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Toxicological information

Carcinogenicity

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Description of key information

No data is available on the carcinogenic potential of MeaTG by the oral and inhalation routes.

In a non-standard study by dermal route, sodium mercaptoacetate was administered to mice as 0, 1.0 and 2.0% solutions, until all animals died. Differences in the life span and the incidence of neoplasms between experimental and negative control mice were not statistically significant.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no study available

Carcinogenicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Carcinogenicity: via dermal route

Link to relevant study records
Reference
Endpoint:
carcinogenicity: dermal
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Justification for type of information:
HYPOTHESIS FOR THE CATEGORY APPROACH
The substances of this category have similar toxicological properties because:
- all substances are small organic molecules;
- they share structural similarities with common functional groups: one or more thiol and/or thioether group(s) and carboxylic acid (as free acid, salt or ester);
- the metabolism (i.e. ester hydrolysis) leads to comparable products (sulfur-containing core structure in its acid form and alcohols of differing chains lengths)

The substances were assigned to subgroups according to their main structural features (see Table 1); further justification for subgrouping based on toxicological properties is given below:
- TGA family: Thioglycolic acid, its salts and esters
- 3-MPA family: 3-Mercaptopropionic acid, its salts and esters
- TLA family: Thiolactic acid and its salts
- Intramolecular-S family: Thiodiglycolic acid or Dithiodiglycolic acid and its esters, Thiodipropionic acid or Dithiodipropionic acid and its esters, Methylene bis(butyl thioglycolate)
- Mercaptanes: Thioglycerol, Bis(2-mercaptoethyl) sulfide, 4-Mercaptomethyl-3,6-dithia-1,8-octanedithiol

The acids and salts will dissociate to the respective Thioglycolate or 3-Mercaptopropionate or Thiolactate and the corresponding cation. In case of the esters, the metabolism expected to occur is ester hydrolysis resulting in the corresponding acid and alcohol.

It was demonstrated, that PETMP and 3-MPA strongly bind to plasma proteins (e.g. via S-S bond to cysteine) in vitro, which is well known for substances containing free SH-groups (Bruno Bock, 2014). Strong protein binding is also expected to occur with the other substances assessed within this paper. The members of the intramolecular-S family are an exception, as they do not contain free SH-groups – protein binding may be less relevant for this family.

This read-across hypothesis corresponds to scenario 4 of the Read-Across Assessment Framework (RAAF), ECHA, March 2017 - different compounds have qualitatively similar properties - of the read-across assessment framework i.e. variations in the properties are observed among the source substances; the prediction is based on a worst-case approach.

Overall, based on close structural similarities, a read-across from the existing repeated dose and reproduction toxicity studies is considered as an appropriate adaptation to the standard information requirements of the REACH Regulation in accordance with the provisions of Annex XI, 1.5 of the REACH Regulation.

A detailed justification for this category approach is attached to Iuclid section 13.
Reason / purpose:
read-across source
Reason / purpose:
read-across: supporting information
Key result
Dose descriptor:
NOAEL
Effect level:
13.3 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Remarks on result:
not determinable due to absence of adverse toxic effects
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
13.3 mg/kg bw/day
Study duration:
chronic
Species:
mouse

Additional information

No carcinogenicity data is available on mercaptoacetic acid and its salts by the inhalation or oral routes. The information on the carcinogenicity potential of mercaptoacetic acid and its salts is limited to a study in mice by chronic cutaneous application of sodium mercaptoacetate.

The carcinogenicity of sodium mercaptoacetate was evaluated using 94 Swiss female mice (7 weeks old) from the Eppley colony. 0.02 ml of a 1.0 and 2.0 % solutions of sodium mercaptoacetate in acetone (equivalent to dose levels of 6.6 and 13.3 mg/kg bw) were applied twice per week to the shaved skin (interscapular region) of each of the 49 or 45 mice, respectively. Ninety-three mice served as negative controls. Positive control groups, 40 mice, were treated with 7,12-dimethylbenz-[a]-anthracene. None of the experimental or control mice survived beyond week 120 of treatment. Infectious diseases, such as pneumonia and hepatitis, occurred in a small number of animals, resulting in an increased number of deaths. Large numbers of neoplasms were observed in treated and negative control mice: lymphomas, pulmonary adenomas, hepatic hemangiomas, ovarian neoplasms, and dermal fibromas. Epidermal neoplasms were not observed. Differences in the incidence of neoplasms between experimental and negative control mice were not statistically significant. No significant decrease in the life span of mice in experimental groups was observed. The authors concluded that sodium mercaptoacetate was not carcinogenic (Stenback et al., 1977).

Justification for classification or non-classification

According to the available carcinogenicity data, no classification is warranted for mercaptoacetic acid and its salts.