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Toxicological Sciences, Vol 50, 155-163, Copyright © 1999 by Society of Toxicology

ARTICLES

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

WM Valentine, HL Valentine, K Amarnath and V Amarnath
Department of Pathology, Vanderbilt University, Nashville, Tennessee 37232-2561, USA. bill.valentine@mcmail.vanderbilt.edu

Carbon disulfide is a neurotoxic compound used in the production of viscose rayon, and is a major decomposition product of dithiocarbamates used in industry, agriculture, and medicine. Methods used currently for assessing exposure to CS2 are limited in their ability to evaluate cumulative exposures and provide useful information for relatively short periods of time after exposure has ended. The present investigation evaluates a method for monitoring CS2 exposure that consists of cleaving the thiocarbonyl function of free 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, dose 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 range of exposure levels, were dependent upon the duration of exposure, and appeared to have an appropriate sensitivity for evaluating occupational levels of exposure. Elimination rates of dithiol reactive functions may also be dependent upon exposure duration and exhibit different kinetics for plasma and hemolysate suggesting that elimination rates may be useful for estimating cumulative exposure and intervals between exposure and sample procurement. Dithiol analysis, used in conjunction with previously established erythrocyte protein cross-linking biomarkers, may provide a means to characterize the internal dose of CS2 resulting from acute through chronic periods, and may provide insight into the level of CS2-mediated covalent protein modifications occurring within the nervous system.
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D. J. Johnson, V. Amarnath, K. Amarnath, H. Valentine, and W. M. Valentine
Characterizing the Influence of Structure and Route of Exposure on the Disposition of Dithiocarbamates Using Toluene-3,4-dithiol Analysis of Blood and Urinary Carbon Disulfide Metabolites
Toxicol. Sci., November 1, 2003; 76(1): 65 - 74.
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