Environmental surveys, specimen bank and health related environmental monitoring in Germany

Production of chemicals, use of products and consumer goods, contamination of food as well as today's living conditions are related to a substantial exposure of humans to chemicals. Safety of human beings and the environment has to be safeguarded by producers and government. Human biomonitoring (HBM) has proven to be a useful and powerful tool to control human exposure and facilitate risk assessment. Therefore, the German Federal Environment Agency (Umweltbundesamt, UBA) employs two major HBM tools, the German Environmental Survey (GerES) and the German Environmental Specimen Bank (ESB). GerES is a nationwide population representative study on HBM and external human exposure, which has, inter alia, been used to identify lead in tap water, lead dustfall, time spent in traffic, and age of dwelling as exposure sources for lead and, thus, to derive risk reduction measures. The ESB is a permanent monitoring instrument and an archive for human specimens. Retrospective monitoring of phthalates and bisphenol A provides a continuous historical record of human exposure in Germany, over the last decades. Additionally it revealed that estimations of human exposure based on production and consumption data may supply misleading information on human exposure. HBM data demonstrated that (a) the use if the restricted isomer di-n-butylphthalat decreased while di-i-butylphthalate levels remained constant and (b) human bisphenol A exposure might be overestimated without monitoring data. The decrease of polycyclic aromatic hydrocarbon-exposure proves the success of German environmental policy after German re-unification. In addition to GerES and ESB UBA is involved in different co-operation networks, the two most prominent of which are (1) the harmonization of HBM in Europe (ESBIO; Expert Team to Support Biomonitoring in Europe, COPHES/DEMOCOPHES; Consortium to Perform Human Biomonitoring on a European Scale/Demonstration of a study to Coordinate and Perform Human Biomonitoring on a European Scale) and (2) the co-operation between BMU and the German Chemical Industry Association (VCI). In the latter project emphasis will be placed on substances with a potential relevance for health and on substances to which the general population might potentially be exposed to a considerable extent and for which HBM methods are not available up to now.     

The European COPHES/DEMOCOPHES project: Towards transnational comparability and reliability of human biomonitoring results

COPHES/DEMOCOPHES has its origins in the European Environment and Health Action Plan of 2004 to “develop a coherent approach on human biomonitoring (HBM) in Europe”. Within this twin-project it was targeted to collect specimens from 120 mother-child-pairs in each of the 17 participating European countries. These specimens were investigated for six biomarkers (mercury in hair; creatinine, cotinine, cadmium, phthalate metabolites and bisphenol A in urine). The results for mercury in hair are described in a separate paper. Each participating member state was requested to contract laboratories, for capacity building reasons ideally within its borders, carrying out the chemical analyses. To ensure comparability of analytical data a Quality Assurance Unit (QAU) was established which provided the participating laboratories with standard operating procedures (SOP) and with control material. This material was specially prepared from native, non-spiked, pooled urine samples and was tested for homogeneity and stability. Four external quality assessment exercises were carried out. Highly esteemed laboratories from all over the world served as reference laboratories. Web conferences after each external quality assessment exercise functioned as a new and effective tool to improve analytical performance, to build capacity and to educate less experienced laboratories. Of the 38 laboratories participating in the quality assurance exercises 14 laboratories qualified for cadmium, 14 for creatinine, 9 for cotinine, 7 for phthalate metabolites and 5 for bisphenol A in urine. In the last of the four external quality assessment exercises the laboratories that qualified for DEMOCOPHES performed the determinations in urine with relative standard deviations (low/high concentration) of 18.0/2.1% for cotinine, 14.8/5.1% for cadmium, 4.7/3.4% for creatinine. Relative standard deviations for the newly emerging biomarkers were higher, with values between 13.5 and 20.5% for bisphenol A and between 18.9 and 45.3% for the phthalate metabolites. Plausibility control of the HBM results of all participating countries disclosed analytical shortcomings in the determination of Cd when using certain ICP/MS methods. Results were corrected by reanalyzes. The COPHES/DEMOCOPHES project for the first time succeeded in performing a harmonized pan-European HBM project. All data raised have to be regarded as utmost reliable according to the highest international state of the art, since highly renowned laboratories functioned as reference laboratories. The procedure described here, that has shown its success, can be used as a blueprint for future transnational, multicentre HBM projects.     

