DETECTION OF HUMAN EXPOSURE TO ELECTROPHILIC COMPOUNDS BY ASSAY OF THIOETHER DETOXICATION PRODUCTS IN URINE

Abstract

In this paper the possibilities of the thioether or mercapturic acid assay as a method for the detection of human exposure to electrophilic agents or their precursors are critically reviewed. The thioether assay is based on the ability of many alkylating or otherwise covalently binding compounds—a class of chemicals that includes the genotoxic compounds—to react with glutathione. Often the glutathione conjugates which are formed in this reaction are excreted in the urine as (pre)mercapturic acids or other thioethers. Thioethers can be determined spectrophotometrically after alkaline hydrolysis of urine extracts. In practice the most important value of the assay appears to be its signal function. Whenever a significant increase in the excretion of thioethers is observed, this is likely to be the result of exposure to one or more suspect compounds. When unknown electrophiles, or a mixture of such compounds, are involved no quantitative conclusions can be drawn with regard to internal exposure. On the other hand, when thioether values are found, ranging within the limits of the normal distribution, it cannot be concluded that no or negligible exposures have occurred