{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T10:07:52Z","timestamp":1787652472366,"version":"build-2736575974"},"reference-count":121,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2019,9,13]],"date-time":"2019-09-13T00:00:00Z","timestamp":1568332800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,9,13]],"date-time":"2019-09-13T00:00:00Z","timestamp":1568332800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Ministry of Education, Science and Technological Development of Serbia","award":["(Project III 46009)"],"award-info":[{"award-number":["(Project III 46009)"]}]},{"name":"the Oklahoma State University Center for Health Science Pilot Grant Program","award":["(#1-54333)"],"award-info":[{"award-number":["(#1-54333)"]}]},{"name":"Research Committee of the University of Crete","award":["ELKE"],"award-info":[{"award-number":["ELKE"]}]},{"name":"Ministry of Research and Innovation in Romania","award":["Program 1\u2014The Improvement of the National System of Research"],"award-info":[{"award-number":["Program 1\u2014The Improvement of the National System of Research"]}]},{"name":"Ministry of Research and Innovation in Romania","award":["Development, Subprogram 1.2\u2014Institutional Excellence"],"award-info":[{"award-number":["Development, Subprogram 1.2\u2014Institutional Excellence"]}]},{"name":"Ministry of Research and Innovation in Romania: Program 1\u2014The Improvement of the National System of Research and Development","award":["7PFE\/16.10.2018."],"award-info":[{"award-number":["7PFE\/16.10.2018."]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Arch Toxicol"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Humans are exposed to multiple chemicals on a daily basis instead of to just a single chemical, yet the majority of existing toxicity data comes from single-chemical exposure. Multiple factors must be considered such as the route, concentration, duration, and the timing of exposure when determining toxicity to the organism. The need for adequate model systems (in vivo, in vitro, in silico and mathematical) is paramount for better understanding of chemical mixture toxicity. Currently, shortcomings plague each model system as investigators struggle to find the appropriate balance of rigor, reproducibility and appropriateness in mixture toxicity studies. Significant questions exist when comparing single-to mixture-chemical toxicity concerning additivity, synergism, potentiation, or antagonism. Dose\/concentration relevance is a major consideration and should be subthreshold for better accuracy in toxicity assessment. Previous work was limited by the technology and methodology of the time, but recent advances have resulted in significant progress in the study of mixture toxicology. Novel technologies have added insight to data obtained from in vivo studies for predictive toxicity testing. These include new in vitro models: omics-related tools, organs-on-a-chip and 3D cell culture, and in silico methods. Taken together, all these modern methodologies improve the understanding of the multiple toxicity pathways associated with adverse outcomes (e.g., adverse outcome pathways), thus allowing investigators to better predict risks linked to exposure to chemical mixtures. As technology and knowledge advance, our ability to harness and integrate separate streams of evidence regarding outcomes associated with chemical mixture exposure improves. As many national and international organizations are currently stressing, studies on chemical mixture toxicity are of primary importance.<\/jats:p>","DOI":"10.1007\/s00204-019-02547-x","type":"journal-article","created":{"date-parts":[[2019,9,13]],"date-time":"2019-09-13T06:02:45Z","timestamp":1568354565000},"page":"2741-2757","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":94,"title":["Critical assessment and integration of separate lines of evidence for risk assessment of chemical mixtures"],"prefix":"10.1007","volume":"93","author":[{"given":"Antonio F.","family":"Hernandez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6942-7040","authenticated-orcid":false,"given":"Aleksandra","family":"Buha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Constantin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R.","family":"Wallace","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimosthenis","family":"Sarigiannis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Neagu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biljana","family":"Antonijevic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Wallace","family":"Hayes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin F.","family":"Wilks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aristidis","family":"Tsatsakis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,9,13]]},"reference":[{"key":"2547_CR1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cotox.2018.05.003","author":"ME Andersen","year":"2018","unstructured":"Andersen ME, Pendse SN, Black MB, McMullen PD (2018) Application of transcriptomic data, visualization tools and bioinformatics resources for informing mode of action. Curr Opin Toxicol. https:\/\/doi.org\/10.1016\/j.cotox.2018.05.003","journal-title":"Curr Opin Toxicol"},{"key":"2547_CR2","doi-asserted-by":"publisher","DOI":"10.1016\/j.envres.2014.10.018","author":"SS Andra","year":"2015","unstructured":"Andra SS, Charisiadis P, Karakitsios S et al (2015) Passive exposures of children to volatile trihalomethanes during domestic cleaning activities of their parents. Environ Res. https:\/\/doi.org\/10.1016\/j.envres.2014.10.018","journal-title":"Environ Res"},{"issue":"12","key":"2547_CR300","doi-asserted-by":"publisher","first-page":"1983","DOI":"10.1038\/sj.bjc.6602297","volume":"91","author":"P Armitage","year":"2004","unstructured":"Armitage P, Doll R (2004) The age distribution of cancer and a multi-stage theory of carcinogenesis. Br J Cancer 91(12):1983\u20131989","journal-title":"Br J Cancer"},{"key":"2547_CR3","unstructured":"ATSDR (2018) Framework for assessing health impacts of multiple chemicals and other stressors (Update)"},{"key":"2547_CR4","doi-asserted-by":"publisher","DOI":"10.1002\/9780470698976.ch21","author":"MS Attene-Ramos","year":"2013","unstructured":"Attene-Ramos MS, Huang R, Sakamuru S et al (2013) Systematic study of mitochondrial toxicity of environmental chemicals using quantitative high throughput screening. Chem Res Toxicol. https:\/\/doi.org\/10.1002\/9780470698976.ch21","journal-title":"Chem Res Toxicol"},{"key":"2547_CR5","doi-asserted-by":"publisher","DOI":"10.1021\/es960192r","author":"LL Aylward","year":"1996","unstructured":"Aylward LL, Hays SM, Karch NJ, Paustenbach DJ (1996) Relative