Biochemical approach to occupational neurotoxicology

Dose-effect and dose-response relationships in occupational neurotoxicology are rarely studied by means of biochemical methods. Some biochemical markers are however available to extrapolate from animal to man and to use in monitoring human exposures. They might be framed in three categories exploring: the delivery of chemicals to the site of action, the modifications of the molecular target induced by chemicals, the biochemical consequences of these modifications. Estimation of absorbed doses in man is possible for virtually every neurotoxic chemical by means of analytical chemistry of body fluids. Protein adducts, as measured in cellular and other blood components, might assess more closely the delivery in vivo, to the site of action. In this way also in vivo comparisons across species will be more precise. Examples include haemoglobin adducts, plasma pseudocholinesterase inhibition etc. In addition measurements of blood enzymes involved in the detoxification (e.g. A-esterases and organophosphorus esters) might contribute to assess metabolic capabilities. Once the molecular target of neurotoxicity is known, extrapolations across species are easy to make. Biochemical markers reflecting in vivo the effect at the site of action are available in very few cases, when the same target is accessible in body fluids. In such circumstances the biochemical marker represents an integrated dose/effect index. Examples include Red Blood Cell Acetylcholinesterase and Lymphocyte Neuropathy Target Esterase for acute and delayed neurotoxicity of organophosphorus esters. The understanding of the pathogenesis of a neurotoxic effect might lead to markers reflecting biochemical consequences of the interaction of the chemical with the target. The specificity of the test will dissect the chain of pathogenetic events from secondary consequences.(ABSTRACT TRUNCATED AT 250 WORDS)