Inorganic lead as a developmental neurotoxicant: some basic issues and the Düsseldorf experience

The developmental neurotoxicity of inorganic lead is well established at different levels of biointegration, as well as in a variety of test models and species. Despite such knowledge some important issues are still being discussed. Work from the Düsseldorf laboratory and from the broader literature is compared for some of those issues, namely the spectrum of lead-induced neurobehavioral deficit in children, as well as issues mainly related to experimental models, namely functional recovery of deficit, developmental periods of particular vulnerability, and dose-response contingencies including the no-threshold hypothesis. Neurobehavioral studies in environmentally lead-exposed children suggest that non-IQ measures relating to visual-motor integration and to reaction performance may be more consistently associated with lead-exposure than psychometric intelligence. Experimental information is important for those issues which cannot convincingly be dealt with in human epidemiology. In animals (rats, monkeys) observations based on a broad spectrum of learning- and retention models with positive and negative reinforcement contingencies, as well as neurophysiological tests of visual and auditory processing, support the idea, that early lead-induced neurobehavioral deficit extends long into adulthood after cessation of exposure, primarily after gestational/preweaning and less clearly so following postweaning lead-exposure, that the no-threshold hypothesis based on epidemiological studies in children is only partly supported by experimental findings, and that both glutamatergic and dopaminergic transmitter systems are involved in lead-induced developmental neurotoxicity.