20933-67-9Relevant articles and documents
The measurement of 2-thiothiazolidine-4-carboxylic acid as an index of the in vivo release of CS2 by dithiocarbamates
Johnson,Graham,Amarnath,Amarnath,Valentine
, p. 910 - 916 (1996)
Dithiocarbamates and their disulfides are used extensively as agricultural fungicides, as accelerators of the vulcanization process of rubber in industry, and as therapeutic agents in medicine. The widespread uses of these compounds in agriculture, industry, and medicine provide many avenues of exposure to the human population. Subchronic to chronic exposures to some dithiocarbamates have resulted in the development of neuropathy in humans and experimental animals. Decomposition to CS2 presents a potential mechanism through which the toxicity of dithiocarbamates may be mediated. The purpose of this study was to determine the potential of dithiocarbamates to release CS2 in vivo. The ability to release CS2 was assessed by measuring urinary 2-thiothiazolidine-4-carboxylic acid (TTCA), which is used in industry to measure the exposure of workers to CS2. In this study, rats were housed individually in metabolic cages and given daily equimolar ip or po doses (1.5 mmol/kg) of N,N-diethyldithiocarbamate (DEDC), disulfiram (DS), N- methyldithiocarbamate (NMDC), or CS2 for 5 days, and TTCA was measured in urine collected at 24 h intervals. For each compound administered, TTCA was produced in all of the treated animals and the amount of TTCA eliminated in urine from po administration was significantly greater than that from ip administration. The relative rates of TTCA elimination in urine were DS > DEDC ? CS2 > NMDC for both routes of administration. Following administration of N,N-diethyl[13C=S]dithiocarbamate, carbon-13 enrichment at the thiocarbonyl carbon of TTCA was demonstrated using 13C NMR. Analysis of urinary TTCA proved to be useful both for establishing the in vive release of CS2 by dithiocarbamate containing compounds and for evaluating the bioavailability of CS2. The results appear especially relevant to disulfiram, which is given orally for sustained periods in the treatment of alcoholism and has resulted in the development of neuropathy in susceptible individuals.
Identification of a new urinary metabolite of carbon disulfide using an improved method for the determination of 2-thioxothiazolidine-4-carboxylic acid
Amarnath,Amarnath,Graham,Qi,Valentine,Zhang,Valentine
, p. 1277 - 1283 (2001)
A new method is reported for the analysis of 2-thioxothiazolidine-4-carboxylic acid (TTCA) in urine that is amenable to automation and provides greatly simplified chromatograms. The method comprises the addition of tetrahydro-2-thioxo-2H-1,3-thiazine-4-carboxylic acid, which is chemically similar to TTCA, as internal standard, purification on an Oasis HLB solid-phase extraction column, and analysis by HPLC with UV detection. The limit of detection for TTCA was 40 pmol/mL of urine, recovery was 79.3 ± 1.0%, and detection was linear over at least 3 orders of magnitude. In addition, during the analysis of urine samples from workers exposed to CS2, a novel urinary metabolite of CS2 was recognized. The new metabolite demonstrated a dose response, was present at approximately 30% the level of TTCA, and was characterized to be 2-thioxothiazolidin-4-ylcarbonylglycine (TTCG). Administration of TTCG to rats resulted in excretion of TTCA suggesting that TTCG is a likely precursor of TTCA. Although urinary excretion of both TTCA and TTCG resulted from administration of captan, only TTCA was detected following administration of methyl isothiocyanate. The greater selectivity of TTCG suggests that co-analysis of TTCA and TTCG in urine may aid in differentiating exposures to CS2, captan and isothiocyanates.
Method for preparing 4-carboxythiazolidine-2-thione
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, (2008/06/13)
Certain thiazolidine- and thiazine-2-thione compounds, including 4-carboxythiazolidine-2-thione and 3,4-tetramethylene-4H,5,6-dihydro-1,3-thiazine-2-thione, and methods for preparing same are disclosed.
