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Mendel rats, respectively), and subcutaneous leiomyosarcoma (7% in Japanese rats). Cirrhosis was
reported in all animals. Due to the small group size, poor survival of several strains and the incomplete
reporting of the total dosage, and most importantly, the inappropriate route of exposure (subcutaneous
injections), this study was not used in a quantitative risk assessment. As in the mouse studies, NCI used
carbon tetrachloride as a positive control in rat bioassays for chloroform, 1,1,1-trichloroethane and
trichloroethylene (NCI, 1976a,b; 1977; Weisburger, 1977). The Osborne-Mendel rats were
administered a time-weighted average dose of carbon tetrachloride by gavage for 78 weeks (47, 97
and 80, 159 mg/kg body weight, respectively for males and females). Hepatic carcinomas were found
at both doses in both sexes (4%, 4% and 8%, 2% in low and high dosage, males and females,
respectively). A lower incidence was reported in the high-dose females, but this may have been a result
of that dose group’s high mortality rate prior to tumor expression. Tumors in other tissues were not
discussed.
Male and female Syrian golden hamsters were administered carbon tetrachloride in corn oil weekly by
gavage (190 and 380 mg/kg of body weight, respectively) for a total of 30 weeks (Della Porta et al.,
1961). Following treatment, the animals were kept 25 weeks, sacrificed and examined. Only eight of
the original 20 animals survived the full 55 weeks. Carcinomas were not observed in the animals that
died prior to the 43 rd week, but one or more liver-cell carcinomas were reported in all the surviving
animals, indicating that tumors may be produced at lower levels in this species. Liver tumor incidence in
carbon tetrachloride-treated animals (males and females combined) was 10/19 (53%) compared to
0/80 (0%) for controls.
In summary, carbon tetrachloride has been shown to produce liver tumors in mice, rats and hamsters by
the oral and subcutaneous routes. No inhalation cancer bioassays have been conducted.
IV.
DERIVATION OF CANCER POTENCY
Basis for Cancer Potency
Carbon tetrachloride has been observed to induce liver tumors in male and female hamsters, mice and
rats, as described above. CDHS (1987) decided that the tumor incidence data from studies by Della
Porta et al. (1961) (hamster), Edwards et al. (1942) (mouse) and NCI (1977a, b) (mouse) were
suitable for use in developing a quantitative risk assessment.
Methodology
A health assessment document for carbon tetrachloride was prepared by US EPA (1984). This
document contained a quantitative cancer risk assessment for carbon tetrachloride. A linearized
multistage procedure was applied to liver tumor incidence data (Della Porta et al., 1961; Edwards et
al., 1942; NCI 1976a, b; 1977 [rat, mouse]) to estimate a cancer unit risk.
The quantitative risk assessment of carbon tetrachloride conducted by US EPA (1984) using the
linearized multistage procedure was modified by DHS (1987) by: 1) applying an absorption fraction of
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