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大鼠中3-甲基-1-丁醇和2-甲基-1-丙醇的亚慢性毒性研究

Subchronic toxicity studies of 3-methyl-1-butanol and 2-methyl-1-propanol in rats.

作者信息

Schilling K, Kayser M, Deckardt K, Küttler K, Klimisch H J

机构信息

BASF Aktiengesellschaft, Department of Toxicology, Ludwigshafen, Germany.

出版信息

Hum Exp Toxicol. 1997 Dec;16(12):722-6. doi: 10.1177/096032719701601205.

DOI:10.1177/096032719701601205
PMID:9429086
Abstract
  1. 90-day subchronic toxicity studies with 3-methyl-1-butanol (MEB) and 2-methyl-1-propanol (MEP) were performed on rats to evaluate the toxicological profile of the compounds under conditions of drinking water studies, to identify the potential target organs, and to determine no-observable-adverse-effect-levels (NOAELs) respective of the substances. The test substances were administered to groups of 10 male and 10 female Wistar rats in drinking water at concentrations of 0, 1000 p.p.m. (about 80 mg/kg/d), 4000 p.p.m. (about 340 mg/kg/d) and 16,000 p.p.m. (about 1250 and 1450 mg/kg/d of MEB and MEP respectively). 2. 16,000 p.p.m. was found to be the maximal concentration for both alcohols applicable to rats in drinking water. Higher concentrations had an influence on palatability and could thus not be tested in drinking water studies. 3. At 16,000 p.p.m. MEB a marginal increase in the red blood cell count as well as a slight decrease in the mean corpuscular volume and the mean corpuscular hemoglobin content was observed in males only. These changes are considered to be treatment-related, although the toxicological significance of these findings is unclear. No other substance-related effects were found on body weight (b.w.), mortality, various parameters of clinical chemistry, organ weights, gross pathology and histopathology. 4000 p.p.m. MEB did not cause any substance-induced changes. Therefore, the NOAEL of MEB was defined as 4000 p.p.m. for male and 16,000 p.p.m. for female rats under conditions of oral application via drinking water. 4. MEP concentrations up to and including 16,000 p.p.m. did not induce any signs of toxicity and were therefore defined as the NOAEL respective of this substance for rats under conditions of drinking water application.
摘要
  1. 对大鼠进行了3-甲基-1-丁醇(MEB)和2-甲基-1-丙醇(MEP)的90天亚慢性毒性研究,以评估在饮用水研究条件下这些化合物的毒理学概况,确定潜在的靶器官,并确定每种物质的无观察到有害作用水平(NOAELs)。将受试物质以0、1000 ppm(约80 mg/kg/天)、4000 ppm(约340 mg/kg/天)和16000 ppm(MEB和MEP分别约为1250和1450 mg/kg/天)的浓度通过饮用水给予每组10只雄性和10只雌性Wistar大鼠。2. 发现16000 ppm是两种醇类在大鼠饮用水中适用的最大浓度。更高的浓度会影响适口性,因此无法在饮用水研究中进行测试。3. 在16000 ppm的MEB组中,仅在雄性大鼠中观察到红细胞计数略有增加以及平均红细胞体积和平均红细胞血红蛋白含量略有下降。这些变化被认为与治疗有关,尽管这些发现的毒理学意义尚不清楚。在体重(b.w.)、死亡率、临床化学的各种参数、器官重量、大体病理学和组织病理学方面未发现其他与物质相关的影响。4000 ppm的MEB未引起任何物质诱导的变化。因此,在通过饮用水口服给药的条件下,MEB对雄性大鼠的NOAEL定义为4000 ppm,对雌性大鼠为16000 ppm。4. MEP浓度高达并包括16000 ppm时未诱导任何毒性迹象,因此在饮用水给药条件下被定义为该物质对大鼠的NOAEL。

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