Immunotoxicity and cancer risk exacerbation induced by tris(1,3-dichloro-2-propyl) phosphate exposure: insights from macrophage inflammatory responses and in vivo tumor models

Tris(1,3-dichloro-2-propyl) phosphate (TDCPP) is widely detected in human tissues and associated with significant health risks. However, the immunotoxicity and health risk mechanisms of long-term TDCPP exposure remain poorly understood. This study integrates mRNA sequencing (mRNA-seq) and high-throughput cytokine profiling to elucidate key transcriptional and secretory changes associated with TDCPP-induced inflammatory responses. The findings underscore the potential health implications of TDCPP exposure, elucidating its inflammatory effects at the cellular level and in a breast cancer mouse model. TDCPP exposure led to significant secretion of TNF-α and other cytokines. mRNA-seq and cytokine analysis demonstrated that TDCPP activates the GSDMD/Caspase-8 pathway through TNF signaling, triggering cell death in THP-1 macrophages, resulting in an inflammation response, and aggravating tumor progression. RIPK1 serves as a pivotal regulatory factor in the TNF signaling pathway, playing a central role in modulating both cell death and inflammatory responses. In vivo studies using BALB/c mice showed that TDCPP enhanced cancer cell proliferation and promoted damage to liver and lung tissues. These results highlight the need for a more rigorous evaluation of the environmental and public health impacts of TDCPP and structurally related compounds, as TDCPP exposure may exacerbate health effects, particularly in vulnerable populations with weakened immunity or pre-existing conditions.