{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T03:05:30Z","timestamp":1789787130234,"version":"4.0.1"},"reference-count":59,"publisher":"Springer Science and Business Media LLC","issue":"11","license":[{"start":{"date-parts":[[2024,8,17]],"date-time":"2024-08-17T00:00:00Z","timestamp":1723852800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,8,17]],"date-time":"2024-08-17T00:00:00Z","timestamp":1723852800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Bundesinstitut f\u00fcr Risikobewertung (BfR)"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Arch Toxicol"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mono-n-hexyl phthalate (MnHexP) is a primary metabolite of di-n-hexyl phthalate (DnHexP) and other mixed side-chain phthalates that was recently detected in urine samples from adults and children in Germany. DnHexP is classified as toxic for reproduction category 1B in Annex VI of Regulation (EC) 1272\/2008 and listed in Annex XIV of the European chemical legislation REACH; thereby, its use requires an authorisation. Health-based guidance values for DnHexP are lacking and a full-scale risk assessment has not been carried out under REACH. The detection of MnHexP in urine samples raises questions about the sources of exposure and concerns of consumer safety. Here, we propose the calculation of a provisional oral tolerable daily intake value (TDI) of 63\u00a0\u00b5g\/kg body weight\/day for DnHexP and compare it to intake levels corresponding to levels of MnHexP found in urine. The resulting mean intake levels correspond to less than 0.2% of the TDI, and maximum levels to less than 5%. The TDI was derived by means of an approximate probabilistic analysis using the credible interval from benchmark dose modelling of published ex vivo data on reduced foetal testosterone production in rats. Thus, for the dose associated to a 20% reduction in testosterone production, a lower and upper credible interval of 14.9 and 30.0\u00a0mg\/kg bw\/day, respectively, was used. This is considered a conservative approach, since apical developmental endpoints (e.g. changed anogenital distance) were only observed at higher doses. In addition, we modelled various scenarios of the exposure to the precursor substance DnHexP from different consumer products, taking measured contamination levels into account, and estimated systemic exposure doses. Of the modelled scenarios including the application of sunscreen (as a lotion or pump spray), the use of lip balm, and the wearing of plastic sandals, and considering conservative assumptions, the use of DnHexP-contaminated sunscreen was highlighted as a major contributing factor. A hypothetical calculation using conservative assumptions for the latter resulted in a margin of safety in relation to the lower credible interval of 3267 and 1007 for adults and young children, respectively. Most importantly, it was found that only a fraction of the TDI is reached in all studied exposure scenarios. Thus, with regard to the reported DnHexP exposure, a health risk can be considered very unlikely.<\/jats:p>","DOI":"10.1007\/s00204-024-03835-x","type":"journal-article","created":{"date-parts":[[2024,8,17]],"date-time":"2024-08-17T08:02:26Z","timestamp":1723881746000},"page":"3659-3671","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Mono-n-hexyl phthalate: exposure estimation and assessment of health risks based on levels found in human urine