IMMUNOCHEMICAL METHODS TO MONITOR TOXIC SUBSTANCES IN HUMANS AND OTHER SPECIES

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For evaluating the risk posed by hazardous substances in humans and the environment, a central problem is analysis. Immunoassays are finding their place among more established methods for measurement of toxic materials in the environment and have a predominant role in human monitoring. Advantages of immunoassays include speed of analysis, cost-effectiveness, sensitivity, specificity, applicability to a wide variety of compounds and adaptability to laboratory or field situations. This proposal has three objectives. The first is to develop rapid, inexpensive assays for hazardous substances and environmental degradation products. Lack of such assays affects site evaluation and limits the development of good models for groundwater movement, human exposure, and research on remediation systems. Several compound classes have been identified for assay development in this proposal. Triazine herbicides are good indicators of agricultural contamination. Assay development for this class of compounds will continue our targets such as prometon, the 2- hydroxy and mono and didealkylated metabolites in order to develop a battery of assays for parents and metabolites. 2,3,7,8- Tetrachlorodibenzodioxin is a compound whose impact in human and environmental health is still subject to debate and is a prime example of a compound for which analysis costs are extremely high. Developing specific immunoassays will be a challenge to the synthetic chemist. In such as lead and cadmium have also been targeted. Levels of contamination have not even begun to be addressed due to the unique problems in sample preparation and analysis. The second objective is to develop assays to assess human exposure and effect. Development of these assays is intimately tied to an understanding of the mechanistic basis of toxicity and also will provide new reagents for probing such fundamental mechanisms. In collaboration with other workers markers for and the mechanisms of cellular toxicity will be addressed. Specifically proposed targets include triazine mercapturates (urinary metabolites of triazines), nitrophenols (metabolites of some industrial intermediates, explosives and organophosphate insecticides), naphthalene mercapturate (urinary metabolites of naphthalene), relaxin (an indicator of occult pregnancy) and the 14K Clara cell protein (an example of a target protein that may be specifically involved in cellular toxicity). Our third objective is the development of new immunochemical technologies for use in the environmental field. Techniques will be developed to interface immunoassay with classical analytical procedures such as utilizing antibodies for affinity separation and cleanup or as detectors following classical cleanup (i.e. supercritical fluid extraction). Use of expert systems in the implementation of immunochemical detection into environmental chemistry will be evaluated. Statistical consideration for analysis of optimum assay strategies, low analyte concentration and multianalyte problems will be developed.