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still alive in the low-dose control, high-dose control, low-dose and high-dose groups, respectively. In
male rats, 54% of the controls, 64% of low-dose and 70% of high-dose animals were alive at the end
of the study. Insufficient numbers of female rats survived to the latter portion of the experimental period
to permit analysis of late-developing tumors.
High-dose male and female mice demonstrated a significantly increased incidence of hepatocellular
carcinomas. Tumor incidence in male mice was 12/46 in low-dose controls, 6/48 in high-dose controls,
20/47 in low-dose animals, and 36/49 (p < 0.001) in high-dose animals; in female mice, the frequencies
were 4/46, 1/50, 5/47 and 12/47 (p < 0.001) (NCI, 1978; Murthy et al., 1979). A dose-dependent
increase in hepatic neoplastic nodules and hepatocellular carcinomas (p < 0.001) was noted in 18/41
low-dose and 18/45 high dose males; tumors were observed in 0/36 control male rats.
IV.
DERIVATION OF CANCER POTENCY
Basis for Cancer Potency
The NCI carcinogenicity bioassay of 2-AA indicated that 2-AA induced tumor formation in both rats
and mice. The cancer potency value derived is based on the dose-response data for hepatic tumors in
the more sensitive sex and species, the male rat (Cal/EPA, 1992).
Methodology
Expedited Proposition 65 methodology (with cross-route extrapolation) was used to derive a cancer
potency factor. The average dose administered to the male rat high-dose group as calculated by Gold
et al. (1984) was 102 mg/kg/day. 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.
Crump KS, Howe RB, Van Landingham C and Fuller WG. 1991. TOXRISK Version 3. TOXicology
RISK Assessment Program. KS Crump Division, Clement International Division, 1201 Gaines Street,
Ruston LA 71270.
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