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Table 1 (continued):
Chloroform carcinogenicity bioassay tumor incidence data used to estimate
cancer potency (CDHS, 1990)
Study Strain/Species Sex Tumor Site Lifetime Daily Dose
(mg/kg-day)
Tumasonis
et al. (1985)
Reuber et al.
(1979) using
NCI (1976)
Wistar rat F cholangiocarcinoma control
220
Wistar rat M cholangiocarcinoma control
160
Osborne-Mendel rat F cholangiocarcinoma and
cholangiofibroma
a
toothpaste base was used as the vehicle; b arachis oil was used as the vehicle
control
50
100
Tumor
Incidence
0/18
34/40
0/22
17/28
0/20
3/39
11/39
IV.
DERIVATION OF CANCER POTENCY
Basis for Cancer Potency
Chloroform is carcinogenic to rats and mice (NCI, 1976; Roe et al., 1979; Jorgenson et al., 1985).
The International Agency for Research on Cancer (IARC) has classified chloroform as a possible
human carcinogen (Group 2B). Similarly, the U.S. EPA has placed chloroform in Group B2 in their
classification scheme, based on sufficient evidence of carcinogenicity in animals, but inadequate
epidemiologic evidence. Current evidence and understanding of the carcinogenic process is insufficient
to classify chloroform as either a genotoxic or epigenetic carcinogen, and it is possible that both types of
effects are involved.
The estimation of cancer risk to humans from exposure to chloroform by CDHS (1990) is based on
animal studies. Data were chosen based primarily on statistical significance, as discussed below.
Methodology
The following data sets were evaluated to estimate chloroform cancer potency: 1) Liver tumor data in
male and female B6C3F 1 mice, and renal tubular cell tumors in male Osborne-Mendel rats from the
NCI (1976) study were chosen because statistically significant increases in these tumor types were
observed in chloroform treated animals relative to controls; 2) Renal tubular cell tumor data in male
Osborne-Mendel rats from the Jorgenson et al. (1985) study and in male ICI mice in the Roe et al.
(1979) study were used for risk estimation based on a statistically significant increase in kidney tumors
in chloroform treated animals relative to controls; 3) Liver cholangiocarcinoma ("adenofibrosis”) data in
female rats from Tumasonis et al. (1985), and from Reuber's reanalysis of the NCI (1976) slides
(Reuber, 1979) were also analyzed with the linearized multistage model (GLOBAL86). Administered
doses were transformed to lifetime doses by adjusting for the number of days exposed per week and
the ratio of the length of exposure to the length of the experiment (exposure plus observation period).
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