Teratogenic effects of trichlorfon (Metrifonate) on the guinea-pig brain. Determination of the effective dose and the sensitive period.

ABSTRACT

The conditions (sensitive period and doses) for producing hypoplasia in guinea-pig offspring after treatment of pregnant guinea-pigs with the organophosphorous agent trichlorfon (metrifonate, 0,0-dimethyl 2,2,2-trichloro-1-hydroxyethylphosphonate) were examined. The results showed that the minimal dose required was 100 mg/kg on three consecutive days. For the cerebellum the most sensitive period was 42-44 day of gestation, for cortex the most vulnerable period was gestational days 48-50. The doses could be given either per os or subcutaneously. Almost all regions of the brain were reduced in weight. Cerebellum was the most vulnerable region, but also the medulla and hypothalamus were greatly reduced in weight. The mechanism behind the teratogenic effect is not known, but alkylation of DNA or an effect on its repair mechanism are possible effects.