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 Caenorhabditis elegans.

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 Caenorhabditis elegans. 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 kri-1-daf-16-lipl-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.