Anzahl der Proben: 54 Gemessener Parameter: Mono-benzylphthalat ist der primäre Metabolit von Butylbenzylphthalat (BBzP) nach Abspaltung der Butylgruppe. Probenart: 24h-Sammelurin Eine ideale Matrix für das Human-Biomonitoring, weil mit dem Urin Chemikalien und/oder deren Metabolite ausgeschiedenen werden, die zuvor in direktem Kontakt mit dem Organismus standen. Messungen im Urin können somit zuverlässige Aussagen über die interne Belastung des Menschen liefern. Probenahmegebiet: Münster Bedeutende Universitätsstadt sowie Dienstleistungs- und Verwaltungszentrum in Nordrhein-Westfalen.
Göen, Thomas; Dobler, Lorenz; Koschorreck, Jan; Müller, Johannes; Wiesmüller, Gerhard A.; Drexler, Hans; Kolossa-Gehring, Marike International Journal of Hygiene and Environmental Health 215 (2011), 1, 36-45 The exposure of the general population to phthalates is of increasing public health concern. Variations in the internal exposure of the population are likely, because the amounts, distribution and application characters of the phthalate use change over time. Estimating the chronological sequences of the phthalate exposure, we performed a retrospective human biomonitoring study by investigating the metabolites of the five most prominent phthalates in urine. Therefore, 24 h-urine samples from the German Environmental Specimen Bank (ESB) collected from 240 subjects (predominantly students, age range 19-29 years, 120 females, 120 males) in the years 2002, 2004, 2006 and 2008 (60 individuals each), were analysed for the concentrations of mono-n-butyl phthalate (MnBP) as metabolite of di-n-butyl phthalate (DnBP), mono-iso-butyl phthalate (MiBP) as metabolite of di-iso-butyl phthalate (DiBP), mono-benzyl phthalate (MBzP) as metabolite of butylbenzyl phthalate (BBzP), mono-(2-ethylhexyl) phthalate (MEHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (5OH-MEHP), mono-(2-ethyl-5-oxohexyl) phthalate (5oxo-MEHP), mono-(2-ethyl-5-carboxypentyl) phthalate (5cx-MEPP) and mono-(2-carboxymethyl hexyl) phthalate (2cx-MMHxP) as metabolites of di(2-ethylhexyl) phthalate (DEHP), monohydroxylated (OH-MiNP), monooxidated (oxo-MiNP) and monocarboxylated (cx-MiNP) mono-iso-nonylphthalates as metabolites of di-iso-nonyl phthalates (DiNP). Based on the urinary metabolite excretion, together with results of a previous study, which covered the years 1988-2003, we investigated the chronological sequences of the phthalate exposure over two decades. In more than 98% of the urine samples metabolites of all five phthalates were detectable indicating a ubiquitous exposure of people living in Germany to all five phthalates throughout the period investigated. The medians in samples from the different years investigated are 65.4 (2002), 38.5 (2004), 29.3 (2006) and 19.6 μg/l (2008) for MnBP, 31.4 (2002), 25.4 (2004), 31.8 (2006) and 25.5 μg/l (2008) for MiBP, 7.8 (2002), 6.3 (2004), 3.6 (2006) and 3.8 μg/l (2008) for MBzP, 7.0 (2002), 5.6 (2004), 4.1 (2006) and 3.3 μg/l (2008) for MEHP, 19.6 (2002), 16.2 (2004), 13.2 (2006) and 9.6 μg/l (2008) for 5OH-MEHP, 13.9 (2002), 11.8 (2004), 8.3 (2006) and 6.4 μg/l (2008) for 5oxo-MEHP, 18.7 (2002), 16.5 (2004), 13.8 (2006) and 10.2 μg/l (2008) for 5cx-MEPP, 7.2 (2002), 6.5 (2004), 5.1 (2006) and 4.6 μg/l (2008) for 2cx-MMHxP, 3.3 (2002), 2.8 (2004), 3.5 (2006) and 3.6 μg/l (2008) for OH-MiNP, 2.1 (2002), 2.1 (2004), 2.2 (2006) and 2.3 μg/l (2008) for oxo-MiNP and 4.1 (2002), 3.2 (2004), 4.1 (2006) and 3.6 μg/l (2008) for cx-MiNP. The investigation of the time series 1988-2008 indicates a decrease of the internal exposure to DnBP by the factor of 7-8 and to DEHP and BzBP by the factor of 2-3. In contrast, an increase of the internal exposure by the factor of 4 was observed for DiNP over the study period. The exposure to DiBP was found to be stable. In summary, we found decreases of the internal human exposure for legally restricted phthalates whereas the exposure to their substitutes increased. Future investigations should verify these trends. This is of increasing importance since the European Commission decided to require ban or authorization from 1.1.2015 for DEHP, DnBP, DiBP and BzBP according to REACh Annex XIV. doi: 10.1016/j.ijheh.2011.07.011
