Schreiner C, Bui Q, Breglia R, Burnett D, Koschier F, Podhasky P, Lapadula L, White R, Feuston M, Krueger A, Rodriquez S
Petroleum Product Stewardship Council, Washington, DC, USA.
J Toxicol Environ Health. 1997 Oct 24;52(3):211-29. doi: 10.1080/00984109708984061.
Hydrodesulfurized kerosine (HDS kerosine), applied dermally, was tested for reproductive and developmental toxicity in Sprague-Dawley rats, using a modified OECD Guideline 421, Reproductive/Developmental Toxicity Screening Protocol. A preliminary acute dermal irritancy test demonstrated that dilution of HDS kerosine in either a light (100 Saybolt universal seconds, SUS) or moderate viscosity (340 SUS) USP mineral oil reduced irritation of the neat material comparably. Similar dermal absorption was observed in vitro for neat HDS kerosine or diluted in either of the mineral oils. HDS kerosine diluted to 494 (60%), 330 (40%), or 165 (20%) mg/kg/day in Squibb mineral oil (340 SUS) was applied daily at 1 ml/kg to the shaved backs of rats for 7 wk (premating, mating to d 19 of gestation) to females and 8 wk to males. Dams and litters were sacrificed on postpartum d 4 and males were sacrificed within the following week. HDS kerosine produced slight to moderate skin irritation at the highest dose in both sexes but no apparent maternal, reproductive, or developmental toxicity. No clinical signs of toxicity and no effects on body weight, food consumption, or absolute organ weights were observed. Relative kidney weights were heavier in male rats at the high dose. Skin changes were observed microscopically in male rats in all groups and in females at the high dose. No microscopic changes were observed in reproductive organs of parental animals. There were no differences in mean number of corpora lutea, implantation sites, and live pups per litter, and no gross anomalies were observed. Pups born from treated dams showed comparable body weights and weight gains to controls. The viability index on postpartum d 4 was > or = 93%. In conclusion, the no observable adverse effect level (NOAEL) for HDS kerosine for reproductive and developmental toxicity in rats is 494 mg/kg/d.
采用经修改的经济合作与发展组织（OECD）第421号准则《生殖/发育毒性筛选试验方案》，对经皮肤涂抹的加氢脱硫煤油（HDS煤油）进行了Sprague-Dawley大鼠生殖和发育毒性试验。一项初步急性皮肤刺激性试验表明，将HDS煤油稀释于轻质（100赛波特通用秒，SUS）或中等粘度（340 SUS）的美国药典（USP）矿物油中，均可同等程度地降低纯品的刺激性。对于纯HDS煤油或稀释于任一矿物油中的HDS煤油，均观察到了相似的体外皮肤吸收情况。将HDS煤油在施贵宝矿物油（340 SUS）中稀释至494（60%）、330（40%）或165（20%）mg/kg/天，以1 ml/kg的剂量每日涂抹于大鼠剃毛的背部，雌性大鼠涂抹7周（从交配前至妊娠第19天），雄性大鼠涂抹8周。在产后第4天处死母鼠及其所产幼崽，在接下来的一周内处死雄性大鼠。HDS煤油在最高剂量时对雌雄两性均产生了轻度至中度的皮肤刺激，但未表现出明显的母体、生殖或发育毒性。未观察到毒性的临床体征，对体重、食物摄入量或绝对器官重量也无影响。高剂量组雄性大鼠的相对肾重较重。在所有组的雄性大鼠以及高剂量组的雌性大鼠中，均在显微镜下观察到了皮肤变化。在亲代动物的生殖器官中未观察到微观变化。每窝的黄体数、着床点数和存活幼崽数的平均值无差异，也未观察到明显的异常。经处理的母鼠所产幼崽的体重和体重增加与对照组相当。产后第4天的活力指数≥93%。总之，大鼠经皮肤接触HDS煤油的生殖和发育毒性无观察到不良作用水平（NOAEL）为494 mg/kg/d。