susceptibility of animals and humans to the cancer hazard posed by 2,3,7,8-tetrachlorodibenzo-p-dioxin using internal measures of dose. Environ Sci Technol. https:\/\/doi.org\/10.1021\/es960192r","journal-title":"Environ Sci Technol"},{"key":"2547_CR6","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2010-1722f","author":"R Ball","year":"2011","unstructured":"Ball R, Horne D, Izurieta H et al (2011) Statistical, epidemiological, and risk-assessment approaches to evaluating safety of vaccines throughout the life cycle at the Food and Drug Administration. Pediatrics. https:\/\/doi.org\/10.1542\/peds.2010-1722f","journal-title":"Pediatrics"},{"key":"2547_CR7","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1007\/978-3-319-12751-4_7","volume-title":"Toxicological risk assessment for beginners","author":"MD Barrie","year":"2015","unstructured":"Barrie MD, Nichols G (2015) Use of epidemiology in risk assessment. In: Torres J, Bobst S (eds) Toxicological risk assessment for beginners. Springer International Publishing, Switzerland, pp 135\u2013159"},{"key":"2547_CR8","doi-asserted-by":"publisher","DOI":"10.1016\/j.yrtph.2010.01.005","author":"R Beaudouin","year":"2010","unstructured":"Beaudouin R, Micallef S, Brochot C (2010) A stochastic whole-body physiologically based pharmacokinetic model to assess the impact of inter-individual variability on tissue dosimetry over the human lifespan. Regul Toxicol Pharmacol. https:\/\/doi.org\/10.1016\/j.yrtph.2010.01.005","journal-title":"Regul Toxicol Pharmacol"},{"key":"2547_CR9","doi-asserted-by":"publisher","DOI":"10.1006\/toxs.1998.2458","author":"VA Benignus","year":"1998","unstructured":"Benignus VA, Boyes WK, Bushnell PJ (1998) A dosimetric analysis of behavioral effects of acute toluene exposure in rats and humans. Toxicol Sci. https:\/\/doi.org\/10.1006\/toxs.1998.2458","journal-title":"Toxicol Sci"},{"key":"2547_CR10","doi-asserted-by":"publisher","DOI":"10.1016\/j.marenvres.2013.10.008","author":"J Beyer","year":"2014","unstructured":"Beyer J, Petersen K, Song Y et al (2014) Environmental risk assessment of combined effects in aquatic ecotoxicology: a discussion paper. Mar Environ Res. https:\/\/doi.org\/10.1016\/j.marenvres.2013.10.008","journal-title":"Mar Environ Res"},{"key":"2547_CR12","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfp036","author":"KT Bogen","year":"2009","unstructured":"Bogen KT, Cullen AC, Frey HC, Price PS (2009) Probabilistic exposure analysis for chemical risk characterization. Toxicol Sci. https:\/\/doi.org\/10.1093\/toxsci\/kfp036","journal-title":"Toxicol Sci"},{"key":"2547_CR13","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2010.06.007","author":"FY Bois","year":"2010","unstructured":"Bois FY, Jamei M, Clewell HJ (2010) PBPK modelling of inter-individual variability in the pharmacokinetics of environmental chemicals. Toxicology. https:\/\/doi.org\/10.1016\/j.tox.2010.06.007","journal-title":"Toxicology"},{"key":"2547_CR14","doi-asserted-by":"publisher","DOI":"10.3109\/10408444.2010.543655","author":"A Boobis","year":"2011","unstructured":"Boobis A, Budinsky R, Collie S (2011) Critical analysis of literature on low-dose synergy for use in screening chemical mixtures for risk assessment. Rev. Toxicol Crit. https:\/\/doi.org\/10.3109\/10408444.2010.543655","journal-title":"Rev. Toxicol Crit"},{"key":"2547_CR15","unstructured":"Bopp S, Berggren E, Kienzler A et al (2015) Scientific methodologies for the assessment of combined effects of chemicals\u2013a survey and literature review. Publications Office of the European Union"},{"key":"2547_CR16","unstructured":"Bopp KS, Kienzler A. van der Linden S, Lamon L, Paini A, Parissis N, Richarz AN, Triebe J Worth A (2016) Review of case studies on the human and environmental risk assessment of chemical mixtures. Publications Office of the European Union"},{"key":"2547_CR17","doi-asserted-by":"publisher","DOI":"10.1016\/j.envint.2018.07.037","author":"SK Bopp","year":"2018","unstructured":"Bopp SK, Barouki R, Brack W et al (2018) Current EU research activities on combined exposure to multiple chemicals. Environ Int. https:\/\/doi.org\/10.1016\/j.envint.2018.07.037","journal-title":"Environ Int"},{"key":"2547_CR18","doi-asserted-by":"publisher","DOI":"10.1080\/10408444.2019","author":"SK Bopp","year":"2019","unstructured":"Bopp SK, Kienzler A, Richarz AN, van der Linden SC, Paini A, Parissis N, Worth AP (2019) Regulatory assessment and risk management of chemical mixtures: challenges and ways forward. Crit Rev Toxicol. https:\/\/doi.org\/10.1080\/10408444.2019","journal-title":"Crit Rev Toxicol"},{"key":"2547_CR19","doi-asserted-by":"publisher","DOI":"10.1002\/widm.1074","author":"C Borgelt","year":"2012","unstructured":"Borgelt C (2012) Frequent item set mining. Wiley Interdiscip Rev Data Min Knowl Discov. https:\/\/doi.org\/10.1002\/widm.1074","journal-title":"Wiley Interdiscip Rev Data Min Knowl Discov"},{"key":"2547_CR20","doi-asserted-by":"publisher","DOI":"10.1080\/20018091094376","author":"CJ Borgert","year":"2001","unstructured":"Borgert CJ, Price B, Wells CS, Simon GS (2001) Evaluating chemical interaction studies for mixture risk assessment. Hum Ecol Risk Assess An Int J. https:\/\/doi.org\/10.1080\/20018091094376","journal-title":"Hum Ecol Risk Assess An Int J"},{"key":"2547_CR21","doi-asserted-by":"publisher","DOI":"10.1038\/s41370-018-0052-y","author":"N Brandon","year":"2018","unstructured":"Brandon N, Dionisio KL, Isaacs K et al (2018) Simulating exposure-related behaviors using agent-based models embedded with needs-based artificial intelligence. J. Expo. Sci. Environ. Epidemio. https:\/\/doi.org\/10.1038\/s41370-018-0052-y","journal-title":"J. Expo. Sci. Environ. Epidemio."