SPECIES EXTRAPOLATION FOR THE 21ST CENTURY
SPECIES EXTRAPOLATION FOR THE 21ST CENTURY
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DOI：
10.1002/etc.382
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发表时间：
2011-01-01
影响因子：
4.1
通讯作者：
Wheeler, James R.
中科院分区：
文献类型：
--
作者：
Celander, Malin C.;Goldstone, Jared V.;Wheeler, James R.
安全系数用于生态风险评估，以便从实验室测试物种的毒性反应外推到代表环境中该群体的所有物种。有毒物质的反应我们强调潜在的短期和中期发展目标，以满足我们的长期愿望，即真正预测野生动物物种对有毒物质的反应的二氧化硅外推提出了考虑跨物种外推的概念方法，需要关键信息来建立证据-基于物种的外推，包括识别与生物作用模式相关的关键分子途径和调控网络和物种同源性一个案例研究，检查类固醇生成抑制后，鱼暴露于法倔唑或咪鲜胺类似的影响，每一个化合物之间的黑头呆鱼青，斑马鱼归因于类似的抑制剂药代动力学/药效学分布和细胞色素P45019 A1/2序列（CYP19A1/2）同源性建模的快速进展允许预测化学品与酶（例如CYP 19芳香酶）的相互作用，这最终将允许预测新化合物的潜在芳香酶毒性。最终将开发出预测模型，以跨物种进行推断，尽管仍需要进行大量研究。需要研究的知识缺口包括确定生活史的差异（例如生殖战略）了解组织特异性基因表达并定义代谢对毒性反应的作用，以及这些如何共同影响种间外推方法的能力Environ Toxicol Chem 2011年30 52-63（C）2010年环境和技术咨询委员会
Safety factors are used in ecological risk assessments to extrapolate from the toxic responses of laboratory test species to all species representing that group in the environment More accurate extrapolation of species responses is important Advances in understanding the mechanistic basis for toxicological responses and identifying molecular response pathways can provide a basis for extrapolation across species and in part an explanation for the variability in whole organism responses to toxicants We highlight potential short and medium term development goals to meet our long term aspiration of truly predictive in silica extrapolation across wildlife species response to toxicants A conceptual approach for considering cross species extrapolation is presented Critical information is required to establish evidence-based species extrapolation including identification of critical molecular pathways and regulatory networks that are linked to the biological mode of action and species homologies A case study is presented that examines steroidogenesis inhibition in fish after exposure to fadrozole or prochloraz Similar effects for each compound among fathead minnow medaka and zebrafish were attributed to similar inhibitor pharmacokinetic/pharmacodynamic distributions and sequences of cytochrome P45019A1/2 (CYP19A1/2) Rapid advances in homology modeling allow the prediction of interactions of chemicals with enzymes for example CYP19 aromatase which would eventually allow a prediction of potential aromatase toxicity of new compounds across a range of species Eventually predictive models will be developed to extrapolate across species although substantial research is still required Knowledge gaps requiring research include defining differences in life histories (e g reproductive strategies) understanding tissue specific gene expression and defining the role of metabolism on toxic responses and how these collectively affect the power of interspecies extrapolation methods Environ Toxicol Chem 2011 30 52-63 (C) 2010 SETAC