samples"],"prefix":"10.1007","volume":"98","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0513-1045","authenticated-orcid":false,"given":"Ralph","family":"Pirow","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrike","family":"Bernauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annegret","family":"Blume","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Cieszynski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Flingelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Astrid","family":"Heiland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Herzler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bettina","family":"Huhse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Riebeling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Rosenthal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moustapha","family":"Sy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Tietz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Achim","family":"Trubiroha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Luch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,8,17]]},"reference":[{"issue":"1","key":"3835_CR1","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1080\/15376516.2019.1650145","volume":"30","author":"M Akkbik","year":"2020","unstructured":"Akkbik M, Turksoy VA, Kocoglu S (2020) Simultaneous quantitative detection of 10 phthalates in PVC children\u2019s toys by HPLC-PDA. Toxicol Mech Methods 30(1):33\u201338. https:\/\/doi.org\/10.1080\/15376516.2019.1650145","journal-title":"Toxicol Mech Methods"},{"issue":"1","key":"3835_CR2","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1007\/s11356-018-3604-8","volume":"26","author":"NN Al Qasmi","year":"2019","unstructured":"Al Qasmi NN, Al-Thaiban H, Helaleh MIH (2019) Indoor phthalates from household dust in Qatar: implications for non-dietary human exposure. Environ Sci Pollut Res Int 26(1):421\u2013430. https:\/\/doi.org\/10.1007\/s11356-018-3604-8","journal-title":"Environ Sci Pollut Res Int"},{"issue":"Pt 1","key":"3835_CR3","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2022.158779","volume":"856","author":"N Ali","year":"2023","unstructured":"Ali N, Rashid MI, Alhakamy NA, Alamri SH, Eqani S (2023) Profiling of phthalates, brominated, and organophosphate flame retardants in COVID-19 lockdown house dust; implication on the human health. Sci Total Environ 856(Pt 1):158779. https:\/\/doi.org\/10.1016\/j.scitotenv.2022.158779","journal-title":"Sci Total Environ"},{"issue":"12","key":"3835_CR4","doi-asserted-by":"publisher","first-page":"1068","DOI":"10.1080\/02652030110050113","volume":"18","author":"WA Anderson","year":"2001","unstructured":"Anderson WA, Castle L, Scotter MJ, Massey RC, Springall C (2001) A biomarker approach to measuring human dietary exposure to certain phthalate diesters. Food Addit Contam 18(12):1068\u20131074. https:\/\/doi.org\/10.1080\/02652030110050113","journal-title":"Food Addit Contam"},{"issue":"9","key":"3835_CR5","doi-asserted-by":"publisher","first-page":"2022","DOI":"10.1016\/j.fct.2011.05.013","volume":"49","author":"WA Anderson","year":"2011","unstructured":"Anderson WA, Castle L, Hird S, Jeffery J, Scotter MJ (2011) A twenty-volunteer study using deuterium labelling to determine the kinetics and fractional excretion of primary and secondary urinary metabolites of di-2-ethylhexylphthalate and di-iso-nonylphthalate. Food Chem Toxicol 49(9):2022\u20132029. https:\/\/doi.org\/10.1016\/j.fct.2011.05.013","journal-title":"Food Chem Toxicol"},{"issue":"1","key":"3835_CR6","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1016\/j.yrtph.2015.04.005","volume":"72","author":"LL Aylward","year":"2015","unstructured":"Aylward LL, Hays SM, Vezina A, Deveau M, St-Amand A, Nong A (2015) Biomonitoring equivalents for interpretation of urinary fluoride. Regul Toxicol Pharmacol 72(1):158\u2013167. https:\/\/doi.org\/10.1016\/j.yrtph.2015.04.005","journal-title":"Regul Toxicol