Sasser L B, Cushing J A, Dacre J C
Biology and Chemistry Department, Pacific Northwest Laboratory, Richland, WA 99352-0999.
J Appl Toxicol. 1993 Sep-Oct;13(5):359-68. doi: 10.1002/jat.2550130511.
Sulfur mustard (HD) (bis(2-chloroethyl)sulfide) is a strong alkylating agent with known mutagenic and suspected carcinogenic properties, but occupational health standards have not been established. The purpose of this study was to determine the dominant lethal effect in male and female rats dosed orally with HD, for which currently available data are ambiguous. Sprague-Dawley rats of each sex, 6-7 weeks old, were orally administered 0, 0.08, 0.20 or 0.50 mg kg-1 HD 5 days a week for 10 weeks, after which dominant lethal studies were conducted during the post-exposure period. The studies were conducted in two phases: a female dominant lethal phase in which treated or untreated males were mated with treated females and their fetuses were evaluated 14 days after copulation; and a male dominant lethal phase in which treated males cohabited with untreated females for 5 days and fetuses were evaluated 14 days after the mid-point of the week of cohabitation, for each of 10 weeks. In addition, motility, population size and morphology were measured in sperm obtained from the cauda epididymis. Parental growth rates were reduced in both sexes treated with the high level of HD. Female dominant lethal effects were not observed, although significant male dominant lethal effects were observed in HD-exposed male rats mated to untreated females at 2 and 3 weeks' post-exposure. These effects, which included increases of early fetal resorptions and preimplantation losses and decrease in total live embryo implants, were most consistently observed at a dose of 0.50 mg kg-1. A significant P(P < 0.05) increase in the percentage of abnormal sperm was detected in males exposed to 0.50 mg kg-1 HD. The timing of dominant lethal effects is consistent with an effect during the post-meiotic stages of spermatogenesis, possibly involving the generally sensitive spermatids.
硫芥（HD）（双（2-氯乙基）硫化物）是一种具有已知诱变特性和疑似致癌特性的强烷基化剂，但尚未制定职业健康标准。本研究的目的是确定口服HD的雄性和雌性大鼠的显性致死效应，目前可得的数据对此尚不明确。选用6-7周龄的各性别的斯普拉格-道利大鼠，每周5天口服给予0、0.08、0.20或0.50 mg/kg的HD，持续10周，之后在暴露后期间进行显性致死研究。研究分两个阶段进行：雌性显性致死阶段，将处理过或未处理过的雄性大鼠与处理过的雌性大鼠交配，并在交配后14天评估其胎儿；雄性显性致死阶段，处理过的雄性大鼠与未处理过的雌性大鼠同居5天，并在同居周中期后的14天评估胎儿，为期10周。此外，还对从附睾尾部获得的精子进行了活力、数量和形态的测量。高剂量HD处理的两性亲代生长速率均降低。未观察到雌性显性致死效应，尽管在暴露后2周和3周，将暴露于HD的雄性大鼠与未处理的雌性大鼠交配时，观察到了显著的雄性显性致死效应。这些效应包括早期胎儿吸收和着床前损失增加以及总活胚胎着床减少，在剂量为0.50 mg/kg时最常观察到。在暴露于0.50 mg/kg HD的雄性大鼠中，检测到异常精子百分比显著升高（P<0.05）。显性致死效应的时间与精子发生减数分裂后阶段的效应一致，可能涉及通常敏感的精子细胞。
