Disruption of the Reproductive–Metabolic–Aging Signaling Cascade by Organophosphate Esters: Comparative Toxicity of Tris(1,3-dichloro-2-propyl) phosphate and Bis(1,3-dichloro-2-propyl) phosphate in <i>Caenorhabditis elegans</i>

Tris(1,3-dichloro-2-propyl) phosphate (TDCPP) is an emerging environmental contaminant of concern due to its widespread presence and potential toxicity. Its metabolite, bis(1,3-dichloro-2-propyl) phosphate (BDCPP), plays a critical role in mediating TDCPP-induced toxicities and may exacerbate aging-related processes. In this study, we quantitatively compared the bioconcentration and toxicity of TDCPP and BDCPP in <i>Caenorhabditis elegans</i>. BDCPP exhibited higher environmental persistence and bioaccumulation potential than TDCPP. Exposure to 0.1-1000 μg/L TDCPP and BDCPP increased Oil red O staining (7.88%-55.44%, 6.42%-33.92%), lipofuscin levels (5.44%-35.98%, 3.54%-28.66%), and reduced the mean lifespan (3.09%-10.31%, 1.84%-8.74%). Overall, TDCPP caused greater triglyceride (TG) accumulation, lipofuscin formation, and lifespan reduction compared to BDCPP. TDCPP reduced brood size by 5.30%-18.95%, while BDCPP exposure increased brood size by up to 13.90%. Mechanism investigations revealed that TDCPP and BDCPP induce aging through distinct pathways. The adverse outcome pathways revealed that BDCPP disrupted germline stem cells (GSCs) apoptosis, transmitting reproductive signals through the <i>kri</i>-1-<i>daf</i>-16-<i>lipl</i>-4 signaling cascade, impairing TG hydrolysis and lifespan, while TDCPP acted through a GSC-independent route. These findings underscore the central role of GSCs in BDCPP-induced aging, enhance our understanding of BDCPP as a secondary pollutant, and provide critical data for assessing the ecological and health risks of chlorinated organophosphate esters.