Fatalities from work related injury or disease are on the decline, while nonfatal injuries or illnesses are increasing at an alarming rate. The U.S. Public Health Service targets a 22% reduction in such incidents by the year 2,000. In chemical industries most such illnesses result from exposure to toxic industrial chemicals; this problem can be ameliorated by minimizing the exposure and using sensitive surveillance procedures. This research seeks to develop newer and more sensitive methods to measure exposure and its effect(s). Occupational exposure to chloroethenes (also known as chloroethylenes) results in such immunological diseases/syndromes as scleroderma, systemic lupus erythematosus (SLE) and Goodpasture's Syndrome. Exposure to these chemicals becomes apparent only when adverse outcome or disease symptoms become evident, and irreversible damage has probably already occurred. Therefore, the focus of this demonstration project is to develop mechanistically based biological markers of exposure to chloroethenes. These compounds bind to proteins. The PI will use this property to develop methods to measure adduct(s) of chloroethene(s) with such circulatory protein(s) as hemoglobin and /or albumin. The covalently bound macromolecule can act as immunogen(s) and elicit the production of chloroethene-specific antibodies which will be quantitated by ELISA. The early detection of these chemical-specific antibodies can alert at-risk individuals to the potential of developing autoimmune disease(s), and therefore, will provide an early opportunity for intervention via preventive or therapeutic strategies. Autoimmunity-prone mice MRL +/+ will be used as animal models. The model compound, will be tetrachloroethane, which is used extensively in the dry cleaning industry, where a significant population is exposed to this chemical on a regular basis. The methods thus developed from their work should lead to new approaches for biomonitoring and medical surveillance of the occupationally exposed population, as well as for risk assessment.
| Green, S M; Khan, M F; Kaphalia, B S et al. (2001) Immunohistochemical localization of trichloroacylated protein adducts in tetrachloroethene-treated mice. J Toxicol Environ Health A 63:145-57 |
