimpanzee) 12-hydroxydieldrin and
    4, 5-aldrin-trans-dihydrodiol were the major metabolites. Regarding
    the ratios of these two metabolites the mouse seems to metabolize the
    test compound predominantly by the opening of the epoxide ring. This
    metabolic pathway on the one hand and a high rate of metabolism

    compared with other animal species examined on the other, could result
    in relatively high concentrations of 4, 5-aldrin-trans-dihydrodiol
    in the mouse liver.

    Dieldrin, as well as other chlorinated pesticides, is a powerful
    inducer of microsomal enzymes. Owing to their high rate of metabolism,
    mice are especially susceptible to such effects (see section 3.1).
    Compared with other animal species, it reacts rather anomalously and
    the mouse, therefore, may not be an appropriate model for humans in
    this case. The results of prolonged enzyme induction are proliferation
    of the endoplasmic reticulum in the cells, and hypertrophy and
    hyperplasia of the liver. These changes are fully reversible if
    treatment is ceased before tumours have developed on the chronically
    over-loaded and damaged cells. Similar effects are produced by

    The results of the different experiments for the study of the possible
    mechanism of the tumorigenic action of dieldrin on mouse liver at the
    sub-cellular level are inconsistent.

    A number of in vitro and in vivo mutagenicity tests have been
    performed. In none of these studies did dieldrin reveal any mutagenic

    These new findings again support the view that dieldrin and aldrin are
    not carcinogens on the basis of knowledge available to the Meeting.
    Therefore no change of the existing ADI for humans me considered


    Level causing no toxicological effect

    Rat: 0.5 mg/kg in the diet, equivalent to 0.025 mg/kg bw

    Dog: 1 mg/kg in the diet, equivalent to 0.025 mg/kg bw


    0-0.0001 mg/kg bw*


    * the ADI is applicable to aldrin and dieldrin separately or to the
    sum of them if both are involved.


    1. Further studies on the possible mechanism of the tumorigenic action
    on mouse liver.


    Ahmed, F.E., Hart, R.W. and Lewis, N.J., (1977) Pesticide induced DNA
    damage and its repair in cultured human cells. Mut. Res. 42,

    NCI (1977a) Bioassays of Aldrin and Dieldrin for Possible
    Carcinogenicity. Carcinogenesis Program, Division of Cancer Cause and
    Prevention. National Cancer Institute, National Institutes of Health.

    NCI (1977b) Bioassay of Dieldrin for possible Carcinogenicity.
    Carcinogenesis Program, Division of Cancer Cause and Prevention.
    National Cancer Institute, National Institutes of Health.

    Bedford, C.T. and Huston, D.H., (1976) The comparative metabolism in
    rodents of the isomeric insecticides dieldrin and endrin.
    Chemistry and Industry, 15 MAY 1977, 440-447.

    Bidwell, K., Weber, E., Nienhold, I., Connor, T. and Legator, M.S.,
    (1975) Comprehensive evaluation for mutagenic activity of dieldrin.
    Presented at 6th annual meeting of Environ. Mutagen Soc. Miami Beach,

    Cabral J.R.P., Shubik, P., Bronczyk, S.A. and Hall, R.K., (1977) A
    carcinogenesis study of the pesticide dieldrin in hamsters. Paper
    given at 68th annual meeting Am. Assoc. Cancer Research and 13th
    annual meeting Am. Soc. Clin. Oncology, Denver Col. USA (Mau 1977).
    Proceedings Abstract 111, 28

    Chernoff, N., Kavlock, R.J., Kathrein, J.R., Dunn, J.M. and Baseman,
    JJ., (1975) Prenatal effects of dieldrin and photodieldrin in mice and
    rats. Tox. appl. Pharmacol. 31, 302-308.

    Dean, B.J., Doak, S.M.A. and Somerville, H., (1975) The potential
    mutagenicity of dieldrin (HEOD) in mammals. Fd. Cosmet. Toxicol. 13,

    Dean, B.J. and Brooks, T.M., (1977) Microbial mutagenicity studies on
    dieldrin metabolites. Preliminary results report. Shell Toxicology
    Laboratory (Tunstall), 30th August (unpublished report).

    Dix, K.M., Van der Pauw, C.L. and McCarthy, W.V., (1975) Toxicity
    studies with dieldrin: Teratological studies in mice given HEOD
    orally. Tunstall Laboratory, Shell Research Ltd. TU/19/75. Submitted
    for publication in Teratology..

    FAO/WHO (1971) 1970 Evaluations of some pesticide residues in food.
    AGP:1970/M/12/1;WHO/Food Add./71.42.

    Jager, K.W., (1970) Adrin, dieldrin, endrin and telodrin. An
    epidemiological and toxicological study of long-term occupational
    exposure. Thesis, 234 p., Elsevier Publ. Co., Amsterdam.

    Müller, W., Nohynek, G., Woods, G., Korte F. and Coulston, F., (1975a)
    Comparative metabolism of Dieldrin-14C in Mouse, Rat, Rabbit, Rhesus
    Monkey and Chimpanzee. Chemosphere 4, 89-92.

    Müller, W., Woods, G. Korte, F. and Coulston, F., (1975b) Metabolism
    and Organ Distribution of Dieldrin-14C in Rhesus Monkeys after single
    oral and intravenous administration. Chemosphere 4, 93-98.

    Ottolenghi, A.D., Haseman, J.K. and Suggs, F., (1974) Teratogenic
    effects of aldrin, dieldrin and endrin in hamsters and mice.
    Teratol. 9, 11-16

    Van Raalte, H.G.S., (1977) Human experience with dieldrin. Accepted
    for publication in Ecotox. and Environm. Safety.

    Versteeg, J.P.J. and Jager, K.W., (1973) Long-term occupational
    exposure to the insecticides aldrin, dieldrin, endrin and telodrin.
    Brit. J. Ind. Med. 30, 201-202.

    Wright A.S., Akintouwa, D.A.A. and Wooder, M.F., (1977) Studies on the
    Interaction of Dieldrin with Mammalian Liver Cells at the Subcellular
    Level. Ecotox. and Environm. Safety 1, 7-16.

    Zelle, B. and Lohman P.H.M., (1977) Repair of DNA in cultured human
    cells treated with dieldrin and 4-nitroquinoline-N-oxide. Medical
    Biological Laboratory TNO report, September 1977 (unpublished report).

    See Also:
       Toxicological Abbreviations
       Aldrin/dieldrin (WHO Pesticide Residues Series 4)
       Aldrin/dieldrin (WHO Pesticide Residues Series 5)