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year; 7/16 animals fed acetamide alone for 1 year followed by control diet for 3 months also developed
liver tumors. In contrast, 1/11 animals fed diet containing acetamide + L-arginine L-glutamate for 1
year developed hepatomas, and 1/19 animals fed diet containing acetamide + L-arginine L-glutamate
for 1 year followed by control diet for 3 months developed hyperplastic liver nodules, but not tumors.
No liver tumors were noted in either the control or 5.6% L-arginine L-glutamate treatment groups
(Weisburger et al., 1969).
Fleischman et al.(1980) fed male and female C57BL/6 mice (50/sex/group) and Fischer 344 rats
(50/sex/group) a diet containing 1.18% (mice) or 2.36% (mice, rats) acetamide for 365 consecutive
days; animals were then fed a control diet for an additional 4 months. Male mice demonstrated a
treatment-related increase in hematopoietic tumors, primarily malignant lymphomas; tumor incidence
was 7/50 and 7/46 for the low and high dose groups, respectively, compared to 0/95 for the pooled
(male and female) control group. Neoplastic nodules and hepatocellular carcinomas were observed in
both male and female rats. However, the incidence, speed of onset and frequency of metastases were
greater in males (Fleischman et al., 1980). No liver tumors were noted in control animals. Incidence
data for hepatocellular carcinomas in F344 rats, the most sensitive species tested, are given in Table 1.
Table 1:
Incidence of hepatocellular carcinomas in F344 rats treated with acetamide by dietary
administration (Fleischman et al., 1980).
Dietary Concentration
(%)
Average Dose 1
(mg/kg-day)
Tumor Incidence 2
Male Female
0 0 0/50 0/49
2.36 710 41/47 33/48
1. Doses as reported by Gold et al. (1984).
2. Decreased survival of treatment group according to Gold et al. (1990) (56% survival at study
termination compared to 86% for controls); potency may be an underestimate (Cal/EPA,
1992).
IV.
DERIVATION OF CANCER POTENCY
Basis for Cancer Potency
The carcinogenicity bioassay by Fleischman et al. (1980) indicated that acetamide causes
hematopoietic tumors in male C57BL/6 mice, and hepatocellular carcinomas in male and female Fischer
344 rats. Rats were more sensitive than mice, and male rats were more sensitive than female rats in this
study; therefore, the male Fischer 344 rat liver tumor data was used as the basis of a cancer potency
factor.
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