Phenethyl phenylacetate

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Ames test: The mutagenicity of the test substance was studied in an Ames test with five strains of Salmonella typhimurium (TA1535, TA1537, TA98, TA100, and TA102) according to OECD guideline 471. The test item was not mutagenic to Salmonella typhimurium strains in the presence and absence of a metabolizing system.
MN in vitro: The potential of the test item to induce micronuclei in human lymphocytes in vitro was assessed in an OECD guideline study. The test substance did not induce micronuclei.
HPRT: The study was performed according to OECD guideline 476 to investigate the potential of the test item to induce gene mutations at the HPRT locus. No mutagenic potential was observerd during the study.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Ames test

The mutagenicity of the test substance was studied with five mutant strains of Salmonella typhimurium (TA1535, TA1537, TA98, TA100, and TA102) according to OECD guideline 471 and EU method B13/14. The investigations were carried using the standard plate incorporation assay with and without liver homogenate (S9) from Aroclor 1254 pretreated male rats as metabolic activation system. The test substance was dissolved in DMSO and tested in concentrations of 15 to 5000 µg per plate in the presence and of 1.5 to 5000 µg per plate in the absence of S9. In the absence of S9-mix the test substance was bacteriotoxic towards the strain TA102 at 150 μg/plate, towards the strains TA1537 and TA100 at 500 μg/plate, towards the strain TA98 at 1500 µg/plate, and towards the strain TA1535 at 5000 µg/plate. In the presence of S9-mix the test substance was bacteriotoxic towards the strain TA100 at 1500 µg/plate and towards the strain TA102 at 5000 µg/plate. In the concentration range investigated, the test substance did not induce a significant increase in the mutation frequency of the tester strains in the presence and absence of a metabolic activation system. In conclusion, these results indicate that under the experimental conditions described, was not mutagenic to Salmonella typhimurium strains TA1535, TA1537, TA98, TA100, and TA102 in the presence and absence of a metabolizing system.

Micronucleus test in vitro

The test item, dissolved in DMSO, was assessed for its potential to induce micronuclei in human lymphocytes in vitro in two independent experiments. In each experimental group two parallel cultures were analysed. Per culture 1000 binucleated cells were evaluated for cytogenetic damage. The highest applied concentration in this study (2000.0 μg/mL of the test item) was chosen with respect to the current OECD Guideline 487. In both cytogenetic experiments, in the absence and presence of S9 mix, no cytotoxicity was observed up to the highest evaluated concentration, which showed phase separation. In the absence and presence of S9 mix, no relevant increase in the number of micronucleated cells was observed after treatment with the test item. However, in Experiment I in the presence of S9 mix after treatment with 39.8 μg/mL the value of 0.70 % micronucleated cells is statistically significant. Since the value is within the laboratory historical control data range (0.15 – 1.45 % micronucleated cells), the finding has to be regarded as biologically irrelevant. Appropriate mutagens were used as positive controls. They induced statistically significant increases in cells with micronuclei. In conclusion, it can be stated that under the experimental conditions reported, the test item did not induce micronuclei as determined by the in vitro micronucleus test in human lymphocytes. Therefore, the test item is considered to be non-mutagenic in this in vitro micronucleus test, when tested up to phase separating concentrations.

HPRT

The study was performed to investigate the potential of the test item to induce gene mutations at the HPRT locus in V79 cells of the Chinese hamster. The treatment period was 4 hours with and without metabolic activation. The highest applied concentration in the pre-test on toxicity (2000 μg/mL) was chosen with regard to the solubility properties of the test item in an appropriate solvent with respect to the current OECD Guideline 476. The concentration range of the main experiment was limited by phase separation of the test item. No substantial and reproducible dose dependent increase of the mutation frequency was observed in the main experiment. Appropriate reference mutagens, used as positive controls, induced a distinct increase in mutant colonies and thus, showed the sensitivity of the test system and the activity of the metabolic activation system. In conclusion it can be stated that under the experimental conditions reported the test item did not induce gene mutations at the HPRT locus in V79 cells. Therefore, the test item is considered to be non-mutagenic in this HPRT assay.

Conclusion: 3 genetic toxicity studies were performed according to OECD guidelines 471, 487 and 476 to determine the genetic toxicity potential of the test item. No genetic toxicity was observed in all three studies.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. As a result the substance is not considered to be classified for genetic toxicity under Regulation (EC) No 1272/2008, as amended for the tenth time in Regulation (EU) No 2017/776.