Hutchinson T H, Pickford D B
AstraZeneca Global Safety, Health and Environment, Brixham Environmental Laboratory, Freshwater Quarry, Brixham, Devon TQ5 8BA, UK.
Toxicology. 2002 Dec 27;181-182:383-7. doi: 10.1016/s0300-483x(02)00471-7.
Field observations of endocrine disruption (ED) in fish and other aquatic species have contributed to a global effort to establish test methods for detecting ED effects in wildlife species. For ecological risk assessment, validated tests are needed for Amphibia, fish and aquatic invertebrates, supported by a tiered approach incorporating mechanistic data and exposure characterisation. The potential for extrapolation of ED data from mammalian to aquatic species may be limited, however, due to significant physiological differences in function and regulation of hormone systems in (aquatic) lower vertebrates and invertebrates. Presently, the OECD is considering a tiered approach for ED risk assessment, incorporating a fish 14-day screening assay (Tier 1); fish development and reproduction tests (both Tier 2); and a fish full life-cycle test (Tier 3). For detection of (anti-)oestrogens, the yolk-precursor protein vitellogenin is an ideal biomarker of exposure and functionally equivalent biomarkers are being sought for (anti-)androgens in fish. At the two higher tiers, impacts are assessed in terms of apical endpoints (e.g. development, breeding behaviour and fecundity) and also gonadal histopathology. Validation of these higher tier tests should include comparison of sensitivity of biochemical and apical endpoints to optimise the value of biomarkers for predicting adverse health effects (e.g. impaired reproduction). The specificity of future OECD fish and amphibian test guidelines for endocrine disrupters needs further consideration through inclusion of mechanistic endpoints based on state-of-the-art molecular endocrinology.
对鱼类和其他水生物种内分泌干扰(ED)的实地观察推动了全球范围内建立检测野生动物物种ED效应测试方法的努力。对于生态风险评估,需要针对两栖动物、鱼类和水生无脊椎动物进行经过验证的测试,并采用结合机制数据和暴露特征描述的分级方法提供支持。然而,由于(水生)低等脊椎动物和无脊椎动物激素系统在功能和调节方面存在显著生理差异,从哺乳动物推断ED数据到水生物种的可能性可能有限。目前,经合组织正在考虑采用一种分级方法进行ED风险评估,包括鱼类14天筛选试验(第1级);鱼类发育和繁殖试验(均为第2级);以及鱼类全生命周期试验(第3级)。对于(抗)雌激素的检测,卵黄前体蛋白卵黄生成素是一种理想的暴露生物标志物,目前正在寻找鱼类中(抗)雄激素的功能等效生物标志物。在较高的两级中,根据顶端终点(如发育、繁殖行为和繁殖力)以及性腺组织病理学评估影响。这些较高层级测试的验证应包括比较生化和顶端终点的敏感性,以优化生物标志物预测不良健康影响(如繁殖受损)的价值。经合组织未来关于内分泌干扰物的鱼类和两栖动物测试指南的特异性需要通过纳入基于最新分子内分泌学的机制终点进行进一步考虑。