CHLORDIMEFORM

    EXPLANATION

         Chlordimeform was evaluated for acceptable intake by previous
    JMPRs in 1971, 1975, 1978, 1979, 1980 and 1985 (Annex 1, FAO/WHO,
    1972a, 1976a, 1978a, 1980a, 1981a, and 1986a). The 1985 Joint
    Meeting established a temporary acceptable daily intake and
    required interpretable epidemiological and urinary monitoring data
    on occupationally exposed workers by 1987. A further long-term
    animal bioassay using a third species for evaluation of the
    carcinogenic hazard and further observations in man were considered
    desirable.

    EVALUATION FOR ACCEPTABLE DAILY INTAKE

    BIOLOGICAL DATA

    Observations in humans

         Results of a programme of monitoring the urine of more than
    200 workers who had received training in the use of chlordimeform
    in cotton in California have been reported. Chlordimeform was
    detectable in urine as early as four hours after dermal exposure.
    Although urinalysis was unremarkable and no significant cytological
    changes were found, a single case of bladder cancer was detected in
    a pilot who had seven seasons of exposure to chlordimeform (Maddy
    et al., 1986).

         A retrospective study of 116 workers occupationally exposed to
    4-chloro-2-toluidine during manufacture prior to 1970 has revealed
    eight cases of bladder cancer, diagnosed between 1967 and 1985.
    This represents an incidence more than 70 fold higher than
    expected. Although occupational exposure to two other aromatic
    amines, 2-toluidine and 6-chloro-2-toluidine, may have occurred, it
    is considered by. the author that exposure to 4-chloro-2-toluidine
    was considerably higher. The manufacture of 4-chloro-2-toluidine
    has ceased at the plant concerned (Strasik, 1987).

    COMMENTS

         Although the results of a urinary monitoring programme have
    been published, the 1985 Joint Meeting's requirement for
    epidemiological data on workers occupationally exposed to
    chlordimeform has not been met.

         The results of the California monitoring programme indicate
    that occupational exposure to chlordimeform can be significantly
    reduced, but not eliminated, during its use in cotton growing. The
    exposed workers excreted 4-chloro-2-toluidine in their urine.

         Workers exposed to 4-chloro-2-toluidine, and to two other
    aniline derivatives in lesser degree, showed a standardized
    incidence rate of bladder cancer 72 times that of unexposed
    workers, suggesting that chlordimeform itself could be a human
    carcinogen.

         The meeting agreed to withdraw the temporary ADI. In view of
    the human data indicating increased incidence of bladder cancer
    following exposure to 4-chloro-2-toluidine, a metabolite of
    chlordimeform, and the occurrence of this compound as a residue in
    treated crops, the meeting recommends that chlordimeform should
    not be used where its residues, or those of its metabolite
    4-chloro-2-toluidine, can arise in food.

    REFERENCES

    Maddy, K.T., Knaak, J.B. & Gibbons, D.B., 1986. Monitoring the
    Urine of Applicators in California for Residues of Chlordimeform
    and its Metabolites 1982-1985,  Toxicology Letters, 33, 37-44.

    Strasik, M.J., 1987. Carcinomas of the Urinary Bladder in a
    4-chloro-0-toluidine Cohort.  International Archives of
     Occupational and Environmental Health, 60, in press.

    

    See Also:
       Toxicological Abbreviations
       Chlordimeform (EHC 199, 1998)
       Chlordimeform (ICSC)
       Chlordimeform (WHO Pesticide Residues Series 1)
       Chlordimeform (WHO Pesticide Residues Series 5)
       Chlordimeform (Pesticide residues in food: 1978 evaluations)
       Chlordimeform (Pesticide residues in food: 1979 evaluations)
       Chlordimeform (Pesticide residues in food: 1980 evaluations)
       Chlordimeform (Pesticide residues in food: 1985 evaluations Part II Toxicology)
       Chlordimeform (IARC Summary & Evaluation, Volume 30, 1983)