IPCS INCHEM Home


    FAO/PL:1969/M/17/1

    WHO/FOOD ADD./70.38

    1969 EVALUATIONS OF SOME PESTICIDE RESIDUES IN FOOD

    THE MONOGRAPHS

    Issued jointly by FAO and WHO

    The content of this document is the result of the deliberations of the
    Joint Meeting of the FAO Working Party of Experts and the WHO Expert
    Group on Pesticide Residues, which met in Rome, 8 - 15 December 1969.

    FOOD AND AGRICULTURE ORGANIZATION OF THE UNITED NATIONS

    WORLD HEALTH ORGANIZATION

    Rome, 1970

    DDT

    Explanation

    This insecticide was evaluated by the Joint FAO/WHO Joint Meeting on
    Pesticide Residues in 1966 (FAO/WHO, 1967b). Additional information,
    particularly on metabolism was considered again in 1967 and resulted
    in a monograph addendum (FAO/WHO, 1968b). The recent public concern
    for the hazards of DDT, especially in relation to the reports of
    Increased tumour incidence in experimental animals fed DDT and to the
    widespread occurrence of DDT in living organisms and generally
    throughout the environment, led to Its further consideration by this
    Joint Meeting. This monograph addendum summarizes data available on
    DDT in relation to its possible ability to induce tumours. Section 2.6
    of the general report of the meeting (FAO/WHO, 1970a) contains
    comments on the general environmental aspects.

    EVALUATION FOR ACCEPTABLE DAILY INTAKE

    TOXICOLOGICAL STUDIES

    Special studies on carcinogenicity

    Monkey

    Rhesus monkeys of mixed sex (12 males and 12 females) were divided
    into groups and fed over periods up to 7.5 years or longer on diets
    containing 0, 5, 50, 200 and 5000 ppm. Biopsies were performed on
    several organs. The histopathology gives no report of tumour formation
    in any animals (Durham et al., 1963).

    Mouse

    A total of 683 mice of the BALB/c strain spread over five generations,
    were fed dietary levels of 2.8 - 3.00 ppm of DDT (0.4 -0.7 mg/kg
    body-weight/day) for six months. The background DDT content of the
    diet given to 406 controls corresponded to an intake of 0.03-0.05
    mg/kg body-weight/day. Altogether leukaemia occurred in 85 test
    animals (12.4 percent) but only in 10 controls (2.5 Percent). The
    significance became apparent in the F3 generation. The incidence of
    tumours in the DDT group attained significance one generation earlier
    (in the F2 group). However, a suspected transgeneration cumulative
    effect resulting in progressive increase in tumour incidence with each
    generation was not substantiated when the results from all five
    generations became available. A total of 196 tumour-bearing animals
    (28.7 percent) was recorded in the DDT group compared to 13 in the
    controls (3.2 percent). The most frequent tumour types were leukaemia,
    carcinoma of the lung, haemangioendothelioma and reticulium cell
    carcinoma (Kemény and Tarjan, 1966; Tarjan and Kemény, 1969).

    Groups of 18 mice of each sex, from two hybrid strains of mice were
    given DDT for 18 months. The dose of 46 mg/kg body weight was given by
    gavage from the seventh day of age to the time of weaning at four
    weeks of age and thereafter DDT was added to the diet in a
    corresponding amount of 140 ppm. The incidence of hepatomas was 18 out
    of 35 treated males (51 percent) and 5 out of 24 treated females (21
    percent) compared with the control value of 13 out of 162 males (18
    percent) and 7 out of 158 (0.6 percent) females (Innes et al., 1969).

    Two strains of mice, namely BALB/cJ and C3HeB/FeJ, were divided into
    groups, each of which contained 100 male and 100 female animals of
    each strain. The groups were fed 0 or 100 ppm of DDT in the diet for
    periods up to two years. In the BALB/cJ strain there was no
    significant increase in tumours in the DDT-treated group when compared
    to the controls, but, because of the high incidence of mortalities in
    both groups of this strain, the results ware considered to be
    questionable. In the C3HeB/FeJ strain the number of deaths was much
    lower. The females of this strain displayed a 24 percent incidence of
    hepatomas in the group fed DDT compared to 9 percent in the controls.
    There was, however, a loiter incidence of tumours at other sites in
    this group when compared to the controls, resulting in no overall
    increase in the total incidence of tumours. The incidence of
    hepatocarcinomas was equally low in treated and control groups of both
    sexes in both strains (Fitzhugh, 1969).