Pharmacol"},{"issue":"6","key":"3835_CR7","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1038\/jes.2016.54","volume":"27","author":"LL Aylward","year":"2017","unstructured":"Aylward LL, Hays SM, Zidek A (2017) Variation in urinary spot sample, 24 h samples, and longer-term average urinary concentrations of short-lived environmental chemicals: implications for exposure assessment and reverse dosimetry. J Expo Sci Environ Epidemiol 27(6):582\u2013590. https:\/\/doi.org\/10.1038\/jes.2016.54","journal-title":"J Expo Sci Environ Epidemiol"},{"issue":"2","key":"3835_CR8","doi-asserted-by":"publisher","first-page":"1808","DOI":"10.1007\/s11356-019-06815-2","volume":"27","author":"B Basaran","year":"2020","unstructured":"Basaran B, Soylu GN, Yilmaz Civan M (2020) Concentration of phthalate esters in indoor and outdoor dust in Kocaeli, Turkey: implications for human exposure and risk. Environ Sci Pollut Res Int 27(2):1808\u20131824. https:\/\/doi.org\/10.1007\/s11356-019-06815-2","journal-title":"Environ Sci Pollut Res Int"},{"key":"3835_CR9","unstructured":"BfR (2023) Bisphenol A: BfR proposes health based guidance value, current exposure data are needed for a full risk assessment BfR Opinion. German Federal Institute for Risk Assessment, 018\/2023 https:\/\/www.bfr.bund.de\/cm\/349\/bisphenol-a-bfr-proposes-health-based-guidance-value-current-exposure-data-are-needed-for-a-full-risk-assessment.pdf"},{"key":"3835_CR10","unstructured":"BfR (2024) MnHexP: Background information on the detection of the degradation product of a plasticizer in urine samples Communication. German Federal Institute for Risk Assessment, 04\/2024. https:\/\/www.bfr.bund.de\/cm\/349\/mnhexp-background-information-on-the-detection-of-the-degradation-product-of-a-plasticizer-in-urine-samples.pdf"},{"key":"3835_CR11","unstructured":"CVUA\u00a0Karlsruhe (2024) [Prohibited Plasticiser as Contamination in Sunscreen? Initial findings of an investigation]\u2014in German. In. https:\/\/www.ua-bw.de\/pub\/beitrag.asp?subid=0&Thema_ID=4&ID=3940&Pdf=No&lang=DE Accessed 18.04.2024 2024"},{"key":"3835_CR12","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2021.146667","volume":"781","author":"H Demirtepe","year":"2021","unstructured":"Demirtepe H, Melymuk L, Codling G et al (2021) Targeted and suspect screening of plasticizers in house dust to assess cumulative human exposure risk. Sci Total Environ 781:146667. https:\/\/doi.org\/10.1016\/j.scitotenv.2021.146667","journal-title":"Sci Total Environ"},{"issue":"1","key":"3835_CR13","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1021\/es502988r","volume":"49","author":"RE Dodson","year":"2015","unstructured":"Dodson RE, Camann DE, Morello-Frosch R, Brody JG, Rudel RA (2015) Semivolatile organic compounds in homes: strategies for efficient and systematic exposure measurement based on empirical and theoretical factors. Environ Sci Technol 49(1):113\u2013122. https:\/\/doi.org\/10.1021\/es502988r","journal-title":"Environ Sci Technol"},{"key":"3835_CR14","unstructured":"ECHA (2013) Registry of SVHC intentions until outcome\u2014Dihexyl phthalate. In. https:\/\/echa.europa.eu\/registry-of-svhc-intentions\/-\/dislist\/details\/0b0236e180e4ab8c Accessed 2024-05-28"},{"key":"3835_CR15","unstructured":"ECHA (2016) Annex XV Restriction Report. Proposal for a restriction\u2014substance names: Four phthalates (DEHP, BBP, DBP, DIBP). ECHA. https:\/\/echa.europa.eu\/documents\/10162\/2700f4f2-579a-1fbe-2c23-311706a3e958"},{"key":"3835_CR16","unstructured":"ECHA (2020) Authorisation List - Dihexyl phthalate. In. https:\/\/echa.europa.eu\/authorisation-list\/-\/dislist\/details\/0b0236e180912a44 Accessed 