Environmental Concerns And Toxicqenetic Endpoints Of DEHP,PAHs,and PPCPs In The Three Gorges Reservoir Area (TGRA),China

This study aims to probe the mechanistic in vivo/vitro toxicity of di-(2-ethylhexyl)phthalate(DEHP),polycyclic aromatic hydrocarbons(PAHs),and pharmaceuticals and personal care products(PPCPs),and their current environmental levels and associated ecological risk in the surface water of the Three Gorges Reservoir Area(TGRA),Yangtze River,China.GC-MS analysis showed that the current environmental levels of these organic pollutants were higher than that of WHO or USEPA standards,especially in the upper reaches of the TGRA.The spatial distribution revealed that the concentration of DEHP,PAHs and PPCPs were decreased from the upper to the middle and the lower reaches of the TGRA.Consistent to the environmental concentrations,the low-high level ecological risks based on risk quotients(RQs)were found in the following order of the risk burden in the TGRA:the upper reaches>the middle reaches>the lower reaches.Further,DEHP at environmental relevant concentrations(ERCs)induced significant levels of in vitro toxicity in terms of significant reduction in the cell viability and elevated levels of DNA damage,and also increased the migration of cancer cells.Similarly,the acute low-level DEHP exposure activated the pi3k-akt-mTOR pathway,and the chronic low-level exposure to DEHP suppressed the hypothalamus pituitary thyroid(HPT)axis in zebrafish.In addition,the acute low-level exposure to DEHP increased the aryl hydrocarbon receptor(AhR)activity in Tg(cyp1a:gfp)zebrafish.For PAHs toxicity assessment,we directly exposed zebrafish to the surface water samples from the TGRA,and found elevated responses of different genes involved in PAHs detoxification.These surface water samples significantly induced the AhR activity in Tg(cyp1a:gfp)zebrafish.Further,we employed the next generation toxicity testing in 21st century(TOX21)tools to predict the environmental concerns and in vitro/vivo toxicogenetic endpoints of PPCPs,and then confirmed them using experimental approaches(analytical and in vitro/vivo toxicity assays).Overall,in both approaches,non-steroid anti-inflammatory drugs(NSAIDs)revealed alarming concerns for environmental impacts and in vitro toxicity,while personal care products(PCPs),i.e.musk xylene(MX)and parabens highlighted more obvious effects for in vivo toxicity.In addition,MX and diclofenac(DIC)as priority congeners highly depressed the hematopoiesis and hepatogenesis markers in zebrafish.Moreover,all the investigated organic compounds significantly induced the AhR activity in terms of augmented fluorescent signals Tg(cypla:gfjp/mCherry)zebrafish.In short,DEHP,PAHs,and PPCPs induced low-high level ecological risks in the TGRA at their current environmental levels,the former two(DEHP and PAHs)exhibited augmented toxicity potentials at ERCs,and NSAIDs(among the studied PPCPs)appeared with priority environmental and toxicological concerns,both in vitro/vivo.