Carcinogenicity studies of 1,4-dioxane administered in drinking-water to rats and mice for 2 years
Carcinogenicity studies of 1,4-dioxane administered in drinking-water to rats and mice for 2 years
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DOI：
10.1016/j.fct.2009.08.012
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发表时间：
2009-11-01
影响因子：
4.3
通讯作者：
Fukushima, Shoji
中科院分区：
文献类型：
--
作者：
Kano, Hirokazu;Umeda, Yumi;Fukushima, Shoji
通过给各组 50 只 F344/DuCrj 大鼠和 50 只 Crj:BDF1 小鼠（每组）饮用 1,4-二恶烷 2 年的饮用水来检查 1,4-二恶烷的致癌性。大鼠的 1,4-二恶烷浓度为 0（对照）、200、1000 和 5000 ppm（重量/重量），小鼠的 1,4-二恶烷浓度为 0、500、2000 和 8000 ppm。最高剂量水平未超过最大耐受剂量。在大鼠中，显着诱发雌性鼻鳞状细胞癌、雄性和雌性肝细胞腺瘤和癌、雄性腹膜间皮瘤和雌性乳腺腺瘤。在小鼠中，雄性和雌性小鼠的肝细胞肿瘤均显着诱导。 8000 ppm 剂量组中自发发生的两例鼻肿瘤很少见，因此归因于 1,4-二恶烷暴露。目前的研究提供了大鼠和小鼠致癌性的明确证据。通过饮用水暴露于 1,4-二恶烷的人类的终生癌症风险通过应用剂量-致癌反应关系的线性多阶段模型，采用非阈值方法进行定量估计，此外还使用未观察到或最低观察到的致癌反应不良效应水平和不确定因素的阈值方法来估计每日耐受摄入量。 (C) 2009 Elsevier Ltd. 保留所有权利。
The carcinogenicity of 1,4-dioxane was examined by giving groups of 50 F344/DuCrj rats and 50 Crj:BDF1 mice of each sex 1,4-dioxane in the drinking-water for 2 years. The concentrations of 1,4-dioxane were 0 (control), 200, 1000 and 5000 ppm (wt./wt.) for rats and 0, 500, 2000 and 8000 ppm for mice. The highest dose levels did not exceed the maximum tolerated dose. In the rat, there was significant induction of nasal squamous cell carcinomas in females and hepatocellular adenomas and carcinomas in males and females, peritoneal mesotheliomas in males, and mammary gland adenomas in females. In the mouse, there was significant induction of hepatocellular tumors in males and females. Two nasal tumors occurring in the 8000 ppm-dosed groups were spontaneously rare and, thus, were attributed to 1,4-dioxane exposure. The present studies provided clear evidence of carcinogenicity in rats and mice. Lifetime cancer risk of humans exposed to 1,4-dioxane through drinking-water was quantitatively estimated with a non-threshold approach by application of a linearized multistage model to dose-carcinogenic response relationships, in addition to a threshold approach for estimation of the tolerable daily intake using no-observed- or lowest-observed-adverse-effect levels of the carcinogenic responses and uncertainty factors. (C) 2009 Elsevier Ltd. All rights reserved.