2-aminophenol

Endpoint summary

Additional information

Overall, the genotoxicity program on o-aminophenol investigated the three endpoints of genotoxicity: gene mutations, structural chromosome aberrations and aneuploidy. However, all tests had some or several deficiencies compared to the minimal current requirements for a genotoxicity test. The number of appropriate tests which in spite of these deficiencies can be used for evaluation of the genotoxic potential of o-aminophenol is very small. Some tests can only be used as supportive evidence, many tests had only limited value and a few tests were even not acceptable for evaluation. Therefore, the conclusion on the genotoxic potential of o-aminophenol is based on a rather limited number of (still) not optimal tests. More weight of evidence was given to the tests which are mentioned in the guidance for genotoxicity testing of hair dyes.

In some of the gene mutation tests in bacteria o-aminophenol was positive in strain TA100 but not in the other strains tested. That the positive result may be a relevant result can be deduced from the fact that o-aminophenol induced a low DNA repair activity in bacteria and was also positive in a rec assay in Bacillus subtilis. A gene mutation test in yeast cells was negative whereas gene mutation tests in mammalian cells were not available. In an in vitro UDS test of poor quality o-aminophenol also scored negative. o-Aminophenol induced sister chromatid exchanges in human cells (fibroblasts and lymphocytes) but was negative in a chromosome aberration test of poor quality in CHO cells.

Under in vivo conditions o-aminophenol induced both sister chromatid exchanges and chromosome aberrations in tests with Vicia faba. These tests in Vicia are not very common and as such are not part of the guidance on genotoxicity testing for hair dyes. The relevance of such tests for a genotoxic hazard for humans is uncertain. In the more common tests o-Aminophenol exposure did not result in an increase of sister chromatid exchanges nor in chromosomal aberrations. Since the micronucleus test was negative, it is not expected that o-aminophenol is a clastogenic and/or an aneugenic compound. Finally, although the test on germ cell genotoxicity was positive, this has only limited value and was not considered suitable for evaluation.

Based on the tests evaluated it can be concluded that the positive in vitro findings for clastogenicity were not confirmed in in vivo tests for chromosome aberrations or micronuclei. Likewise, the positive in vitro results found for gene mutations are overruled by a negative in vivo UDS test. Based on these experiments, o-aminophenol might be considered as non genotoxic.

However, as stated above, these conclusions are based on the results of a few inadequate tests. Therefore, to strengthen this conclusion both a well performed gene mutation test and a chromosomal aberration/micronucleus test in mammalian cells according to current guidelines are required.

Short description of key information:
Several in vitro and in vivo studies concerning mutagenicity and clastogenicity were performed. The majority of the in vitro test was positive for mutagenicity and clastogencity though many of the studies are of limited value and have to be considered as supportive information. In contrast, most of the in vivo studies were negative and did not confirm the in vitro data. Similar to the in vitro assays, only a few of the in vivo assays are guideline conform and, therefore, suitable for evaulation.

Endpoint Conclusion:

Justification for classification or non-classification

These data from secondary sources are not suiteable to derive or to change the current classification and labelling of the substance according the dangerous substance directive (67/548/EEC) or theClassification, Labeling, and Packaging Regulation (EC) No. 1272/2008.