    Rat

    Groups of 12 male rats were subjected for two years to diets
    containing 0, 100, 200, 400 and 800 ppm of DDT. In another experiment,
    groups each of 24 rats (12 males and 12 females) were given, during
    the came period, diets containing 0, 200, 400, 600 and 800 ppm. Also
    additional groups of 24 animals received 600 and 800 ppm incorporated
    in their feed in a dry state. In the groups receiving 400 ppm and
    above, an increase in the mortality rate was seen in relation to the
    does. Apart from nervous symptoms at doses of 400 ppm and above,
    typical liver lesions were found at all concentrations. Hepatic cell
    tumours were seen in four out of 75 animals and 11 other rats showed
    nodular adenomatoid hyperplasia. The authors concluded that a minimum
    tendency for the formation of hepatic cell tumours was evident and
    that this feature was apparent only after 18 months of feeding
    (Fitzhugh and Nelson, 1947).

    Trout

    Rainbow trout were fed varying levels of DDT ranging from 0 to 9600
    ppm for periods up to two years. At the 75 ppm level hepatomas were
    present in 7 out of 19 fish after 15 months of feeding DDT. Mortality
    was high in the 2400 and 9600 ppm groups (Halver, 1967).

    Studies (sponsored by WHO) on the investigation of the potential
    carcinogenicity of DDT to mice or rats are presently being conducted
    at the International Agency for Research on Cancer, Lyon, France; the
    National Institute for the Study and Cure of Tumours, Milan, Italy;

    the Institute of Experimental and Clinical Oncology, Moscow, U.S.S.R.,
    and the Research Institute of Oncology, Leningrad, U.S.S.R. The
    results of these studies should be available in 1971.

    OBSERVATIONS IN MAN

    A study was made on 35 men with 11 to 19 years' exposure to DDT in a
    plant producing the compound. Levels of DDT and its metabolites in
    these workers ranged from 38 to 647 ppm. Physical examinations and
    clinical laboratory tests did not reveal any incidences of cancer or
    blood dyscrasias, the only abnormality being a high
    lymphocyte-granulocyte ratio (>1.0) in five men (Laws et al., 1967).

    Levels of organo-chlorine pesticides were determined at autopsy in the
    fat of 271 patients who, prior to death, had exhibited various
    pathological states of the liver, brain, and other organs. These
    pesticide levels were compared with those found in the fat of random
    autopsy cases. Concentrations of DDT were 2 to 3 times the normal
    levels in those patients who died from carcinomas of the lungs,
    stomach, rectum, pancreas, prostate and bladder. Data obtained by
    interviewing next-of-kin also revealed a marked relationship between
    home use of DDT and the levels of DDT and its metabolites in the fat.
    Because of the emaciated condition of many of the patients, it was
    considered possible that the high pesticide levels were related to
    loss of fat in the adipose tissue resulting in a higher concentration
    of pesticides in the remaining fat. However, when the loss of
    body-weight was compared to pesticide concentration, no such
    relationship was observed. It is therefore not known whether the
    disease caused the elevated pesticide level or vice versa (Radomski et
    al., 1968).

    Other epidemiological studies have failed to demonstrate any
    association between human cancer and DDT (Hayes, 1961; New York,
    1969).

    COMMENTS

    The available experimental data do not provide sufficient information
    to allow a definite evaluation of the potential carcinogenicity of
    DDT, however they strongly indicate that DDT ought to be extensively
    tested. In fact the 1967 Joint FAO/WHO Meeting already recognized the
    need for further studies. Following this recommendation, work was
    initiated by WHO and IARC. The results of these studies will not be
    available until 1971. For these reasons a definite decision on the
    potential hazard of DDT to man cannot be taken now. However, because
    the hazard to man from DDT has not been ruled out, it is recommended
    that uses of DDT should be limited to those situations where there are
    no satisfactory substitutes.

    In the light of this consideration it was decided to lower the adi and
    change it to a conditional adi in order to limit the use of DDT except
    where it is absolutely necessary.

    TOXICOLOGICAL EVALUATION

    Level causing no significant toxicological effect

    Rat: 1 ppm in the diet, equivalent to 0.05 mg/kg body-weight/day

    ESTIMATE OF CONDITIONAL ACCEPTABLE DAILY INTAKE FOR MAN

    0-0.005 mg/kg body-weight

    RESIDUES IN FOOD AND THEIR EVALUATION

    USE PATTERN

    The meeting was aware that, in several countries, use patterns and
    scale of use of DDT are being revised. As a consequence, the residue
    levels in many food crops are likely to be reduced considerably. New
    information on the amended use patterns in various countries are
    required, with details of residues resulting from pertinent trials in
    order to reconsider the recommendations for temporary tolerances.

