Sodium O-ethyl dithiocarbonate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics, other

Remarks:

Assessment based on chemistry and data derived from key metabolites

Type of information:

calculation (if not (Q)SAR)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

Assessment of existing data on the substance and key metabolites formed by hydrolysis.

Cross-reference

Reason / purpose for cross-reference:

assessment report

Data source

Reference

Reference Type:

other company data

Title:

Unnamed

Year:

2022

Report date:

2022

Materials and methods

Objective of study:

absorption

distribution

excretion

metabolism

other: Hydrolysis

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Assessment of gastric hydrolysis and potential adsorption, distribution and excretion of hydrolysis products based on published data for the metabolites

The approach taken is to consider the chemical structure and class of this substance and to look at the existing data set for the substance itself and for the well-defined hydrolysis products.

Searches for similar substances have been performed using commercial directories and the ECHA web-site to help provide a weight of evidence for metabolic processes of the parent substance and the hydrolysis products

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Sodium O-ethyl dithiocarbonate

EC Number:

205-440-9

EC Name:

Sodium O-ethyl dithiocarbonate

Cas Number:

140-90-9

Molecular formula:

C3H6OS2.Na

IUPAC Name:

sodium (ethoxymethanethioyl)sulfanide

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

92.1 wt.% of sodium ethyl xanthate (CAS# 140-90-9)

Radiolabelling:

no

Test animals

Species:

other: Non-animal assessment

Results and discussion

Main ADME results

Main ADME results 1

Type:

absorption

Results:

The substance is unlikely to be directly absorbed in view of the extremely rapid hydrolysis to carbon disulphide and corresponding aliphatic alcohol

Main ADME results 2

Type:

absorption

Results:

Carbon disulphide and low molecular weight aliphatic alcohols are readily absorbed by inhalation.

Main ADME results 3

Type:

distribution

Results:

Impart to spleen and liver, mainly through blood chemistry changes, demonstrate distribution of the hydrolysis products and their metabolites

Main ADME results 4

Type:

metabolism

Results:

Low molecular weight aliphatic alcohols metabolise to carbon dioxide and water and used in metabolic processes associated with energy.

Main ADME results 5

Type:

excretion

Results:

No evidence of significant excretion of parent substance or hydrolysis products through urine

Main ADME results 6

Type:

clearance

Results:

Low molecular weight aliphatic alcohols can be excreted through air
Carbon disulphide shown to be excreted through air exchange

Toxicokinetic / pharmacokinetic studies

Details on absorption:

• The substance is unlikely to be absorbed orally in view of the extremely rapid hydrolysis to carbon disulphide and corresponding aliphatic alcohol
• The substance is considered highly irritating to skin and there is no evidence of dermal absorption, although in the presence of moisture, hydrolysis is likely. It is possible that the reported local dermal reaction is directly linked to reactivity on the skin surface.
• Inhalation exposure to the parent substance is not considered significant, although exposure to the hydrolysis products cannot be ignored.

Details on distribution in tissues:

• The metabolites are considered to be readily transported and metabolised further.
• Impact on organs including spleen and liver are consistent with carbon disulphide and alcohols.

Transfer into organs

Test no.:

#1

Transfer type:

blood/placenta barrier

Remarks:

Research into carbon disulphide demonstrates transfer across the placenta following inhalation exposure.

Observation:

slight transfer

Remarks:

Not quantified

Details on excretion:

No evidence of excretion of the parent substance or immediate hydrolysis products. Kidneys and urine appear not to be affected in any studies performed on the parent or hydrolysis products.

Metabolite characterisation studies

Metabolites identified:

yes

Remarks:

Research into thiocarbamates found radiolabelled material was found to be excreted in urine in the form of complex sulphur-containing thiocarbonates Carbon disulphide found in urine and exhaled air in animal and humans following exposure to ethyl xanthate

Details on metabolites:

Low molecular weight aliphatic alcohols metabolise to carbon dioxide and water and used in metabolic processes associated with energy.

Enzymatic activity

Enzymatic activity measured:

Not specified

Applicant's summary and conclusion

Conclusions:

Non accumulative

Executive summary:

From evidence derived from direct testing and from information obtained on the hydrolysis products, it can be concluded that:

 

• The substance is unlikely to be absorbed orally in view of the extremely rapid hydrolysis to carbon disulphide and corresponding aliphatic alcohol


• The substance is considered highly irritating to skin and there is no evidence of dermal absorption, although in the presence of moisture, hydrolysis is likely. It is possible that the reported local dermal reaction is directly linked to reactivity on the skin surface.


• A human study shows that CS₂ is absorbed through the skin from aqueous solutions.


• Inhalation exposure to the parent substance is not considered significant, although exposure to the hydrolysis products cannot be ignored.


• The metabolites are considered to be readily transported and metabolised further.


• Impact on organs including spleen and liver are consistent with carbon disulphide and alcohols.


• No evidence of excretion of the parent substance or immediate hydrolysis products. Kidneys and urine appear not to be affected in any studies performed on the parent or hydrolysis products.


• CS₂ is eliminated via exhaled air. After termination of exposure, the elimination of unaltered CS₂ via the exhaled air amounts roughly to 5 -50% of the absorbed amount.


• Unaltered CS₂ is hardly excreted via the kidneys: less than 1%


• Radiolabelled material was found to be excreted in urine in the form of complex sulphur-containing thiocarbonates suggesting incorporation of carbon disulphide into other substances


• Low molecular weight aliphatic alcohols can be excreted through air, but typically metabolise to carbon dioxide and water and used in metabolic processes associated with energy.


• The substance and the hydrolysis products and biological metabolites are not considered accumulative