Long-term exposure to triclocarban induces splenic injuries in mice: Insights from spatial metabolomics and lipidomics.

Triclocarban (TCC) is a widely used antimicrobial agent and known endocrine-disrupting chemical found in various products. While its potential toxicities on endocrine-related organs have been highlighted in previous studies, the effects of TCC on non-endocrine organs, particularly the spleen, remain largely unknown. Here, we employed a novel approach combining long-term TCC exposure in a mouse model with spatial metabolomics and lipidomics to investigate the effects of TCC on the spleen. Our results showed that TCC exposure significantly altered the splenic organ weight and coefficient and induced obvious pathological alterations. Omic analysis revealed that TCC exposure disrupted the splenic homeostasis, as indicated by the upregulation of glutathione metabolism, ceramide-to-sphingomyelin signaling and biosynthesis of glycerophospholipids. Notably, the data of mass spectrometry imaging (MSI) revealed that TCC accumulated in the red pulp of the mouse spleen, while its metabolites concentrated in the white pulp. Further MSI analyses identified region-specific metabolic disruptions, including upregulated ceramide signaling in the red pulp, indicating localized inflammation, and upregulated glutathione metabolism throughout the spleen, suggesting widespread oxidative damage. Our findings provide crucial insights into the spatial distribution and biochemical impact of TCC on mice spleens, highlighting the potential risks of long-term TCC exposure to immune function.