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mg/kg-day for rats and mice, respectively. Two control groups were used, an untreated control, and a
control group of animals with restricted access to water.
Jorgenson et al. observed a dose-related significant increase in renal tubular cell adenomas and
adenocarcinomas in male rats, but found no treatment-related increases in tumor incidence in the female
mice (Table 1). The lack of liver tumors in female B6C3F 1 mice is in sharp contrast to the results of the
NCI study. A major difference between the NCI study and the Jorgenson study is the mode of
administration. Administration of chloroform to rats in a corn oil vehicle slowed the gastrointestinal
absorption of chloroform relative to the absorption rate observed after administration as a bolus in water
(Withey et al., 1983). In the Jorgenson et al. study, the rats received small doses of chloroform each
time they drank water. The corn oil vehicle effect (Withey et al., 1983) may have diminished the
differences in absorption kinetics expected with the two different methods of administration. Therefore,
any differences in peak blood concentrations between the NCI study and the Jorgenson study may not
have been sufficient to account for the difference in liver tumor incidence. Physiologic or metabolic
changes produced by corn oil consumption might interact with chemical carcinogens altering the
production of liver tumors (Bull et al., 1986; Newberne et al., 1979).
A series of experiments was conducted by the Huntingdon Research Center to determine the effects of
chronic ingestion of chloroform in a toothpaste base in mice, rats, and beagle dogs. In the first set of
experiments (Roe et al., 1979), doses of 17 and 60 mg chloroform/kg were administered by gavage in
toothpaste to male and female ICI mice, 6 days/week for 80 weeks followed by a 16 week observation
period (Experiment I). Controls (N=104) were treated with 1 ml chloroform-free toothpaste/kg-day.
Aside from increased nonneoplastic liver lesions (moderate fatty degeneration), the only significant
difference in pathology reported was an increase in the incidence of kidney tumors in high dose male
mice, three were hypernephromas (tubular adenocarcinoma) and the remainder were adenomas (tumor
incidences listed in Table 1). The incidence of renal tumors in high-dose male ICI mice was significantly
greater than control mice (p = 0.00012, Fisher exact test). None of the female ICI mice examined
developed renal tumors (Roe et al., 1979). Roe et al. (1979) also investigated other components of
the toothpaste base for carcinogenicity using male ICI mice. No lesion in this part of the study could be
correlated with treatment.
In a third mouse experiment (Experiment III), Roe et al. (1979) compared the effects of toothpaste
containing 3.5% chloroform on male mice of four different strains (C57BL, CBA, CF/1, and ICI).
Treatment with chloroform was not associated with any increase in liver or lung neoplasms relative to
vehicle-treated controls in any of the four strains tested but was associated with significantly higher
incidences of moderate to severe kidney pathology in CBA and CF/1 mice relative to the controls (p <
0.0001, chi-square test).
Palmer et al. (1979) gave groups of 50 Sprague-Dawley rats (both sexes) 0 or 60 mg chloroform/kgday,
6 days/week by gavage in a toothpaste base for 80 weeks, followed by a 15 week observation
period. There were no differences in the incidences of tumors of any site examined, including brain,
lung, liver, kidney, and mammary gland, between treated and control animals. Heywood et al. (1979)
investigated the carcinogenicity of chloroform in a toothpaste base in beagle dogs. Groups of male and
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