Toluene-3,4-dithiol analysis of blood for assessing carbon disulfide exposure

Carbon disulfide is a neurotoxic compound used in the production of viscose rayon, and is a major decomposition product of dithiocarbamates used in in dustry, agriculture, and medicine. Methods used currently for assessing exp osure to CS2 are limited in their ability to evaluate cumulative exposures and provide useful information for relatively short periods of time after e xposure has ended. The present investigation evaluates a method for monitor ing CS2 exposure that consists of cleaving the thiocarbonyl function of fre e CS2 or certain CS2-generated modifications on proteins using toluene-3,4- dithiol. The resulting toluene trithiocarbonate product is then quantified using reverse-phase high-performance liquid chromatography. The sensitivity , those response, kinetics and specificity of this biomarker in blood were examined in rats administered CS2 by inhalation, intraperitoneal injection, or gavage for acute through subchronic periods. Dithiol reactive functions in plasma and hemolysate demonstrated a linear dose response over a wide r ange of exposure levels, were dependent upon the duration of exposure, and appeared to have an appropriate sensitivity for evaluating occupational lev els of exposure. Elimination rates of dithiol reactive functions may also b e dependent upon exposure duration and exhibit different kinetics for plasm a and hemolysate suggesting that elimination rates may be useful for estima ting cumulative exposure and intervals between exposure and sample procurem ent. Dithiol analysis, used in conjunction with previously established eryt hrocyte protein crosslinking biomarkers, may provide a means to characteriz e the internal dose of CS2 resulting from acute through chronic periods, an d may provide insight into the level of CS2-mediated covalent protein modif ications occurring within the nervous system.