Use of the laboratory rat as a model in endocrine disruptor screening and testing

被引：42

作者：

Gray, LE ^{[1
]}

Wilson, V ^{[1
]}

Noriega, N ^{[1
]}

Lambright, C ^{[1
]}

Furr, J ^{[1
]}

Stoker, TE ^{[1
]}

Laws, SC ^{[1
]}

Goldman, J ^{[1
]}

Cooper, RL ^{[1
]}

Foster, PMD ^{[1
]}

机构：

[1] US EPA, Natl Hlth & Environm Effects Res Lab, Reprod Toxicol Div, Endocrinol Branch, Res Triangle Pk, NC 27711 USA

来源：

ILAR JOURNAL | 2004年 / 45卷 / 04期

关键词：

androgens; antiandrogens; endocrine disruption; estrogens;

D O I：

10.1093/ilar.45.4.425

中图分类号：

S85 [动物医学（兽医学）];

学科分类号：

0906 ;

摘要：

The screening and testing program the US Environmental Protection Agency (EPA) is Currently developing to detect endocrine-disrupting chemicals (EDCs) is described. EDCs have been shown to alter the following activities: hypothalamic-pituitary-gonadal (HPG) function; estrogen, androgen , and thyroid hormone synthesis; and androgen and estrogen receptor-mediated effects in mammals and other animals. The value and limitations of mammalian in vivo assays are described that involve the use of the laboratory rat, the EPA Endocrine Disruptor Screening and Testing Advisory Committee species of choice. The discussion includes the evaluation of high-priority chemicals positive in the Tier I Screening (T1S) battery, and of subsequent testing, in the Tier 2 (T2) battery, with additional short-term screening assays proposed for use in T1.5 to eliminate any uncertainty about TIS results. Descriptions include the in vivo uterotropic assay, which detects estrogens and antiestrogens the pubertal female assay, which assesses steroidogenesis, antithyroid activity, antiestrogenicity, and HPG function: and the Hershberger assay, which detects the weight of androgen-dependent tissues in castrate-immature-male rats (antiandrogens). Of the several alternative mammalian in vivo assays proposed, a short-term pubertal male rat assay appears most promising for inclusion in T1 or T1.5. An additional in utero-lactational screening protocol is being evaluated. but appears to be better Suited for T1.5 or T2 due to the size, complexity, and duration of the assay. The adult intact male assay, also proposed as an alternative for T1, attempts to identify EDCs in a hormonal battery, but has limited value as a screen due to lack of sensitivity and specificity. For Tier 2 testing, the number of endocrine-sensitive endpoints and offspring (F1) examined in multi-generational tests must be thoughtfully expanded for EDCs on a mode-of-action-specific basis, with consideration given to tailoring T2 based on the results of T1S.

引用

页码：425 / 437

页数：13

共 66 条

[1] Concept evaluation: An assay for receptor-mediated and biochemical antiestrogens using pubertal rats [J].