Bioassay of 2-(Chloromethyl)Pyridine Hydrochloride for Possible Carcinogenicity

2-(Chloromethyl)pyridine hydrochloride, an aromatic heterocycle used in a variety of syntheses, was selected for bioassay by the National Cancer Institute because of the structural similarity of this compound to 2-(a,b-dichloroethyl)-pyridine hydrochloride, a carcinogen in rats, mice, Syrian hamsters, and Mongolian gerbils.

A bioassay for the possible carcinogenicity of 2-(chloromethyl)pyridine hydrochloride was conducted using Fischer 344 rats and B6C3F1 mice. 2-(Chloromethyl)pyridine hydrochloride was administered by gavage, at either of two dosages, to groups of 50 male and 50 female animals of each species, with the exception of 49 male rats in the high dose group. Twenty animals of each sex and species were placed on test as vehicle controls. The high and low dosages of 2-(chloromethyl)pyridine hydrochloride administered were, respectively, 150 and 75 mg/kg for rats and 250 and 125 mg/kg for mice. The compound was administered for 99 weeks to rats and mice. The period of compound administration was followed by an observation period of 6 weeks for rats and 5 weeks for mice. There were no significant positive associations between the dosages of 2-(chloromethyl)pyridine hydrochloride 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 mice of both sexes, indicating that the dosages of 2-(chloromethyl)pyridine hydrochloride administered tothese animals in this bioassay may have approximated the maximum tolerated concentrations. Since no distinct mean body weight depression relative to vehicle controls, no significant accelerated mortality, and no other signs of toxicity were associated with administration of 2-(chloromethyl)pyridine hydrochloride to rats, it is possible that these animals may have been able to tolerate a higher dosage. None of the statistical tests for any site in female rats or in mice of either sex indicated a significant positive association between compound administration and tumor incidence. There was a significant positive trend between the dosages administered and the incidences of subcutaneous fibromas in male rats. The Fisher exact comparisons, however, were not significant. Under the conditions of this bioassay, administration of 2-(chloromethyl)pyridine hydrochloride was not carcinogenic to Fischer 344 rats or B6C3F1 mice.

Levels of Evidence of Carcinogenicity: Male Rats: Negative Female Rats: Negative Male Mice: Negative Female Mice: Negative Synonyms: 2-(Cl-methyl)pyridineHCl; 2-pyridylmethyl chloride hydrochloride; 2-picolylchloride hydrochloride

References:

[1] Bioassay of 2-(Chloromethyl)Pyridine Hydrochloride for Possible Carcinogenicity (CAS No. 6959-47-3).[J]. National Toxicology Program technical report series, 1979.

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