Biomarker Research in Neurotoxicology: The Role of Mechanistic Studies to Bridge the Gap between the Laboratory and Epidemiological Investigations

Abstract

There is an increasing interest in the development and validation of biomarkers for use in biochemical/molecular epidemiological studies. Though the area of neurotoxicology has received much attention in the past several years, it still lags behind with regard to the development of biomarkers, particularly those of health effects and susceptibility. This review discusses several aspects of biomarker research as it relates to neurotoxic compounds and focuses on selected agents (organophosphorus insecticides, styrene, n-hexane, carbon disulfide, acrylamide), which have been the subject of a number of investigations in animals and humans. While traditional biomonitoring approaches and novel techniques (e.g., hemoglobin adducts) provide several measurements for monitoring exposure to neurotoxic chemicals, potential markers of genetic susceptibility have been seldom investigated in a neurotoxicology context. Furthermore, the complexity of the nervous system, together with the multiplicity of end points and the limited knowledge of the exact mechanism(s) of action of neurotoxicants, has led to only limited advancements in the development of biomarkers for neurotoxic effects. Significant progress in this area will depend upon an increased understanding of the cellular, biochemical, and molecular targets directly involved in neurotoxicity. Environ Health Perspect 1 04(Suppl 1): 55-67 (1996)

Biosensor Detection of Neuropathy Target Esterase in Whole Blood as a Biomarker of Exposure to Neuropathic Organophosphorus Compounds

“…The relationship between NTE inhibition/aging and the development of OPIDN has the potential to be further exploited as a biomarker (Costa, 1996;Johnson, 1982;Richardson, 1992). Inhibition of brain NTE within hours of exposure to a neuropathic OP compound predicts the potential for OPIDN to appear in susceptible animal models (e.g., adult hens) after a delay of 1 to 3 wk.…”

Pesticides and Human Health

“…Evaluations of human exposure might be performed at any stage of this process but their significant is obviously different. The best available tools are in the area of biomarkers of exposure is the of measurement of neurotoxic chemicals and their metabolites in biological fluid which provide useful and reliable indicators of exposure (Henderson et al, 1987, Costa, 1996. An ideal biomarker of exposure is chemical specific, detectable in trace quantities, inexpensive and quantitatively relatable to prior exposures.…”

Pesticides and Human Health

“…The term biomarker is used to mean biological biochemical/molecular markers, which can be measured by chemical, biochemical or molecular biological techniques (Costa, 1996). Biomarkers are usually divided in three categories : biomarkers of exposure, of effect and of susceptibility (NRC, 1987).…”