Hayakawa Kazuhiro, Mimura Yuichi, Tachibana Shigehiro, Furuya Mami, Kodama Terutaka, Aoki Toyohiko, Hosokawa Satoru, Fukui Motoko, Shibata Seiji, Yoshida Masanao, Masuyama Takeshi, Narita Takahiro, Kuwagata Makiko, Hisada Shigeru, Maki Eiji
Kawashima Drug Safety, Global Drug Safety, Biopharmaceutical Assessment Core Function Unit, Eisai Co., Ltd., Present address; Preclinical Safety Research Laboratories, Sunplanet Co., Ltd.
J Toxicol Sci. 2013;38(6):855-73. doi: 10.2131/jts.38.855.
The purpose of the present study was to collect background data from repeated dose toxicity studies in Wistar Hannover [Crl:WI(Han)] (hereafter Wistar Han) rats with dosing periods of 4, 13 and 26 weeks from four safety research facilities of pharmaceutical companies and contract research organizations participating in the International Genetic Standardization (IGS) rat forum supported by Charles River Laboratories Japan, Inc. The data from Wistar Han rats were compared with those from Sprague Dawley Crl:CD(SD) rats. In addition, the effects of restricted feeding of SD rats were also investigated by one facility. As a result, body weights and food consumption in Wistar Han rats were lower than those of SD rats. White blood cell (WBC), neutrophil, lymphocyte, monocyte and eosinophil counts were almost half of those noted for SD rats and platelet counts were almost 20% less than those in SD rats. Minimal strain differences were noted in several biochemical parameters including aspartate aminotransferase (AST), alanine aminotransferase, total cholesterol, triglyceride and phospholipids, and in thymus, ovary and testis weights. Ophthalmologic or histopathologic examinations revealed a higher incidence of corneal opacities or corneal mineralization in Wistar Han rats. Restricted feeding of SD rats resulted in intermediate values for body weights and food consumption between the ad libitum fed SD and Wistar Han rats, and WBC and AST were lower than those in the ad libitum fed SD rats. Based on these results, some strain differences might be ascribable to reduced food consumption and associated body weight changes in Wistar Han rats.
本研究的目的是从参与由日本查尔斯河实验室支持的国际遗传标准化（IGS）大鼠论坛的制药公司和合同研究组织的四个安全研究机构，收集在Wistar Hannover [Crl:WI(Han)]（以下简称Wistar Han）大鼠中进行的为期4周、13周和26周重复剂量毒性研究的背景数据。将Wistar Han大鼠的数据与Sprague Dawley Crl:CD(SD)大鼠的数据进行比较。此外，一个机构还研究了限制SD大鼠进食的影响。结果显示，Wistar Han大鼠的体重和食物消耗量低于SD大鼠。白细胞（WBC）、中性粒细胞、淋巴细胞、单核细胞和嗜酸性粒细胞计数几乎是SD大鼠的一半，血小板计数比SD大鼠低近20%。在包括天冬氨酸转氨酶（AST）、丙氨酸转氨酶、总胆固醇、甘油三酯和磷脂等几个生化参数以及胸腺、卵巢和睾丸重量方面，品系差异极小。眼科或组织病理学检查显示，Wistar Han大鼠角膜混浊或角膜矿化的发生率较高。限制SD大鼠进食导致其体重和食物消耗量处于自由进食的SD大鼠和Wistar Han大鼠之间的中间值，且WBC和AST低于自由进食 的SD大鼠。基于这些结果，一些品系差异可能归因于Wistar Han大鼠食物消耗量减少及相关的体重变化。
