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Administrative data

Key value for chemical safety assessment

Additional information

4, 4'-methylene bis (2 -chloro-aniline) "MOCA" induced revertants in S. typhimurium TA100 and TA98 under conditions of metabolic activation (rat S9), but not in TA 1535 and 1537 nor in E. Coli (with or without activation). These results are confirmed in several literature publications. Moreover, the Niehs database contains data of 8 experimental studies where "MOCA" is positive in 6 out of 8 experiments in TA 100 (with activiation) and weakly positive in TA 98 (with activation) in 6 out of 8 experiments. "MOCA" was negative in TA 1535 and 1537 (with and without activation). The results of the chromosomal aberration assay in culture lung-derived fibroblast cells suggest a weak positive tendency for "MOCA" for inducing chromosomal aberrrations in experiments with S9 activation. One should note that a positive response is only observed in experiments with a very long incubation period. Additional supportive data in the Niehs database do not confirm a positive reaction for "MOCA" in the chromosomal aberration tests of two independent experiments, wherease a weak positive result is found in the sister chromatid exchange test in the same experiments (with activation). In addition the Niehs database contains data of 2 independent experiments in cultured mouse lymphoma cells. "MOCA" induced a dose-dependent increase in mutants in both experiments in the presence of S9. In literature it is described that "MOCA" induced a weak positive response in Drosophila melanogaster. Moreover, a weak positive response of "MOCA" in freshly isolated rat fibroblasts was obervered, which could however not be repeated in the second experiment. Upon radiolabeled administration of "MOCA" to male rats, covalent binding of radiolabeled "MOCA" to DNA in the liver and lung was observed. Moreover, administration of radiolabeled "MOCA" to rats for 28 consecutive days revealed adduct formation with globin and albumin. Overall, "MOCA" induced a positive response in the presence of a suitable activation system in two bacterial strains, wherease weak positive responses were reported in other cell culture systems such as in cultured lung-derived fibroblasts. In addition adduct formation/covalent binding to liver and lung DNA in rats was observed upon administration of radiolabeled "MOCA". Thus, "MOCA" is expressing genotoxic potential under the experimental conditions described.


Short description of key information:
In vitro genotoxicity of 4,4'-methylene bis (2-chloro-aniline) was tested in various cell systems. In two key studies the experimental results of 4,4'-methylene bis (2-chloro-aniline) in a chromosomal aberration assay and in cultured E. Coli and S. Typhimurium cells (Ames test) are described. In several bibliographic publications and in the Niehs database supportive data in other cell systems are described as well.
In vivo genotoxicity was studied by administration of radiolabeled MOCA to male rats.

Endpoint Conclusion: Adverse effect observed (positive)

Justification for classification or non-classification

Based on the occurrence of DNA adducts in rats MOCA is self-classified as mutagen category 3 (DSD)/category 2 (CLP).