The low-dose issue and stochastic responses to endocrine disruptors
The low-dose issue and stochastic responses to endocrine disruptors
复制标题
内分泌干扰物的低剂量问题和随机反应
作者：
Hirabayashi Y;Inoue T
内分泌干扰物的影响，特别是低剂量问题，涉及跨学科科学。因此，在过去，这些主题已在毒理学领域广泛发表。由于生物学的最新发展，包括全基因组阅读程序，低剂量问题的潜在机制已得到澄清。已发现这些机制涉及内分泌干扰物诱导的随机和概率性受体介导的不良反应。低剂量的内分泌干扰化学品所引起的影响仍然存在争议，其潜在机制仍然知之甚少。三个独立的因素，每一个都是最近才发现的，在毒理学研究史上从未遇到过，与所谓的“低剂量问题”有关。首先，毒理学风险仅通过从高剂量效应的不良表型外推来估计，因此无法提供在具有足够灵敏度的实验范式下在正确时间观察到的低剂量效应的可靠信息。第二，毒性是基于体内平衡调节的紊乱，这是毒理学中一个很大程度上未探索的领域。第三，毒性是基于随机和概率的异生物素反应，这是一个新的毒理学领域，专门与低剂量和不太频繁的事件有关。为了解决低剂量问题，无论是它引起的影响，还是在低剂量下观察到的影响是否应被视为“不良”-或两者兼而有之，这些因素都需要得到解决。版权所有© 2010约翰威利父子有限公司.
The impact of endocrine disruptors, and specifically the low‐dose issue, involves interdisciplinary sciences. Thus, in the past these topics have been published widely in the toxicology area. Owing to recent developments in biology, including the whole‐genome reading program, the mechanisms underlying the low‐dose issue have been clarified. These mechanisms have been found to involve stochastic and probabilistic receptor‐mediated adverse effects induced by endocrine disruptors. The effects thought to be induced by low doses of endocrine‐disrupting chemicals remain disputed, and the underlying mechanisms remain poorly understood. Three independent factors, each only recently identified and never before encountered in the history of toxicological studies, are associated with what is termed the ‘low‐dose issue’. First, toxicological risk has been estimated only by extrapolation of adverse phenotypes from high‐dose effects and thus provides no reliable information on low‐dose effects observed at the right time under experimental paradigm with sufficient sensitivity. Second, toxicity is based on disturbances of homeostatic regulation, a largely unexplored area in toxicology. Third, toxicity is based on stochastic and probabilistic xenobiotic response, a new field of toxicology that is specifically linked to low‐dose and less‐frequent events. To resolve the low‐dose issue whether it causes effects or whether effects observed at low‐doses should be considered ‘adverse’ – or both, each of these factors needs to be addressed. Copyright © 2010 John Wiley & Sons, Ltd.