Adenuga David, Carrillo Juan-Carlos, Mckee Richard H
ExxonMobil Biomedical Sciences, Inc., 1545 Route 22 E., Annandale, NJ 08801, USA.
Shell Health, Shell International B.V., P.O. Box 162, 2501 AN The Hague, The Netherlands.
Regul Toxicol Pharmacol. 2014 Jul;69(2):143-53. doi: 10.1016/j.yrtph.2014.03.006. Epub 2014 Apr 2.
The systemic toxicity of a trimethylbenzene isomer and constituent of C9 aromatic solvents (1,3,5-trimethylbenzene, 135-TMB) was studied in Sprague-Dawley rats following a 90-day oral gavage exposure to 0, 50, 200 and 600 mg/kg/day. No statistically significant effects on body weight, body weight gain or food consumption were observed at study termination. Treatment-related changes in clinical chemistry parameters at the end of the 90-day dosing period were limited to small, but statistically significant, increases in phosphorus levels in high dose males and females. Liver enlargement in high dose male/female rats was considered an adaptive response as this was reversible and was not associated with histopathological lesions or increased liver enzyme markers indicative of liver damage. Kidney weight changes were limited to a small, but statistically significant, increase in relative weights in high dose males. This was not associated with histopathological lesions and thus not considered toxicologically relevant. Overall, the No-Observed-Adverse-Effect-Level (NOAEL) was the highest concentration tested (600 mg/kg/day). The results of the present study are relevant for assessing the risk of trimethylbenzenes through the oral route of exposure and provide a basis for the development of provisional screening values for trimethylbenzene isomers while avoiding the uncertainty associated with route-to-route extrapolation.
在给予Sprague-Dawley大鼠0、50、200和600mg/kg/天的1,3,5-三甲基苯（135-TMB）90天经口灌胃暴露后，研究了其作为C9芳烃溶剂的一种三甲基苯异构体及其成分的全身毒性。在研究结束时，未观察到对体重、体重增加或食物消耗有统计学显著影响。在90天给药期结束时，与治疗相关的临床化学参数变化仅限于高剂量雄性和雌性大鼠的磷水平有小幅度但具有统计学显著性的升高。高剂量雄性/雌性大鼠的肝脏肿大被认为是一种适应性反应，因为这是可逆的，且与组织病理学损伤或表明肝脏损伤的肝酶标志物增加无关。肾脏重量变化仅限于高剂量雄性大鼠的相对重量有小幅度但具有统计学显著性的增加。这与组织病理学损伤无关，因此不被认为具有毒理学相关性。总体而言，未观察到有害作用水平（NOAEL）是测试的最高浓度（600mg/kg/天）。本研究结果对于评估通过口服途径接触三甲基苯的风险具有相关性，并为制定三甲基苯异构体的临时筛查值提供了依据，同时避免了与不同途径外推相关的不确定性。