},{"key":"2547_CR22","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.1510569","author":"JM Braun","year":"2016","unstructured":"Braun JM, Gennings C, Hauser R, Webster TF (2016) What can epidemiological studies tell us about the impact of chemical mixtures on human health? Environ Health Perspect. https:\/\/doi.org\/10.1289\/ehp.1510569","journal-title":"Environ Health Perspect"},{"key":"2547_CR23","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfx097","author":"EK Brockmeier","year":"2017","unstructured":"Brockmeier EK, Hodges G, Hutchinson TH et al (2017) The role of omics in the application of adverse outcome pathways for chemical risk assessment. Toxicol Sci. https:\/\/doi.org\/10.1093\/toxsci\/kfx097","journal-title":"Toxicol Sci"},{"key":"2547_CR24","doi-asserted-by":"publisher","DOI":"10.1021\/acs.est.5b02641","author":"P Browne","year":"2015","unstructured":"Browne P, Judson RS, Casey WM et al (2015) Screening chemicals for estrogen receptor bioactivity using a computational model. Environ Sci Technol. https:\/\/doi.org\/10.1021\/acs.est.5b02641","journal-title":"Environ Sci Technol"},{"key":"2547_CR25","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2008.05.012","author":"B Brunekreef","year":"2008","unstructured":"Brunekreef B (2008) Environmental epidemiology and risk assessment. Toxicol Lett. https:\/\/doi.org\/10.1016\/j.toxlet.2008.05.012","journal-title":"Toxicol Lett"},{"key":"2547_CR26","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2013.06.216","author":"A Buha","year":"2013","unstructured":"Buha A, Antonijevi\u0107 B, Bulat Z et al (2013) The impact of prolonged cadmium exposure and co-exposure with polychlorinated biphenyls on thyroid function in rats. Toxicol Lett. https:\/\/doi.org\/10.1016\/j.toxlet.2013.06.216","journal-title":"Toxicol Lett"},{"key":"2547_CR27","doi-asserted-by":"publisher","DOI":"10.1002\/etc.2299","author":"RM Burgess","year":"2013","unstructured":"Burgess RM, Ho KT, Brack W, Lamoree M (2013) Effects-directed analysis (EDA) and toxicity identification evaluation (TIE): complementary but different approaches for diagnosing causes of environmental toxicity. Environ Toxicol Chem. https:\/\/doi.org\/10.1002\/etc.2299","journal-title":"Environ Toxicol Chem"},{"key":"2547_CR28","doi-asserted-by":"publisher","DOI":"10.1039\/c6tx00193a","author":"H Chen","year":"2016","unstructured":"Chen H, Liu Z, Zhang X et al (2016) Assessment of synergistic thyroid disrupting effects of a mixture of EDCs in ovariectomized rats using factorial analysis and dose addition. Toxicol Res (Camb). https:\/\/doi.org\/10.1039\/c6tx00193a","journal-title":"Toxicol Res (Camb)"},{"key":"2547_CR29","doi-asserted-by":"publisher","DOI":"10.1016\/j.copbio.2016.11.019","author":"S Cho","year":"2017","unstructured":"Cho S, Yoon JY (2017) Organ-on-a-chip for assessing environmental toxicants. Curr Opin Biotechnol. https:\/\/doi.org\/10.1016\/j.copbio.2016.11.019","journal-title":"Curr Opin Biotechnol"},{"key":"2547_CR30","doi-asserted-by":"publisher","DOI":"10.1021\/acs.est.6b06230","author":"RB Conolly","year":"2017","unstructured":"Conolly RB, Ankley GT, Cheng W et al (2017) Quantitative adverse outcome pathways and their application to predictive toxicology. Environ Sci Technol. https:\/\/doi.org\/10.1021\/acs.est.6b06230","journal-title":"Environ Sci Technol"},{"key":"2547_CR31","doi-asserted-by":"publisher","DOI":"10.1016\/j.etap.2014.07.021","author":"M Curcic","year":"2014","unstructured":"Curcic M, Durgo K, Kopjar N et al (2014) Cadmium and decabrominated diphenyl ether mixture: in vitro evaluation of cytotoxic, prooxidative and genotoxic effects. Environ Toxicol Pharmacol. https:\/\/doi.org\/10.1016\/j.etap.2014.07.021","journal-title":"Environ Toxicol Pharmacol"},{"key":"2547_CR32","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2016.05.011","author":"M Curcic","year":"2017","unstructured":"Curcic M, Buha A, Stankovic S et al (2017) Interactions between cadmium and decabrominated diphenyl ether on blood cells count in rats\u2014Multiple factorial regression analysis. Toxicology. https:\/\/doi.org\/10.1016\/j.tox.2016.05.011","journal-title":"Toxicology"},{"key":"2547_CR33","doi-asserted-by":"publisher","first-page":"255","DOI":"10.2478\/10004-1254-63-2012-2179","volume":"63","author":"M \u0106ur\u010di\u0107","year":"2012","unstructured":"\u0106ur\u010di\u0107 M, Jankovi\u0107 S, Ja\u0107evi\u0107 V et al (2012) Combined effects of cadmium and decabrominated diphenyl ether on thyroid hormones in rats. Arh Hig Rada Toksikol 63:255\u2013262. https:\/\/doi.org\/10.2478\/10004-1254-63-2012-2179","journal-title":"Arh Hig Rada Toksikol"},{"key":"2547_CR34","doi-asserted-by":"publisher","DOI":"10.1289\/ehp474","author":"KK Dennis","year":"2017","unstructured":"Dennis KK, Marder E, Balshaw DM et al (2017) Biomonitoring in the era of the exposome. Environ. Health Perspect. https:\/\/doi.org\/10.1289\/ehp474","journal-title":"Environ. Health Perspect."},{"key":"2547_CR35","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2018.03.052","author":"AO Docea","year":"2018","unstructured":"Docea AO, Gofita E, Goumenou M et al (2018) Six months exposure to a real life mixture of 13 chemicals\u2019 below individual NOAELs induced non monotonic sex-dependent biochemical and redox status changes in rats. Food Chem Toxicol. https:\/\/doi.org\/10.1016\/j.fct.2018.03.052","journal-title":"Food Chem Toxicol"},{"key":"2547_CR36","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2019.04.005","author":"AO Docea","year":"2019","unstructured":"Docea AO, Goumenou M, Calina D et al (2019) Adverse and hormetic effects in rats exposed for 12\u00a0months to low dose mixture of 13 chemicals: RLRS part III. Toxicol Lett. https:\/\/doi.org\/10.1016\/j.toxlet.2019.04.005","journal-title":"Toxicol Lett"},{"key":"2547_CR37","unstructured":"ECETOC (European centre for ecotoxicology and toxicology of chemicals) (2009) Framework for the integration of human and animal data in chemical risk assessment. technical report No. 104. Brussels. http:\/\/www.ecetoc.org\/uploads\/Publications\/documents\/TR%20104.pdf . Accessed 2 May 2019"},{"key":"2547_CR38","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.0800073","author":"AN Edginton","year":"2009","unstructured":"Edginton AN, Ritter L (2009) Predicting plasma concentrations of bisphenol A in children younger than 2\u00a0years of age after typical feeding schedules, using a physiologically based toxicokinetic model. Environ Health Perspect. https:\/\/doi.org\/10.1289\/ehp.0800073","journal-title":"Environ Health Perspect"},{"key":"2547_CR39","doi-asserted-by":"publisher","DOI":"10.2903\/j.efsa.2013.3472","author":"EFSA Panel on Plant Protection Products and their Residues","year":"2013","unstructured":"EFSA Panel on Plant Protection Products and their Residues (2013) Scientific opinion on relevance of dissimilar mode of action and its appropriate application for cumulative risk assessment of pesticides residues in food. EFSA J. https:\/\/doi.org\/10.2903\/j.efsa.2013.3472","journal-title":"EFSA J"},{"key":"2547_CR40","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.98106s61281","author":"VJ Feron","year":"1998","unstructured":"Feron VJ, Cassee FR, Groten JP (1998) Toxicology of chemical mixtures: international perspective. Environ Health Perspect. https:\/\/doi.org\/10.1289\/ehp.98106s61281","journal-title":"Environ Health Perspect."