@article {127, title = {Screening of House Dust from Chinese Homes for Chemicals with Liver X Receptors Binding Activities and Characterization of Atherosclerotic Activity Using an Macrophage Cell Line and Mice.}, journal = {Environ Health Perspect}, volume = {127}, year = {2019}, month = {2019 11}, pages = {117003}, abstract = {

BACKGROUND: Atherosclerotic cardiovascular disease has become the leading cause of death worldwide, and environmental pollutants are increasingly recognized as risk factors for atherosclerosis. Liver X receptors (LXRs) play a central role in atherosclerosis; however, LXR activity of organic pollutants and associated potential risk of atherosclerosis have not yet been characterized.

OBJECTIVES: This study aimed to explore whether LXR-antagonistic chemicals are present in indoor house dust and, if so, to characterize this activity in relation to changes in macrophages and cardiovascular disease indicators in an atherosclerosis mouse model.

METHODS: We used a -down assay and a nontarget high-resolution mass spectrometry method to screen house dust collected from Chinese homes for - and -antagonist activity. A chemical identified in this manner was assessed for its ability to induce cholesterol efflux and foam cell formation in RAW264.7 macrophages, to down-regulate the expression of two LXR-dependent genes, and , and finally to induce atherosclerotic lesions using an mouse model.

RESULTS: We identified the flame retardants triphenyl phosphate (TPHP) and 2-ethylhexyl diphenyl phosphate (EHDPP) in house dust samples and demonstrated their ability to antagonize LXRs. The potency of TPHP was similar to that of the LXR-antagonist SR9238. TPHP could also inhibit cholesterol efflux and promote foam cell formation in RAW264.7 macrophages and mouse peritoneal macrophages and significantly promoted atherosclerotic lesion formation in the mouse model.

CONCLUSIONS: We found LXR-antagonist chemicals in environmental samples of indoor dust from Chinese homes. One of the chemicals, TPHP, was able to promote the development of atherosclerotic lesions in the mouse model. These results highlight the need to assess the LXR-antagonist activities of pollutants in future environmental management programs. https://doi.org/10.1289/EHP5039.

}, keywords = {Air Pollutants, Air Pollution, Indoor, Animals, Atherosclerosis, China, Dust, Liver X Receptors, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, ApoE, RAW 264.7 Cells}, issn = {1552-9924}, doi = {10.1289/EHP5039}, author = {Hu, Wenxin and Jia, Yingting and Kang, Qiyue and Peng, Hui and Ma, Haojia and Zhang, Shiyi and Hiromori, Youhei and Kimura, Tomoki and Nakanishi, Tsuyoshi and Zheng, Lemin and Qiu, Yifu and Zhang, Zhaobin and Wan, Yi and Hu, Jianying} } @article {104, title = {p,p{\textquoteright}-DDE Induces Gonadal Intersex in Japanese Medaka (Oryzias latipes) at Environmentally Relevant Concentrations: Comparison with o,p{\textquoteright}-DDT.}, journal = {Environ Sci Technol}, volume = {50}, year = {2016}, month = {2016 Jan 05}, pages = {462-9}, abstract = {

Previous studies have reported high body burdens of dichlorodiphenyltrichloroethane (DDT) and its metabolites in wild fishes worldwide. This study evaluated the adverse effects of 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p{\textquoteright}-DDE) and o,p{\textquoteright}-DDT on gonadal development and reproduction by exposing transgenic Japanese medaka (Oryzias latipes) from hatch for 100 days. While both p,p{\textquoteright}-DDE and o,p{\textquoteright}-DDT induced intersex in male medaka, the lowest observable effective concentration (LOEC) of o,p{\textquoteright}-DDT was 57.7 ng/g ww, about 5-fold lower than that (272 ng/g ww) of p,p{\textquoteright}-DDE. Since LOECs of both chemicals were comparable to the body concentrations in wild fish, DDT contamination would likely contribute to the occurrence of intersex observed in wild fish. Exposure to o,p{\textquoteright}-DDT resulted in much higher expression of vitellogenin in liver of males than p,p{\textquoteright}-DDE, accordant with the higher potency of o,p{\textquoteright}-DDT than p,p{\textquoteright}-DDE to induce intersex. This phenomenon could be partly explained by the significantly elevated levels of 17β-estradiol in plasma of males exposed to o,p{\textquoteright}-DDT, in addition to its estrogenic activity via the estrogen receptor. Significantly lower fertilization (p = 0.006) and hatchability (p = 0.019) were observed in the 13 intersex males. This study for the first time demonstrated the induction of intersex and reproductive effects of p,p{\textquoteright}-DDE and o,p{\textquoteright}-DDT at environmentally relevant concentrations.

