(Group 3)

For definition of Groups, see Preamble Evaluation.

VOL.: 66 (1996) (p. 427)

CAS No.: 25812-30-0
Chem. Abstr. Name: 5-(2,5-Dimethylphenoxy)-2,2-dimethylpentanoic acid

5. Summary of Data Reported and Evaluation

5.1 Exposure data

Gemfibrozil has been used since the early 1980s to lower serum triglycerides and raise high-density lipoprotein-cholesterol in patients at high risk for coronary heart disease.

5.2 Human carcinogenicity data

In a Finnish trial that aimed to reduce cholesterol concentration with gemfibrozil, no difference was found in cancer incidence or mortality between the treated and control groups.

5.3 Animal carcinogenicity data

Gemfibrozil was tested for carcinogenicity by oral administration in the diet in one experiment in mice and one experiment in rats. There was a slight, not dose-related increase in the incidence of hepatocellular carcinomas in male mice and the incidence of lung adenomas was decreased. In male rats, increases were observed in the incidence of hepatocellular tumours, interstitial-cell tumours of the testis and adrenal phaeochromocytomas; the latter was not dose-related.

5.4 Other relevant data

Gemfibrozil exerts similar pharmacological responses in humans and laboratory rodents. It is readily absorbed, metabolized and eliminated in human subjects. Data are not available to characterize adequately its pharmacokinetic behaviour in animals, although maximal serum levels of gemfibrozil in rats are similar to those in humans receiving therapeutic doses of gemfibrozil. Gemfibrozil-induced peroxisome proliferation has been demonstrated in rats. An indirect measure of cell proliferation, liver weight, is also increased in rats. Peroxisome proliferation has not been observed in studies of human livers with gemfibrozil. There are a number of case reports of reversible impotence in men treated with gemfibrozil. No noteworthy effects on the fetus have been observed in studies in rats or rabbits. Neither gemfibrozil nor its metabolites were mutagenic in bacteria in a single study.

Mechanistic considerations

The data on gemfibrozil are too limited to allow mechanistic assessment. In particular, genotoxicity has not been excluded. Upon exposure to gemfibrozil, proliferation of peroxisomes occurs in rat liver, whereas proliferation of peroxisomes does not occur in human liver. These observations suggest that the mechanism of liver carcinogenesis in gemfibrozil-treated rats would not be operative in humans.

5.5 Evaluation

There is inadequate evidence in humans for the carcinogenicity of gemfibrozil.

There is limited evidence in experimental animals for the carcinogenicity of gemfibrozil.

Overall evaluation

Gemfibrozil is not classifiable as to its carcinogenicity in humans (Group 3).

For definition of the italicized terms, see Preamble Evaluation


Last updated 05/23/97

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       Toxicological Abbreviations