Sodium O-ethyl dithiocarbonate

Endpoint summary

Additional information

Xanthates are metabolized in the human or animal bodies to carbon disulfide(CAS# 75-15-0)due to presence of the CS₂/cysteine (glutathione) conjugation product , 2-thiothiazolidine-4-carboxilic acid (TTCA) in urine of exposed workers or animals.

The lungs are the primary rout of excretion of unmetabolized carbon disulfide in humans and animals exposed by inhalation, whereas the kidneys are the primary route of excretion of carbon disulfide metabolites.

Assessment of the toxicokinetics behavior of the substance to the extent that can be derived from the relevant available information..(Donoghue A.M., Occup. Med. Vol. 48, 469-470,1998)

The expired CS₂in the exhaled air was monitored in the study of the metabolism of xanthates with humans and guinea pigs. After injection of 50 or 100mg/kg of sodium ethyl xanthate in guinea pigs up to 7% was expired as CS₂during 8 hours. The rate of elimination was dose-related, however the total percentage recovered was independent of dose after administration of sodium or

potassium xanthate. Co injection of ethyl alcohol with sodium ethyl xanthate increased rate of CS₂elimination and greater total recovery.

Study of CS₂elimination in breath after oral intake in human volunteers of 150 and 250 mg of sodium ethyl xanthate showed a maximum rate 13-57 µm/m³/h between 1-2h, complete elimination by 6h.

Sodium ethyl xanthate is metabolized to CS₂(CAS# 75-15-0) due to presence in urine of exposed workers, of the CS₂/cysteine conjugated product, 2-thiothiazolidine-4-carboxylic acid (TTCA).

The metabolite was detected in urine of a worker exposed to extensive skin contamination with the xanthate powder

and solution during the reagent mixing. An illness consisting of predominantly gastrointestinal symptoms began 20h after the exposure.

Carbon disulphide is readily absorbed by inhalation.6 Studies also indicate that carbon disulphide as a liquid, such as a solvent or aqueous solution, is absorbed through the skin. Studies in humans have shown that approximately 70–90% of carbon disulphide absorbed into the body is metabolised, with 1% excreted unchanged and the remainder exhaled. Due to its affinity for lipid-rich tissues and organs, carbon disulphide rapidly disappears from the bloodstream. In humans, carbon disulphide is metabolised to give organo-sulphur compounds such as thiourea in the urine. Studies in rats and guinea pigs have indicated that carbon disulphide is initially accumulated in the liver, brain, blood and adrenals.

Carbon disulfide is metabolized by cytochrome P-450 to an unstable oxygen intermediate which may either degrade to atomic sulfur and carbonyl sulfide or hydrolyze to form atomic sulfur and monothiocarbonate. The atomic sulfur may either bind to macromolecules or be oxidized to sulfate. The carbonyl sulfide may be converted to monothiocarbonate by carbonic anhydrase. Dithiocarbamates are the products of the reaction of CS2with amino acids. In vitro studies found that carbon disulfide reacts with amino acids in human blood, the half time of this reaction was 6,5h. Thiocarbamide has been found in the urine of exposed workers. After inhalation exposure of male human , up to 90% of the retained carbon disulfide was metabolized , the remainder was excreted by the lungs (6-10%) and in urine (about 1%) Carbon disulfide is oxidized by the liver mixed-function oxidase system to carbonyl sulfide and then undergoes further desulfurizatioin releasing elemental sulfur.

Metabolism of xanthates:

Sodium ethyl xanthate is metabolized to CS₂(CAS# 75-15-0)due to presence in urine of exposed workers, of the CS₂/cysteine conjugated product, 2-thiothiazolidine-4-carboxylic acid (TTCA). The metabolite was detected in urine of a worker exposed to extensive skin contamination with the xanthate powder and solution during the reagent mixing. An illness consisting of predominantly gastrointestinal symptoms began 20h after the exposure.(Donoghue A.M., Occup. Med. Vol. 48, 469-470,1998)

Study of CS₂elimination in breath after oral intake in human volunteers of 150 and 250 mg of sodium ethyl xanthate showed a maximum rate 13-57 µm/m³/h between 1-2h, complete elimination by 6h(Merlevede E., Peters J., 1965, Archives of the Belgian Medical Society, 23(8): 513-551).

Metabolism of carbon disulfide(CAS# 75-15-0)

Carbon disulfide is metabolized by cytochrome P-450 to an unstable oxygen intermediate which may either degrade to atomic sulfur and carbonyl sulfide or hydrolyze to form atomic sulfur and monothiocarbonate. The atomic sulfur may either bind to macromolecules or be oxidized to sulfate. The carbonyl sulfide may be converted to monothiocarbonate by carbonic anhydrase(Beauchamp R.D., et all, 1983, CRC Critical Reviews in Toxicology 11: 169-278)

Dithiocarbamates are the products of the reaction of CS₂with amino acids. In vitro studies found that carbon disulfide reacts with amino acids in human blood, the half time of this reaction was 6,5h. Thiocarbamide has been found in the urine of exposed workers(Pergal M.,et all , 1972, Arch. Environ Health 25:42-44). After inhalation exposure of male human , up to 90% of the retained carbon disulfide was metabolized , the remainder was excreted by the lungs (6-10%) and in urine (about 1%)(McKee R.W., et all, JAMA 122:217-222).

Carbon disulfide is oxidized by the liver mixed-function oxidase system to carbonyl sulfide and then undergoes further desulfurizatioin releasing elemental sulfur(Dalvi R.R. , et all, 1974, Life Sci. 14:1785-1796).

Conjugation of carbon disulfide or carbonyl sulfide with endogenous glutathione yields thiazolidine-2-thione-4-carboxylic acid (TTCA) and 2-oxythiazolidine-4-carboxylic acid, respectively(Van Doorn R., et all,1981, Arch. Environ. Health 36:289-2970). High concentration about 320mM of TTCA were detected in the urine of women exposed to approximately 32 ppm (100 mg/m³) CS₂through inhalation.