Foote R H, Berndtson W E, Rounsaville T R
Fundam Appl Toxicol. 1986 May;6(4):638-47. doi: 10.1016/0272-0590(86)90176-4.
Dibromochloropropane (DBCP) was administered orally to 36 sexually mature male Dutch Belted rabbits assigned at random to one of six groups to receive 0, 0.94, 1.88, 3.75, 7.5, or 15.0 mg DBCP per kilogram of body weight daily 5 days per week during a 69-day treatment period. Animals were euthanized and necropsied on Day 70. Body weights and weights of the kidneys, liver, epididymides, and accessory sex glands were not influenced by DBCP treatment. The highest dosage reduced mean paired testes weight to 45% of control values (p less than 0.01). Mean seminiferous tubular diameter was reduced by 15 and 29% with the two highest dosages of DBCP, respectively (p less than 0.01), and the percentage of seminiferous tubules containing elongating and round spermatids, as the most advanced cell type present, was decreased (p less than 0.01). The number of leptotene primary spermatocytes per Sertoli cell, and the numbers of spermatogonia, young and old primary spermatocytes, and Step 1 spermatids per Stage I seminiferous tubular cross section likewise indicated a general depression (p less than 0.01) of spermatogenesis. Based upon the number of Step 1 spermatids per cross section at Day 70, production of sperm at this time by rabbits receiving the highest dose of DBCP was estimated to be less than one-fourth of control values. No significant effect (p greater than 0.05) of 0.94 mg DBCP/kg on any parameters was found, so this could be considered to be the no effect dose. However, the regressions and mean values are interpreted to indicate that the no effect level of DBCP may be less than 0.94 mg DBCP/kg of body weight. It is suggested that the most sensitive tests described here be included in future screening tests for potential effects of agents on male reproduction.
将二溴氯丙烷（DBCP）经口给予36只性成熟的荷兰带兔，这些兔子被随机分为六组，在为期69天的试验期内，每周5天上下午各给药1次，剂量分别为0、0.94、1.88、3.75、7.5或15.0毫克/千克体重的DBCP。在第70天对动物实施安乐死并进行尸检。DBCP处理对体重以及肾脏、肝脏、附睾和附属性腺的重量没有影响。最高剂量组的平均双侧睾丸重量降至对照值的45%（p<0.01）。两个最高剂量的DBCP分别使生精小管平均直径降低了15%和29%（p<0.01），并且含有伸长型和圆形精子细胞（作为最成熟细胞类型）的生精小管百分比下降（p<0.01）。每个支持细胞中的细线期初级精母细胞数量，以及每个I期生精小管横切面中的精原细胞、年轻和老龄初级精母细胞以及第1步精子细胞数量同样表明精子发生普遍受到抑制（p<0.01）。根据第70天时每个横切面的第1步精子细胞数量估算，接受最高剂量DBCP的兔子此时的精子生成量不到对照值的四分之一。未发现0.94毫克/千克体重的DBCP对任何参数有显著影响（p>0.05），因此该剂量可被视为无作用剂量。然而，通过回归分析和平均值判断，DBCP的无作用水平可能低于0.94毫克/千克体重。建议在未来对雄性生殖毒性的筛选试验中纳入本文描述的最敏感试验。
