Exploring Mode of Action for Acute Toxicity of Primary Aromatic Amines with Daphnia Magna Using Differential Gene Expression Analysis

The diverse structures and modes of action (MOAs) of organic pollutants present a challenge in forecasting their environmental toxicity. Aromatic amines, widely used in industrial applications, are of particular interest due to their broad structural variation. Although they have been classified as polar narcotics, due to their narcotic MOA in fish, certain substitution patterns of the aromatically bound amino group exert excess toxicity towards species such as Daphnia magna. The underlying mechanisms bebind this phenomenon remain unclear. Therefore, we investigated how substitution patterns affect the MOA in this aquatic invertebrate. We used transcriptomics to study how three primary aromatic amines (PAAs), namely 4,4'-methylenedianiline (4,4'-MDA), 2,2'-methylenedianiline (2,2'-MDA) and 2,4-toluenediamine (2,4-TDA), affect D. magna. Our experimental design also included two reference compounds, 1-octanol (a non-polar narcotic) and aniline (a polar narcotic in fish, but excess toxicant in D. magna). Our analysis suggests very distinct biological MOAs for the three PAAs. While the para-substituted 4,4'-MDA treatment showed similar effects as the excess toxicant aniline, its ortho-substituted isomer 2,2'-MDA showed similar effects as the narcotic 1-octanol. Our results indicate a specific influence of substituent positioning in PAAs on their toxicity and MOA towards D. magna. This study illustrates the use of transcriptomics and its associated functional analysis to guide industrial chemical development towards more environmentally safe alternatives.