},{"key":"2547_CR41","unstructured":"Fryer \u039c, Collins C, Colvile R, Ferrier H, Nieuwenhuijsen M (2004) Evaluation of currently used exposure models to define a human exposure model for use in chemical risk assessment in the UK. Department of Environmental Science and Technology, Imperial College, London"},{"key":"2547_CR42","doi-asserted-by":"publisher","DOI":"10.1080\/10937400600755929","author":"PG Georgopoulos","year":"2006","unstructured":"Georgopoulos PG, Lioy PJ (2006) From a theoretical framework of human exposure and dose assessment to computational system implementation: the modeling environment for total risk studies (MENTOR). J Toxicol Environ Heal\u2014Part B Crit Rev. https:\/\/doi.org\/10.1080\/10937400600755929","journal-title":"J Toxicol Environ Heal\u2014Part B Crit Rev"},{"key":"2547_CR43","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jea.7500422","author":"PG Georgopoulos","year":"2005","unstructured":"Georgopoulos PG, Wang SW, Vyas VM et al (2005) A source-to-dose assessment of population exposures to fine PM and ozone in Philadelphia, PA, during a summer 1999 episode. J Expo Anal Environ Epidemiol. https:\/\/doi.org\/10.1038\/sj.jea.7500422","journal-title":"J Expo Anal Environ Epidemiol"},{"key":"2547_CR44","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jes.7500462","author":"PG Georgopoulos","year":"2006","unstructured":"Georgopoulos PG, Wang SW, Georgopoulos IG et al (2006) Assessment of human exposure to copper: a case study using the NHEXAS database. J Expo Sci Environ Epidemiol. https:\/\/doi.org\/10.1038\/sj.jes.7500462","journal-title":"J Expo Sci Environ Epidemiol"},{"key":"2547_CR45","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jes.7500637","author":"PG Georgopoulos","year":"2008","unstructured":"Georgopoulos PG, Wang SW, Yang YC et al (2008) Biologically based modeling of multimedia, multipathway, multiroute population exposures to arsenic. J Expo Sci Environ Epidemiol. https:\/\/doi.org\/10.1038\/sj.jes.7500637","journal-title":"J Expo Sci Environ Epidemiol"},{"key":"2547_CR46","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxrep.2019.06.010","author":"M Goumenou","year":"2019","unstructured":"Goumenou M, Tsatsakis A (2019) Proposing new approaches for the risk characterisation of single chemicals and chemical mixtures: the source related hazard quotient (HQS) and hazard index (HIS) and the adversity specific hazard index (HIA). Toxicol Reports. https:\/\/doi.org\/10.1016\/j.toxrep.2019.06.010","journal-title":"Toxicol Reports"},{"key":"2547_CR47","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-6147(00)01720-X","author":"JP Groten","year":"2001","unstructured":"Groten JP, Feron VJ, S\u00fchnel J (2001) Toxicology of simple and complex mixtures. Trends Pharmacol Sci. https:\/\/doi.org\/10.1016\/S0165-6147(00)01720-X","journal-title":"Trends Pharmacol Sci."},{"key":"2547_CR48","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jproteome.7b00693","author":"Y Han","year":"2018","unstructured":"Han Y, Zhao J, Huang R et al (2018) Omics-based platform for studying chemical toxicity using stem cells. J Proteome Res. https:\/\/doi.org\/10.1021\/acs.jproteome.7b00693","journal-title":"J Proteome Res"},{"key":"2547_CR49","volume-title":"Guidelines for good exposure assessment practice for human health effects of chemicals","author":"D Harper","year":"2004","unstructured":"Harper D (2004) Guidelines for good exposure assessment practice for human health effects of chemicals. The Interdepartmental Group on Health Risks from Chemicals, Leicester"},{"key":"2547_CR50","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1016\/j.fct.2017.03.012","volume":"103","author":"AF Hern\u00e1ndez","year":"2017","unstructured":"Hern\u00e1ndez AF, Tsatsakis AM (2017) Human exposure to chemical mixtures: challenges for the integration of toxicology with epidemiology data in risk assessment. Food Chem Toxicol 103:188\u2013193. https:\/\/doi.org\/10.1016\/j.fct.2017.03.012","journal-title":"Food Chem Toxicol"},{"key":"2547_CR51","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2012.06.009","author":"AF Hern\u00e1ndez","year":"2013","unstructured":"Hern\u00e1ndez AF, Parr\u00f3n T, Tsatsakis AM et al (2013) Toxic effects of pesticide mixtures at a molecular level: their relevance to human health. Toxicology. https:\/\/doi.org\/10.1016\/j.tox.2012.06.009","journal-title":"Toxicology"},{"key":"2547_CR52","doi-asserted-by":"publisher","DOI":"10.1007\/s00204-017-2043-5","author":"AF Hern\u00e1ndez","year":"2017","unstructured":"Hern\u00e1ndez AF, Gil F, Lacasa\u00f1a M (2017) Toxicological interactions of pesticide mixtures: an update. Arch Toxicol. https:\/\/doi.org\/10.1007\/s00204-017-2043-5","journal-title":"Arch Toxicol"},{"key":"2547_CR53","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.1002952","author":"R Huang","year":"2011","unstructured":"Huang R, Xia M, Cho MH et al (2011) Chemical genomics profiling of environmental chemical modulation of human nuclear receptors. Environ Health Perspect. https:\/\/doi.org\/10.1289\/ehp.1002952","journal-title":"Environ Health Perspect"},{"key":"2547_CR54","doi-asserted-by":"publisher","DOI":"10.1002\/minf.201700129","author":"J Hur","year":"2018","unstructured":"Hur J, Danes L, Hsieh JH et al (2018) Tox21 Enricher: web-based chemical\/biological functional annotation analysis tool based on Tox21 toxicity screening platform. Mol Inform. https:\/\/doi.org\/10.1002\/minf.201700129","journal-title":"Mol Inform"},{"key":"2547_CR55","doi-asserted-by":"publisher","DOI":"10.1016\/j.copbio.2011.05.512","author":"NK Inamdar","year":"2011","unstructured":"Inamdar NK, Borenstein JT (2011) Microfluidic cell culture models for tissue engineering. Curr Opin Biotechnol. https:\/\/doi.org\/10.1016\/j.copbio.2011.05.512","journal-title":"Curr Opin Biotechnol."},{"key":"2547_CR56","doi-asserted-by":"publisher","DOI":"10.1016\/j.yrtph.2017.06.010","author":"J Kaltenh\u00e4user","year":"2017","unstructured":"Kaltenh\u00e4user J, Kneuer C, Marx-Stoelting P et al (2017) Relevance and reliability of experimental data in human health risk assessment of pesticides. Regul Toxicol Pharmacol. https:\/\/doi.org\/10.1016\/j.yrtph.2017.06.010","journal-title":"Regul Toxicol Pharmacol"},{"key":"2547_CR57","doi-asserted-by":"publisher","DOI":"10.1016\/j.yrtph.2016.05.020","author":"A Kienzler","year":"2016","unstructured":"Kienzler A, Bopp SK, van der Linden S et al (2016) Regulatory assessment of chemical mixtures: requirements, current approaches and future perspectives. Regul Toxicol Pharmacol. https:\/\/doi.org\/10.1016\/j.yrtph.2016.05.020","journal-title":"Regul Toxicol Pharmacol"},{"key":"2547_CR58","doi-asserted-by":"publisher","DOI":"10.1002\/etc.4125","author":"D Knapen","year":"2018","unstructured":"Knapen D, Angrish MM, Fortin MC et al (2018) Adverse outcome pathway networks I: development and applications. Environ Toxicol Chem. https:\/\/doi.org\/10.1002\/etc.4125","journal-title":"Environ Toxicol Chem"},{"key":"2547_CR59","doi-asserted-by":"publisher","DOI":"10.1002\/jat.3577","author":"S Kohno","year":"2018","unstructured":"Kohno S, Katsu Y, Cipoletti N et al (2018) Divergent responsiveness of two isoforms of the estrogen receptor to mixtures of contaminants of emerging concern in four vertebrates. J Appl Toxicol. https:\/\/doi.org\/10.1002\/jat.3577","journal-title":"J Appl Toxicol"},{"key":"2547_CR60","doi-asserted-by":"publisher","DOI":"10.1016\/j.envres.2014.07.012","author":"A Kokkinaki","year":"2014","unstructured":"Kokkinaki A, Kokkinakis M, Kavvalakis MP et al (2014) Biomonitoring of dialkylphosphate metabolites (DAPs) in urine and hair samples of sprayers and rural residents of Crete, Greece. Environ Res. https:\/\/doi.org\/10.1016\/j.envres.2014.07.012","journal-title":"Environ Res"},{"key":"2547_CR61","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxrep.2018.10.010","author":"RN Kostoff","year":"2018","unstructured":"Kostoff RN, Goumenou M, Tsatsakis A (2018) The role of toxic stimuli combinations in determining safe exposure limits. Toxicol Reports. https:\/\/doi.org\/10.1016\/j.toxrep.2018.10.010","journal-title":"Toxicol Reports"},{"key":"2547_CR62","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2011.10.007","author":"M Koureas","year":"2012","unstructured":"Koureas M, Tsakalof A, Tsatsakis A, Hadjichristodoulou C (2012) Systematic review of biomonitoring studies to determine the association between exposure to organophosphorus and pyrethroid insecticides and human health outcomes. Toxicol Lett. https:\/\/doi.org\/10.1016\/j.toxlet.2011.10.007","journal-title":"Toxicol Lett"},{"key":"2547_CR63","doi-asserted-by":"publisher","DOI":"10.1289\/ehp2207","author":"N Lazarevic","year":"2019","unstructured":"Lazarevic N, Barnett AG, Sly PD, Knibbs LD (2019) Statistical methodology in studies of prenatal exposure to mixtures of endocrine-disrupting chemicals: a review of existing approaches and new alternatives. Environ Health Perspect. https:\/\/doi.org\/10.1289\/ehp2207","journal-title":"Environ Health Perspect"},{"key":"2547_CR64","volume-title":"EUSES version 2.0.","author":"J Lijzen","year":"2004","unstructured":"Lijzen J, Rikken M (2004) EUSES version 2.0. RIVM, Bilthoven"},{"key":"2547_CR65","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jes.7500567","author":"PJ Lioy","year":"2007","unstructured":"Lioy PJ, Vallero D, Foley G et al (2007) A personal exposure study employing scripted activities and paths in conjunction with atmospheric releases of perfluorocarbon tracers in Manhattan, New York. J Expo Sci Environ Epidemiol. https:\/\/doi.org\/10.1038\/sj.jes.7500567","journal-title":"J Expo Sci Environ Epidemiol"},{"key":"2547_CR66","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2017.09.011","author":"Y Liu","year":"2017","unstructured":"Liu Y, Hardie J, Zhang X, Rotello VM (2017) Effects of engineered nanoparticles on the innate immune system. Semin Immunol. https:\/\/doi.org\/10.1016\/j.smim.2017.09.011","journal-title":"Semin Immunol"},{"key":"2547_CR67","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2012.09.015","author":"MEB Meek","year":"2013","unstructured":"Meek MEB (2013) International experience in addressing combined exposures: increasing the efficiency of assessment. Toxicology. https:\/\/doi.org\/10.1016\/j.tox.2012.09.015","journal-title":"Toxicology"},{"key":"2547_CR68","doi-asserted-by":"publisher","DOI":"10.1081\/dmr-100100572","author":"RL Melnick","year":"2000","unstructured":"Melnick RL, Kohn MC (2000) Dose-response analyses of experimental cancer data. Drug Metab Rev. https:\/\/doi.org\/10.1081\/dmr-100100572","journal-title":"Drug Metab Rev"},{"key":"2547_CR69","doi-asserted-by":"publisher","DOI":"10.1002\/9783527630196.ch1","volume-title":"Introduction to mixtures toxicology and risk assessment. In: Moiz Mumtaz M (ed) Principles and practice of mixtures toxicology","author":"MM Mumtaz","year":"2010","unstructured":"Mumtaz MM, William Suk WA, Yang RSH (2010) Introduction to mixtures toxicology and risk assessment. In: Moiz Mumtaz M (ed) Principles and practice of mixtures toxicology. Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. https:\/\/doi.org\/10.1002\/9783527630196.ch1"},{"key":"2547_CR70","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.6987","author":"E Monosson","year":"2005","unstructured":"Monosson E (2005) Chemical mixtures: considering the evolution of toxicology and chemical assessment. Environ Health Perspect. https:\/\/doi.org\/10.1289\/ehp.6987","journal-title":"Environ Health Perspect"},{"key":"2547_CR71","doi-asserted-by":"publisher","DOI":"10.1007\/s00477-007-0143-0","author":"CM Mutshinda","year":"2008","unstructured":"Mutshinda CM, Antai I, O\u2019Hara RB (2008) A probabilistic approach to exposure risk assessment. Stoch Environ Res Risk Assess. https:\/\/doi.org\/10.1007\/s00477-007-0143-0","journal-title":"Stoch Environ Res Risk Assess"},{"key":"2547_CR72","volume-title":"Toxicity testing in the 21st century: A vision and a strategy","author":"National Research Council (NRC)","year":"2007","unstructured":"National Research Council (NRC) (2007) Toxicity testing in the 21st century: A vision and a strategy. National Academy Press, DC"},{"key":"2547_CR73","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1007\/978-3-319-56234-6_7","volume-title":"Chemical mixtures and combined chemical and nonchemical stressors","author":"MD Nelms","year":"2018","unstructured":"Nelms MD, Simmons JA, Edwards SW (2018) Adverse outcome pathways to support the assessment of chemical mixtures. In: Rider CV, Simmons JE (eds) Chemical mixtures and combined chemical and nonchemical stressors. Springer International Publishing AG, Basel, pp 177\u2013201"},{"key":"2547_CR74","doi-asserted-by":"publisher","DOI":"10.2903\/j.efsa.2017.5007","author":"C Ockleford","year":"2017","unstructured":"Ockleford C, Adriaanse P, Berny P et al (2017) Scientific Opinion of the PPR Panel on the follow-up of the findings of the External Scientific Report \u2018Literature review of epidemiological studies linking exposure to pesticides and health effects\u2019. EFSA J. https:\/\/doi.org\/10.2903\/j.efsa.2017.5007","journal-title":"EFSA J"},{"key":"2547_CR75","doi-asserted-by":"publisher","DOI":"10.1787\/5jlv1m9d1g32-en","volume-title":"Users\u2019 Handbook supplement to the guidance document for developing and assessing adverse outcome pathways\u201d, OECD series on adverse outcome pathways, No. 1","author":"OECD","year":"2018","unstructured":"OECD (2018) Users\u2019 Handbook supplement to the guidance document for developing and assessing adverse outcome pathways\u201d, OECD series on adverse outcome