Comparative evaluation of three methylene dianiline isomers in the bacterial reverse mutation assay, the in vitro gene mutation test, and the in vitro chromosomal aberration test

Abstract

4,4′-MDA is classified as a genotoxic carcinogen based on numerous in vitro and animal data. The consequential assumption that a safe threshold does not exist is not only applied to 4,4′-MDA but also to its structural isomers and impurities 2,2′- and 2,4′-MDA in the absence of substance-specific data. This constitutes a problem in human risk assessments for all three substances as the inherent risks of 2,2′- and 2,4′-MDA and their contribution as impurities to that of 4,4′-MDA are essentially unknown. A comparative in vitro genotoxicity dataset consisting of the bacterial reverse mutation (Ames) test and the chromosomal aberration test in human lymphocytes (both performed according to the current OECD Guidelines) was generated for all three isomers. Furthermore, an in vitro gene mutation test in Chinese hamster ovary (CHO) cells (HPRT locus assay) was conducted with 2,4′-MDA. The results indicate differences regarding the genotoxic mechanism and potential, respectively, between the three structures and suggest that the no-threshold assumption for 4,4′-MDA may not be appropriate for 2,2′- and 2,4′-MDA.

Risk assessment—based verification of the CertiPURTM limit values for toluene diamine and methylene dianiline in flexible polyurethane foam

“…There is no chronic study available for 2,4’-MDA (CASRN 1208-52-2) either. Even though 2,4’-MDA may not be genotoxic based on negative bacterial reverse mutation ( OECD, 2020 ), chromosomal aberration ( OECD, 2016a ), and in vitro gene mutation (HPRT) ( OECD, 2016b ) tests ( Unterberger-Henig, 2022 ), the hazard profile of 4,4’-MDA was conservatively assumed to apply to 2,4’-MDA as well.…”

Emission and time-resolved migration rates of aromatic diamines from two flexible polyurethane foams

“…For the MDA-isomers, the individual LOQ were 10.0 ng (0.07 μg.m −2 .h −1 ) for 2,2′-MDA, 4.0 ng (0.03 μg.m −2 .h −1 ) for 2,4′-MDA, and 4.0 ng (0.03 μg.m −2 .h −1 ) for 4,4′-MDA. While the 2,4′-MDA isomer was shown to be negative in three genotoxicity screening tests ( Unterberger-Henig, 2022 ), there is currently no conclusive evidence about its potential carcinogenicity. Hence, for a RA, the combined MDA-isomers have to be considered.…”

Дослідження Мутацій Та Генетичних Змін У Бактеріальних Популяціях

“…Це включає призначення антибіотиків без необхідності, неправильне дозування або недотримання тривалості лікування. Антибіотикорезистентність є глобальною загрозою здоров'ю населення, оскільки зниження ефективності антибіотиків ускладнює лікування інфекцій [5,8]. Це вимагає розробки нових стратегій для боротьби з резистентністю та підвищення обізнаності про раціональне використання антибіотиків.…”