Koch, Holger M.; Rüther, Maria; Schütze, André; Conrad, André; Pälmke, Claudia; Apel, Petra; Brüning, Thomas, Kolossa-Gehring, Marike International Journal of Hygiene and Environmental Health (2016), online 9. November 2016 The German Environmental Specimen Bank (ESB) continuously collects 24-h urine samples since the early 1980s in Germany. In this study we analyzed 300 urine samples from the years 2007 to 2015 for 21 phthalate metabolites (representing exposure to 11 parent phthalates) and combined the data with two previous retrospective measurement campaigns (1988 to 2003 and 2002 to 2008). The combined dataset comprised 1162 24-h urine samples spanning the years 1988 to 2015. With this detailed set of human biomonitoring data we describe the time course of phthalate exposure in Germany over a time frame of 27 years. For the metabolites of the endocrine disrupting phthalates di(2-ethylhexyl) phthalate (DEHP), di-n-butyl phthalate (DnBP) and butylbenzyl phthalate (BBzP) we observed a roughly ten-fold decline in median metabolite levels from their peak levels in the late 1980s/early 1990s compared to most recent levels from 2015. Probably, bans (first enacted in 1999) and classifications/labelings (enacted in 2001 and 2004) in the European Union lead to this drop. A decline in di-isobutyl phthalate (DiBP) metabolite levels set in only quite recently, possibly due to its later classification as a reproductive toxicant in the EU in 2009. In a considerable number of samples collected before 2002 health based guidance values (BE, HBM I) have been exceeded for DnBP (27.2%) and DEHP (2.3%) but also in recent samples some individual exceedances can still be observed (DEHP 1.0%). A decrease in concentration for all low molecular weight phthalates, labelled or not, was seen in the most recent years of sampling. For the high molecular weight phthalates, DEHP seems to have been substituted in part by di-isononyl phthalate (DiNP), but DiNP metabolite levels have also been declining in the last years. Probably, non-phthalate alternatives increasingly take over for the phthalates in Germany. A comparison with NHANES (National Health and Nutrition Examination Survey) data from the United States covering the years 1999 to 2012 revealed both similarities and differences in phthalate exposure between Germany and the US. Exposure to critical phthalates has decreased in both countries with metabolite levels more and more aligning with each other, but high molecular weight phthalates substituting DEHP (such as DiNP) seem to become more important in the US than in Germany. doi:10.1016/j.ijheh.2016.11.003
Wittassek, Matthias; Wiesmüller, Gerhard A.; Koch, Holger M.; Eckard, Rolf; Dobler, Lorenz; Helm, Dieter; Müller, Johannes; Angerer, Jürgen; Schlüter, Christoph International Journal of Hygiene and Environmental Health 210 (2007), 3-4, 319-333 In a retrospective human biomonitoring study we analysed 24h urine samples taken from the German Environmental Specimen Bank for Human Tissues (ESBHum), which were collected from 634 subjects, (predominantly students, age range 20-29 years, 326 females, 308 males) in 9 years between 1988 and 2003 (each n≥60), for the concentrations of primary and/or secondary metabolites of di-n-butyl phthalate (DnBP), di-iso-butyl phthalate (DiBP), butylbenzyl phthalate (BBzP), di(2-ethylhexyl) phthalate (DEHP) and di-iso-nonyl phthalate (DiNP). Based on the urinary metabolite excretion we estimated daily intakes of the parent phthalates and investigated the chronological course of the phthalate exposure. In over 98% of the urine samples metabolites of all five phthalates were detectable indicating a ubiquitous exposure of the German population to all five phthalates throughout the last 20 years. The median daily intakes in the subsets between 1988 and 1993 were quite constant for DnBP (approx. 