Mechanisms of neurotoxicity: applications to human biomonitoring

Interactions of chemicals with cerebral neurotransmitters, receptors, and second messenger systems are often accompanied by similar changes involving components in non-neural tissues. On this basis, indirect strategies have been developed to investigate neural cell function parameters by methods using accessible cells such as platelets or peripheral blood lymphocytes. The validity of certain surrogate markers of biochemical events occurring in the nervous system has been documented by recent studies in both laboratory animals and humans. Although experience with neurotoxicants is still limited, advantages and limitations of methods using peripheral blood cells as indicators of chemically-induced nervous system changes have been documented by a number of studies in psychopharmacology and biological psychiatry. Applicability of this approach in conventional population studies of environmental chemicals remains to be demonstrated. However, recent data regarding the action of low doses of mercury and organophosphates on receptors and signal transduction pathways in peripheral lymphocytes suggest useful applications of certain surrogate markers in mechanistic studies of neurotoxicity in vivo and, possibly, in assessing early biochemical effects of neurotoxicants in humans.