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大鼠和小鼠吸入1-溴丙烷的多部位致癌性及呼吸道毒性

Multisite carcinogenicity and respiratory toxicity of inhaled 1-bromopropane in rats and mice.

作者信息

Morgan Daniel L, Nyska Abraham, Harbo Sam Jens, Grumbein Sondra L, Dill Jeffrey A, Roycroft Joseph H, Kissling Grace E, Cesta Mark F

机构信息

National Institute of Environmental Health Sciences, National Toxicology Program, Research Triangle Park, North Carolina 27709, USA.

出版信息

Toxicol Pathol. 2011 Oct;39(6):938-48. doi: 10.1177/0192623311416374. Epub 2011 Aug 22.

Abstract

Two-year 1-bromopropane (1-BP) inhalation studies were conducted because of the potential for widespread exposure, the lack of chronic toxicity and carcinogenicity data, and the known carcinogenicity of structurally related compounds. Male and female F344/N rats and B6C3F1/N mice were exposed by inhalation to 0, 62.5 (mice only), 125, 250, or 500 (rats only) ppm 1-BP for 6 hr/day, 5 days/week for 105 weeks. Exposure of male and female rats to 1-BP resulted in significantly increased incidences of adenomas of the large intestine and skin neoplasms. In male rats, the incidence of malignant mesothelioma of the epididymis was statistically significantly increased at 500 ppm, but the biological significance of this common lesion is unclear. Incidences of pancreatic islet adenoma in male rats were significantly increased at all concentrations relative to concurrent controls but were within the historical control range for inhalation studies. There was no evidence of carcinogenic activity of 1-BP in male B6C3F1 mice; however, significantly increased incidences of alveolar/bronchiolar neoplasms of the lung were present in female mice. Exposure to 1-BP also resulted in increased incidences of nonneoplastic lesions in the nose of rats and mice, the larynx of rats and male mice, the trachea of female rats and male and female mice, and the lungs of mice. Inflammatory lesions with Splendore Hoeppli (S-H) material were present primarily in the nose and skin of exposed male and female rats, indicating that 1-BP caused immunosuppression.

摘要

由于1-溴丙烷(1-BP)存在广泛暴露的可能性、缺乏慢性毒性和致癌性数据,以及结构相关化合物已知的致癌性,因此开展了为期两年的吸入研究。将雄性和雌性F344/N大鼠以及B6C3F1/N小鼠通过吸入暴露于0、62.5(仅针对小鼠)、125、250或500(仅针对大鼠)ppm的1-BP,每天6小时,每周5天,持续105周。雄性和雌性大鼠暴露于1-BP导致大肠腺瘤和皮肤肿瘤的发生率显著增加。在雄性大鼠中,500 ppm时附睾恶性间皮瘤的发生率在统计学上显著增加,但这种常见病变的生物学意义尚不清楚。相对于同期对照组,雄性大鼠在所有浓度下胰岛腺瘤的发生率均显著增加,但在吸入研究的历史对照范围内。在雄性B6C3F1小鼠中没有1-BP致癌活性的证据;然而,雌性小鼠肺部肺泡/细支气管肿瘤的发生率显著增加。暴露于1-BP还导致大鼠和小鼠鼻子、大鼠和雄性小鼠喉部、雌性大鼠以及雄性和雌性小鼠气管以及小鼠肺部非肿瘤性病变的发生率增加。伴有Splendore Hoeppli(S-H)物质的炎性病变主要出现在暴露的雄性和雌性大鼠的鼻子和皮肤中,表明1-BP引起了免疫抑制。

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