Aida Y, Yasuhara K, Takada K, Kurokawa Y, Tobe M
Division of Risk Assessment, National Institute of Hygienic Sciences, Tokyo, Japan.
J Toxicol Sci. 1992 May;17(2):51-68. doi: 10.2131/jts.17.51.
A chronic feeding study was carried out in Wistar rats using microencapsulated bromodichloromethane. The test substance was administered in the diet at doses of 0, 0.014, 0.055 and 0.22% for 24 months. Rats were sacrificed after 6, 12, 18 and 24 months of continuous dosing. The results showed a suppression of body weight gain in the 0.22% group for both males and females. Dose related changes were clearly observed in the liver with histopathological findings including fatty degeneration in the 0.014% or higher dose male groups, and fatty degeneration and granuloma in the 0.055 and 0.22% group females, as well as bile duct proliferation and cholangiofibrosis in the 0.22% group for both males and females. No significant differences in incidences or numbers of neoplastic changes were seen between control and any of the treatment groups. There were no dose-related non-neoplastic lesions in the kidneys of either sex. Lowest-observed-adverse-effect-level was determined to be 6.1 mg/kg/day under the present experimental conditions.
使用微囊化溴二氯甲烷对Wistar大鼠进行了一项慢性喂养研究。受试物质以0%、0.014%、0.055%和0.22%的剂量添加到饲料中,持续给药24个月。在连续给药6个月、12个月、18个月和24个月后处死大鼠。结果显示,0.22%剂量组的雄性和雌性大鼠体重增加均受到抑制。在肝脏中明显观察到与剂量相关的变化,组织病理学结果包括:0.014%及以上剂量雄性组出现脂肪变性;0.055%和0.22%剂量组雌性出现脂肪变性和肉芽肿;0.22%剂量组的雄性和雌性均出现胆管增生和胆管纤维化。在对照组和任何治疗组之间,肿瘤性变化的发生率或数量均无显著差异。两性肾脏中均未出现与剂量相关的非肿瘤性病变。在当前实验条件下,确定最低观察到有害作用水平为6.1毫克/千克/天。