Species-specific toxic effects of α-chlorohydrin and 6-chloro-6-deoxyglucose on astrocytes

Abstract

In 1969 α-chlorohydrin was reported to have a reversible antifertility effect in male rats. It has since been reported to have a reversible antifertility effect in many other species but not in mice and rabbits. In chronic high-dosage regimens it was reported to be neurotoxic to mice. At high doses the 6-chloro-6-deoxysugars were found to have a reversible, complete antifertility effect. 6-Chloro-6-deoxyglucose had an antifertility effect in rats and marmosets but not in mice, hamsters, guinea-pigs or rabbits. However, repeated high doses were found to be neurotoxic in the mouse and marmoset, the most prominent pathological feature being vacuolation of astrocytes. In the studies reported here the ability of α-chlorohydrin and 6-chloro-6-deoxyglucose to induce vacuolation of mouse astrocytes has been confirmed in vitro. The failure of either agent to induce vacuolation of rat astrocytes suggests that both the antifertility effect of these agents and their neurotoxic effects are species-specific. The lack of correlation between neurotoxic and antifertility effects of such agents suggests that in vitro techniques may aid the development of a safe, reversible male antifertility agent and also aid in the design of further agents for rodent control.