First Insight into the Formation of In Vivo Transformation Products of 2-Ethylhexyl diphenyl phosphate in Zebrafish and Prediction of Their Potential Toxicities

Abstract

As a frequently detected organophosphorus flame retardant in the environment, 2-ethylhexyl diphenyl phosphate (EHDPHP) is vulnerable to biotransformation, while the transformation mechanisms and potential toxicities of its transformation products remain unclear. In the present study, in vivo transformation products of EHDPHP in exposed zebrafish for 21d were analyzed by suspect screening and identified by mass spectrometry. Fifteen metabolites were identified, including 10 phase I and 5 phase II products with monohydroxylated products being primary, among which 5-OH-EHDPHP was the most predominant. Two sulfation products and one terminal desaturation metabolite of EHDPHP were reported for the first time. A density functional calculation coupled with molecular docking disclosed that the specific conformation of EHDPHP docked in the protein pockets favored the primary formation of 5-OH-EHDPHP, which was fortified to be a more suitable biomarker of EHDPHP exposure. The in vitro tests suggested that EHDPHP transformation took place not only in liver but also in intestine, where gut microbes played an important role. Due to lack of standards, in silico toxicity prediction combined with molecular docking indicated that several metabolites potentially cause higher toxicities than EHDPHP. The results provide deep insight into the potential health risks due to specific in vivo transformation of EHDPHP.

2-Ethylhexyl Diphenyl Phosphate Causes Obesity in Zebrafish by Stimulating Overeating via Inhibition of Dopamine Receptor D2

“…Water samples were collected on days 1, 10, and 21 after renewed (0 h) to monitor the stability of EHDPHP during exposure, and three replicates were conducted at each time point. 43 The mean concentration (mean ± standard deviation) of EHDPHP at three time points was 4.6 ± 0.7, 36.3 ± 5.5, and 249 ± 23.3 μg/L in the three exposure solutions, respectively, which were very close to the respective nominal exposure levels (i.e., 5, 35, and 245 μg/L, respectively) (Table S1). No EHDPHP was detected in the control solution.…”

New Perspective to Understand and Prioritize the Ecological Impacts of Organophosphate Esters and Transformation Products in Urban Stormwater and Sewage Effluents

“…This information is critical for urban wastewater management. Furthermore, some transformation products (TPs) of OPEs can exhibit similar or even higher toxicities than OPEs. , If the ecological risks posed by TPs are not considered, the ecological risk posed by OPEs in the aquatic environment might be underestimated.…”

“…Furthermore, some transformation products (TPs) of OPEs can exhibit similar or even higher toxicities than OPEs. 17,18 If the ecological risks posed by TPs are not considered, the ecological risk posed by OPEs in the aquatic environment might be underestimated. Previous studies investigating OPEs in sewage effluents or stormwater runoffs have focused mainly on one single transport pathway of OPEs.…”

Nontargeted Identification of Organic Components in Fine Particulate Matter Related to Lung Tumor Metastasis Based on an Adverse Outcome Pathway Strategy

“…As reported, the challenge in understanding the health effects of pollution lies not only in identifying a large number of chemicals in the environment but also in elucidating the complex ways through which chemicals interact with cells. 34 The AOP framework provides a solution strategy for clarifying the interaction between chemicals with biomolecules to identify the MIE leading to adverse outcomes. EMT-ATFs (TWIST, SNAI1, SNAI2, ZEB1, and ZEB2) can activate EMT by enhancing mesenchymal markers and inhibiting the expression of epithelial markers.…”