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
EVALUATION FOR ACCEPTABLE DAILY INTAKE
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).
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
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.
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.