{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T12:51:13Z","timestamp":1792155073622,"version":"4.4.0"},"reference-count":54,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,4,22]],"date-time":"2022-04-22T00:00:00Z","timestamp":1650585600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>Bisphenol A (BPA) is an endocrine-disrupting chemical that affects lipid metabolism and contributes to non-alcoholic fatty liver disease (NAFLD). The mechanism of BPA exposure in hepatic lipid accumulation and its potential effect on NAFLD remain unclear. This study investigated the effect of BPA-exposure-induced hepatic lipid deposition on the pathology of NAFLD and its underlying mechanism in vitro and in vivo. BPA increased intracellular reactive oxygen species (ROS) levels, and promoted fatty acid uptake through upregulation of a free fatty acid uptake transporter, cluster of differentiation 36 (CD36), in HUH-7 cells. Additionally, C57BL\/6 mice administered a high-fat\/high-cholesterol\/high-cholic acid diet (HFCCD) and BPA (50 mg\/kg body weight) for 8 weeks developed a steatohepatitis-like phenotype, characterized by alpha-smooth muscle actin (\u03b1-SMA, an indicator of hepatic fibrosis) and cleaved caspase 3 (an indicator of apoptosis) in hepatic tissue; moreover, they had a higher oxidative stress index of 8-hydroxydeoxyguanosine (8-OHdG) in liver tissue compared to the control group. Treatment with ROS scavenger n-acetylcysteine (NAC) ameliorated BPA-mediated HFCCD-induced lipid accumulation and steatohepatitis in the livers of treated mice. Our study indicates that BPA acts synergistically to increase hepatic lipid uptake and promote NAFLD development by stimulating ROS-induced CD36 overexpression.<\/jats:p>","DOI":"10.3390\/toxics10050208","type":"journal-article","created":{"date-parts":[[2022,4,24]],"date-time":"2022-04-24T00:45:21Z","timestamp":1650761121000},"page":"208","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Bisphenol A Coupled with a High-Fat Diet Promotes Hepatosteatosis through Reactive-Oxygen-Species-Induced CD36 Overexpression"],"prefix":"10.3390","volume":"10","author":[{"given":"Jyun-Lin","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 300, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao-Chien","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Taichung Tzu Chi Hospital, Taichung 427, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-An","family":"Hsu","sequence":"additional","affiliation":[{"name":"School of Chinese Medicine, China Medical University, Taichung 404, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Sheng","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Chinese Medicine, Asia University Hospital, Taichung 413, Taiwan"},{"name":"Department of Food Nutrition and Health Biotechnology, Asia University, Taichung 401, Taiwan"},{"name":"Department of Chinese Medicine, China Medicine University Hospital, Taichung 404, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui-Cian","family":"Weng","sequence":"additional","affiliation":[{"name":"Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei 106, Taiwan"},{"name":"National Applied Research Laboratories, Taiwan Instrument Research Institute (TIRI), Hsinchu 300, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yen-Pei","family":"Lu","sequence":"additional","affiliation":[{"name":"National Applied Research Laboratories, Taiwan Instrument Research Institute (TIRI), Hsinchu 300, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8060-192X","authenticated-orcid":false,"given":"Chun-Yu","family":"Chuang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 300, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Wan","sequence":"additional","affiliation":[{"name":"School of Chinese Medicine, China Medical University, Taichung 404, Taiwan"},{"name":"Department of Obstetrics and Gynecology, China Medical University Hospital, Taichung 404, Taiwan"},{"name":"Department of Medical Laboratory Science and Biotechnology, Asia University, Taichung 413, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1038\/nrgastro.2013.171","article-title":"The global NAFLD epidemic","volume":"10","author":"Loomba","year":"2013","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1007\/s10620-016-4143-0","article-title":"Global Epidemiology of Nonalcoholic Fatty Liver Disease and Perspectives on US Minority Populations","volume":"61","author":"Sherif","year":"2016","journal-title":"Dig. Dis. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1146\/annurev-pathol-012615-044224","article-title":"Nonalcoholic Fatty Liver Disease: Pathogenesis and Disease Spectrum","volume":"11","author":"Hardy","year":"2016","journal-title":"Annu. Rev. Pathol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1038\/nrgastro.2013.149","article-title":"From NAFLD to NASH to cirrhosis-new insights into disease mechanisms","volume":"10","author":"Wree","year":"2013","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1016\/j.jhep.2011.08.025","article-title":"The interaction of hepatic lipid and glucose metabolism in liver diseases","volume":"56","author":"Bechmann","year":"2012","journal-title":"J. Hepatol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Perla, F.M., Prelati, M., Lavorato, M., Visicchio, D., and Anania, C. (2017). The Role of Lipid and Lipoprotein Metabolism in Non-Alcoholic Fatty Liver Disease. Children, 4.","DOI":"10.3390\/children4060046"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"E713","DOI":"10.1152\/ajpendo.00194.2007","article-title":"Macrophage TNF-alpha contributes to insulin resistance and hepatic steatosis in diet-induced obesity","volume":"293","author":"Novitskaya","year":"2007","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/S0890-6238(99)00017-9","article-title":"Reproductive function in rats exposed neonatally to bisphenol A and estradiol benzoate","volume":"13","author":"Nagao","year":"1999","journal-title":"Reprod. Toxicol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1111\/apt.14499","article-title":"Role of bisphenol A as environmental factor in the promotion of non-alcoholic fatty liver disease: In vitro and clinical study","volume":"47","author":"Dallio","year":"2018","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Federico, A., Dallio, M., Gravina, A.G., Diano, N., Errico, S., Masarone, M., Romeo, M., Tuccillo, C., Stiuso, P., and Morisco, F. (2020). The Bisphenol A Induced Oxidative Stress in Non-Alcoholic Fatty Liver Disease Male Patients: A Clinical Strategy to Antagonize the Progression of the Disease. Int. J. Environ. Res. Public Health, 17.","DOI":"10.3390\/ijerph17103369"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/j.tiv.2012.03.017","article-title":"Low concentrations of bisphenol A induce lipid accumulation mediated by the production of reactive oxygen species in the mitochondria of HepG2 cells","volume":"26","author":"Huc","year":"2012","journal-title":"Toxicol. In Vitro"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1016\/j.chemosphere.2013.01.016","article-title":"Direct effects of Bisphenol A on lipid homeostasis in rat hepatoma cells","volume":"91","author":"Grasselli","year":"2013","journal-title":"Chemosphere"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1530\/JOE-17-0028","article-title":"Bisphenol A promotes hepatic lipid deposition involving Kupffer cells M1 polarization in male mice","volume":"234","author":"Lv","year":"2017","journal-title":"J. Endocrinol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"087005","DOI":"10.1289\/EHP664","article-title":"Hepatic Lipid Accumulation and Nrf2 Expression following Perinatal and Peripubertal Exposure to Bisphenol A in a Mouse Model of Nonalcoholic Liver Disease","volume":"125","author":"Shimpi","year":"2017","journal-title":"Environ. Health Perspect."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3228","DOI":"10.1038\/s41598-019-40105-8","article-title":"Ameliorative effect of Silybin on bisphenol A induced oxidative stress, cell proliferation and steroid hormones oxidation in HepG2 cell cultures","volume":"9","author":"Lama","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"118012","DOI":"10.1016\/j.lfs.2020.118012","article-title":"Bisphenol-A exposure worsens hepatic steatosis in ovariectomized mice fed on a high-fat diet: Role of endoplasmic reticulum stress and fibrogenic pathways","volume":"256","author":"Figueiredo","year":"2020","journal-title":"Life Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/s10565-020-09535-3","article-title":"Gestational bisphenol A exposure induces fatty liver development in male offspring mice through the inhibition of HNF1b and upregulation of PPARgamma","volume":"37","author":"Long","year":"2021","journal-title":"Cell Biol. Toxicol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4020249","DOI":"10.1155\/2020\/4020249","article-title":"An Overview of Lipid Metabolism and Nonalcoholic Fatty Liver Disease","volume":"2020","author":"Pei","year":"2020","journal-title":"Biomed. Res. Int."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"178","DOI":"10.3390\/cells4020178","article-title":"Scavenger receptor structure and function in health and disease","volume":"4","author":"Zani","year":"2015","journal-title":"Cells"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1194\/jlr.R083121","article-title":"Scavenger receptor B type 1: Expression, molecular regulation, and cholesterol transport function","volume":"59","author":"Shen","year":"2018","journal-title":"J. Lipid Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e99","DOI":"10.1038\/emm.2014.38","article-title":"CD36, a scavenger receptor implicated in atherosclerosis","volume":"46","author":"Park","year":"2014","journal-title":"Exp. Mol. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3996","DOI":"10.1172\/JCI42823","article-title":"CD36 participates in a signaling pathway that regulates ROS formation in murine VSMCs","volume":"120","author":"Li","year":"2010","journal-title":"J. Clin. Investig."