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Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Justification for type of information:
Currently, do data on toxicokinetics/metabolism is available for this category. Based on structural features (e.g. sterical hindrance) it is however assumed, that ester cleavage would not be fast and complete, especially since the substances contain up to 6 ester functions, which are in addition sterically shielded. Therefore, it seems more reasonable to base the category hypothesis on structural similarity.
In addition, it is not clear yet, whether the strength of the effects vary in a predictable manner, or if no relevant variations occur. However, there are variations in structure (number of ester bonds and consequently number of free -SH groups) and physicochemical properties (especially water solubility and log Kow). It is assumed that these variations will also be reflected by variations in effect levels. Therefore, scenario 4 is the working hypothesis for the time being.
More data points within the category are needed to further strengthen the category hypothesis. The scenario selection will be re-evaluated after the studies are finished.
This currently selected scenario covers the category approach for which the read-across hypothesis is based on structural similarity. For the REACH information requirement under consideration, the property investigated in studies conducted with different source substances is used to predict the property that would be observed in a study with the target substance if it were to be conducted. Similar properties are observed for the different source substances; this may include absence of effects for every member of the category.
There are expected to be differences in strength of the effects forming a regular pattern. The prediction will be based on a worst-case approach. The read-across is a category approach based on the hypothesis that the substances in this category share structural similarities with common functional groups. This approach serves to use existing data on acute toxicity, repeated-dose toxicity, and reproductive toxicity endpoints for substances in this category.
The hypothesis corresponds to Scenario 4 of the RAAF. The substances GDMP, TMPMP, PETMP, and Di-PETMP are esters of a common acid, 3-mercaptopropionic acid (3-MPA). The key functionality of the substances within this category is the presence of free SH-groups. It is hypothesised that the strength of effects correlates with the number of SH-groups. In addition, differences in bioavailability are expected to influence the strength of effects.
For details, please refer to the category document attached to Iuclid section 13.

Data source

Materials and methods

Test material

1
Chemical structure
Reference substance name:
2-[[3-(3-mercapto-1-oxopropoxy)-2,2-bis[(3-mercapto-1-oxopropoxy)methyl]propoxy]methyl]-2-[(3-mercapto-1-oxopropoxy)methyl]propane-1,3-diyl bis[3-mercaptopropionate]
EC Number:
246-893-2
EC Name:
2-[[3-(3-mercapto-1-oxopropoxy)-2,2-bis[(3-mercapto-1-oxopropoxy)methyl]propoxy]methyl]-2-[(3-mercapto-1-oxopropoxy)methyl]propane-1,3-diyl bis[3-mercaptopropionate]
Cas Number:
25359-71-1
Molecular formula:
C28H46O13S6
IUPAC Name:
3-[(3-sulfanylpropanoyl)oxy]-2-[(3-[(3-sulfanylpropanoyl)oxy]-2,2-bis{[(3-sulfanylpropanoyl)oxy]methyl}propoxy)methyl]-2-{[(3-sulfanylpropanoyl)oxy]methyl}propyl 3-sulfanylpropanoate (non-preferred name)
Test material form:
liquid

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Group:
positive control
Remarks on result:
not measured/tested
Group:
negative control
Remarks on result:
other: not reported
Key result
Reading:
other: two readings combined
Hours after challenge:
48
Group:
test chemical
Dose level:
0.5%
No. with + reactions:
19
Total no. in group:
20
Key result
Reading:
other: two readings combined
Hours after challenge:
48
Group:
test chemical
Dose level:
1%
No. with + reactions:
20
Total no. in group:
20
Key result
Reading:
other: two readings combined
Hours after challenge:
48
Group:
test chemical
Dose level:
5%
No. with + reactions:
20
Total no. in group:
20
Key result
Reading:
other: two readings combined
Hours after challenge:
48
Group:
test chemical
Dose level:
10%
No. with + reactions:
20
Total no. in group:
20

Applicant's summary and conclusion

Interpretation of results:
Category 1A (indication of significant skin sensitising potential) based on GHS criteria
Conclusions:
Based on the category hypothesis and the presence of four thiol groups, Di-PETMP should be classified as strong skin sensitiser.