7 μg/kg bw/d) and DEHP (approx. 4 μg/kg bw/d). However, from 1996 the median levels of both phthalates decreased continuously until 2003 (DnBP 1.9 μg/kg bw/d; DEHP 2.4 μg/kg bw/d). By contrast, the daily intake values for DiBP were slightly increasing over the whole time frame investigated (median 1989: 1.0 μg/kg bw/d; median 2003: 1.4 μg/kg bw/d), approximating the levels for DnBP and DEHP. For BBzP we observed slightly decreasing values, even though the medians as of 1998 levelled off at around 0.2 μg/kg bw/d. Regarding daily DiNP exposure we found continuously increasing values, with the lowest median being 0.20 μg/kg bw/d for the subset of 1988 and the highest median for 2003 being twice as high. The trends observed in phthalate exposure may be associated with a change in production and usage pattern. Female subjects exhibited significantly higher daily intakes for the dibutyl phthalates (DnBP p=0.013; DiBP p=0.004). Compared to data from US National Health and Nutrition Examination Surveys (NHANES) exposure levels of the dibutyl phthalates were generally higher in our German study population, while levels of BBzP were somewhat lower. Overall, for a considerable 14% of the subjects we observed daily DnBP intakes above the tolerable daily intake (TDI) value deduced by the European Food Safety Authority (EFSA) (10 μg/kg bw/d). However, the frequency of exceedance decreased during the years and was beneath 2% in the 2003 subset. Even though transgressions of the exposure limit values of the EFSA and the US Environmental Protection Agency (US EPA) occurred only in a relatively small share of the subjects, one has to take into account the cumulative exposure to all phthalates investigated and possible dose-additive endocrine effects of these phthalates. doi: 10.1016/j.ijheh.2007.01.037
MBzP MBzP Erläuterung: Mono-benzylphthalat ist der primäre Metabolit von Butylbenzylphthalat (BBzP) nach Abspaltung der Butylgruppe.
Butylbenzylphthalat BBzP BBP Benzylbutylphthalat Formel: 2-[CH3(CH2)3O2C]C6H4CO2CH2C6H5 oder C19H20O4 CAS-Nummer: 85-68-7 Erläuterung: Einziges industriell bedeutsames Phthalat mit unterschiedlichen Seitenketten, wobei eine davon eine Benzylgruppe darstellt
Die Weichmacher können aus Plastik austreten und können in Humanproben nachgewiesen werden Unternehmen setzen Phthalate vor allem als Weichmacher in PVC ein. Die chemische Industrie in Europa produziert jährlich etwa eine Million Tonnen Phthalate. Über 90 Prozent davon gehen in die Weich-PVC Herstellung. Als Weichmacher bilden Phthalate keine festen Bindungen mit dem PVC, so kann ein Teil der Phthalate aus den Produkten, wie beispielsweise Fussböden, Tapeten oder Verpackungsmaterial, entweichen. Das Human-Biomonitoring verschiedener Länder hat gezeigt, dass die Bevölkerung industrialisierter Länder durchgehend mit Phthalaten belastet ist. In zwei retrospektiven Untersuchungen der Umweltprobenbank wurden in nahezu sämtlichen Urinproben Phthalate nachgewiesen. Dies weist auf eine ubiquitäre Belastung der deutschen Bevölkerung hin. Unter REACH sind ca. 600 Phthalate vorregistriert worden; die sechs am häufigsten verwendeten Verbindungen sind DiDP (Diisodecylphthalat), DiNP ( Diisononylphthalat ), DEHP ( Diethylhexylphthalat ), DnBP ( Di-n-butylphthalat ), DiBP ( Diisobutylphthalat ) und BBzP ( Butylbenzylphthalat ). 