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1038\/mp.2011.109","article-title":"Pharmacogenetics of antipsychotic-induced weight gain: Review and clinical implications","volume":"17","author":"Lett","year":"2012","journal-title":"Mol. Psychiatry"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.mrgentox.2014.04.019","article-title":"Bisphenol A induces oxidative stress-associated DNA damage in INS-1 cells","volume":"769","author":"Xin","year":"2014","journal-title":"Mutat. Res. Genet. Toxicol. Environ. Mutagen."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.taap.2016.11.013","article-title":"The regulation of cellular apoptosis by the ROS-triggered PERK\/EIF2alpha\/chop pathway plays a vital role in bisphenol A-induced male reproductive toxicity","volume":"314","author":"Yin","year":"2017","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e12895","DOI":"10.1111\/acel.12895","article-title":"Reactive oxygen species-induced changes in glucose and lipid metabolism contribute to the accumulation of cholesterol in the liver during aging","volume":"18","author":"Seo","year":"2019","journal-title":"Aging Cell"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.cbi.2006.11.004","article-title":"A human hepatocellular in vitro model to investigate steatosis","volume":"165","author":"Donato","year":"2007","journal-title":"Chem. Biol. Interact."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"114941","DOI":"10.1016\/j.taap.2020.114941","article-title":"Benzyl isothiocyanate ameliorates high-fat\/cholesterol\/cholic acid diet-induced nonalcoholic steatohepatitis through inhibiting cholesterol crystal-activated NLRP3 inflammasome in Kupffer cells","volume":"393","author":"Chen","year":"2020","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1751","DOI":"10.1210\/en.2015-1384","article-title":"Bisphenol A Induces Fatty Liver by an Endocannabinoid-Mediated Positive Feedback Loop","volume":"157","author":"Martella","year":"2016","journal-title":"Endocrinology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s12940-018-0356-3","article-title":"Bisphenol a increases risk for presumed non-alcoholic fatty liver disease in Hispanic adolescents in NHANES 2003\u20132010","volume":"17","author":"Verstraete","year":"2018","journal-title":"Environ. Health"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"12","DOI":"10.7603\/s40681-014-0012-3","article-title":"Auricularia polytricha aqueous extract supplementation decreases hepatic lipid accumulation and improves antioxidative status in animal model of nonalcoholic fatty liver","volume":"4","author":"Chiu","year":"2014","journal-title":"Biomedicine"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Simoes, I.C.M., Amorim, R., Teixeira, J., Karkucinska-Wieckowska, A., Carvalho, A., Pereira, S.P., Simoes, R.F., Szymanska, S., Dabrowski, M., and Janikiewicz, J. (2021). The Alterations of Mitochondrial Function during NAFLD Progression-An Independent Effect of Mitochondrial ROS Production. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22136848"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Gassman, N.R., Coskun, E., Stefanick, D.F., Horton, J.K., Jaruga, P., Dizdaroglu, M., and Wilson, S.H. (2015). Bisphenol a promotes cell survival following oxidative DNA damage in mouse fibroblasts. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0118819"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Provvisiero, D.P., Pivonello, C., Muscogiuri, G., Negri, M., de Angelis, C., Simeoli, C., Pivonello, R., and Colao, A. (2016). Influence of Bisphenol A on Type 2 Diabetes Mellitus. Int. J. Environ. Res. Public Health, 13.","DOI":"10.3390\/ijerph13100989"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1007\/s12020-016-1158-4","article-title":"The influence of phthalates and bisphenol A on the obesity development and glucose metabolism disorders","volume":"55","author":"Stojanoska","year":"2017","journal-title":"Endocrine"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"273","DOI":"10.3109\/15376516.2012.753969","article-title":"Prooxidant actions of bisphenol A (BPA) phenoxyl radicals: Implications to BPA-related oxidative stress and toxicity","volume":"23","author":"Babu","year":"2013","journal-title":"Toxicol. Mech. Methods"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e1959","DOI":"10.1038\/cddis.2015.319","article-title":"Evaluation of low doses BPA-induced perturbation of glycemia by toxicogenomics points to a primary role of pancreatic islets and to the mechanism of toxicity","volume":"6","author":"Carchia","year":"2015","journal-title":"Cell Death Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"129212","DOI":"10.1016\/j.chemosphere.2020.129212","article-title":"Endocrine disrupting chemicals and metabolic disorders in the liver: What if we also looked at the female side?","volume":"268","year":"2021","journal-title":"Chemosphere"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1002\/em.22072","article-title":"Induction of oxidative stress by bisphenol A and its pleiotropic effects","volume":"58","author":"Gassman","year":"2017","journal-title":"Environ. Mol. Mutagen."