    In considering whether there was any need for priority in reviewing
    these recommendations, it was noted that the few total diet studies
    that had been carried out had revealed that the maximum intakes of DDT
    and its metabolites were well below the adi as established at this
    meeting.

    RECOMMENDATIONS FOR TOLERANCES, TEMPORARY TOLERANCES OR PRACTICAL 
    RESIDUE LIMITS

    With the exception of a previously recommended tolerance on fish which
    has been withdrawn because adequate information on residue levels in
    fish moving in trade channels wan not available, the Meeting agreed
    that all other tolerances should remain in effect pending further
    study.

    FURTHER WORK OR INFORMATION

    REQUIRED (before 30 June 1971)

    1. Results of the carcinogenicity studies which are currently in
    progress.

    2. Information on any officially acceptable uses on agricultural
    commodities, together with residues resulting from pertinent trials.

    REFERENCES

    Durham, W.F., Ortega, P. and Hayes, W.J. Jr. (1963) Effect of various
    dietary levels of  on liver function, cell morphology and DDT storage
    in the Rhesus monkey. Arch. internat. Pharmacodyn., 141: 111-29

    FAO/WHO (1967b) Evaluation of some pesticide residues in food. FAO,
    PL: CM/115; WHO/Food Add./  67/32

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

    FAO/WHO (1970a) Pesticide residues in food; report of the 1969 Joint
    Meeting of the FAO Working Party of Exports on Pesticide Residues and
    the WHO Export Group on Pesticide Residues. FAO Agricultural Studies
    No. 84 Wld Hlth Org Techn Rep Series No. 458

    Fitzhugh, O.G. and Nelson, A.A. (1947) Chronic oral toxicity of DDT.
    J. Pharmacol. exp. Therap. 89: 18-30

    Fitzhugh, O.G. (1969) A summary of a carcinogenic study of DDT in
    mice. Unpub. rept. from the Bureau of Science, Food and Drug
    Administration, USA

    Halver, J.E. (1967) Crystalline aflatoxin and other vectors for trout
    hepatoma. Trout hepatoma research conference papers. Bureau of Sport,
    Fisheries and Wild Life, Research Report No. 70 ; 78-102

    Hayes, W.J., Jr. (1961) Diagnostic problems in toxicology
    (Agriculture). Arch. environm. Hlth. 3: 49-56

    Innes, J.R.M., Ulland, E.M., Valerio, M.G., Petrucelli, L., Fishbein,
    L., Hart, E.R.,  Pallotta, A.J., Bates, R.R. Falk, E.L., Cart, J.J.,
    Klein, M., Mitchell, I., and Peters, J. (1969) Bioassay of pesticides
    and industrial chemicals for tumorigenicity in mice. A preliminary
    note J. Nat. Cancer Inst., 42: 1101-14

    Kemény, T. and Tarjan, R. (1966) Investigations on the effects of
    chronically administered small amounts of DDT in mice. Experientia, 22
    : 748-49

    Laws, E.R., Jr., Curley, A. and Biros, F.J. (1967) Men with intensive
    occupational exposure to DDT. Arch. environm. Hlth. 15 : 766-75

    New York. Health Research Ins. (1969) report on contract no. PH
    86-65-121. Studies of cancer morbidity and mortality in New York State
    as a basis for assessing potential relationships to pesticide usage,
    February 1969.

    Radomski, J.L., Deichmann, W.B. and Clizer, E.E., (1968) Pesticide
    concentrations in the liver, brain and adipose tissue of terminal
    hospital patients. Food Cosmet. Toxicol., 6: 209-20

    Tarjan, R. and Kemény, T. (1969) Multigeneration Studies on DDT in
    mice. Food Cosmet. Toxicol. 7: 215-22
    


    See Also:
       Toxicological Abbreviations
       Ddt (ICSC)
       DDT (JECFA Evaluation)
       DDT (PIM 127)
       DDT (FAO Meeting Report PL/1965/10/1)
       DDT (FAO/PL:CP/15)
       DDT (FAO/PL:1967/M/11/1)
       DDT (FAO/PL:1968/M/9/1)
       DDT (Pesticide residues in food: 1979 evaluations)
       DDT (Pesticide residues in food: 1980 evaluations)
       DDT (Pesticide residues in food: 1984 evaluations)
       DDT (JMPR Evaluations 2000 Part II Toxicological)