Munson A E, White K L, Barnes D W, Musgrove D L, Lysy H H, Holsapple M P
Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298.
Fundam Appl Toxicol. 1988 May;10(4):691-700. doi: 10.1016/0272-0590(88)90196-0.
Adult female B6C3F1 mice were gavaged with 4,4'-thiobis-(6-t-butyl-m-cresol) (TBBC) in corn oil at doses of 10, 100, or 200 mg/kg daily for 14 consecutive days. There was no overt toxicity, as manifested by grossly observable behavioral changes, decreased growth rate over the exposure period, or mortality. There were also no marked effects on serum chemistries or hematology, with the exception of a significant increase (41%) in the number of leukocytes at the highest dose. Absolute differential counts indicated that significant increases occurred in the number of lymphocytes (31%) and neutrophils (177%). Studies with bone marrow indicated a significant 30% increase in the number of cells/femur from animals treated with the highest dose of TBBC. The number of macrophage progenitors (CFU-M)/femur was significantly increased by 28%, while the number of granulocyte-monocyte progenitors (CFU-GM)/femur was nonsignificantly increased by 20% in the high dose animals. The weight of both the spleen and liver was increased in a dose-related fashion, although the histopathology of the spleen of TBBC-treated mice was not different from control. The livers of mice receiving the high dose showed mild focal hydropic degeneration, mild hepatitis, and a slight increase in the number of Kupffer cells. No other organs were affected. Liver microsomal protein and cytochrome P-450 levels were increased in a dose-related fashion. Enzyme activities of aminopyrine demethylase and aniline hydroxylase, but not arylhydrocarbon hydroxylase, were also increased in a dose-related fashion.
成年雌性B6C3F1小鼠连续14天每天经口灌胃给予玉米油溶解的4,4'-硫代双-(6-叔丁基间甲酚)(TBBC)，剂量分别为10、100或200mg/kg。未观察到明显毒性，表现为无明显的行为变化、暴露期间生长速率无下降或无死亡情况。除最高剂量组白细胞数量显著增加(41%)外，对血清生化指标或血液学指标也无明显影响。绝对分类计数表明，淋巴细胞数量显著增加(31%)，中性粒细胞数量显著增加(177%)。骨髓研究表明，接受最高剂量TBBC处理的动物每根股骨的细胞数量显著增加30%。高剂量组动物每根股骨的巨噬细胞祖细胞(CFU-M)数量显著增加28%，而每根股骨的粒细胞-单核细胞祖细胞(CFU-GM)数量非显著增加20%。脾脏和肝脏重量均呈剂量相关增加，尽管TBBC处理小鼠的脾脏组织病理学与对照组无差异。接受高剂量的小鼠肝脏表现出轻度局灶性水样变性、轻度肝炎和库普弗细胞数量略有增加。其他器官未受影响。肝脏微粒体蛋白和细胞色素P-450水平呈剂量相关增加。氨基比林脱甲基酶和苯胺羟化酶的酶活性也呈剂量相关增加，但芳烃羟化酶的酶活性未增加。
