Schreiner C, Lapadula E, Breglia R, Bui Q, Burnett D, Koschier F, Podhasky P, White R, Mandella R, Hoffman G
Petroleum Product Stewardship Council, Washington, DC, USA.
J Toxicol Environ Health A. 1998 Oct 23;55(4):277-96. doi: 10.1080/009841098158449.
A 13-wk inhalation study was conducted with Sprague-Dawley CD rats (12/sex/group) were exposed by inhalation for 13 weeks to a light alkylate naphtha distillate (LAND-2, C4-C10; average molecular weight 89.2) at actual average concentrations of 0 (room air), 668, 2220, or 6646 ppm, 6 h/d, 5 d/wk; 12 additional rats/sex in the control and high dose groups were held after final exposure for a 4-wk recovery period. The highest exposure concentration was 75% of the lower explosive limit. Standard parameters of subchronic toxicity were measured throughout the study; at necropsy, organs were weighed and tissues processed for microscopic evaluation. Neurotoxicity evaluations consisted of motor activity (MA) and a functional operational battery (FOB) measured pretest, during 5, 9, and 14 wk of the study, and after the 4-wk recovery period. Whole-body perfusion and microscopic examination of selected organs and nervous tissue from the control and high dose rats were conducted at the end of exposure. No test-related mortality or effects on physical signs, body weight, or food consumption were observed. Statistically significant increases in absolute and relative kidney weights in high-exposure males correlated with microscopically observed hyaline droplet formation and renal nephropathy, effects in male rats that are not toxicologically significant for humans. Increased liver weights in both sexes at the highest dose had no microscopic correlate and appeared reversible after the 4-wk recovery period. Exposure to LAND-2 at any dose did not produce neurotoxicity measured by MA, FOB, or neuropathology. The no-observed-effects level (NOEL) for LAND-2 was 2220 ppm for subchronic toxicity and > or =26646 ppm for neurotoxicity.
对斯普拉格-道利CD大鼠（每组雌雄各12只）进行了一项为期13周的吸入研究，大鼠每天6小时、每周5天吸入轻烷基化石脑油馏分（LAND-2，C4-C10；平均分子量89.2），实际平均浓度分别为0（室内空气）、668、2220或6646 ppm；对照组和高剂量组在末次暴露后另外各留12只大鼠/性别进行4周的恢复期观察。最高暴露浓度为爆炸下限的75%。在整个研究过程中测量亚慢性毒性的标准参数；尸检时，对器官进行称重，并对组织进行显微镜评估。神经毒性评估包括在研究的第5、9和14周以及4周恢复期后测量的运动活动（MA）和功能性操作电池（FOB）（预测试时测量）。在暴露结束时，对对照组和高剂量组大鼠的选定器官和神经组织进行全身灌注和显微镜检查。未观察到与试验相关的死亡或对身体体征、体重或食物消耗的影响。高暴露雄性大鼠的绝对和相对肾脏重量在统计学上显著增加，与显微镜下观察到的透明滴形成和肾肾病相关，这些影响在雄性大鼠中对人类没有毒理学意义。最高剂量时两性肝脏重量增加，但无显微镜下对应变化，且在4周恢复期后似乎可逆。无论剂量如何，暴露于LAND-2均未产生通过MA、FOB或神经病理学测量的神经毒性。LAND-2的亚慢性毒性未观察到效应水平（NOEL）为2220 ppm，神经毒性的NOEL为≥26646 ppm。
