Developmental aspects of environmental neurotoxicology: lessons from lead and polychlorinated biphenyls.

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.