Reaction products of sodium sulphide, sulphur, carbon disulphide and potassium hydroxide

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics, other

Type of information:

other: Expert judgement

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Chemical degredation of the substance at low pH is well documented and understood.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Objective of study:

absorption

distribution

excretion

metabolism

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Expert judgement

GLP compliance:

no

Test material

Test material information

1

Reference substance name:

Reaction products of sodium sulphide, sulphur, carbon disulphide and potassium hydroxide

EC Number:

944-003-3

IUPAC Name:

Reaction products of sodium sulphide, sulphur, carbon disulphide and potassium hydroxide

Test material form:

liquid

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

The substance is expected to be rapidly absorbed from all routes of exposure, with much of this absorption attributable to the substance’s rapid degradation to carbon disulphide at physiologically-relevant pH levels. However, given the corrosive nature of the product and it’s handling only under “Strictly Controlled Conditions”, exposures are negligible.

Details on distribution in tissues:

As a consequence of exposure and physiological pH, the substance will be rapidly converted to carbon disulphide and absorbed. Carbon disulphide is lipophilic and thus expected to partition into fatty tissues, namely the brain, kidney, and liver initially. In addition, following inhalation exposures, radiolabeled carbon disulphide was found to be present in the fatty tissues within minutes to a few hours after exposure. In other non-fatty tissues, carbon disulphide concentrations approached steady state within 4-5 hrs of exposure and rapid distribution of carbon disulphide to embryonic and fetal tissues were noted after exposure to pregnant mice.

Details on excretion:

The kidneys are the primary route of excretion of carbon disulfide metabolites. Conjugation of carbon disulfide or carbonyl sulfide with endogenous glutathione results in formation of thiozolidine-2-thione-4-carboxylic acid and 2-oxythiazolidine-4-carboxylic acid, respectively, which are excreted in the urine. The unmetabolized carbon disulfide is excreted unchanged in the breath, and small amounts (<1%) have been detected in the urine. In a study conducted on humans, it was demonstrated that carbon disulfide levels in the exhaled breath decreased rapidly on cessation of exposure. The excretion by the lung accounted for 10-30% of the absorbed carbon disulfide. Less than 1% was excreted unchanged in the urine. The remaining 70-90% of the dose was metabolized. After dermal exposure in rabbits, only 3% of carbon disulfide was expired via the lungs.

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

The biotransformation and metabolism pathway of carbon disulfide in humans is not completely known, however major parts have been deduced through studies in humans as well as in laboratory animals. Carbon disulfide is either metabolized by cytochrome P-450 to an unstable oxygen intermediate (which proceeds to form smaller carbon-sulfur species) or is conjugated by glutathione (in advance of excretion), or is reacted with amino acids (to form dithiocarbamates prior to excretion). Regardless of pathway, metabolism appears to be rapid, occurring within minutes to a few hours after exposure. Metabolites include: sulfur, carbonyl sulphide, monothiocarbonate, carbon dioxide, hydrogen sulphide, thiozolidine-2-thione¬ 4-carboxylic acid, and 2-oxythiazolidine-4-carboxylic acid.

Applicant's summary and conclusion

Conclusions:

Based on available information, the substance is expected to be readily absorbed, distributed, metabolized, and rapidly excreted and, thus, is expected to have a low potential for bioaccumulation.

Executive summary:

The substance is the reaction products of sodium sulphide, sulphur, carbon disulphide and potassium hydroxide and is produced and placed on the market as 92% water and 8% inorganics. The inorganics are dominated by tetrathiocarbonate and trithiocarbonate anions, which are the focus of this review. These substances are well known to rapidly degrade to carbon disulphide at pH <11. As such, the absorption, distribution, metabolism, and excretion of the substance is expected to follow that of carbon disulphide and its metabolites. Based on available information, the substance is expected to be readily absorbed, distributed, metabolized, and rapidly excreted and, thus, is expected to have a low potential for bioaccumulation.