2024-05-28"},{"issue":"12","key":"3835_CR17","doi-asserted-by":"publisher","DOI":"10.2903\/j.efsa.2019.5838","volume":"17","author":"EFSA","year":"2019","unstructured":"EFSA (2019) Update of the risk assessment of di-butylphthalate (DBP), butyl-benzyl-phthalate (BBP), bis(2-ethylhexyl)phthalate (DEHP), di-isononylphthalate (DINP) and di-isodecylphthalate (DIDP) for use in food contact materials. EFSA J 17(12):e05838. https:\/\/doi.org\/10.2903\/j.efsa.2019.5838","journal-title":"EFSA J"},{"issue":"10","key":"3835_CR18","doi-asserted-by":"publisher","DOI":"10.2903\/j.efsa.2022.7584","volume":"20","author":"EFSA","year":"2022","unstructured":"EFSA (2022) Guidance on the use of the benchmark dose approach in risk assessment. EFSA J 20(10):e07584. https:\/\/doi.org\/10.2903\/j.efsa.2022.7584","journal-title":"EFSA J"},{"key":"3835_CR19","unstructured":"EFSA (2024) Bayesian Benchmark Dose Modelling. In: EFSA. https:\/\/r4eu.efsa.europa.eu\/app\/bmdbayesian Accessed 2024-05-06"},{"issue":"1","key":"3835_CR20","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/0272-0590(89)90063-8","volume":"12","author":"AE Elsisi","year":"1989","unstructured":"Elsisi AE, Carter DE, Sipes IG (1989) Dermal absorption of phthalate diesters in rats. Fundam Appl Toxicol 12(1):70\u201377. https:\/\/doi.org\/10.1016\/0272-0590(89)90063-8","journal-title":"Fundam Appl Toxicol"},{"issue":"9","key":"3835_CR21","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1080\/10408440600894914","volume":"36","author":"E Fabjan","year":"2006","unstructured":"Fabjan E, Hulzebos E, Mennes W, Piersma AH (2006) A category approach for reproductive effects of phthalates. Crit Rev Toxicol 36(9):695\u2013726. https:\/\/doi.org\/10.1080\/10408440600894914","journal-title":"Crit Rev Toxicol"},{"key":"3835_CR22","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/j.fct.2016.05.020","volume":"94","author":"AS Ficheux","year":"2016","unstructured":"Ficheux AS, Dornic N, Bernard A, Chevillotte G, Roudot AC (2016) Probabilistic assessment of exposure to cosmetic products by French children aged 0\u20133 years. Food Chem Toxicol 94:85\u201392. https:\/\/doi.org\/10.1016\/j.fct.2016.05.020","journal-title":"Food Chem Toxicol"},{"issue":"3","key":"3835_CR23","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1038\/jes.2014.65","volume":"25","author":"M Fisher","year":"2015","unstructured":"Fisher M, Arbuckle TE, Mallick R et al (2015) Bisphenol A and phthalate metabolite urinary concentrations: daily and across pregnancy variability. J Expo Sci Environ Epidemiol 25(3):231\u2013239. https:\/\/doi.org\/10.1038\/jes.2014.65","journal-title":"J Expo Sci Environ Epidemiol"},{"issue":"5","key":"3835_CR24","doi-asserted-by":"publisher","first-page":"656","DOI":"10.1016\/j.envres.2011.03.005","volume":"111","author":"H Frederiksen","year":"2011","unstructured":"Frederiksen H, Aksglaede L, Sorensen K, Skakkebaek NE, Juul A, Andersson AM (2011) Urinary excretion of phthalate metabolites in 129 healthy Danish children and adolescents: estimation of daily phthalate intake. Environ Res 111(5):656\u2013663. https:\/\/doi.org\/10.1016\/j.envres.2011.03.005","journal-title":"Environ Res"},{"issue":"2","key":"3835_CR25","doi-asserted-by":"publisher","first-page":"958","DOI":"10.1021\/es303640b","volume":"47","author":"H Frederiksen","year":"2013","unstructured":"Frederiksen H, Kranich SK, Jorgensen N, Taboureau O, Petersen JH, Andersson AM (2013) Temporal variability in urinary phthalate metabolite excretion based on spot, morning, and 24-h urine samples: considerations for epidemiological studies. Environ Sci Technol 47(2):958\u2013967. https:\/\/doi.org\/10.1021\/es303640b","journal-title":"Environ Sci Technol"},{"issue":"2","key":"3835_CR26","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1093\/toxsci\/kfu081","volume":"140","author":"JR