END-POINTS OF SPERMATOTOXICITY IN THE RAT AFTER SHORT DURATION EXPOSURES TO 14 REPRODUCTIVE TOXICANTS
END-POINTS OF SPERMATOTOXICITY IN THE RAT AFTER SHORT DURATION EXPOSURES TO 14 REPRODUCTIVE TOXICANTS
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DOI：
10.1016/0890-6238(92)90034-q
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发表时间：
1992-01-01
影响因子：
3.3
通讯作者：
SUAREZ, JD
中科院分区：
文献类型：
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作者：
LINDER, RE;STRADER, LF;SUAREZ, JD
在短期试验（1-5天暴露; 2.5周试验间隔）中，研究了一些化学品的精子毒性的多个终点，据报告，当亚慢性给药时，这些化学品会产生轻微至严重的生殖影响。其中6种化学品（硼酸、地乐酚、2，5-己二酮、甲氧滴滴涕、甲硝唑、奥硝唑）在1 - 5次给药后产生显著的精子毒性。杀虫脒的精子毒性作用不明确，而p，p '-DDT、正己烷和亚氯酸钠的作用则被判定为阴性。四种已知具有急性效应的化学品（苯菌灵、白消安、乙二醇单甲醚、硝基苯）在单次给药后引起预期的组织病理学反应。在一项或多项研究中，睾丸组织学、睾丸精子头计数、尾部精子计数、精子形态和精子速度被证明是最敏感的毒理学终点，但睾丸和附睾的组织病理学是生殖损伤的最一致指标。附睾液中活动精子的百分比和精子浓度是最不敏感的测量方法。这些数据表明，大多数有可能产生中度至重度精子损伤的化学物质都可以在短时间内检测到。互补的多个终点增强了对结果的解释，通常确定了细胞靶点，并提供了对可能机制的见解。具体的反应往往类似于亚慢性接触所报告的具体影响。短期试验可作为结构-活性研究中的筛选或确定需要进一步评价的化学品的优先次序。作为育种研究的补充，在短期测试中产生的数据也可用于增强长期测试的设计和解释。
Multiple endpoints of spermatotoxicity in short duration tests (1-5 days exposure; 2.5-week assay interval) were investigated in a number of chemicals reported to produce minimal to severe reproductive effects when administered subchronically. Six of these chemicals (boric acid, dinoseb, 2,5-hexanedione, methoxychlor, metronidazole, ornidazole) produced substantial spermatotoxicity after 1 to 5 doses. Spermatotoxic effects of chlordimeform were equivocal while p,p'-DDT, n-hexane, and sodium chlorite were judged negative. Four chemicals with known acute effects (benomyl, busulfan, ethylene glycol monomethyl ether, nitrobenzene) elicited expected histopathologic responses after a single dose. Testicular histology, testicular sperm head counts, cauda sperm counts, sperm morphology, and sperm velocity proved to be the most toxicologically sensitive endpoints in one or more of the studies, but histopathology of the testis and epididymis was the most consistent indicator of reproductive damage. The percentage of motile sperm and sperm concentration in the epididymal fluid were the least sensitive measurements. The data suggested that most chemicals with the potential to produce moderate to severe sperm damage are detectable with a short duration test. Complementary multiple endpoints enhanced the interpretation of results, often identified cellular targets, and provided insight on possible mechanisms. Specific responses were often similar to specific effects reported for subchronic exposures. A short duration test could be of value as a screen in structure-activity studies or to set priorities for chemicals requiring further evaluation. As a supplement to breeding studies, the data generated in the short test could also be used to enhance the design and interpretation of the longer tests.