Hess R A, Moore B J, Forrer J, Linder R E, Abuel-Atta A A
Department of Veterinary Biosciences, University of Illinois, Urbana 61801.
Fundam Appl Toxicol. 1991 Nov;17(4):733-45. doi: 10.1016/0272-0590(91)90181-3.
Adult male Sprague-Dawley rats (100 days of age) were given single oral doses of the fungicide benomyl (methyl 1-(butylcarbamoyl)-2- benzimidazolecarbamate) in dosages ranging from 25 to 800 mg/kg body weight. The testis and excurrent ducts were examined at 2 and 70 days posttreatment to determine the chemical effects on spermatogenesis and the epididymis. Primary effects seen at 2 days postexposure were testicular swelling and occlusions of the efferent ductules. Mean testis weight peaked with 400 mg/kg. Premature release of germ cells (sloughing), detected even with the lowest dosage (25 mg/kg), was the most sensitive short-term response to benomyl. Sloughing was found primarily in Stage VII of the spermatogenic cycle at the lower dosages, but at higher dosages sloughing extended into all stages except for Stages VIII-XI. Occlusions of the efferent ductules of the testis were dose-dependent and correlated with testis weight. Sperm and sloughed germ cells were compacted in the ductal lumen of occluded ductules, which were surrounded by two to four layers of polymorphonuclear leukocytes and other inflammatory cells. Although the caput epididymidis contained sloughed germ cells and appeared swollen, evidence of permanent occlusion was not found. The long-term (70 days) effects of benomyl were decreased testis weight (at 400 mg/kg), dose-dependent increases in seminiferous tubular atrophy, and increases in the number of reproductive tracts containing occluded efferent ductules. Fibrosis, granulomas, and abnormal growth were long-term consequences of occluded ductules, which were present 100% of the time in testes containing 26-100% seminiferous tubular atrophy. Only a few testes were found to be completely regressed. Occlusion of efferent ductules and disruption of the seminiferous epithelium by sloughing of germ cells are overlapping dose-dependent mechanisms responsible for short- and long-term effects of benomyl on the rat testis.
成年雄性斯普拉格 - 道利大鼠（100日龄）单次口服剂量范围为25至800毫克/千克体重的杀菌剂苯菌灵（甲基1 - （丁基氨基甲酰基）-2 - 苯并咪唑氨基甲酸酯）。在处理后2天和70天检查睾丸和输出管道，以确定该化学物质对精子发生和附睾的影响。暴露后2天观察到的主要影响是睾丸肿胀和输出小管阻塞。平均睾丸重量在400毫克/千克时达到峰值。即使是最低剂量（25毫克/千克）也检测到生殖细胞过早释放（脱落），这是对苯菌灵最敏感的短期反应。在较低剂量下，脱落主要发生在生精周期的VII期，但在较高剂量下，脱落扩展到除VIII - XI期之外的所有阶段。睾丸输出小管的阻塞呈剂量依赖性，且与睾丸重量相关。精子和脱落的生殖细胞在阻塞小管的管腔内聚集，周围有两到四层多形核白细胞和其他炎症细胞。虽然附睾头含有脱落的生殖细胞并出现肿胀，但未发现永久性阻塞的证据。苯菌灵的长期（70天）影响包括睾丸重量减轻（400毫克/千克时）、生精小管萎缩的剂量依赖性增加以及含有阻塞输出小管的生殖道数量增加。纤维化、肉芽肿和异常生长是阻塞小管的长期后果，在含有26 - 100％生精小管萎缩的睾丸中，100％出现这种情况。仅发现少数睾丸完全退化。输出小管阻塞和生殖细胞脱落导致的生精上皮破坏是苯菌灵对大鼠睾丸短期和长期影响的重叠剂量依赖性机制。