2011 hat die EU entschieden, dass DEHP, DnBP und BBzP zu den ersten Chemikalien gehören, deren Anwendung durch REACH umfassend geregelt wird: Der Verkauf und die Verwendung dieser Chemikalien war somit ab dem 1.1.2015 verboten. Ausnahmen gibt es nur, wenn die EU Kommission einem Unternehmen eine eigene Zulassung für die Verwendung der Phthalate erteilt. Dafür müsste das Unternehmen darlegen, dass mögliche Risiken durch entsprechende Maßnahmen adäquat begrenzt werden können oder dass der sozioökonomische Nutzen der Verwendung dieser Chemikalien die möglichen Risiken für Mensch und Umwelt überwiegt. Bereits 2005 hatten die Mitgliedsstaaten der Europäischen Union DEHP, DnBP, DiBP und BBzP als reproduktionstoxische Stoffe eingestuft. Seitdem ist die Verwendung dieser Chemikalien in Kinderspielzeug, Babyartikeln und Kosmetika verboten. Der Gebrauch dreier weiterer Phthalate - DiNP, DnOP (Di-n-octylphthalat) und DiDP - in Kleinspielzeug sowie Babyartikeln, die Kinder in den Mund nehmen können, wurde ebenfalls untersagt. Für diese Phthalate gibt es bereits seit 1999 ein Verbot entsprechender Verwendungen. Um die Belastung des Menschen zu erfassen und die Wirksamkeit der regulatorischen Maßnahmen zu überprüfen, wurden in drei retrospektiven Studien fast 1200 archivierte 24-h-Sammelurinproben der Umweltprobenbank auf Primär- und Sekundärmetabolite der Phthalate DMP (Dimethylphthalat), DEP (Diethylphthalat), BBzP, DiBP, DnBP, DCHP (Dicyclohexylphthalat), DnPeP (Di-n-pentylphthalat), DEHP, DiNP, DiDP, DPHP (Di-propyl-heptylphthalat) und DnOPuntersucht. Studierende der Universität Münster im Alter von 20 bis 29 Jahren spendeten die Proben zwischen 1998 und 2015. Die erste Messreihe umfasst die Probenahmejahre 1988, 1989, 1991, 1993, 1996, 1998, 1999, 2001 und 2003. Die zweite Messreihe umfasst überlappend die Probenahmejahre 2002, 2004, 2006 und 2008; die dritte Messreihe die Jahre 2007, 2009, 2011, 2013 und 2015. In nahezu sämtlichen Urinproben wurden die Metabolite der meisten Phthalate nachgewiesen. Dies weist auf eine ubiquitäre Belastung der deutschen Bevölkerung hin. Diese Ergebnisse stimmen gut mit den Untersuchungen in anderen Industrieländern überein. Die Untersuchungen zeigen, dass die Phthalat-Belastung junger Erwachsener in Deutschland in den letzten zwanzig Jahren gesunken ist. Mitte der 1990er Jahre erreichten die Messwerte für DEHP, BBzP und DnBP ihr Maximum, anschließend sanken die Belastungen. Im Gegensatz dazu stieg die Belastung mit DiNP, das auch als Ersatzstoff für DEHP eingesetzt wird, an. Die Konzentration von DiBP sank erst während der letzten Messreihe. Alle Daten zur Ergebnisbeschreibung anzeigen In den 1980er Jahren begann die Diskussion um die Risiken der Verwendung des Weichmachers DEHP in Plastik. Wie der an Umweltprobenbank-Proben gemessene Zeittrend zeigt, stieg die Belastung der weiblichen und männlichen Probanden mit DEHP in dieser Zeit noch an. Erst Mitte der 1990er Jahre, als die Debatte um die sichere Verwendung von DEHP die breite Öffentlichkeit erreichte, endete der Anstieg der Belastung. 1997 verlangten Dänemark und Spanien von der EU Kommission eine vorsorgliche Anwendungsbeschränkung. Die EU Kommission entschied sich wenig später für die zunächst temporäre, dann unbefristete Beschränkungsregelung zum Schutz der Kinder vor DEHP. Der Zeittrend der Umweltprobenbank deutet an, dass die chemischen Unternehmen die Verwendung von DEHP neu bewertet haben, als sich die Pläne der Kommission zur Anwendungsbeschränkung abzeichneten: Die Konzentration der DEHP Metabolite in den 24-h-Sammelurin Proben begann ab 1997 kontinuierlich zu sinken. Da die Proben von jungen Erwachsenen stammen, zeigt sich deutlich, dass die Veränderung des Marktes für Weichmacher offensichtlich nicht nur Kinderspielzeug betraf, sondern vor allem auch Produkte, die zu einer Phthalat-Belastung von Lebensmitteln führen. Dies ist von besonderer Bedeutung, da die Phthalat-Belastung des Menschen in erster Linie aus kontaminierten Lebensmitteln stammt. 