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served as untreated controls. One treated dog died at 3.4 years of age because of an infection. The
other animals were killed at 8.3-9 years. Transitional-cell carcinomas of the urinary bladder occurred in
4 of 5 treated dogs (p < 0.025, Fisher exact test), and a composite tumor (transitional-cell
carcinoma/adenocarcinoma) of the urethra was noted in one dog. No urinary tract tumors were noted
in the untreated controls. Tumor incidence data is listed in Table 2.
Table 2.
4, 4'-Methylene bis(2-chloroaniline) (MOCA) -induced urinary bladder tumor
incidence in female beagle dogs (Stula et al., 1977)
Average Dose 1 Tumor Incidence 2
(mg/kg-day)
0 0/6
7.31 4/5
1. Doses as reported by Gold et al. (1984).
2. Tumor incidences as reported by Gold et al. (1984)
IV.
DERIVATION OF CANCER POTENCY
Basis for Cancer Potency
Results from a number of studies using Charles River CD and Wistar rats, as well as female beagle
dogs, are listed in Gold et al. (1984). 4, 4'-Methylene bis(2-chloroaniline) induced papillary transitional
cell carcinomas of the urinary bladder in dogs, whereas the liver was the most common target site in the
rat studies. Dogs are more sensitive to the carcinogenic effects of the compound than rats. The
compound is similar in structure to benzidine, a human bladder carcinogen, which appears to be
significantly more potent in humans than rodents. Results from the Stula et al. (1977) dog study are
used as the basis of potency estimation, despite the small numbers of animals used, because dogs may
be better predictors of human carcinogenicity of this compound than rodents (Cal/EPA, 1992). Doseresponse
data are listed in Table 2.
Methodology
Expedited Proposition 65 methodology (with cross-route extrapolation) was used to derive a cancer
potency factor. A unit risk factor was then calculated by OEHHA/ATES from the cancer potency
factor using a reference human body weight of 70 kg and an inspiration rate of 20 m 3 /day.
V. REFERENCES
California Environmental Protection Agency (Cal/EPA) 1992. Expedited Cancer Potency Values and
Proposed Regulatory Levels for Certain Proposition 65 Carcinogens. Office of Environmental Health
Hazard Assessment, Reproductive and Cancer Hazard Assessment Section, Berkeley, CA.
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