Furr","year":"2014","unstructured":"Furr JR, Lambright CS, Wilson VS, Foster PM, Gray LE Jr (2014) A short-term in vivo screen using fetal testosterone production, a key event in the phthalate adverse outcome pathway, to predict disruption of sexual differentiation. Toxicol Sci 140(2):403\u2013424. https:\/\/doi.org\/10.1093\/toxsci\/kfu081","journal-title":"Toxicol Sci"},{"issue":"8","key":"3835_CR27","doi-asserted-by":"publisher","first-page":"3788","DOI":"10.1021\/es2002106","volume":"45","author":"Y Guo","year":"2011","unstructured":"Guo Y, Kannan K (2011) Comparative assessment of human exposure to phthalate esters from house dust in China and the United States. Environ Sci Technol 45(8):3788\u20133794. https:\/\/doi.org\/10.1021\/es2002106","journal-title":"Environ Sci Technol"},{"key":"3835_CR28","unstructured":"HBM\u00a0Commission (2024) [HBM-I value derivation for the di-n-hexyl phthalate metabolite mono-n-hexyl phthalate in the urine of adults and children] - in German. UBA. https:\/\/www.umweltbundesamt.de\/sites\/default\/files\/medien\/11901\/dokumente\/240325_kurz-stellungnahme_hbm-k_fin.pdf"},{"key":"3835_CR29","unstructured":"HBM4EU (2022) Suggested list of biomarkers, matrices and analytical methods for the 1st prioritisation round of substances. https:\/\/www.hbm4eu.eu\/?mdocs-file=2662"},{"issue":"2","key":"3835_CR30","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1016\/j.taap.2012.08.009","volume":"264","author":"W Kessler","year":"2012","unstructured":"Kessler W, Numtip W, Volkel W et al (2012) Kinetics of di(2-ethylhexyl) phthalate (DEHP) and mono(2-ethylhexyl) phthalate in blood and of DEHP metabolites in urine of male volunteers after single ingestion of ring-deuterated DEHP. Toxicol Appl Pharmacol 264(2):284\u2013291. https:\/\/doi.org\/10.1016\/j.taap.2012.08.009","journal-title":"Toxicol Appl Pharmacol"},{"issue":"3","key":"3835_CR31","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1007\/s00204-003-0522-3","volume":"78","author":"HM Koch","year":"2004","unstructured":"Koch HM, Bolt HM, Angerer J (2004) Di(2-ethylhexyl)phthalate (DEHP) metabolites in human urine and serum after a single oral dose of deuterium-labelled DEHP. Arch Toxicol 78(3):123\u2013130. https:\/\/doi.org\/10.1007\/s00204-003-0522-3","journal-title":"Arch Toxicol"},{"issue":"7","key":"3835_CR32","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1007\/s00204-004-0642-4","volume":"79","author":"HM Koch","year":"2005","unstructured":"Koch HM, Bolt HM, Preuss R, Angerer J (2005) New metabolites of di(2-ethylhexyl)phthalate (DEHP) in human urine and serum after single oral doses of deuterium-labelled DEHP. Arch Toxicol 79(7):367\u2013376. https:\/\/doi.org\/10.1007\/s00204-004-0642-4","journal-title":"Arch Toxicol"},{"issue":"4","key":"3835_CR33","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1038\/sj.jes.7500526","volume":"17","author":"HM Koch","year":"2007","unstructured":"Koch HM, Becker K, Wittassek M, Seiwert M, Angerer J, Kolossa-Gehring M (2007) Di-n-butylphthalate and butylbenzylphthalate\u2014urinary metabolite levels and estimated daily intakes: pilot study for the German Environmental Survey on children. J Expo Sci Environ Epidemiol 17(4):378\u2013387. https:\/\/doi.org\/10.1038\/sj.jes.7500526","journal-title":"J Expo Sci Environ Epidemiol"},{"issue":"12","key":"3835_CR34","doi-asserted-by":"publisher","first-page":"1829","DOI":"10.1007\/s00204-012-0908-1","volume":"86","author":"HM Koch","year":"2012","unstructured":"Koch HM, Christensen KL, Harth V, Lorber M, Bruning T (2012) Di-n-butyl phthalate (DnBP) and diisobutyl phthalate (DiBP) metabolism in a human volunteer