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Carcinogenicity

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Description of key information

Based on available repeated dose toxicity and genotoxicity studies, as well as two independent QSAR methods, m-phenylene-bis(methylamine) is not expected to be carcinogenic. 

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Justification for classification or non-classification

Based on the evaluation of all available studies on repeated dose toxicity and genotoxicity of m-phenylene-bis(methylamine) as well as predictions by two independent QSAR methods, there are no indications of potential carcinogenicity of the substance. Respectively, classification of m-phenylene-bis(methylamine) for carcinogenicity is considered to be not warranted.

Additional information

Potential carcinogenic properties of m-phenylene-bis(methylamine) have been evaluated using all available repeated dose toxicity and genotoxicity studies with the substance and the predictions of two independent QSAR software packages, DEREK Nexus v.4.1.0 and Toxtree v.2.6.13, based on the substance structural properties.

The substance gave negative results in all available in vitro and in vivo genotoxicity tests and is thus not expected to be genotoxic. Available genotoxicity studies fulfil the data requirements under REACH Annex X and no further genotoxicity studies are warranted at the moment. In the available 90-day inhalation toxicity study with rats, local effects in the respiratory tract were observed, including bronchial epithelium degeneration and subacute inflammation in the lungs, which are considered to be caused by the corrosive nature of the substance. This is consistent with the fact that the observed local effects were not accompanied by any systemic effects or macroscopic changes, and that the observed histopathological changes were reversible in nature and not observed after a recovery period of 27 days. The observed local effects were also consistent with the results of the in vivo skin corrosion test, indicating the substance to be corrosive, and local effects at the port of entry (stomach) in the available reproductive and developmental screening study, in which the substance was administered in water by gavage. The only systemic effect which could potentially be regarded as a precursor of neoplastic lesions, was a diffuse hyperplasia of adrenal cortex observed in the available reproductive/developmental screening study. However, based on the available genotoxicity data, the substance is not a genotoxic carcinogen, which means, that even if it is indeed able to induce neoplastic lesions in long-term studies, a threshold level would exist for such effects, below which they would not occur. As the derived NOAELs in the reproductive/screening toxicity studies take the observed hyperplasia of adrenal cortex into account, potential carcinogenic effects are considered to be covered in the risk assessment. It should also be noted that the observed systemic effects were seen only following the test substance administration by oral route, and not by inhalation route, as was confirmed by the results of the available 90 -day inhalation toxicity study.

Potential carcinogenic and genotoxic properties of m-phenylene-bis(methylamine) have also been predicted using DEREK Nexus v.4.1.0 and Toxtree v.2.6.13 software. Neither of the used QSAR methods indicated the presence of structural alerts for either genotoxic or non-genotoxic carcinogenicity based on the structure of the substance. Respectively, the substance was predicted to be not carcinogenic.

In summary, based on all available data, there are no indications of potential carcinogenicity of m-phenylene-bis(methylamine). The performance of additional carcinogenicity studies with this substance is therefore considered to be not warranted.

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