Cyclopropanecarboxylic acid, 1-amino-2-ethenyl-, ethyl ester, (1R,2S)-, sulfate (2:1)

Endpoint summary

Additional information

Genetic toxicity in vitro:

Bacterial reverse mutation assay: The purpose of this study was to evaluate JNJ-31052047-ABI (T3325) and/or its metabolites for their ability to induce reverse mutations at the histidine locus in four strains of Salmonella typhimurium (TA98, TA100, TA1535 and TA1537), and at the tryptophan locus of Escherichia coli strain WP2uvrA, in the presence and absence of an exogenous mammalian metabolic activation system (S9) containing rat microsomal enzymes. JNJ-31052047-ABI was positive in the In Vitro Bacterial/Microsomal Activation Assay under the conditions, and according to the criteria, of the test protocol.

Following test concentrations were applied in triplicate: 250, 500, 1000, 2000, 3000, 4000 and 5000 ug/plate with and without S9 µg/plate (standard plate test, following a range-finding assay). Solvent and positive controls were run in duplicate for the range-finding assay, in triplicate for the mutation assay and were considered to be valid.

These results indicate JNJ-31052047-ABI was positive in the in vitro bacterial/microsomal activation reverse mutation assay under the conditions, and according to the criteria of the test protocol.

Chromosome aberration test: The test article, JNJ-31052047-ABI, was tested in the in vitro mammalian chromosome aberration test using human peripheral blood lymphocytes (HPBL) in both the absence and presence of an Aroclor-induced rat liver S9 metabolic activation system. A preliminary toxicity test was performed to establish the dose range for testing in the cytogenetic test.

In the preliminary toxicity assay, human peripheral blood lymphocytes were treated in the absence and presence of an Aroclor-induced S9 activation system for 4 hours, and continuously for 20 hours in the absence of S9 activation, at the concentrations of 100, 250, 532, 760, 1080, 1552 µg/mL.

The chromosome aberration assay was used to evaluate the clastogenic potential of the test article. The substance was tested at the same concentrations of the preliminary assay, but the dose levels selected for analysis of chromosome aberrations were 250, 532 and 1080 µg/mL.

The positive and solvent controls fulfilled the requirements for a valid test.

Under the conditions of the assay described in this report, JNJ-31052047-ABI was concluded to be negative for the induction of structural and numerical chromosome aberrations in the non-activated and S9-activated test systems in the in vitro mammalian chromosome aberration test using human peripheral blood lymphocytes.

Short description of key information:
Genetic toxicity in vitro:
Bacterial reverse mutation assay: conducted in the spirit of compliance with 21 CFR Part 588, OECD principles of Good Laboratory Practice (1998), OECD guideline 471 (1997) in S. typhimurium TA 1535, TA 1537, TA 98 and TA 100 and E. coli WP2 uvrA.The results indicate JNJ-31052047-ABI was positive in the in vitro bacterial/microsomal reverse mutation assay under the conditions, and according to the criteria of the test protocol.
Chromosome aberration test: performed inhuman peripheral blood lymphocytes according to OECD Guideline 471. Based on the results of this test, it is concluded that the test substance is negative in the presence of S9 and in the absence of S9.

Endpoint Conclusion:

Justification for classification or non-classification

The available data are not sufficient to conclude on the classification of the test substance for mutagenicity, according to the criteria of the DSD and CLP Regulation (EC) 1272/2008.