after single oral doses. Arch Toxicol 86(12):1829\u20131839. https:\/\/doi.org\/10.1007\/s00204-012-0908-1","journal-title":"Arch Toxicol"},{"issue":"2 Pt A","key":"3835_CR35","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1016\/j.ijheh.2016.11.003","volume":"220","author":"HM Koch","year":"2017","unstructured":"Koch HM, Ruther M, Schutze A et al (2017) Phthalate metabolites in 24-h urine samples of the German Environmental Specimen Bank (ESB) from 1988 to 2015 and a comparison with US NHANES data from 1999 to 2012. Int J Hyg Environ Health 220(2 Pt A):130\u2013141. https:\/\/doi.org\/10.1016\/j.ijheh.2016.11.003","journal-title":"Int J Hyg Environ Health"},{"key":"3835_CR36","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph15112514","author":"AM Krais","year":"2018","unstructured":"Krais AM, Andersen C, Eriksson AC et al (2018) Excretion of urinary metabolites of the phthalate esters DEP and DEHP in 16 volunteers after inhalation and dermal exposure. Int J Environ Res Public Health. https:\/\/doi.org\/10.3390\/ijerph15112514","journal-title":"Int J Environ Res Public Health"},{"key":"3835_CR37","unstructured":"Kremer C, Oluwafemi O, Shkedy Z et al (2024) Bayesian benchmark dose modelling WEB app. In: Zenodo. https:\/\/zenodo.org\/records\/10523648. Accessed 2024-05-06"},{"issue":"6","key":"3835_CR38","doi-asserted-by":"publisher","first-page":"506","DOI":"10.1111\/ina.12048","volume":"23","author":"C Kubwabo","year":"2013","unstructured":"Kubwabo C, Rasmussen PE, Fan X et al (2013) Analysis of selected phthalates in Canadian indoor dust collected using household vacuum and standardized sampling techniques. Indoor Air 23(6):506\u2013514. https:\/\/doi.org\/10.1111\/ina.12048","journal-title":"Indoor Air"},{"key":"3835_CR39","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijheh.2021.113722","volume":"234","author":"R Lange","year":"2021","unstructured":"Lange R, Apel P, Rousselle C et al (2021) The European Human Biomonitoring Initiative (HBM4EU): human biomonitoring guidance values for selected phthalates and a substitute plasticizer. Int J Hyg Environ Health 234:113722. https:\/\/doi.org\/10.1016\/j.ijheh.2021.113722","journal-title":"Int J Hyg Environ Health"},{"key":"3835_CR40","unstructured":"LANUV (2021) Determination of pollutants and pollutant metabolites in the urine of 2- to 6-year-old children from North Rhine-Westphalia, report on the 3rd cross-section (2017\/18), module 1 (plasticisers)\u2014in German. Landesamt f\u00fcr Natur, Umwelt und Verbraucherschutz Nordrhein-Westfalen. https:\/\/www.lanuv.nrw.de\/fileadmin\/lanuv\/gesundheit\/pdf\/2021\/1_Modul_HBM_201718_final.pdf"},{"key":"3835_CR41","unstructured":"LANUV (2022) Determination of pollutants and pollutant metabolites in the urine of 2- to 6-year-old children from North Rhine-Westphalia, report on the 4th cross-section (2020\/21), module 1 (plasticisers)\u2014in German. Landesamt f\u00fcr Natur, Umwelt und Verbraucherschutz Nordrhein-Westfalen. https:\/\/www.lanuv.nrw.de\/fileadmin\/lanuv\/gesundheit\/pdf\/2022\/Modul_1_HBM_202021_final.pdf"},{"key":"3835_CR42","unstructured":"LANUV (2024) Determination of pollutants and pollutant metabolites in the urine of 2- to 6-year-old children from North Rhine-Westphalia\u2014LANUV follow-up study on the plasticiser metabolite mono-n-hexyl phthalate (MnHexP)]\u2014in German. Landesamt f\u00fcr Natur, Umwelt und Verbraucherschutz Nordrhein-Westfalen, V.01\/2024. https:\/\/www.lanuv.nrw.de\/fileadmin\/lanuv\/gesundheit\/pdf\/2024\/2024-01_Nachuntersuchung_DnHexP.pdf"},{"issue":"7","key":"3835_CR43","doi-asserted-by":"publisher","first-page":"4019","DOI":"10.1021\/es505233b","volume":"49","author":"S Net","year":"2015","unstructured":"Net