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Toxicological information

Basic toxicokinetics

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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

Constituent 1
Chemical structure
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 resultsopen allclose all
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
Type:
absorption
Results:
Carbon disulphide and low molecular weight aliphatic alcohols are readily absorbed by inhalation.
Type:
distribution
Results:
Impart to spleen and liver, mainly through blood chemistry changes, demonstrate distribution of the hydrolysis products and their metabolites
Type:
metabolism
Results:
Low molecular weight aliphatic alcohols metabolise to carbon dioxide and water and used in metabolic processes associated with energy.
Type:
excretion
Results:
No evidence of significant excretion of parent substance or hydrolysis products through urine
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