2008 war die Konzentration der DEHP Metabolite in den Proben junger Erwachsener aus der UPB auf die Hälfte bis ein Drittel der Messwerte der späten 1980er Jahre gesunken. Dennoch überschreiten immernoch 1% der Proben den BE Richtwert (biomonitoring equivalents). Vor diesem Hintergrund dokumentieren die Zeittrends eine positive Entwicklung, zeigen aber auch, dass die toxikologisch bedenklichen Phthalate immer noch so breit eingesetzt werden, dass weitere Regulierungsschritte sinnvoll erscheinen. Durch den aufgezeigten abnehmenden Trend der Phthalatexposition ist es von hoher Priorität, die Exposition gegenüber alternativen Weichmachern, wie beispielsweise Hexamoll DINCH, zu untersuchen. Aktualisiert am: 12.01.2022 Datenrecherche Datenrecherche Datenrecherche Datenrecherche
Background Phthalates, bisphenol A (BPA) and triclosan (TCS) are detectable in the vast majority of people. Most humans are continuously exposed to these chemicals due to their presence in food or in everyday consumer products. The measurement of these compounds in family members may help to explore the impact of major lifestyle factors on exposure. Mothers and (young) children are especially interesting to study, as they mostly share considerable parts of daily life together. Materials and methods Phthalate metabolites, bisphenol A (BPA) and triclosan (TCS) were measured in first morning void urine, collected in mother-child pairs (n=129) on the same day. The mothers (27-45y) and their children (6-11y) were recruited in the Brussels agglomeration and rural areas of Belgium in the context of the European COPHES-DEMOCOPHES human biomonitoring project. Face-to-face questionnaires gathered information on major exposure sources and lifestyle factors. Exposure determinants were assessed by multiple linear regression analysis. Results The investigated compounds were detectable in nearly all mothers (92.8-100%) and all children (95.2-100%). The range (P90 vs. P10) of differences in urinary concentrations within each age group was for most compounds around 10-20 fold, and was very high for TCS up to 35 and 350-fold in children and mothers respectively. Some participants exceeded the tolerable daily intake guidelines as far as they were available from the European Food Safety Authority (EFSA). Overall, for BPA, the urinary concentrations were similar among both age groups. Most urinary phthalate metabolites were higher in children compared to the mothers, except for monoethyl phthalate (MEP). TCS levels were generally higher in the mothers. Despite the difference in mothers' and children's urinary concentrations, the creatinine-corrected levels were correlated for all biomarkers (Spearman rank r=0.32 to 0.66, p<0.001). Furthermore, for phthalates, similar home and lifestyle factors were associated with the urinary concentrations in both age groups: home renovation during last two years or redecoration during the last year for di-ethyl phthalate (DEP); PVC in home for di-n-butyl phthalate (DnBP), di-iso-butyl phthalate (DiBP) and butyl benzyl phthalate (BBzP), and personal care products use for DiBP and DnBP. Based on questionnaire information on general food type consumption patterns, the exposure variability could not be explained. However, comparing the phthalate intake from the current study with earlier assessed Belgian food intake calculations for both ages, food in general was estimated to be the major intake source for di-ethyl hexyl phthalate (DEHP), with diminishing importance for BBzP, DiBP and DnBP. Conclusion Our results confirm, that children and their mothers, sharing diets and home environments, also share exposure in common consumer products related chemicals. By collecting morning urine levels on the same day, and using basic questionnaires, suspected exposure routes could be unraveled.
