Calcium sulphidoacetate

Repeated dose toxicity: dermal

Administrative data

Endpoint:

sub-chronic toxicity: dermal

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Justification for type of information:

The read-across is a category approach based on the hypothesis that compounds in this category are transformed to a common compound. This approach serves to use existing data on genotoxicity, repeated-dose toxicity, and reproductive toxicity endpoints for substances in this category.
There are no relevant variations in properties among source substances and the same potency is predicted for all target substances. This is Scenario 5 of the RAAF . Substances ATG, MEATG, KTG, CaTG, and NaTG are different inorganic salts of a common acid, thioglycolic acid (TGA; synonym: 2- mercaptoacetic acid). They dissociate rapidly in aqueous media, e.g., the test organism, to the common thioglycolate anion and to their different counter ions. The water solubility of all category members is high, except for CaTG which is only moderately soluble in water.
In the repeated-dose toxicity studies with NaTG, specific toxicity is exerted via the well-investigated inhibition of mitochondrial fatty acid beta-oxidation by the thioglycolate (2-mercaptoacetate) anion 2,3,4. Inhibition of beta-oxidation leads to increased triglycerides and decreased acetyl-CoA in liver, and subsequently reduced gluconeogenesis. The latter presents as hypoglycaemia in NaTGtreated rats, which is aggravated by fasting (Grosdidier, 2011; Report No. 37043 TSR). This mode of action (MoA) is thought to mediate the acute oral toxicity in fasted rats observed with all category members.
It can be predicted with high confidence that the target substances will display the same MoA and lead to the same effects seen with NaTG.

For more detailed information please refer to part 13.2.

Cross-reference

Reason / purpose for cross-reference:

read-across: supporting information

Materials and methods

Test material

Test material information

Constituent 1

Reference substance name:

calcium hydroxide sulfanylacetate hydrate (1:1:1:2)

Cas Number:

65208-41-5

Molecular formula:

C2 H4 O2 S.Ca.3H2O

IUPAC Name:

calcium hydroxide sulfanylacetate hydrate (1:1:1:2)

Constituent 2

Reference substance name:

CaTG

IUPAC Name:

CaTG

Test material form:

aerosol dispenser: not specified

Remarks:

migrated information: aerosol

Results and discussion

Effect levels

1

Key result

Dose descriptor:

NOAEL

Effect level:

>= 290.6 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Remarks on result:

not determinable due to absence of adverse toxic effects

Remarks:

corrected for molecular weight differences

2

Key result

Dose descriptor:

LOAEL

Effect level:

<= 18.16 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

dermal irritation

Target system / organ toxicity

Key result

Critical effects observed:

no

Applicant's summary and conclusion

Conclusions:

Based on data for NaTG, the subchronic systemic dermal NOAEL of CaTG in rats is assumed to be greater than or equal to 290 mg/kg bw/day, the highest dose tested, corrected for molecular weight differences.