Functional aspects of developmental toxicity of polyhalogenated aromatic hydrocarbons in experimental animals and human infants

Abraham Brouwer , Ulf G. Ahlborg , Martin Van den Berg , Linda S. Birnbaum , E. Ruud Boersma , Bart Bosveld , Michael S. Denison , L. Earl Gray , Lars Hagmar , Edel Holene , Marcel Huisman , Sandra W. Jacobson , Joseph L. Jacobson , Corine Koopman-Esseboom , Janna G. Koppe , Beverly M. Kulig , Dennis C. Morse , Gina Muckle , Richard E. Peterson , Pieter J.J. Sauer , Gerhard Winneke
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引用次数: 282

Abstract

A scientific evaluation was made of functionalspects of developmental toxicity of polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) in experimental animals and in human infants. Persistent neurobehavioral, reproductive and endocrine alterations were observed in experimental animals, following in utero and lactational exposure to PCBs, PCDDs and PCDFs. The lowest observable adverse effect levels (LOAELs) for developmental neurobehavioral and reproduction endpoints, based on bodyen of TCDD-toxic equivalents (TEQs) in animals, are within the range of current background human body burdens. Relatively subtle adverse effects on neurobehavioral development and thyroid hormone alterations have also been observed in infants and children exposed to background levels. Exclusive use of the toxic equivalency factor (TEF) approach may underestimate the risk of neurodevelopmental effects, because both Ah receptor dependent and independent mechanisms may be involved in these effects. The use of marker congeners and/or bioassays based on Ah receptor mediated mechanisms are rapid, low cost pre-screening alternatives for expensive and time consuming gas chromatographic-mass spectrometric analysis.

多卤芳烃对实验动物和人类婴儿发育毒性的功能方面
对多氯联苯(PCBs)、多氯二苯并对二恶英(PCDDs)和多氯二苯并呋喃(PCDFs)在实验动物和人类婴儿发育毒性的功能方面进行了科学评价。实验动物在子宫和哺乳期暴露于多氯联苯、多氯联苯和多氯联苯后,观察到持续的神经行为、生殖和内分泌改变。基于动物体内tcdd毒性当量(teq),对发育神经行为和生殖终点可观察到的最低不良影响水平(loels)在当前人体背景负荷范围内。在暴露于背景水平的婴儿和儿童中,也观察到对神经行为发育和甲状腺激素改变的相对微妙的不良影响。单独使用毒性等效因子(TEF)方法可能会低估神经发育影响的风险,因为Ah受体依赖性和独立机制都可能涉及这些影响。使用标记同源物和/或基于Ah受体介导机制的生物测定是快速,低成本的预筛选替代昂贵且耗时的气相色谱-质谱分析。
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