Inhalation carcinogenicity and toxicity of 1,2-dichloropropane in rats
Inhalation carcinogenicity and toxicity of 1,2-dichloropropane in rats
复制标题
DOI：
10.3109/08958378.2010.526973
复制
发表时间：
2010-11-01
影响因子：
2.1
通讯作者：
Fukushima, Shoji
中科院分区：
文献类型：
--
作者：
Umeda, Yumi;Matsumoto, Michiharu;Fukushima, Shoji
用F344大鼠经口吸入1，2-二氯丙烷（DCP）13周和2年，观察DCP的毒性和致癌性。在为期13周的研究中，使用的DCP浓度为125、250、500、1000或2000 ppm（v/v），在为期2年的研究中，DCP浓度为80、200或500 ppm（v/v）。暴露于125 ppm及以上的DCP 13周可诱导呼吸上皮增生和嗅上皮萎缩。在较高的接触水平下，观察到溶血性贫血以及肝脏和肾上腺病变。两年暴露于DCP显着增加的发病率乳头状瘤在鼻腔中的雄性和雌性大鼠暴露于500 ppm的DCP。此外，在接触DCP的雄性大鼠中观察到3例感觉神经上皮瘤。总鼻肿瘤以浓度依赖性方式增加。移行上皮增生和鳞状细胞增生（两者在形态上均不同于13周暴露研究中观察到的呼吸道上皮增生）以浓度依赖性方式发生;认为这些病变为癌前病变。在2年研究中还观察到嗅上皮萎缩、呼吸道上皮炎症和鳞状细胞化生。这些结果表明DCP是大鼠鼻致癌物。使用非阈值和阈值方法，从2年的研究中获得的数据，在环境空气和工作环境中暴露于DCP的人的终身癌症风险进行了定量估计。
The toxicity and carcinogenicity of 1,2-dichloropropane (DCP) were examined by inhalation exposure of male and female F344 rats to DCP for either 13 wk or 2 years. In the 13-wk study, the DCP concentrations used were 125, 250, 500, 1000, or 2000 ppm (v/v), and in the 2-year study the DCP concentrations were 80, 200, or 500 ppm (v/v). Thirteen-week exposure to DCP induced hyperplasia in the respiratory epithelium and atrophy of the olfactory epithelium at 125 ppm and above. At the higher levels of exposure, hemolytic anemia and lesions of liver and adrenal gland were observed. Two-year exposure to DCP significantly increased incidences of papilloma in the nasal cavity of male and female rats exposed to 500 ppm DCP. In addition, three cases of esthesioneuroepithelioma were observed in the DCP-exposed male rats. Total nasal tumors increased in a concentration-dependent manner. Hyperplasia of the transitional epithelium and squamous cell hyperplasia, both of which were morphologically different from the hyperplasia of the respiratory epithelium observed in the 13-wk exposure study, occurred in a concentration-dependent manner; these lesions are considered to be preneoplastic lesions. Atrophy of the olfactory epithelium, inflammation of the respiratory epithelium, and squamous cell metaplasia were also seen in the 2-year study. These results demonstrate that DCP is a nasal carcinogen in rats. Lifetime cancer risks for humans exposed to DCP in the ambient air and work environment were quantitatively estimated, using both nonthreshold and threshold approaches, with the data obtained from the 2-year study.