Propanoic acid, 2-(4-hydroxyphenoxy)-, sodium salt (1:1), (2R)-

Endpoint summary

Additional information

Genetic toxicity of sodium (2R)-2-(4-hydroxyphenoxy)propanoate, (CAS 133647-88-8) was determined by read-across from genetic toxicity studies conducted with the free acid, namely (R)-2-(4-hydroxyphenoxy)propanoic acid (CAS 94050-90 -5).

Bacterial reverse mutation (Ames test): negative

Two studies conducted according to guidelines and under GLP are available for the source substance (R)-2-(4-hydroxyphenoxy)-propanoic acid (CAS 94050-90-5). The key study (Hertner 1995) is considered to be complete, reliable and adequate for the purposes of risk assessment, classification and labelling. No increase in the incidence of either histidine- or tryptophan-prototrophic mutants was elicited in strains S. typhimurium TA 98, TA 100, TA 102, TA1535, TA1537 and E. coli WP2 uvrA, with and without metabolic activation, i.e. the source substance and its metabolites did not induce gene mutations.

The bacterial mutagenicity of the target substance propanoic acid, 2-(4-hydroxyphenoxy)-, sodium salt (2R) (CAS 133647-88-8) is determined by read-across from the Ames test with the free acid. The analogue approach is based on the facts that source and target contain the identical molecular structure and the same functional groups (except the Na+ counterion), and that they form a pH-dependent equilibrium. In the assay mixture (top agar), the free acid is neutralized to the Na+ salt (by the buffer, with a possible pH decrease to 6.4), which makes the two forms indistinguishable. The additional sodium introduced via the sodium salt is in fact negligible compared to the overall sodium content in the assay.

No mutagenic effect was observed with the acid. As a conclusion, the target substance propanoic acid, 2-(4-hydroxyphenoxy)-, sodium salt (2R) is also unlikely to be a bacterial mutagen in the Ames test.

Cytogenetic test (chromosome aberration): negative

Only a single study (cytogenetic test on Chinese hamster ovary cells in vitro) conducted according to guideline OECD 473 and under GLP is available for the source substance (R)-2-(4-hydroxyphenoxy)-propanoic acid (CAS 94050-90-5). The study is considered to be relevant, reliable (Klimisch 1) and adequate for the purposes of risk assessment, classification and labelling. With and without metabolic activation, no increase in specific chromosomal aberrations, i.e. no evidence of clastogenic effects, was observed with the source substance.

The clastogenic potential of the target substance propanoic acid, 2-(4-hydroxyphenoxy)-, sodium salt (2R) (CAS 133647-88-8) is determined by read-across from the chromosome aberration test with the free acid. The analogue approach is based on the facts that source and target contain the identical molecular structure and the same functional groups (except the Na+ counterion), and that they form a pH-dependent equilibrium. In the test, the free acid was intentionally neutralized to the Na+ salt (by addition of NaOH). Whereas the Na+ salt would have a negigible effect on pH an additional amount of Na+ would be introduced into the incubation medium which is likely to be in the same range as the sodium introduced above during the neutralization of the free acid.

No clastogenic effect was observed with the acid. As a conclusion, the target substance propanoic acid, 2-(4-hydroxyphenoxy)-, sodium salt (2R) is also unlikely to be a clastogen in the CHO chromosome aberration test.

Justification for selection of genetic toxicity endpoint
Both available study types provide valid information on genotoxicity and chromosome aberration.

Short description of key information:
Negative, Ames test, [(R)-2-(4-hydroxyphenoxy)-propanoic acid], OECD 471, Hertner 1995
Negative, Ames test, [(R)-2-(4-hydroxyphenoxy)-propanoic acid], OECD 471, Callander 1984
Negative, Chromosome aberration, [(R)-2-(4-hydroxyphenoxy)-propanoic acid], OECD 473, Ogorek 1996

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on read-across it is highly likely that sodium (2R)-2-(4-hydroxyphenoxy)propanoate demonstrates negative results both in an in vitro bacterial gene mutation tests (Ames) and in an in vitro chromosome aberration test with mammalian cells. As a result, and in accordance with Regulation (EC) No. 1272/2008, Annex I, Part 3, 3.5.2, sodium (2R)-2-(4-hydroxyphenoxy)propanoate is not considered to be classified for germ cell mutagenicity.

The conclusion given above only takes into consideration the properties of the constituent in this mono constituent substance. As indicated in the composition under section 1.2 one of the impurities is relevant for C&L of the substance. This is finally included in the Classification and Labelling section 2 where necessary based on the typical concentration value given and the harmonized classification and labelling that is available for this impurity under CLP/GHS.