Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

Although the o-isomer of the chloroanilines exhibits genetic toxicity the profile of activity is inconsistent. It was not mutagenic in S. typhimurium, but induced gene mutations in mouse lymphoma cells. o-Chloroaniline was positive for induction of micronuclei in rat, but not in mouse, bone marrow cells. It was also not mutagenic in peripheral blood cells of mice of a 13 week gavage study (NTP report Tox 43). o-Chloroaniline has not been evaluated for potential carcinogenicity in laboratory animals, yet. The toxicity data for o-chloroaniline suggest that if progression of erythrocyte toxicity leads to the formation of splenic lesions in rats, then o-chloroaniline would likely be positive in the rodent carcinogen bioassay. However, if carcinogenicity is dependent on genotoxicity, then the o-chloroaniline which displays if any only weak genotoxic activity, may not be carcinogenic in a rodent bioassay. It is therefore difficult to predict carcinogenic activity of o-chloroaniline based on the available information. Due to the fact that o-chloroaniline is solely used under strictly controlled conditions in a closed system and exposure is only expected in case of accidental release, further studies leading to classification or non-classification as carcinogenic do not seem necessary.


Short description of key information:
1. o-Chloroaniline ( 3.3, 10, 33, 100, 333, 1000 and 3333 µg/plate) was tested for genotoxicity in a bacterial reverse mutation assay with Salmonella typhimurium TA97, TA98, TA100 and TA 1535 with and without metabolic activation with either Aroclor 1254 induced male Syrian hamster liver S9-mix or male Sprague Dawley rat liver S9-mix (10 and 30 %) equivalent to OECD471. The obtained results were negative in all strains tested, whereas the positive and negative controls acted as expected and were therefore valid (Zeiger, E, (1987)).
2. o-Chloroaniline was tested for mutagenicity in an in vitro mammalian cell gene mutation assay with L5178Y (TK+/TK-) mouse lymphoma cells equivalent to OECD476. Revertant colonies are deficient in thymidine kinase due to the mutation of TK+/TK- to TK-/TK- and will therefore be resistant to the cytotoxic effects of trifluorothymidine. o-Chloroaniline induced significant increases in trifluorothymidine mutations in L5178Y mouse lymphoma cells with S9 activation enzymes. The lowest effective dose that produced a mutagenic response was 300 µg/mL. o-Chloroaniline produced a significant increase in mutant colonies only at the highest concentration tested (400 µg/mL) in the second trial performed without S9 mix; results of the first trial without S9 mix were considered to be inconclusive, because although no increase in mutant colonies was observed, the relative total growth (33%) observed at the highest dose indicated that higher concentrations of o-chloroaniline could have been tested (McGregor, DB et al. (1991)).
3. o-Chloroaniline was tested for its ability to induce unschedulded DNA-synthesis in primary rat hepatocytes equivalent to EU method B.18. The results do not indicate an increase of DNA- repair synthesis at non-cytotoxic doses of o-chloroaniline (Yoshimi, N et al., (1988)).
4. o-Chloroaniline was orally administed (gavage) to NMRI mice at a concentration of 500, 1000 or 1500 mg/kg body weight in polyethylene glycol and the clas...

Endpoint Conclusion:

Justification for classification or non-classification

Various substances structurally related to aniline have been proven to be mutagenic. o-Chloroaniline itself was tested positiv for mutagenicity in an in vitro mammalian cell gene mutation assay with L5178Y (TK+/TK-) mouse lymphoma cells equivalent to OECD476 and showed a weakly clastogenic effect on polychromatic erythrocytes of the bone marrow (femur) when orally administered to NMRI mice at a concentration of 500, 1000 or 1500 mg/kg body weight (EU method B.12). Therefore it is suggested to classify o-chloroaniline as Category 3 (DSD-DPD) and Category 2 (GHS) Mutagen.