Person: Apel, Petra
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Veröffentlichung The exposure of German children and young adults to chemicals of concern(2013) Apel, Petra; Conrad, André; Fiddicke, Ulrike; Schröter-Kermani, Christa; Schulz, Christine; Seiwert, MargareteVeröffentlichung 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(2017) Koch, Holger M.; Apel, Petra; Schütze, Andre; Conrad, André; Pälmke, Claudia; Kolossa-Gehring, Marike; Brüning, Thomas; Rüther, MariaThe 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.
© 2016 Elsevier GmbH. All rights reservedVeröffentlichung Human biomonitoring reference values: Differences and similarities between approaches for identifying unusually high exposure of pollutants in humans(2019) Apel, Petra; Conrad, André; Kolossa-Gehring, Marike; Rucic, Enrico; Vogel, NinaIn exposure and risk assessment, the indication of unusually high exposure levels in humans to chemicals has been considered as an important objective for decades. To realize this objective, reference values (RV) need to be derived. However, while there is a tendency towards using the 95th percentile as a basis for deriving these reference values there is still no consensus. Moreover, side approaches have evolved including deriving RVs based on other percentiles, reporting multiple RVs or only reporting percentiles. The purpose of this article is to give an overview of the current literature, to point out differences and similarities between existing approaches, and to highlight important criteria for the derivation of RVs. We observe the majority of studies to base RVs on the 95th percentile and its 95% confidence interval which can been justified by statistical paradigms, present arguments for a single defined reference value, and discuss characteristics which call for more consistency. To conclude, our overview provides a first step towards a more homogenous and standardized derivation procedure to identify unusually high exposures in exposure science. © 2018 The Authors. Published by Elsevier GmbH.Veröffentlichung Time course of phthalate cumulative risks to male developmental health over a 27-year period: Biomonitoring samples of the German Environmental Specimen Bank(2020) Apel, Petra; Kortenkamp, Andreas; Conrad, André; Koch, Holger Martin; Kolossa-Gehring, Marike; Rüther, MariaIn several human biomonitoring surveys, changes in the usage patterns of phthalates have come to light, but their influence on the risks associated with combined exposures is insufficiently understood. Based on the largest study to date, the 27-year survey of urinary phthalate metabolite levels in 24-hour urine samples from the German Environmental Specimen Bank, we present a deep analysis of changing phthalate exposures on mixture risks. This analysis adopts the Hazard Index (HI) approach based on the five phthalates DBP, DIBP, BBP, DEHP and DINP. Calculations of the hazard index for each study participant included updated phthalate reference doses for anti-androgenicity (RfDAAs) that take account of new evidence of phthalates' developmental toxicity. The Maximum Cumulative Ratio (MCR) approach was used to establish whether a subjectâ€Ìs combined exposure was dominated by one phthalate or was influenced by several phthalates simultaneously. Generally, over the years there was a shift towards lower HIs and higher MCRs, reflecting an increased complexity of the combined exposures. The decade from 1988 to about 1999 was characterised by rather high HIs of between 3 and 7 (95th percentile) which were driven by exposure to DBP and DEHP, often exceeding their single acceptable exposures. Traditional single phthalate risk assessments would have underestimated these risks by up to 50%. From 2006 onwards, no study participant experienced exposures above acceptable levels for a single phthalate, but combined exposures were still in excess of HI = 1. From 2011 onwards most individuals stayed below HI = 1. In interpreting these results, we caution against the use of HI = 1 as an acceptable limit and develop proposals for improved and more realistic mixture risk assessments that take account of co-exposures to other anti-androgenic substances also capable of disrupting the male reproductive system. From this perspective, we regard HIs between 0.1 and 0.2 as more appropriate for evaluating combined phthalate exposures. Assessed against lowered HIs of 0.1 - 0.2, the combined phthalate exposures of most study participants exceeded acceptable levels in all study years, including 2015. Continued monitoring efforts for phthalate combinations are required to provide the basis for appropriate risk management measures. © 2020 The Authors.