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Description of key information

Key value for chemical safety assessment

Skin sensitisation

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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.
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
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.
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1977
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: non guideline, non-GLP, but with sufficient reporting detail to accept the positive result
Reason / purpose for cross-reference:
reference to same study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
A reliability check was not included; this is not necessary in light of the positive result. The test material was not characterised.
GLP compliance:
no
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
An guinea pig maximisatoin test is used. Due to animal welfare no LLNA test system was conducted.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Route:
intradermal and epicutaneous
Vehicle:
petrolatum
Concentration / amount:
Induction: 1% (intradermal), 20% (topical)
Challenge: 0.5, 1, 5, 10%
Route:
epicutaneous, occlusive
Vehicle:
petrolatum
Concentration / amount:
Induction: 1% (intradermal), 20% (topical)
Challenge: 0.5, 1, 5, 10%
No. of animals per dose:
20
Group:
positive control
Remarks on result:
not measured/tested
Group:
negative control
Remarks on result:
other: not reported
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
Reading:
other: two readings combined
Hours after challenge:
48
Group:
test chemical
Dose level:
1%
No. with + reactions:
20
Total no. in group:
20
Reading:
other: two readings combined
Hours after challenge:
48
Group:
test chemical
Dose level:
5%
No. with + reactions:
20
Total no. in group:
20
Reading:
other: two readings combined
Hours after challenge:
48
Group:
test chemical
Dose level:
10%
No. with + reactions:
20
Total no. in group:
20
Interpretation of results:
Category 1A (indication of significant skin sensitising potential) based on GHS criteria
Conclusions:
PETMP is a strong sensitizer in the GPMT
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

Skin sensitisation


Compounds with free SH groups are widely known to be skin sensitizers. PETMP has displayed a high skin sensitising potency in a GPMT with 100% sensitised animals following a 0.5% intradermal induction dose. The other compounds in this category are assumed to be of similarly high potency since they also have more than one free SH group per molecule.

Justification for classification or non-classification

PETMP shows strong skin sensitising properties. Based on the category approach Di-PETMP has to be classified as Skin Sens. 1A.