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1530\/JOE-14-0356","article-title":"Perinatal exposure to bisphenol A exacerbates nonalcoholic steatohepatitis-like phenotype in male rat offspring fed on a high-fat diet","volume":"222","author":"Wei","year":"2014","journal-title":"J. Endocrinol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1016\/j.freeradbiomed.2010.02.003","article-title":"Aging and oxidatively damaged nuclear DNA in animal organs","volume":"48","author":"Moller","year":"2010","journal-title":"Free Radic. Biol. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1111\/IGC.0b013e3181ad0f0d","article-title":"DNA adduct 8-hydroxydeoxyguanosine, a novel putative marker of prognostic significance in ovarian carcinoma","volume":"19","author":"Karihtala","year":"2009","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.plefa.2010.02.029","article-title":"Fatty acid transport across the cell membrane: Regulation by fatty acid transporters","volume":"82","author":"Schwenk","year":"2010","journal-title":"Prostaglandins Leukot. Essent. Fat. Acids"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4032","DOI":"10.1074\/jbc.M113.524512","article-title":"Endoplasmic reticulum stress promotes macrophage-derived foam cell formation by up-regulating cluster of differentiation 36 (CD36) expression","volume":"289","author":"Yao","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Dludla, P.V., Nkambule, B.B., Mazibuko-Mbeje, S.E., Nyambuya, T.M., Marcheggiani, F., Cirilli, I., Ziqubu, K., Shabalala, S.C., Johnson, R., and Louw, J. (2020). N-Acetyl Cysteine Targets Hepatic Lipid Accumulation to Curb Oxidative Stress and Inflammation in NAFLD: A Comprehensive Analysis of the Literature. Antioxidants, 9.","DOI":"10.3390\/antiox9121283"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4339","DOI":"10.1590\/1413-812320202511.01852018","article-title":"Large-scale contamination by Bisphenol A: Are we aware of the risk and forms of exposure?","volume":"25","author":"Daronch","year":"2020","journal-title":"Cienc. Saude Colet."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2571","DOI":"10.4315\/0362-028X-72.12.2571","article-title":"Migration of bisphenol A from can coatings to liquid infant formula during storage at room temperature","volume":"72","author":"Cao","year":"2009","journal-title":"J. Food Prot."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1080\/026520300750038126","article-title":"Migration of bisphenol-A diglycidyl ether (BADGE) and its reaction products in canned foods","volume":"17","author":"Hammarling","year":"2000","journal-title":"Food Addit. Contam."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1289\/ehp.02110427","article-title":"Summary of the National Toxicology Program\u2019s report of the endocrine disruptors low-dose peer review","volume":"110","author":"Melnick","year":"2002","journal-title":"Environ. Health Perspect."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1002\/hep.24685","article-title":"Low doses of bisphenol A induce gene expression related to lipid synthesis and trigger triglyceride accumulation in adult mouse liver","volume":"55","author":"Marmugi","year":"2012","journal-title":"Hepatology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"110786","DOI":"10.1016\/j.fct.2019.110786","article-title":"Bisphenol A exposure induces cholesterol synthesis and hepatic steatosis in C57BL\/6 mice by down-regulating the DNA methylation levels of SREBP-2","volume":"133","author":"Li","year":"2019","journal-title":"Food Chem. Toxicol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"100322","DOI":"10.1016\/j.jhepr.2021.100322","article-title":"Non-alcoholic fatty liver disease: A patient guideline","volume":"3","author":"Francque","year":"2021","journal-title":"JHEP Rep."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1538\/expanim.20-0094","article-title":"A high-fat diet and high-fat and high-cholesterol diet may affect glucose and lipid metabolism differentially through gut microbiota in mice","volume":"70","author":"Liang","year":"2021","journal-title":"Exp. Anim."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1194\/jlr.M800042-JLR200","article-title":"Mechanisms of hepatic steatosis in mice fed a lipogenic methionine choline-deficient diet","volume":"49","author":"Rinella","year":"2008","journal-title":"J. Lipid Res."}],"container-title":["Toxics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2305-6304\/10\/5\/208\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:58:39Z","timestamp":1760137119000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2305-6304\/10\/5\/208"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,22]]},"references-count":54,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,5]]}},"alternative-id":["toxics10050208"],"URL":"https:\/\/doi.org\/10.3390\/toxics10050208","relation":{},"ISSN":["2305-6304"],"issn-type":[{"value":"2305-6304","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,22]]}}}