pathways, No. 1. OECD Publishing, Paris. https:\/\/doi.org\/10.1787\/5jlv1m9d1g32-en"},{"key":"2547_CR76","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrestox.6b00269","author":"D Pamies","year":"2017","unstructured":"Pamies D, Hartung T (2017) 21st century cell culture for 21st century toxicology. Chem Res Toxicol. https:\/\/doi.org\/10.1021\/acs.chemrestox.6b00269","journal-title":"Chem Res Toxicol"},{"key":"2547_CR77","doi-asserted-by":"publisher","DOI":"10.1177\/1535370214537738","author":"D Pamies","year":"2014","unstructured":"Pamies D, Hartung T, Hogberg HT (2014) Biological and medical applications of a brain-on-a-chip. Exp Biol Med. https:\/\/doi.org\/10.1177\/1535370214537738","journal-title":"Exp Biol Med"},{"key":"2547_CR78","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2017.10.044","author":"KC Papadaki","year":"2017","unstructured":"Papadaki KC, Karakitsios SP, Sarigiannis DA (2017) Modeling of adipose\/blood partition coefficient for environmental chemicals. Food Chem Toxicol. https:\/\/doi.org\/10.1016\/j.fct.2017.10.044","journal-title":"Food Chem Toxicol"},{"key":"2547_CR79","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1007\/978-3-319-56234-6_5","volume-title":"Chemical mixtures and combined chemical and nonchemical stressors","author":"CJ Patel","year":"2018","unstructured":"Patel CJ (2018) Introduction to environment and exposome-wide association studies: a data-driven method to identify multiple environmental factors associated with phenotypes in human populations. In: Rider CV, Simmons JE (eds) Chemical mixtures and combined chemical and nonchemical stressors. Springer International Publishing AG, Basel, pp 129\u2013149"},{"key":"2547_CR80","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2009.10.046","author":"A Pistocchi","year":"2010","unstructured":"Pistocchi A, Sarigiannis DA, Vizcaino P (2010) Spatially explicit multimedia fate models for pollutants in Europe: state of the art and perspectives. Sci Total Environ. https:\/\/doi.org\/10.1016\/j.scitotenv.2009.10.046","journal-title":"Sci Total Environ"},{"issue":"4","key":"2547_CR200","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1517\/17460441.2014.886562","volume":"9","author":"A Polini","year":"2014","unstructured":"Polini A, Prodanov L, Bhise NS, Manoharan V, Dokmeci MR, Khademhosseini A (2014) Organs-on-a-chip: a new tool for drug discovery. Expert Opin Drug Discov 9(4):335\u2013352","journal-title":"Expert Opin Drug Discov"},{"key":"2547_CR81","doi-asserted-by":"publisher","DOI":"10.2903\/sp.efsa.2015.EN-861","author":"N Quignot","year":"2015","unstructured":"Quignot N, Grech A, Amzal B (2015) Data collection on combined toxicity of multiple chemicals for animal health and ecological risk assessment. EFSA Support Publ. https:\/\/doi.org\/10.2903\/sp.efsa.2015.EN-861","journal-title":"EFSA Support Publ"},{"key":"2547_CR82","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2019.03.027","author":"EA Renieri","year":"2019","unstructured":"Renieri EA, Goumenou M, Kardonsky DA et al (2019) Indicator PCBs in farmed and wild fish in Greece\u2014Risk assessment for the Greek population. Food Chem Toxicol. https:\/\/doi.org\/10.1016\/j.fct.2019.03.027","journal-title":"Food Chem Toxicol"},{"key":"2547_CR83","doi-asserted-by":"publisher","DOI":"10.1016\/j.envint.2016.07.011","author":"N Roth","year":"2016","unstructured":"Roth N, Ciffroy P (2016) A critical review of frameworks used for evaluating reliability and relevance of (eco)toxicity data: perspectives for an integrated eco-human decision-making framework. Environ Int. https:\/\/doi.org\/10.1016\/j.envint.2016.07.011","journal-title":"Environ Int"},{"key":"2547_CR84","unstructured":"Rotter S, Beronius A, Hanberg A, Zilliacus J, Nikolopoulou D, Machera K, Solecki R (2017). Report on mixtures and implementation strategy in Europe\u2013Assessment of chemical mixtures under consideration of current and future regulatory requirements and scientific approaches. EuroMix\u2014European Test and Risk Assessment Strategies for Mixtures\u2014Deliverable 9.1\u2013Report. 10.5281\/zenodo.1067586, Accessed 10 April 2019"},{"key":"2547_CR85","doi-asserted-by":"publisher","DOI":"10.3109\/10408444.2014.986054","author":"D Rouqui\u00e9","year":"2015","unstructured":"Rouqui\u00e9 D, Heneweer M, Botham J et al (2015) Contribution of new technologies to characterization and prediction of adverse effects. Crit Rev Toxicol. https:\/\/doi.org\/10.3109\/10408444.2014.986054","journal-title":"Crit Rev Toxicol"},{"key":"2547_CR86","doi-asserted-by":"publisher","DOI":"10.26356\/plantprotectionproducts","volume-title":"Improving authorisation processes for plant protection products in Europe: a scientific perspective on the potential risks to human health","author":"SAPEA (Science Advice for Policy by European Academies)","year":"2018","unstructured":"SAPEA (Science Advice for Policy by European Academies) (2018) Improving authorisation processes for plant protection products in Europe: a scientific perspective on the potential risks to human health. SAPEA, Berlin. https:\/\/doi.org\/10.26356\/plantprotectionproducts"},{"key":"2547_CR87","first-page":"1439","volume":"17","author":"DA Sarigiannis","year":"2008","unstructured":"Sarigiannis DA, Gotti A (2008) Biology-based dose-response models for health risk assessment of chemical mixtures. Fresenius Environ Bull 17:1439\u20131451","journal-title":"Fresenius Environ Bull"},{"key":"2547_CR88","doi-asserted-by":"publisher","DOI":"10.1186\/1476-069x-11-s1-s18","author":"DA Sarigiannis","year":"2012","unstructured":"Sarigiannis DA, Hansen U (2012) Considering the cumulative risk of mixtures of chemicals\u2014A challenge for policy makers. Environ Health. https:\/\/doi.org\/10.1186\/1476-069x-11-s1-s18","journal-title":"Environ Health"},{"key":"2547_CR89","doi-asserted-by":"publisher","DOI":"10.1097\/01.ede.0000392202.15822.bf","author":"D Sarigiannis","year":"2011","unstructured":"Sarigiannis D, Karakitsios S (2011) Perinatal Exposure to Bisphenol A: the Route of Administration Makes the Dose. Epidemiology. https:\/\/doi.org\/10.1097\/01.ede.0000392202.15822.bf","journal-title":"Epidemiology"},{"key":"2547_CR90","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1007\/978-3-319-56234-6_4","volume-title":"Chemical mixtures and combined chemical and nonchemical stressors","author":"DA Sarigiannis","year":"2018","unstructured":"Sarigiannis DA, Karakitsios SP (2018) Modeling complex exposures. In: Rider CV, Simmons JE (eds) Chemical mixtures and combined chemical and nonchemical stressors. Springer International Publishing AG, Berlin, pp 81\u2013125"},{"key":"2547_CR91","unstructured":"Sarigiannis D, Karakitsios S, Gotti