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IV.
DERIVATION OF CANCER POTENCY
Basis for Cancer Potency
4, 4'-Methylenedianiline
The potency for this compound was derived from the potency for the dihydrochloride using a
molecular weight conversion:
q (anhydrous) = q (hydrate)
h h
×
MW (hydrate)
MW (anhydrous)
where q h is the human potency and MW is the molecular weight. This conversion assumes that the
intake of equivalent moles of the two forms of the chemical (e.g. the anhydrous and hydrate forms)
results in equivalent concentrations of the active species in vivo.
4, 4'-Methylenedianiline didihydrochloride
Results are listed for the drinking water studies by NTP (1983) in male and female B6C3F 1
mice and F344 rats. Significant increases in tumors of the liver or thyroid or both are observed for all
sex/species combinations tested, with male mice the most sensitive. The cancer potency listed is based
on the combined incidence of benign and malignant liver tumors in male mice (Cal/EPA, 1992).
Methodology
Expedited Proposition 65 methodology (with cross-route extrapolation) was used to derive a cancer
potency factor. Analysis of the data set using the computer program TOX_RISK (Crump et al., 1991)
indicated that inclusion of the high dose group resulted in a p-value of = 0.05 based on the chi-square
goodness-of-fit test, indicating non-linearity. Following procedures described by US EPA (Anderson
et al., 1983), the high dose group was excluded from the analysis to correct for the poor fit (Cal/EPA,
1992). 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
Anderson EL and the Carcinogen Assessment Group of the U.S. Environmental Protection Agency
1983. Quantitative approaches in use to assess cancer risk. Risk Anal 3:277-295.
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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