Holger Martin Koch

Publications (82) View all

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  Available from: Holger Martin Koch

  Article: The contribution of diet to total bisphenol A body burden in humans: Results of a 48 hour fasting study

  K.L.Y. Christensen, M. Lorber, S. Koslitz, T. Brüning, H.M. Koch
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  ABSTRACT: Human biomonitoring studies measuring bisphenol A (BPA) in urine have shown widespread exposure in the general population. Diet is thought to be a major route of exposure. We studied urinary BPA patterns in five individuals over a 48-h period of fasting (bottled water only). Personal activity patterns were recorded with a diary to investigate non-dietary routes of exposure. All urine void events during the fast were collected, as well as events before and after the fast. The pattern of BPA concentrations was similar for all participants: they rose near the beginning of the fast (after the pre-fast meal), declined over the next 24 h, fluctuated at lower levels during the second day, and then rose after the post-fast meal. Concentrations (~ 2 μg/g creatine) and calculated BPA intakes (~ 0.03 μg/kg-day) in these individuals during the first 24 h were consistent with general population exposures. For the second 24 h, concentrations and intakes declined by about two-thirds. One of the individuals had an e
  Environment International 12/2012; 50:7-14. · 5.30 Impact Factor
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  Article: Di-n-butyl phthalate (DnBP) and diisobutyl phthalate (DiBP) metabolism in a human volunteer after single oral doses.

  H M Koch, K L Y Christensen, V Harth, M Lorber, T Brüning
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  ABSTRACT: An individual (male, 36 years, 87 kg) ingested two separate doses of di-n-butyl phthalate (DnBP) and diisobutyl phthalate (DiBP) at a rate of ~60 μg/kg. Key monoester and oxidized metabolites were identified and quantified in urine continuously collected until 48 h post-dose. For both DnBP and DiBP, the majority of the dose was excreted in the first 24 h (92.2 % of DnBP, 90.3 % of DiBP), while only <1 % of the dose was excreted in urine on day 2. In each case, the simple monoesters were the major metabolites (MnBP, 84 %; MiBP, 71 %). For DnBP, ~8 % was excreted as various side chain oxidized metabolites. For DiBP, approximately 20 % was excreted mainly as the oxidized side chain metabolite 2OH-MiBP, indicating that the extent of oxidative modification is around 2.5 times higher for DiBP than for DnBP. All DnBP and DiBP metabolites reached peak concentrations between 2 and 4 h post-exposure, followed by a monotonic decline. For DnBP metabolites, the elimination halftime of MnBP was 2.6 h; longer elimination halftimes were estimated for the oxidized metabolites (2.9-6.9 h). For DiBP metabolites, MiBP had the shortest halftime (3.9 h), and the oxidized metabolites had somewhat longer halftimes (4.1 and 4.2 h). Together with the simple monoesters, secondary oxidized metabolites are additional and valuable biomarkers of phthalate exposure. This study provides basic human metabolism and toxicokinetic data for two phthalates that have to be considered human reproductive toxicants and that have been shown to be omnipresent in humans.
  Archive für Toxikologie 07/2012; · 4.67 Impact Factor
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  Article: Framework for the development and application of environmental biological monitoring guidance values.

  Ruth Bevan, Juergen Angerer, John Cocker, Kate Jones, Holger M Koch, Ovnair Sepai, Greet Schoeters, Roel Smolders, Len Levy
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  ABSTRACT: Human biomonitoring (HBM) is widely recognised as a useful tool to aid assessment of exposure to chemical substances, but our ability to detect hazardous substances (or their metabolites and health effects) often exceeds our understanding of their biological relevance. There are only a few established frameworks for developing and using occupational and environmental biological guidance values (BGVs), mostly for data-rich substances that have been in use for some time. BGVs for new substances and those with unknown dose-response relationships are difficult to derive. An accepted framework based on current scientific knowledge and best practice is therefore urgently needed to help scientists, regulators, and stakeholders to design appropriate HBM studies, interpret HBM data (both for groups and individuals) understand the limitations and to take appropriate action when required. The development and application of such a tool is described here. We derived a conceptual framework that was refined by consultation with an advisory group and workshop. The resulting framework comprised four levels defined by increasing data, with increasing confidence for human health risk assessment. Available data were used for 12 chemicals with expert judgement to illustrate the utility of the framework.
  Regulatory Toxicology and Pharmacology 06/2012; 63(3):453-60. · 2.43 Impact Factor
• Article: Population variability of phthalate metabolites and bisphenol A concentrations in spot urine samples versus 24- or 48-h collections.

