Bioassay of Lithocholic Acid for Possible Carcinogenicity (CAS No. 434-13-9)
Chemical Formula: C24H40O3
Lithocholic acid, a naturally occurring bile acid, was selected for bioassay by the National Cancer Institute because it has been reported to promote the development of hepatoma and hyperplastic nodules induced by DL-ethionine in rat liver, and because of the strong correlation between concentrations of neutral sterols and bile acid derivatives in human feces and the incidence of human colon cancer.
A bioassay for the possible carcinogenicity of lithocholic acid was conducted using Fischer 344 rats and B6C3F1 mice. Lithocholic acid was administered by gavage, at either of two dosages, to groups of 50 male and 50 female animals of each species, except for 49 low dose female rats. Twenty animals of each sex and species were placed on test as controls. The high and low dosages of lithocholic acid administered were, respectively, 500 and 250 mg/kg for rats and 250 and 125 mg/kg for mice. The compound was administered to rats and mice for 103 weeks. The period of compound administration was followed by an observation period of 1 week for rats and 2 weeks for mice.
There were no significant positive associations between the dosages of lithocholic acid administered and mortality in rats or mice of either sex. Adequate numbers of animals in all groups survived sufficiently long to be at risk from late-developing tumors. Slight dose-related mean body weight depression was observed in male rats and female mice and high incidences of chronic kidney inflammation were observed in female rats, indicating that the dosages of lithocholic acid administered to these animals in this bioassay may have approximated the maximum tolerateddosages. Since no mean body weight depression, relative to controls, no significant accelerated mortality, and no other signs of toxicity were associated with administration of lithocholic acid to male mice, it is possible that these animals may have been able to tolerate a higher dosage. However, in the subchronic study there were deaths among all dosed male mouse groups, even those receiving lithocholic acid at a level only twofold greater than the high dose utilized in the chronic study.
None of the statistical tests for any site in rats or in mice of either sex indicated a significant positive association between compound administration and tumor incidence.
Under the conditions of this bioassay, lithocholic acid was not carcinogenic when administered by gavage to Fischer 344 rats or B6C3F1 mice.
Synonyms: (3a,5b)-3-Hydroxycholan-24-oic acid; 3a-Hydroxy-5b-cholan-24-oic acid; 3 a-Hydroxy-5b-cholanic acid; 3a-Hydroxychloanic acid; 3-Monohydroxycholanic acid; 17b-(1-methyl-3-carboxypropyl)ethiocholan-3 a-ol.
Report Date: 1979