The German Environmental Specimen Bank (ESB) continuously collects 24-h urine samples since theearly 1980s in Germany. In this study we analyzed 300 urine samples from the years 2007 to 2015 for 21phthalate metabolites (representing exposure to 11 parent phthalates) and combined the data with twoprevious retrospective measurement campaigns (1988 to 2003 and 2002 to 2008). The combined datasetcomprised 1162 24-h urine samples spanning the years 1988 to 2015. With this detailed set of humanbiomonitoring data we describe the time course of phthalate exposure in Germany over a time frame of27 years. For the metabolites of the endocrine disrupting phthalates di(2-ethylhexyl) phthalate (DEHP),di-n-butyl phthalate (DnBP) and butylbenzyl phthalate (BBzP) we observed a roughly ten-fold decline inmedian metabolite levels from their peak levels in the late 1980s/early 1990s compared to most recentlevels from 2015. Probably, bans (first enacted in 1999) and classifications/labelings (enacted in 2001 and2004) in the European Union lead to this drop. A decline in di-isobutyl phthalate (DiBP) metabolite levelsset in only quite recently, possibly due to its later classification as a reproductive toxicant in the EU in 2009.In a considerable number of samples collected before 2002 health based guidance values (BE, HBM I) havebeen exceeded for DnBP (27.2%) and DEHP (2.3%) but also in recent samples some individual exceedancescan still be observed (DEHP 1.0%). A decrease in concentration for all low molecular weight phthalates,labelled or not, was seen in the most recent years of sampling. For the high molecular weight phthalates,DEHP seems to have been substituted in part by di-isononyl phthalate (DiNP), but DiNP metabolite levelshave also been declining in the last years. Probably, non-phthalate alternatives increasingly take overfor the phthalates in Germany. A comparison with NHANES (National Health and Nutrition ExaminationSurvey) data from the United States covering the years 1999 to 2012 revealed both similarities anddifferences in phthalate exposure between Germany and the US. Exposure to critical phthalates hasdecreased in both countries with metabolite levels more and more aligning with each other, but highmolecular weight phthalates substituting DEHP (such as DiNP) seem to become more important in theUS than in Germany.<BR>© 2016 Elsevier GmbH. All rights reserved
During the population representative German Environmental Survey of Children and Adolescents (GerES V, 2014-2017) 2256 first-morning void urine samples from 3 to 17 years old children and adolescents were analysed for 21 metabolites of 11 different phthalates (di-methyl phthalate (DMP), di-ethyl phthalate (DEP), butylbenzyl phthalate (BBzP), di-iso-butyl phthalate (DiBP), di-n-butyl phthalate (DnBP), di-cyclohexyl phthalate (DCHP), di-n-pentyl phthalate (DnPeP), di-(2-ethylhexyl) phthalate (DEHP), di-iso-nonyl phthalate (DiNP), di-iso-decyl phthalate (DiDP) and di-n-octyl phthalate (DnOP)). Metabolites of DMP, DEP, BBzP, DiBP, DnBP, DEHP, DiNP and DiDP were found in 97-100% of the participants, DCHP and DnPeP in 6%, and DnOP in none of the urine samples. Geometric means (GM) were highest for metabolites of DiBP (MiBP: 26.1 my g/L), DEP (MEP: 25.8 my g/L), DnBP (MnBP: 20.9 my g/L), and DEHP (cx-MEPP: 11.9 my g/L). For all phthalates but DEP, GMs were consistently higher in the 3-5 years old children than in the 14-17 years old adolescents. For DEHP, the age differences were most pronounced. All detectable phthalate biomarker concentrations were positively associated with the levels of the respective phthalate in house dust. In GerES V we found considerably lower phthalate biomarker levels than in the preceding GerES IV (2003-2006). GMs of biomarker levels in GerES V were only 18% (BBzP), 23% (MnBP), 23% (DEHP), 29% (MiBP) and 57% (DiNP) of those measured a decade earlier in GerES IV. However, some children and adolescents still exceeded health-based guidance values in the current GerES V. 0.38% of the participants had levels of DnBP, 0.08% levels of DEHP and 0.007% levels of DiNP which were higher than the respective health-based guidance values. Accordingly, for these persons an impact on health cannot be excluded with sufficient certainty. The ongoing and substantial exposure of vulnerable children and adolescents to many phthalates confirms the need of a continued monitoring of established phthalates, whether regulated or not, as well as of potential substitutes. With this biomonitoring approach we provide a picture of current individual and cumulative exposure developments and body burdens to phthalates, thus providing support for timely and effective chemicals policies and legislation. © 2020 The Authors. Published by Elsevier GmbH.