S, Sempere R, Delmont A, Paluselli A, Ouddane B (2015) Occurrence, fate, behavior and ecotoxicological state of phthalates in different environmental matrices. Environ Sci Technol 49(7):4019\u20134035. https:\/\/doi.org\/10.1021\/es505233b","journal-title":"Environ Sci Technol"},{"key":"3835_CR44","unstructured":"Pakalin S, Aschberger K, Cosgrove O et al (2008) European Union Risk Assessment Report\u2014bis (2-ethylhexyl) phthalate (DEHP). Luxembourg (Luxembourg), EUR 23384 EN. https:\/\/publications.jrc.ec.europa.eu\/repository\/bitstream\/JRC45705\/dehpreport042.pdf"},{"key":"3835_CR45","unstructured":"Pfaff K, Kappenstein O, Ebner I, W\u00fcrtz A (2012) Phthalate exposure of the population in Germany: Exposure-relevant sources, uptake pathways and toxicokinetics using the example of DEHP and DINP - Volume II: Supplementary measurements of DEHP, DINP and DiNCH in food and migration measurements in consumer products\u2014in German. In: Conrad A, Wintermeyer D (eds). German Federal Environmental Agency, Dessau-Ro\u00dflau, 03\/2012. https:\/\/www.umweltbundesamt.de\/sites\/default\/files\/medien\/378\/publikationen\/umwelt_und_gesundheit_03_2012_conrad_phthalatbelastung_bevoelkerung_band2_a.pdf"},{"issue":"1","key":"3835_CR46","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1002\/jat.1565","volume":"31","author":"AM Saillenfait","year":"2011","unstructured":"Saillenfait AM, Roudot AC, Gallissot F, Sabate JP, Chagnon MC (2011) Developmental toxic potential of di-n-propyl phthalate administered orally to rats. J Appl Toxicol 31(1):36\u201344. https:\/\/doi.org\/10.1002\/jat.1565","journal-title":"J Appl Toxicol"},{"issue":"9","key":"3835_CR47","doi-asserted-by":"publisher","first-page":"1027","DOI":"10.1002\/jat.2896","volume":"33","author":"AM Saillenfait","year":"2013","unstructured":"Saillenfait AM, Sabate JP, Robert A et al (2013) Dose-dependent alterations in gene expression and testosterone production in fetal rat testis after exposure to di-n-hexyl phthalate. J Appl Toxicol 33(9):1027\u20131035. https:\/\/doi.org\/10.1002\/jat.2896","journal-title":"J Appl Toxicol"},{"key":"3835_CR48","unstructured":"SCCP (2007) Opinion on phthalates in cosmetic products. SCCP\/1016\/06. https:\/\/ec.europa.eu\/health\/ph_risk\/committees\/04_sccp\/docs\/sccp_o_106.pdf"},{"key":"3835_CR49","unstructured":"SCCS (2021) Opinion on homosalate. SCCS\/1622\/20. https:\/\/health.ec.europa.eu\/document\/download\/ddf0b68f-5c47-4ace-a87f-0a0e42ebd4a9_en?filename=sccs_o_244.pdf"},{"key":"3835_CR50","unstructured":"SCCS (2023) The SCCS Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation, 12th revision. In: (SCCS) SCoCS (ed). 20231222 edn. European Union, SCCS\/1647\/22. https:\/\/health.ec.europa.eu\/document\/download\/32a999f7-d820-496a-b659-d8c296cc99c1_en?filename=sccs_o_273_final.pdf"},{"issue":"4","key":"3835_CR51","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1080\/10408444.2016.1241756","volume":"47","author":"W Slob","year":"2017","unstructured":"Slob W (2017) A general theory of effect size, and its consequences for defining the benchmark response (BMR) for continuous endpoints. Crit Rev Toxicol 47(4):342\u2013351. https:\/\/doi.org\/10.1080\/10408444.2016.1241756","journal-title":"Crit Rev Toxicol"},{"issue":"1","key":"3835_CR52","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.toxlet.2014.03.005","volume":"227","author":"W Steiling","year":"2014","unstructured":"Steiling W, Bascompta M, Carthew P et al (2014) Principle considerations for the risk assessment of sprayed consumer products. Toxicol Lett 227(1):41\u201349. https:\/\/doi.org\/10.1016\/j.toxlet.2014.03.005","journal-title":"Toxicol