The embryotoxicity of a new class of antispermatogenic agents: the 3-indazole-carboxylic acids.

The effects of two antispermatogenic 3-indazole-carboxylic acids on pregnancy in the rat have been studied. AF 1312/TS (1-(4-chlorobenzyl)-1H-indazole-3-carboxylic acid) when administered from day 6 to day 15 of pregnancy produced embryolethality with an LD50 of 145 mg/kg. The more potent antispermatogenic lonidamine was 7.25 times more effective, with an LD50 of 20 mg/kg. No significant teratogenicity was exerted by AF 1312/TS, whilst lonidamine was slightly effective only at embryolethal doses. The latter was also effective after a single administration on day 9, with an embryonal LD50 of 25 mg/kg, whereas the teratogenic effect was greatest on day 10. The similarity of the embryonal LD50 after single or repeated administrations suggests an interference with a specific epigenetic crisis.