}, keywords = {Animals, DDT, Dichlorodiphenyl Dichloroethylene, Disorders of Sex Development, Estradiol, Gonads, Male, Oryzias, Vitellogenins, Water Pollutants, Chemical}, issn = {1520-5851}, doi = {10.1021/acs.est.5b05042}, author = {Sun, Jianxian and Wang, Chen and Peng, Hui and Zheng, Guomao and Zhang, Shiyi and Hu, Jianying} } @article {112, title = {Isomer-specific accumulation of perfluorooctanesulfonate from (N-ethyl perfluorooctanesulfonamido)ethanol-based phosphate diester in Japanese Medaka (Oryzias latipes).}, journal = {Environ Sci Technol}, volume = {48}, year = {2014}, month = {2014 Jan 21}, pages = {1058-66}, abstract = {

While (N-ethyl perfluorooctanesulfonamido)ethanol (FOSE) -based phosphate diester (diSPAP) has been proposed as a candidate precursor of perfluorooctanesulfonate (PFOS), its potential biotransformation to PFOS has not been verified. Metabolism of diSPAP was investigated in Japanese medaka ( Oryzias latipes ) after exposure in water for 10 days, followed by 10 days of depuration. Branched isomers of diSPAP (B-diSPAP) were preferentially enriched in medaka exposed to diSPAP, with the proportion of branched isomers (BF) ranging from 0.56 to 0.80, which was significantly greater than that in the water to which the medaka were exposed (0.36) (p \< 0.001). This enrichment was due primarily to preferential uptake of B-diSPAP. PFOS together with perfluorooctanesulfonamide (PFOSA), N-ethyl perfluorooctanesulfonamide (NEtFOSA), 2-(perfluorooctanesulfonamido)acetic acid (FOSAA), NEtFOSAA, FOSE, and NEtFOSE were detected in medaka exposed to diSPAP, which indicated the potential for biotransformation of diSPAP to PFOS via multiple intermediates. Due to preferential metabolism of branched isomers, FOSAA and PFOSA exhibited greater BF values (\>0.5) than those of NEtFOSA, NEtFOSAA, and NEtFOSE (\<0.2). Such preferential metabolism of branched isomers along the primary pathway of metabolism and preferential accumulation of B-diSPAP led to enrichment of branched PFOS (B-PFOS) in medaka. Enrichment of B-PFOS was greater for 3-, 4-, and 5-perfluoromethyl PFOS (P3MPFOS, P4MPFOS, and P5MPFOS), for which values of BF were 0.58 {\textpm} 0.07, 0.62 {\textpm} 0.06, and 0.61 {\textpm} 0.05 (day 6), respectively; these values are 5.8-, 7.8-, and 6.4-fold greater than those of technical PFOS. This work provides evidence on the isomer-specific accumulation of PFOS from diSPAP and will be helpful to track indirect sources of PFOS in the future.

}, keywords = {Alkanesulfonic Acids, Animals, Biotransformation, Chromatography, High Pressure Liquid, Environmental Monitoring, Esters, Fluorocarbons, Gas Chromatography-Mass Spectrometry, Half-Life, Hydrocarbons, Fluorinated, Isomerism, Kinetics, Metabolic Networks and Pathways, Organophosphorus Compounds, Oryzias, Phosphates, Reference Standards, Sulfonamides}, issn = {1520-5851}, doi = {10.1021/es404867w}, author = {Peng, Hui and Zhang, Shiyi and Sun, Jianxian and Zhang, Zhong and Giesy, John P and Hu, Jianying} }