Endpoints of Spermatotoxicity in the Rat After Short Duration Exposures toFourteen Reproductive Toxicants

摘要

Multiple endpoints of spermatotoxicity in short in vivo tests were investigatedin several chemicals which produce minimal to severe subchronic reproductive effects. Six chemicals (boric acid, dinoseb, 2,5-hexanedione, methoxychlor, metronidazole, ornidazole) produced spermatotoxicity. Chlordimeform was equivocal while pp'-DDT, n-hexane, and sodium chlorite were negative. Chemicals with known acute effects (benomyl, busulfan, EGME, nitrobenzene) elicited expected responses. Testicular histology, sperm head counts, cauda sperm counts, sperm morphology and velocity were the most sensitive endpoints, but histopathology was the most consistent indicator of damage. The data suggested that most chemicals which produce moderate sperm damage are detectable in a short duration test. Multiple endpoints enhanced interpretations, identified cellular targets, and provided insight on mechanisms. The responses often predicted effects seen in subchronic exposures. The short test could be used as a screen in SAR studies or to prioritize further evaluations. As a supplement, the short test could enhance the design and interpretation of longer tests.