Bellinger David C
Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts 02115, USA.
Pediatrics. 2004 Apr;113(4 Suppl):1016-22.
Children differ from adults in the relative importance of lead sources and pathways, lead metabolism, and the toxicities expressed. The central nervous system effects of lead on children seem not to be reversible. Periods of enhanced vulnerability within childhood have not consistently been identified. The period of greatest vulnerability might be endpoint specific, perhaps accounting for the failure to identify a coherent "behavioral signature" for lead toxicity. The bases for the substantial individual variability in vulnerability to lead are uncertain, although they might include genetic polymorphisms and contextual factors. The current Centers for Disease Control and Prevention screening guideline of 10 micro g/dL is a risk management tool and should not be interpreted as a threshold for toxicity. No threshold has been identified, and some data are consistent with effects well below 10. Historically, most studies have concentrated on neurocognitive effects of lead, but higher exposures have recently been associated with morbidities such as antisocial behavior and delinquency. Studies of lead toxicity in experimental animal models are critical to the interpretation of nonexperimental human studies, particularly in addressing the likelihood that associations observed in the latter studies can be attributed to residual confounding. Animal models are also helpful in investigating the behavioral and neurobiological mechanisms of the functional deficits observed in lead-exposed humans. Studies of adults who have been exposed to lead are of limited use in understanding childhood lead toxicity because developmental and acquired lead exposure differ in terms of the maturity of the organs affected, the presumed mechanisms of toxicity, and the forms in which toxicities are expressed.
儿童在铅源和途径的相对重要性、铅代谢以及所表现出的毒性方面与成人有所不同。铅对儿童中枢神经系统的影响似乎是不可逆的。儿童期内易感性增强的时期尚未得到一致确认。最易受影响的时期可能因终点不同而异，这或许可以解释为何未能确定一致的铅毒性“行为特征”。尽管可能包括基因多态性和环境因素，但个体对铅易感性存在显著差异的原因尚不确定。美国疾病控制与预防中心目前10微克/分升的筛查指南是一种风险管理工具，不应被解释为毒性阈值。尚未确定阈值，而且一些数据表明在远低于10的水平时就有影响。从历史上看，大多数研究都集中在铅对神经认知的影响上，但最近较高的铅暴露水平与反社会行为和犯罪等疾病有关。实验动物模型中的铅毒性研究对于解释非实验性人体研究至关重要，尤其是在确定后者研究中观察到的关联是否可归因于残余混杂因素方面。动物模型也有助于研究铅暴露人群中观察到的功能缺陷的行为和神经生物学机制。由于发育性铅暴露和后天性铅暴露在受影响器官的成熟度、假定的毒性机制以及所表现出的毒性形式方面存在差异，因此对铅暴露成人的研究在理解儿童铅毒性方面的作用有限。
