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Diss Factsheets



Category name:
3-MPA family, polyol esters

Justifications and discussions

Category definition:
This category includes esters of 3-MPA with poly-alcohols with different numbers of alcohol functions and accordingly, different numbers (ranging from two to six) of 3-MPA moieties linked to those hydroxyl groups.
The members of this category share a common chemical reactivity, metabolism pathways and biological properties that enable interpolation and read across between category members for systemic toxicity endpoints.
Category description:
The category members have a similar core structure comprised of a poly-alcohol which is either ethylenglycol, trimethylolpropane (TMP), pentaerythritol (PET), or di-pentaerythritol (Di-PET). The same structural element, 3-mercaptopropionic acid, is linked
Category rationale:
Currently, no 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 (refer to Table 8). 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 skin/eye irritation, skin sensitisation, genetic toxicity, 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.

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