  Krista L Yorita Christensen, Matthew Lorber, Holger M Koch, Marike Kolossa-Gehring, Marsha K Morgan
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  ABSTRACT: Human exposure to phthalates and bisphenol A (BPA) can be assessed through urinary biomonitoring, but methods to infer daily intakes assume that spot sample concentrations are comparable to daily average concentrations. We evaluate this assumption using human biomonitoring data from Germany and the United States (US). The German data comprised three regional studies with spot samples and one with full-day samples analyzed for phthalate metabolites. The US data included: a study on DEHP metabolites and BPA involving eight persons supplying all urine voids (from which 24-h samples were constructed) for seven consecutive days; NHANES spot sample data on DEHP metabolites and BPA; and a regional study of children with 48-h samples analyzed for BPA. In the German data, measures of central tendency differed, but spot and 24-h samples showed generally comparable variance including 95th percentiles and maxima equidistant from central tendency measures. In contrast, the US adult data from the eight-person study showed similar central tendencies for phthalate metabolites and BPA, but generally greater variability for the spot samples, including higher 95th percentiles and maxima. When comparing children's BPA concentrations in NHANES spot and 48-h samples, distributions showed similar central tendency and variability. Overall, spot urinary concentrations of DEHP metabolites and BPA have variability roughly comparable with corresponding 24-h average concentrations obtained from a comparable population, suggesting that spot samples can be used to characterize population distributions of intakes. However, the analysis also suggests that caution should be exercised when interpreting the high end of spot sample data sets.
  Journal of Exposure Science and Environmental Epidemiology 06/2012; 22(6):632-40. · 2.93 Impact Factor
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  Article: Bisphenol A in 24 h urine and plasma samples of the German Environmental Specimen Bank from 1995 to 2009: A retrospective exposure evaluation.

  Holger M Koch, Marike Kolossa-Gehring, Christa Schröter-Kermani, Jürgen Angerer, Thomas Brüning
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  ABSTRACT: Human exposure to Bisphenol A (BPA) is omnipresent. Both the extent of the exposure and its toxicological relevance are controversially discussed. We aim to reliably determine and evaluate the extent of BPA body burden in the German population from 1995 to 2009 based on 600 24 h urine samples and corresponding plasma samples from the Environmental Specimen Bank. We determined total and unconjugated BPA in urine and plasma using on-line solid-phase extraction high-performance liquid chromatography coupled to isotope dilution tandem mass spectrometry with a limit of quantification (LOQ) of 0.1 μg/l. In the stored urines, total BPA was quantifiable in >96% (median: 1.49 μg/l; 95th percentile: 7.37 μg/l), whereas unconjugated BPA was quantifiable only in <15% of the samples. Total BPA concentrations decreased over time, but 24 h urine volumes increased. Therefore, daily intakes calculated from the 24 h urines remained rather constant at a median of 0.037 and a 95th percentile of 0.171 μg BPA/kg body weight/day. In 60 corresponding plasma samples, total BPA levels were generally below the LOQ of 0.1 μg/l and, if quantifiable, most BPA was unconjugated, thus hinting to external contamination. We see total BPA in urine as the most appropriate and robust marker for BPA exposure assessment (if controlled for BPA contamination). Unconjugated BPA in urine and unconjugated or total BPA in plasma where contamination or breakdown of the glucuronide cannot be ruled out are of no value for human exposure assessment.
  Journal of Exposure Science and Environmental Epidemiology 05/2012; 22(6):610-6. · 2.93 Impact Factor