Sasser L B, Miller R A, Kalkwarf D R, Cushing J A, Dacre J C
Pacific Northwest Laboratory, Richland, WA 99352-0999, USA.
J Appl Toxicol. 1996 Jan-Feb;16(1):5-13. doi: 10.1002/(SICI)1099-1263(199601)16:1<5::AID-JAT295>3.0.CO;2-W.
Occupational exposure criteria have not been established for sulfur mustard (bis(2-chlorethyl) sulfide), a strong alkylating agent with known mutagenic properties. Seventy-two Sprague-Dawley rats of each sex, 6-7 weeks old, were divided into six groups (12 of each sex per group) and gavaged with 0, 0.003, 0.01, 0.03, 0.1 or 0.3 mg kg-1 sulfur mustard in sesame oil for 5 days a week for 13 weeks. No dose-related mortality was observed. A significant decrease (P > 0.05) in body weight was observed in both sexes of rats only in the 0.3 mg kg-1 group. Hematological evaluations and clinical chemistry measurements found non consistent treatment-related effects at the doses studied. The only treatment-related lesion associated with gavage exposure upon histopathological evaluation was epithelial hyperplasia of the forestomach of both sexes at 0.3 mg kg-1 and of males at 0.1 mg kg-1. The hyperplastic change was minimal and characterized by cellular disorganization of the basilar layer, apparent increase in mitotic activity of the basilar epithelial cells and thickening of the epithelial layer due to the apparent increase in cellularity. The estimated no-observed-effect level (NOEL) for sulfur mustard in this 90-day study was 0.1 mg kg-1 day-1 when administered orally.
硫芥（双（2-氯乙基）硫化物）是一种具有已知诱变特性的强烷基化剂，目前尚未制定职业接触标准。选用72只6-7周龄的Sprague-Dawley大鼠，雌雄各半，分为六组（每组雌雄各12只），每周5天，连续13周，分别用0、0.003、0.01、0.03、0.1或0.3mg/kg-1的硫芥芝麻油溶液灌胃。未观察到与剂量相关的死亡率。仅在0.3mg/kg-1组的雌雄大鼠中观察到体重显著下降（P>0.05）。血液学评估和临床化学测量结果显示，在所研究的剂量下，与治疗相关的效应并不一致。在组织病理学评估中，与灌胃暴露相关的唯一治疗相关病变是0.3mg/kg-1组雌雄大鼠及0.1mg/kg-1组雄性大鼠的前胃上皮增生。增生变化轻微，其特征为基底层细胞排列紊乱、基底上皮细胞有丝分裂活性明显增加以及由于细胞数量明显增加导致上皮层增厚。在这项为期90天的研究中，口服硫芥的估计未观察到效应水平（NOEL）为0.1mg/kg-1/天。
