Impact of S-metolachlor, atrazine and their metabolites on the morphological, structural and functional properties of the intestinal barrier

S-metolachlor (MTC) and atrazine (ATZ) are herbicides commonly applied to corn and soybean crops. Their persistence in water and soil has led to frequent detection of these compounds and their metabolites in the environment, supporting the need to better understand their potential impact on organisms. Contaminated water and food represent important routes of human exposure to MTC and ATZ through ingestion, bringing these compounds into direct contact with intestinal epithelial cells. Such exposure may affect intestinal epithelial function and compromise barrier integrity. We used Caco-2 cells as an in vitro model to assess the effects of exposure to MTC, ATZ and their metabolites on the morphological, structural, and functional properties of the intestinal barrier. Despite the absence of functional or morphological effects following exposure to ATZ and its metabolites, ATZ fully crossed the epithelial barrier, indicating a potential route to systemic exposure and warranting further investigation of its effects beyond the intestinal compartment. After prolonged exposure, MTC induced an epithelial hypertrophic response characterized by increased cell and nuclear size and reduced proliferation, without overt disruption of intercellular junctions or barrier integrity. In contrast, its metabolites did not induce the hypertrophic phenotype observed with MTC but displayed distinct molecular effects, highlighting the need to consider both parent compounds and their metabolites in toxicological assessments. The biological significance of this hypertrophic response and the consequences of repeated or chronic exposure remain to be determined.