Division of Neurobehavioral Toxicology, Medical Institute of Environmental Hygiene, Heinrich-Heine-Universität, Auf'm Hennekamp 50, D-40225, Düsseldorf, Germany.
J Neurol Sci. 2011 Sep 15;308(1-2):9-15. doi: 10.1016/j.jns.2011.05.020. Epub 2011 Jun 15.
The particular vulnerability of the developing nervous system for low-level exposure to chemicals is well established. It has been argued that some degree of developmental neurotoxicity was found for a large number of industrial chemicals. However, for only few of these, namely inorganic lead, arsenic, organic mercury and polychlorinated biphenyls (PCBs), human evidence is available to suggest that these may cause neurodevelopmental adversity and may, thus, be involved in contributing to neurodevelopmental disorders like autism, attention-deficit disorder, mental retardation or cerebral palsy. The focus of this overview is on PCBs and inorganic lead as developmental neurotoxicants at environmental levels of exposure. The adverse effects of inorganic lead on the developing brain have long been studied, and much emphasis has been on subtle degrees of mental retardation in terms of intelligence (IQ). The evidence is consistent, but the effect sizes are typically small. Research interest has also been devoted to studying aspects of "attention-deficit hyperactivity disorder" (ADHD) in children in relation to environmental exposure to lead in both cross-sectional and case-control studies. More recently, we have also studied core elements of ADHD according to ICD-10 and DSM-IV in relation to environmental exposure to lead, mercury and aluminum in asymptomatic school children in Romania. Both, performance measures (several attention tasks) and questionnaire-based behavior ratings from parents and teachers showed that lead, but not Hg or Al, was consistently and adversely associated with core elements of ADHD. These findings in asymptomatic children nicely fit into the overall pattern of observations and suggest that, apart from genetic influences, low-level exposure to lead contributes to this neurodevelopmental disorder. Polychlorinated biphenyls (PCBs) are persistent organic pollutants with lipophilic properties. Due to their persistence, they are still present in environmental media at potentially harmful concentrations, although production and use of PCBs was already banned in the early 1980s. Several prospective cohort studies-including our Düsseldorf study-have demonstrated that pre- and early postnatal exposure to PCBs is associated with deficit or retardation of mental and/or motor development, even after adjusting for maternal intelligence and developmental effects of the quality of the home environment. The pathophysiology is still unclear, although interference with thyroid metabolism during brain development is being discussed. Based on these reviews, three aspects, namely pre- vs. postnatal impact, effect scaling for comparative purposes, and integration of neurobehavioral findings into clinical and neuroscience contexts, are outlined as lessons learned from neurodevelopmental observations in children environmentally exposed to lead or PCBs.
发育中的神经系统容易受到低水平化学物质暴露的影响，这一点已得到充分证实。有观点认为，大量工业化学品都具有一定程度的发育神经毒性。然而，仅有少数几种化学品，即无机铅、砷、有机汞和多氯联苯（PCBs），有人类证据表明它们可能导致神经发育不良，并可能导致自闭症、注意力缺陷障碍、智力迟钝或脑瘫等神经发育障碍。本综述的重点是环境暴露水平下的 PCBs 和无机铅作为发育神经毒物。无机铅对发育中大脑的不良影响早已被研究，并且重点是智力方面的轻微智力迟钝。证据是一致的，但效应大小通常较小。研究兴趣还致力于研究儿童在横断面和病例对照研究中接触环境铅时的“注意力缺陷多动障碍”（ADHD）的各个方面。最近，我们还根据 ICD-10 和 DSM-IV 研究了罗马尼亚无症状学龄儿童的 ADHD 核心要素与环境铅、汞和铝暴露之间的关系。家长和教师的行为问卷调查以及表现测量（多项注意力任务）均表明，铅而非汞或铝，与 ADHD 的核心要素呈一致且不利的关联。这些在无症状儿童中的发现很好地符合整体观察模式，并表明，除了遗传影响外，低水平的铅暴露也会导致这种神经发育障碍。多氯联苯（PCBs）是具有亲脂性的持久性有机污染物。由于其持久性，尽管早在 20 世纪 80 年代初就已禁止生产和使用 PCBs，但它们仍以潜在有害的浓度存在于环境介质中。几项前瞻性队列研究——包括我们的杜塞尔多夫研究——表明，产前和产后早期接触 PCBs 与精神和/或运动发育迟缓或缺陷有关，即使在调整了母亲智力和家庭环境发育影响后也是如此。尽管正在讨论脑发育过程中甲状腺代谢的干扰，但病理生理学仍不清楚。基于这些综述，从儿童环境暴露于铅或 PCB 中观察到的神经发育情况中，我们总结了三个方面，即产前与产后的影响、用于比较目的的效应规模以及将神经行为研究结果整合到临床和神经科学背景中。
