Verdier F, Virat M, Schweinfurth H, Descotes J
Laboratoire d'Immunotoxicologie Fondamentale et Clinique, Faculté de Médecine A. Carrel, Lyon, France.
J Toxicol Environ Health. 1991 Mar;32(3):307-17. doi: 10.1080/15287399109531484.
Previous studies in the rat have shown that bis(tri-n-butyltin) oxide (TBTO), used as a biocide, was immunotoxic at dose levels that did not affect other organs. In order to determine a no-effect level, weanling rats were treated for at least 28 consecutive days with TBTO at 0, 0.5, 2, 5, or 50 mg/kg of diet. Studies on clinical chemistry, hematology, pathology, and immune function, that is, plaque-forming cell (PFC) assay, delayed-type hypersensitivity (DTH) response, and the splenic clearance of Listeria monocytogenes, were performed at the end of treatment. No treatment-related effects were noted on clinical chemistry and hematology parameters and on PFC and DTH response, whereas thymic atrophy and impaired clearance of L. monocytogenes were noted only at a dietary concentration of 50 mg/kg. These results confirm the thymus as a target organ of TBTO immunotoxicity. Under the conditions of these experiments the dietary concentration of 5 mg/kg, equivalent to a dose of 0.5 mg/kg body weight, represents a no observed effect level (NOEL) for immunotoxicity in the Sprague-Dawley rat.
以往对大鼠的研究表明,用作杀生剂的双(三正丁基锡)氧化物(TBTO)在不影响其他器官的剂量水平下具有免疫毒性。为了确定无作用水平,将断乳大鼠连续至少28天用0、0.5、2、5或50mg/kg饲料的TBTO进行处理。在处理结束时进行了临床化学、血液学、病理学和免疫功能研究,即空斑形成细胞(PFC)测定、迟发型超敏反应(DTH)应答以及单核细胞增生李斯特菌的脾脏清除。在临床化学和血液学参数以及PFC和DTH应答方面未观察到与处理相关的影响,而仅在饲料浓度为50mg/kg时观察到胸腺萎缩和单核细胞增生李斯特菌清除受损。这些结果证实胸腺是TBTO免疫毒性的靶器官。在这些实验条件下,饲料浓度为5mg/kg,相当于体重剂量0.5mg/kg,代表了Sprague-Dawley大鼠免疫毒性的未观察到作用水平(NOEL)。