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多氯联苯混合物Aroclors 1016、1242、1254和1260在斯普拉格-道利大鼠中的比较致癌性。

Comparative carcinogenicity in Sprague-Dawley rats of the polychlorinated biphenyl mixtures Aroclors 1016, 1242, 1254, and 1260.

作者信息

Mayes B A, McConnell E E, Neal B H, Brunner M J, Hamilton S B, Sullivan T M, Peters A C, Ryan M J, Toft J D, Singer A W, Brown J F, Menton R G, Moore J A

机构信息

General Electric Corporate Research & Development, Schenectady, New York, USA.

出版信息

Toxicol Sci. 1998 Jan;41(1):62-76. doi: 10.1006/toxs.1997.2397.

Abstract

A comprehensive chronic toxicity and carcinogenicity study was conducted on a series of Aroclors (1016, 1242, 1254, and 1260). Each Aroclor was assessed at multiple dietary concentrations, ranging from 25 to 200 ppm, for 24 months in male and female Sprague-Dawley rats. Liver toxicity was indicated by elevated serum enzyme activity (AST, ALT, and GGT), elevated serum cholesterol concentration, decreases in hematologic parameters (RBC, Hb, and Hct), hepatocellular hypertrophy, an increased incidence of altered hepatocellular foci, and an increased incidence of hepatocellular neoplasms (primarily adenomas). Liver toxicity was distinctly more severe in females than in males. The incidence of hepatocellular neoplasms was highly sex-dependent (females >> males), differed between Aroclor mixtures and, for females, increased with dose and followed the general incidence pattern of Aroclor 1254 > Aroclor 1260 approximately Aroclor 1242 > Aroclor 1016. A significant response (p < 0.05) in males was seen only for the high dose of Aroclor 1260. A small increase in the incidence of thyroid gland follicular cell adenomas was noted in males for Aroclors 1242, 1254, and 1260, with the incidence being uniform across dose groups and Aroclor mixtures. For females, increased survival relative to controls was observed for all Aroclor treatment groups. A significantly decreased trend in the incidence of mammary gland neoplasms compared to control was also noted for females receiving Aroclors 1242, 1254, and 1260.

摘要

对一系列多氯联苯混合物(1016、1242、1254和1260)进行了全面的慢性毒性和致癌性研究。在雄性和雌性斯普拉格-道利大鼠中,以25至200 ppm的多种膳食浓度对每种多氯联苯混合物进行了24个月的评估。肝毒性表现为血清酶活性(AST、ALT和GGT)升高、血清胆固醇浓度升高、血液学参数(RBC、Hb和Hct)降低、肝细胞肥大、肝细胞灶性改变的发生率增加以及肝细胞肿瘤(主要是腺瘤)的发生率增加。肝毒性在雌性中明显比雄性更严重。肝细胞肿瘤的发生率高度依赖性别(雌性>>雄性),在不同的多氯联苯混合物之间存在差异,并且对于雌性而言,随剂量增加,遵循多氯联苯1254>多氯联苯1260≈多氯联苯1242>多氯联苯1016的一般发生率模式。仅在高剂量的多氯联苯1260组中,雄性出现了显著反应(p<0.05)。在雄性中,多氯联苯1242、1254和1260组的甲状腺滤泡细胞腺瘤发生率有小幅增加,各剂量组和多氯联苯混合物之间的发生率一致。对于雌性,所有多氯联苯处理组的存活率相对于对照组均有所提高。在接受多氯联苯1242、1254和1260的雌性中,还观察到与对照组相比,乳腺肿瘤的发生率有显著下降趋势。

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