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- Buekers, J, et al.
(författare)
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Development of Policy Relevant Human Biomonitoring Indicators for Chemical Exposure in the European Population
- 2018
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Ingår i: International journal of environmental research and public health. - : MDPI AG. - 1660-4601. ; 15:10
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Tidskriftsartikel (refereegranskat)abstract
- The European Union’s 7th Environmental Action Programme (EAP) aims to assess and minimize environmental health risks from the use of hazardous chemicals by 2020. From this angle, policy questions like whether an implemented policy to reduce chemical exposure has had an effect over time, whether the health of people in specific regions or subpopulations is at risk, or whether the body burden of chemical substances (the internal exposure) varies with, for example, time, country, sex, age, or socio-economic status, need to be answered. Indicators can help to synthesize complex scientific information into a few key descriptors with the purpose of providing an answer to a non-expert audience. Human biomonitoring (HBM) indicators at the European Union (EU) level are unfortunately lacking. Within the Horizon2020 European Human Biomonitoring project HBM4EU, an approach to develop European HBM indicators was worked out. To learn from and ensure interoperability with other European indicators, 15 experts from the HBM4EU project (German Umweltbundesamt (UBA), Flemish research institute VITO, University of Antwerp, European Environment Agency (EEA)), and the World Health Organization (WHO), European Core Health Indicator initiative (ECHI), Eurostat, Swiss ETH Zurich and the Czech environmental institute CENIA, and contributed to a workshop, held in June 2017 at the EEA in Copenhagen. First, selection criteria were defined to evaluate when and if results of internal chemical exposure measured by HBM, need to be translated into a European HBM-based indicator. Two main aspects are the HBM indicator’s relevance for policy, society, health, and the quality of the biomarker data (availability, comparability, ease of interpretation). Secondly, an approach for the calculation of the indicators was designed. Two types of indicators were proposed: ‘sum indicators of internal exposure’ derived directly from HBM biomarker concentrations and ‘indicators for health risk’, comparing HBM concentrations to HBM health-based guidance values (HBM HBGVs). In the latter case, both the percentage of the studied population exceeding the HBM HBGVs (PE) and the extent of exceedance (EE), calculated as the population’s exposure level divided by the HBM HBGV, can be calculated. These indicators were applied to two examples of hazardous chemicals: bisphenol A (BPA) and per- and polyfluoroalkyl substances (PFASs), which both have high policy and societal relevance and for which high quality published data were available (DEMOCOPHES, Swedish monitoring campaign). European HBM indicators help to summarize internal exposure to chemical substances among the European population and communicate to what degree environmental policies are successful in keeping internal exposures sufficiently low. The main aim of HBM indicators is to allow follow-up of chemical safety in Europe.
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- Primikyri, Alexandra, et al.
(författare)
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Method development and validation for the quantitation of the complement inhibitor Cp40 in human and cynomolgus monkey plasma by UPLC-ESI-MS
- 2017
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Ingår i: Journal of chromatography. B. - : Elsevier BV. - 1570-0232 .- 1873-376X. ; 1041, s. 19-26
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Tidskriftsartikel (refereegranskat)abstract
- Cp40 is a 14-amino acid cyclic analog of the peptidic complement inhibitor compstatin that binds with sub-nanomolar affinity to complement component C3 and has already shown promise in various models of complement-related diseases. The preclinical and clinical development of this compound requires a robust, accurate, and sensitive method for quantitatively monitoring Cp40 in biological samples. In this study, we describe the development and validation of an ultra-high performance liquid chromatography electrospray mass spectrometry method for the quantitation of Cp40 in human and non-human primate (NHP) plasma. Isotope-labeled Cp40 was used as an internal standard, allowing for the accurate and absolute quantitation of Cp40. Labeled and non-labeled Cp40 were extracted from plasma using reversed phase-solid phase extraction, with recovery rates exceeding 80%, indicating minor matrix effects. The triply charged states of Cp40 and isotope-labeled Cp40 were detected at m/z 596.60 and 600.34, respectively, via a Q-TOF mass spectrometer and were used for quantitation. The method was linear in the range of 0.18-3.58 mu g/mL (r(2) >= 0.99), with precision values below 0.71% in NHP and 0.77% in human plasma. The accuracy of the method ranged from -2.17% to 17.99% in NHP and from -0.26% to 15.75% in 'human plasma. The method was successfully applied to the quantitation of Cp40 in cynomolgus monkey plasma after an initial intravenous bolus of 2 mg/kg followed by repetitive subcutaneous administration at 1 mg/kg. The high reproducibility, accuracy, and robustness of the method developed here render it suitable for drug monitoring of Cp40, and potentially other compstatin analogs, in both human and NHP plasma samples during pharmacokinetic and pharmacodynamic studies.
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