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Key value for chemical safety assessment

Additional information

Genotoxicity in vitro:

Ames test

One Ames test with reliability 2 (Hazleton, 1986) was available and selected as key study. The summary of this study was the following:

In a reverse gene mutation assay in bacteria (Hazleton, 1986), strains TA 98, TA 100, TA 1535, TA 1537 and TA 1538 of S. typhimurium were exposed to paratrifluoromethylaniline at concentrations of 0.05, 0.1, 0.5, 1 or 2 µl/plate in the presence and absence of mammalian metabolic activation.
Paratrifluoromethylaniline was tested up to cytotoxic concentrations. The positive controls induced the appropriate responses in the corresponding strains.

In this study, the test item presented mutagenic activity with and without S9 -mix in Salmonella typhimurium TA100 and TA1535. A weak positive response in TA1537 and negative response for TA98 and TA1538.

Therefore, p-TFMA is considered as mutagenic for Salmonella typhimurium under the test conditions.
 
This study is classified as acceptable. This study satisfies the requirement for Test Guideline OECD 471 for in vitro mutagenicity (bacterial reverse gene mutation) data.

Another one study (Quillardet, 1993) was with reliabilty 3 was not retained for the assesment, because it was not well described, and it was not an usual genotoxicity test.

In vitro mammalian cell gene mutation test

One HPRT study (Hoechst, 1994) was available and selected as key study because it was with reliability 1. The summary of this study was the following:

The study (Hoechst, 1993) was performed to investigate the potential of p-trifluoromethylaniline to induce gene mutations at the HGPRT locus in V79 cells of the Chinese hamster in vitro.

The assay was performed in two independent experiments, using identical procedures, both with and without rat liver microsomal activation (S9 -mix).

The test substance was tested at the following concentrations: 10, 25, 50, 100 and 250 µg/ml without S9 -mix; 50, 100, 250, 500 and 750 µg/ml with S9 -mix.

The concentration ranges were selected according to the preliminary experiment for toxicity. The concentration of 500 µg/ml with metabolic activation produced a distinct decrease of the plating efficiency in the main experiment.

P-trifluoromethylaniline produced a statistically significant increase in mutant colony number in the absence and the presence of S9 -mix. This effect was reproductible and slightly dose-dependent.

Appropriate reference mutagens were used as positive controls ans showed a distinct increase in induced mutant colonies.

In conclusion, p-trifluoromethylaniline induce gene mutations in the HGPRT-test with V79 Chinese hamster cells, in the presence and in the absence of a metabolic activation system, under the experimental described.

Therefore p-trifluoromethylaniline is considered to be mutagenic in this HGPRT assay.

In vitro mammalian chromosome aberration test

One Chromosome aberration study (Hoechst, 1994) was available and was selected as key study because it was with reliability 1. The summary of this study was the following:

The study (Hoechst, 1994) was performed to investigate the potential of p-trifluoromethylaniline to induced chromosome aberrations in V79 cells of the Chinese hamster in vitro.

The assay was performed in two independent experiments, using identical procedures, both with and without rat liver microsomal activation (S9-mix). For each experiment two cell cultures were used.

The test article was tested at the following concentrations:

Without S9-mix:

18h: 10, 50 and 100 µg/ml

28h: 100 µg/ml

With S9-mix:

18h: 10, 250 and 500 µg/ml

28h: 500 µg/ml

The concentration ranges were selected according to the preliminary experiment for solubility and toxicity. The highest concentration produced a distinct decrease of the mitotic index with metabolic activation.

The test compound induced a statistically significant increase in the number of chromosome aberrations inclusive and exclusive gaps at the fixation intervals 18 and 28 h with metabolic activation. Without S9 -mix, 18 hours after treatment only the aberration rate inclusive gaps was significative enhanced, while at fixation interval 28 hours also an increased number of aberrant cells exclusive gaps was observed.

Appropriate reference mutagens were used as positive controls and showed a distinct increase in chromosome aberrations, thus indicating the sensitivity of the assay.

In conclusion, p-trifluoromethylaniline does induce chromosome mutations (=aberrations) in V79 Chinese hamster cells, in the presence and in the absence of a metabolic activation system, under the experimental conditions described.

Therefore p-trifluoromethylaniline is considered to be mutagenic in this chromosome aberration assay.


Short description of key information:
p-TFMA gave positive results in Ames tests, with and without metabolic activation system.
p-TFMA gave positive results in gene mutation test with V79 Chinese hamster cells, with and without metabolic activation system.
p-TFMA gave positive results in chromosome aberration test with V79 Chinese hamster cells, with and without metabolic activation system.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

P-trifluoromethylaniline showed positive results in Ames test, in mammalian gene mutation test and in chromosome aberration test with mammalian cells, in vitro.

However, these positive results in in-vitro studies are not sufficient to classify p-TFMA as mutagenic. An in-vivo study is needed, but such a test is not required for strictly controlled intermediates.