A, Loizou G, Cherrie J, Smolders R, De Brouwere K, Galea K, Jones K, Handakas E, Papadaki K, Sleeuwenhoek A (2014) Integra: from global scale contamination to tissue dose. Proceedings\u20147th international congress on environmental modelling and software: bold visions for environmental modeling, iEMSs, pp. 1001-1008"},{"key":"2547_CR92","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2016.10.017","author":"DA Sarigiannis","year":"2016","unstructured":"Sarigiannis DA, Karakitsios SP, Handakas E et al (2016) Integrated exposure and risk characterization of bisphenol-A in Europe. Food Chem Toxicol. https:\/\/doi.org\/10.1016\/j.fct.2016.10.017","journal-title":"Food Chem Toxicol"},{"key":"2547_CR93","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2017.05.029","author":"D Sarigiannis","year":"2017","unstructured":"Sarigiannis D, Papadaki K, Kontoroupis P, Karakitsios SP (2017) Development of QSARs for parameterizing Physiology Based ToxicoKinetic models. Food Chem Toxicol. https:\/\/doi.org\/10.1016\/j.fct.2017.05.029","journal-title":"Food Chem Toxicol"},{"key":"2547_CR94","doi-asserted-by":"publisher","DOI":"10.1186\/1742-4682-7-17","author":"AF Sasso","year":"2010","unstructured":"Sasso AF, Isukapalli SS, Georgopoulos PG (2010) A generalized physiologically-based toxicokinetic modeling system for chemical mixtures containing metals. Theor Biol Med Model. https:\/\/doi.org\/10.1186\/1742-4682-7-17","journal-title":"Theor Biol Med Model"},{"key":"2547_CR95","doi-asserted-by":"publisher","DOI":"10.1016\/j.yrtph.2017.09.020","author":"UG Sauer","year":"2017","unstructured":"Sauer UG, Deferme L, Gribaldo L et al (2017) The challenge of the application of\u2019omics technologies in chemicals risk assessment: background and outlook. Regul Toxicol Pharmacol. https:\/\/doi.org\/10.1016\/j.yrtph.2017.09.020","journal-title":"Regul Toxicol Pharmacol"},{"key":"2547_CR96","unstructured":"Sch\u00e4ffer A, Filser J, Frische T, Gessner M, K\u00f6ck W, Kratz W, Liess M, Nuppenau EA, Ro\u00df-Nickoll M, Sch\u00e4fer R, Scheringer M (2018) The silent spring\u2013On the need for sustainable plant protection. Leopoldina Discussions No. 16. Deutsche Akademie der Naturforscher Leopoldina e. V. \u2013 Nationale Akademie der Wissenschaften \u2013 German National Academy of Sciences Leopoldina. J\u00e4gerberg 1 06108 Halle (Saale). https:\/\/www.leopoldina.org\/uploads\/tx_leopublication\/2018_Diskussionspapier_Pflanzenschutzmittel_EN_02.pdf"},{"key":"2547_CR97","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1007\/978-3-319-56234-6_13","volume-title":"Chemical mixtures and combined chemical and nonchemical stressors","author":"JE Simmons","year":"2018","unstructured":"Simmons JE, Eide I, Rice G, Feder P (2018) Mixture experimental design. In: Rider CV, Simmons JE (eds) Chemical mixtures and combined chemical and nonchemical stressors. Springer International Publishing AG, Berlin, pp 335\u2013366"},{"key":"2547_CR98","doi-asserted-by":"publisher","DOI":"10.1186\/1476-069x-12-85","author":"Z Sun","year":"2013","unstructured":"Sun Z, Tao Y, Li S et al (2013) Statistical strategies for constructing health risk models with multiple pollutants and their interactions: possible choices and comparisons. Environ Heal A Glob Access Sci Source. https:\/\/doi.org\/10.1186\/1476-069x-12-85","journal-title":"Environ Heal A Glob Access Sci Source"},{"key":"2547_CR99","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2019.05.019","author":"SF Taghizadeh","year":"2019","unstructured":"Taghizadeh SF, Goumenou M, Rezaee R et al (2019) Cumulative risk assessment of pesticide residues in different Iranian pistachio cultivars: applying the source specific HQS and adversity specific HIA approaches in Real Life Risk Simulations (RLRS). Toxicol Lett. https:\/\/doi.org\/10.1016\/j.toxlet.2019.05.019","journal-title":"Toxicol Lett"},{"key":"2547_CR100","doi-asserted-by":"publisher","DOI":"10.1016\/j.watres.2014.04.043","author":"JYM Tang","year":"2014","unstructured":"Tang JYM, Busetti F, Charrois JWA, Escher BI (2014) Which chemicals drive biological effects in wastewater and recycled water? Water Res. https:\/\/doi.org\/10.1016\/j.watres.2014.04.043","journal-title":"Water Res"},{"key":"2547_CR101","doi-asserted-by":"publisher","DOI":"10.1289\/ehp547","author":"KW Taylor","year":"2016","unstructured":"Taylor KW, Joubert BR, Braun JM et al (2016) Statistical approaches for assessing health effects of environmental chemical mixtures in epidemiology: lessons from an innovative workshop. Environ Health Perspect. https:\/\/doi.org\/10.1289\/ehp547","journal-title":"Environ Health Perspect"},{"key":"2547_CR102","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfm092","author":"RS Thomas","year":"2007","unstructured":"Thomas RS, Allen BC, Nong A et al (2007) A method to integrate benchmark dose estimates with genomic data to assess the functional effects of chemical exposure. Toxicol Sci. https:\/\/doi.org\/10.1093\/toxsci\/kfm092","journal-title":"Toxicol Sci"},{"key":"2547_CR103","doi-asserted-by":"publisher","DOI":"10.1016\/j.yrtph.2014.09.009","author":"KE Tollefsen","year":"2014","unstructured":"Tollefsen KE, Scholz S, Cronin MT et al (2014) Applying adverse outcome pathways (AOPs) to support integrated approaches to testing and assessment (IATA). Regul Toxicol Pharmacol. https:\/\/doi.org\/10.1016\/j.yrtph.2014.09.009","journal-title":"Regul Toxicol Pharmacol"},{"key":"2547_CR104","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2016.08.011","author":"AM Tsatsakis","year":"2016","unstructured":"Tsatsakis AM, Docea AO, Tsitsimpikou C (2016) New challenges in risk assessment of chemicals when simulating real exposure scenarios; simultaneous multi-chemicals\u2019 low dose exposure. Food Chem Toxicol. https:\/\/doi.org\/10.1016\/j.fct.2016.08.011","journal-title":"Food Chem Toxicol"},{"key":"2547_CR105","doi-asserted-by":"publisher","DOI":"10.1177\/0960327116681652","author":"AM Tsatsakis","year":"2017","unstructured":"Tsatsakis AM, Kouretas D, Tzatzarakis MN et al (2017) Simulating real-life exposures to uncover possible risks to human health: a proposed consensus for a novel methodological approach. Hum Exp Toxicol. https:\/\/doi.org\/10.1177\/0960327116681652","journal-title":"Hum Exp Toxicol"},{"key":"2547_CR106","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxrep.2018.10.001","author":"AM Tsatsakis","year":"2018","unstructured":"Tsatsakis AM, Vassilopoulou L, Kovatsi L et al (2018) The dose response principle from philosophy to modern toxicology: the impact of ancient philosophy and medicine in modern toxicology science. Toxicol Reports. https:\/\/doi.org\/10.1016\/j.toxrep.2018.10.001","journal-title":"Toxicol