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

Endpoint summary

Additional information

Genetic toxicity of potassium (R)-2-(4-hydroxyphenoxy)propionate, (CAS 1184648-08-5) 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

Only a single study conducted according to guideline OECD 471 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. 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)-, potassium salt (2R) (CAS 1184648-08-5) 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 K+ 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), whereas the K+ counterion of the salt would be exchanged to Na+ (due to the sodium excess), which makes the two forms indistinguishable. Potassium (in the form of KCl) has been shown to cause no increase in mutation frequencies.

No mutagenic effect was observed with the acid. As a conclusion, the target substance propanoic acid, 2-(4-hydroxyphenoxy)-, potassium 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)-, potassium salt (2R) (CAS 1184648-08-5) 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 K+ 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 K+ counterion of the salt would be exchanged to Na+ (due to the sodium excess), which makes the two forms indistinguishable. Potassium (in the form of KCl) was shown to cause no chromosome aberrations up to 54 mM, twice the amount of K+ that would be introduced into the assay by a limit concentration of propanoic acid, 2-(4-hydroxyphenoxy)-, potassium salt (5000 microgram/mL, equivalent to 23 mM).

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

Short description of key information:
Ames test [(R)-2-(4-hydroxyphenoxy)-propanoic acid]: not mutagenic in bacteria (Hertner 1995)
Chromosome aberration CHO in vitro [(R)-2-(4-hydroxyphenoxy)-propanoic acid]: not clastogenic (Ogorek 1996)

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on read-across it is highly likely that potassium (R)-2-(4-hydroxy-phenoxy)-propionate 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 Directive 2001/59/EC, Annex VI, 4.2.2.3, potassium (R)-2-(4-hydroxy-phenoxy)-propionate is not considered to be classified as mutagenic.

Based on read-across it is highly liekly that potassium (R)-2-(4-hydroxy-phenoxy)-propionate 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, potassium (R)-2-(4-hydroxy-phenoxy)-propionate is not considered to be classified for germ cell mutagenicity.