Organophosphate Ester, 2-Ethylhexyl Diphenyl Phosphate (EHDPP), Elicits Cytotoxic and Transcriptomic Effects in Chicken Embryonic Hepatocytes and Its Biotransformation Profile Compared to Humans
- 17 January 2019
- journal article
- research article
- Published by American Chemical Society (ACS) in Environmental Science & Technology
- Vol. 53 (4), 2151-2160
- https://doi.org/10.1021/acs.est.8b06246
Abstract
The effects of 2-ethylhexyl diphenyl phosphate (EHDPP) on cytotoxicity and mRNA expression, as well as its metabolism, were investigated using a chicken embryonic hepatocyte (CEH) assay. After incubation for 36 h, the lethal concentration 50 (LC50) was 50 ± 11 μM, suggesting that EHDPP is one of a small cohort of highly toxic organophosphate esters (OPEs). By use of a ToxChip polymerase chain reaction (PCR) array, we report modulation of 6, 11 or 16/43 genes in CEH following exposure to 0.1, 1 or 10 μM EHDPP, respectively. The altered genes were from all 9 biological pathways represented on the ToxChip including bile acids/cholesterol regulation, glucose metabolism, lipid homeostasis and the thyroid hormone pathway. After incubation for 36 h, 92.5 % of EHDPP was transformed, and one of its presumed metabolites, diphenyl phosphate (DPHP), only accounted for 12% of the original EHDPP concentration. Further screening by use of high-resolution spectrometry revealed a novel EHDPP metabolite, hydroxylated 2-ethylhexyl monophenyl phosphate (OH-EHMPP), which was also detected in a human blood pool. Additional EHDPP metabolites detected in the human blood pool included EHMPP and DPHP. Overall, this study provided novel information regarding the toxicity of EHDPP and identified a potential EHDPP metabolite, OH-EHMPP, in both avian species and humans.Keywords
Funding Information
- Ministry of Education of the People's Republic of China (30917011305)
- Natural Science Foundation of Jiangsu Province (BK20170830, BK20180498)
- Government of Jiangsu Province
- Central Committee of the Communist Party of China
- Jiangsu Key Laboratory of Chemical Pollution Control and Resources Reuse, Nanjing University of Science and Technology (30918014102)
This publication has 72 references indexed in Scilit:
- Concentrations and variability of organophosphate esters, halogenated flame retardants, and polybrominated diphenyl ethers in indoor and outdoor air in Stockholm, SwedenEnvironmental Pollution, 2018
- Children's residential exposure to organophosphate ester flame retardants and plasticizers: Investigating exposure pathways in the TESIE studyEnvironment International, 2018
- Occurrence, Removal, and Environmental Emission of Organophosphate Flame Retardants/Plasticizers in a Wastewater Treatment Plant in New York StateEnvironmental Science & Technology, 2017
- Organophosphorus Flame Retardants in Pregnant Women and Their Transfer to Chorionic VilliEnvironmental Science & Technology, 2017
- Contaminants of emerging concern in Caspian tern compared to herring gull eggs from Michigan colonies in the Great Lakes of North AmericaEnvironmental Pollution, 2017
- Brominated, chlorinated and phosphate organic contaminants in house dust from PortugalScience of The Total Environment, 2016
- Organophosphate Flame Retardants and Plasticizers in Aqueous Solution: pH-Dependent Hydrolysis, Kinetics, and PathwaysEnvironmental Science & Technology, 2016
- Organophosphorus flame retardants and plasticizers: Sources, occurrence, toxicity and human exposureEnvironmental Pollution, 2015
- Comparative Body Compartment Composition and In Ovo Transfer of Organophosphate Flame Retardants in North American Great Lakes Herring GullsEnvironmental Science & Technology, 2014
- Phosphorus flame retardants: Properties, production, environmental occurrence, toxicity and analysisChemosphere, 2012