Reports"},{"key":"2547_CR107","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2018.12.003","author":"A Tsatsakis","year":"2019","unstructured":"Tsatsakis A, Goumenou M, Liesivuori J et al (2019a) Toxicology for real-life risk simulation\u2013Editorial preface to this special issue. Toxicol Lett. https:\/\/doi.org\/10.1016\/j.toxlet.2018.12.003","journal-title":"Toxicol Lett"},{"key":"2547_CR108","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2018.12.043","author":"AM Tsatsakis","year":"2019","unstructured":"Tsatsakis AM, Docea AO, Calina D et al (2019b) Hormetic Neurobehavioral effects of low dose toxic chemical mixtures in real-life risk simulation (RLRS) in rats. Food Chem Toxicol. https:\/\/doi.org\/10.1016\/j.fct.2018.12.043","journal-title":"Food Chem Toxicol"},{"key":"2547_CR109","doi-asserted-by":"publisher","DOI":"10.1016\/j.progpolymsci.2016.09.004","author":"K Uto","year":"2017","unstructured":"Uto K, Tsui JH, DeForest CA, Kim DH (2017) Dynamically tunable cell culture platforms for tissue engineering and mechanobiology. Prog Polym Sci. https:\/\/doi.org\/10.1016\/j.progpolymsci.2016.09.004","journal-title":"Prog Polym Sci"},{"key":"2547_CR110","doi-asserted-by":"publisher","DOI":"10.1016\/j.yrtph.2010.10.008","author":"M Valcke","year":"2011","unstructured":"Valcke M, Krishnan K (2011) Evaluation of the impact of the exposure route on the human kinetic adjustment factor. Regul Toxicol Pharmacol. https:\/\/doi.org\/10.1016\/j.yrtph.2010.10.008","journal-title":"Regul Toxicol Pharmacol"},{"key":"2547_CR111","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrfmmm.2005.02.006","author":"JHM Van Delft","year":"2005","unstructured":"Van Delft JHM, Van Agen E, Van Breda SGJ et al (2005) Comparison of supervised clustering methods to discriminate genotoxic from non-genotoxic carcinogens by gene expression profiling. Mutat Res. https:\/\/doi.org\/10.1016\/j.mrfmmm.2005.02.006","journal-title":"Mutat Res"},{"key":"2547_CR113","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.10917","author":"MA Verner","year":"2008","unstructured":"Verner MA, Charbonneau M, L\u00f3pez-Carrillo L, Haddad S (2008) Physiologically based pharmacokinetic modeling of persistent organic pollutants for lifetime exposure assessment: a new tool in breast cancer epidemiologic studies. Environ Health Perspect. https:\/\/doi.org\/10.1289\/ehp.10917","journal-title":"Environ Health Perspect"},{"key":"2547_CR114","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1007\/978-3-319-56234-6_10","volume-title":"Chemical mixtures and combined chemical and nonchemical stressors","author":"TF Webster","year":"2018","unstructured":"Webster TF (2018) Mixtures: Contrasting Perspectives from Toxicology and Epidemiology. In: Rider CV, Simmons JE (eds) Chemical mixtures and combined chemical and nonchemical stressors. Springer International Publishing AG, Berlin, pp 271\u2013289"},{"key":"2547_CR400","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/67.2.207","author":"MG Wade","year":"2002","unstructured":"Wade MG, Parent S, Finnson KW et al (2002) Thyroid toxicity due to subchronic exposure to a complex mixture of 16 organochlorines, lead, and cadmium. Toxicol Sci. https:\/\/doi.org\/10.1093\/toxsci\/67.2.207","journal-title":"Toxicol Sci"},{"key":"2547_CR115","doi-asserted-by":"publisher","DOI":"10.1006\/rtph.1999.1361","author":"CF Wilkinson","year":"2000","unstructured":"Wilkinson CF, Christoph GR, Julien E et al (2000) Assessing the risks of exposures to multiple chemicals with a common mechanism of toxicity: how to cumulate? Regul Toxicol Pharmacol. https:\/\/doi.org\/10.1006\/rtph.1999.1361","journal-title":"Regul Toxicol Pharmacol"},{"key":"2547_CR117","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2014.08.003","author":"MF Wilks","year":"2014","unstructured":"Wilks MF, Tsatsakis AM (2014) Environmental contaminants and target organ toxicities\u2013new insights into old problems. Toxicol Lett. https:\/\/doi.org\/10.1016\/j.toxlet.2014.08.003","journal-title":"Toxicol Lett"},{"key":"2547_CR118","doi-asserted-by":"publisher","DOI":"10.1038\/jes.2009.29","author":"Y Yang","year":"2010","unstructured":"Yang Y, Xu X, Georgopoulos PG (2010) A Bayesian population PBPK model for multiroute chloroform exposure. J Expo Sci Environ Epidemiol. https:\/\/doi.org\/10.1038\/jes.2009.29","journal-title":"J Expo Sci Environ Epidemiol"},{"key":"2547_CR119","unstructured":"Zartarian VG, Xue J, \u00d6zkaynak H, Glen G, Stallings C, Smith L, Dang W, Cook N, Aviado D, Mostaghimi S, Chen J (2002) SHEDS-wood stochastic human exposure and dose simulation model for a wood preservative exposure scenario, technical manual: using sheds-wood for the assessment of children\u2019s exposure and dose from treated wood preservatives on playsets and residential decks. US EPA, DC"},{"key":"2547_CR120","doi-asserted-by":"publisher","DOI":"10.1016\/j.aquatox.2014.10.011","author":"B Zhu","year":"2014","unstructured":"Zhu B, Wang Q, Wang X, Zhou B (2014) Impact of co-exposure with lead and decabromodiphenyl ether (BDE-209) on thyroid function in zebrafish larvae. Aquat Toxicol. https:\/\/doi.org\/10.1016\/j.aquatox.2014.10.011","journal-title":"Aquat Toxicol"},{"key":"2547_CR121","doi-asserted-by":"publisher","DOI":"10.1002\/env.716","author":"JV Zidek","year":"2005","unstructured":"Zidek JV, Shaddick G, White R et al (2005) Using a probabilistic model (pCNEM) to estimate personal exposure to air pollution. Environmetrics. https:\/\/doi.org\/10.1002\/env.716","journal-title":"Environmetrics"}],"container-title":["Archives of Toxicology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00204-019-02547-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s00204-019-02547-x\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00204-019-02547-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,20]],"date-time":"2023-09-20T06:33:53Z","timestamp":1695191633000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s00204-019-02547-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,9,13]]},"references-count":121,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2019,10]]}},"alternative-id":["2547"],"URL":"https:\/\/doi.org\/10.1007\/s00204-019-02547-x","relation":{},"ISSN":["0340-5761","1432-0738"],"issn-type":[{"value":"0340-5761","type":"print"},{"value":"1432-0738","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,9,13]]},"assertion":[{"value":"22 May 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 August 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 September 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"The authors declare that they have no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}