Lett"},{"key":"3835_CR53","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhazmat.2019.121681","volume":"387","author":"Z Tang","year":"2020","unstructured":"Tang Z, Chai M, Wang Y, Cheng J (2020) Phthalates in preschool children\u2019s clothing manufactured in seven Asian countries: occurrence, profiles and potential health risks. J Hazard Mater 387:121681. https:\/\/doi.org\/10.1016\/j.jhazmat.2019.121681","journal-title":"J Hazard Mater"},{"key":"3835_CR54","doi-asserted-by":"publisher","unstructured":"UBA (2011) Substance monograph for phthalates - New and updated reference and oxidised monoester metabolites in urine of children-and adults. Opinion of the Commission \u201cHuman-Biomonitoring\u201d by the Federal Environment Agency\u2014in German. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 54(6):770\u2013785. https:\/\/doi.org\/10.1007\/s00103-011-1278-1","DOI":"10.1007\/s00103-011-1278-1"},{"key":"3835_CR55","unstructured":"UBA (2024a) Assessment value set for plasticisers in urine\u2014HBM Commission at the German Environment Agency publishes statement German Federal Environmental Agency, Dessau-Ro\u00dflau. https:\/\/www.umweltbundesamt.de\/en\/press\/pressinformation\/assessment-value-set-for-plasticisers-in-urine"},{"key":"3835_CR56","unstructured":"UBA (2024b) German Environmental Survey, GerES VI (2023\u20132024). In. https:\/\/www.umweltbundesamt.de\/en\/topics\/health\/assessing-environmentally-related-health-risks\/german-environmental-survey-geres\/german-environmental-survey-geres-vi-2023-2024. Accessed 18.04.2024"},{"issue":"1","key":"3835_CR57","doi-asserted-by":"publisher","first-page":"8580E","DOI":"10.2903\/sp.efsa.2024.EN-8580","volume":"21","author":"W Verlinden","year":"2024","unstructured":"Verlinden W, Varewyck M, Verbeke T (2024) Web application for bayesian benchmark dose modelling. EFSA Support Public 21(1):8580E. https:\/\/doi.org\/10.2903\/sp.efsa.2024.EN-8580","journal-title":"EFSA Support Public"},{"key":"3835_CR58","doi-asserted-by":"publisher","DOI":"10.1016\/j.ntt.2023.107161","volume":"96","author":"M Vilmand","year":"2023","unstructured":"Vilmand M, Beck IH, Bilenberg N et al (2023) Prenatal and current phthalate exposure and cognitive development in 7-year-old children from the Odense child cohort. Neurotoxicol Teratol 96:107161. https:\/\/doi.org\/10.1016\/j.ntt.2023.107161","journal-title":"Neurotoxicol Teratol"},{"key":"3835_CR59","unstructured":"WHO (2018) Guidance document on evaluating and expressing uncertainty in hazard characterization, 2nd edn. World Health Organization, Geneva. https:\/\/iris.who.int\/handle\/10665\/259858"}],"container-title":["Archives of Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00204-024-03835-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00204-024-03835-x\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00204-024-03835-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,18]],"date-time":"2024-10-18T10:03:40Z","timestamp":1729245820000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00204-024-03835-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,17]]},"references-count":59,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2024,11]]}},"alternative-id":["3835"],"URL":"https:\/\/doi.org\/10.1007\/s00204-024-03835-x","relation":{},"ISSN":["0340-5761","1432-0738"],"issn-type":[{"value":"0340-5761","type":"print"},{"value":"1432-0738","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,17]]},"assertion":[{"value":"3 July 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 August 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 August 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors do not declare any competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}