A systematic approach for designing a HBM Pilot Study for Europe

The objective of COPHES (Consortium to Perform Human biomonitoring on a European Scale) was to develop a harmonised approach to conduct human biomonitoring on a European scale. COPHES developed a systematic approach for designing and conducting a pilot study for an EU-wide cross-sectional human biomonitoring (HBM) study and for the implementation of the fieldwork procedures. The approach gave the basis for discussion of the main aspects of study design and conduct, and provided a decision making tool which can be applied to many other studies. Each decision that had to be taken was listed in a table of options with their advantages and disadvantages. Based on this the rationale of the decisions could be explained and be transparent. This was important because an EU-wide HBM study demands openness of all decisions taken to encourage as many countries as possible to participate and accept the initiative undertaken.Based on this approach the following study design was suggested: a cross-sectional study including 120 children aged 6–11 years and their mothers aged up to 45 years from each participating country. For the pilot study the children should be sampled in equal shares in an urban and a rural location. Only healthy children and mothers (no metabolic disturbances) should be included, who have a sufficient knowledge of the local language and have been living at least for 5 years at the sampling location. Occupational exposure should not be an exclusion criterion. Recruitment should be performed via inhabitant registries or schools as an alternative option. Measures suitable to increase the response rate should be applied. Preferably, the families should be visited at home and interviewed face-to-face. Various quality control measures to guarantee a good fieldwork performance were recommended.This comprehensive overview aims to provide scientists, EU officials, partners and stakeholders involved in the EU implementation process full transparency of the work carried out in COPHES. Thus this report presents the discussion and consensus in COPHES on the main aspects of designing and conducting fieldwork of a human biomonitoring study. Furthermore, it provides an example for a systematic approach that may be useful to other research groups or pan-European research initiatives. In the study protocol that will be published elsewhere these aspects are elaborated and additional aspects are covered (Casteleyn et al., 2012). Meanwhile the respective pilot study DEMOCOPHES had been conducted and assessed. The results and lessons learned will be published elsewhere.     

Reprint of "Update of the reference and HBM values derived by the German Human Biomonitoring Commission"

In 2007, we reviewed the working principles and working procedures of the German Human Biomonitoring Commission together with the reference values and human biomonitoring (HBM) values derived up to that time. Since then, the Commission has decided to derive additionally HBM I values on the basis of tolerable daily intakes and has used and evaluated this new approach on the metabolites of (2-ethylhexyl) phthalate (DEHP) in urine. Furthermore, the Commission has derived a HBM I value for thallium in urine, has recinded the HBM values for lead in blood, and has updated the HBM values for cadmium in urine. Based on the representative data of the German Environmental Survey on Children from 2003 to 2006 (GerES IV), the Commission has updated the reference values for a large number of environmental pollutants in urine and blood of children in Germany. Since 2007, the Commission has derived new and updated reference values for PFOS and PFOA in human plasma, for thallium in urine, for aromatic amines in urine, for a comprehensive number of phthalate metabolites in urine, and for organochlorine pesticides in human breast milk. Furthermore, the Commission has evaluated background exposure levels for two naphthalene metabolites and acrylamide (using acrylamide-haemoglobin adduct) for the general population. This paper reports the new values, including those already published, in order to provide an updated overview.     

Harmonised human biomonitoring in Europe: activities towards an EU HBM framework

Human biomonitoring (HBM) can be an effective tool to assess human exposure to environmental pollutants and potential health effects and is increasingly seen as an essential element in a strategy when integrating health and environment. HBM can be used (i) to prioritise actions and measures for policy making; (ii) to evaluate policy actions aimed at reducing exposure to potentially hazardous environmental stressors; and (iii) to promote more comprehensive health impact assessments of policy options. In support of the European Environment and Health Action Plan 2004-2010, European scientists, experts from authorities and other stakeholders joined forces to work towards developing a functional framework and standards for a coherent HBM in Europe. Within the European coordination action on human biomonitoring, 35 partners from 27 European countries in the COPHES consortium aggregated their experiences and expertise and developed harmonized approaches and recommendations for better comparability of HBM data in Europe via the elaboration of a harmonized study protocol. This protocol is the product of discussion and compromises on the selection of environmental exposures, national environmental health concerns, and political and health priorities. The harmonised approach includes sampling recruitment, and analytical procedures, communication strategies and biobanking initiatives. The protocols and the harmonised approach are a means to increase acceptance and policy support and to in the future to enable determination of time trends. The common pilot study protocol will shortly be tested, adapted and assessed in the framework of the DEMOCOPHES in 17 European countries, including 16 EU Member States. COPHES and DEMOCOPHES constitute important steps towards establishing human biomonitoring as a tool for EU environmental and health policy and to improve quantification of exposure of the general European population to existing and emerging pollutants.     

Human biomonitoring in health risk assessment in Europe: Current practices and recommendations for the future

Human biomonitoring (HBM) is an important tool to survey the internal exposure of humans which represents the real life chemical body burden to chemicals and/or their metabolites. It results from total exposure to chemical substances from different sources and via different routes. These substances may be regulated under different legislative frameworks on chemicals (e.g., environmental, occupational, food safety etc). In occupational health, HBM has long traditions to control the exposures at workplaces. By providing accurate data on internal exposure, HBM data can improve human health risk assessment (RA) for both the general population and workers. Although the past few years have shown good examples on the use of HBM in the RA of chemicals, there is still quite some work to be done to improve its use in a regulatory RA.Under the scope of the European Human Biomonitoring Initiative (project HBM4EU, 2017–2021), the current study reviews the state-of-the-art of HBM use in chemicals RA with a special focus in Europe, and attempts to identify hurdles and challenges faced by regulators. To gather information on the use of HBM, including the availability of guidance on how to use it in RA, the RA schemes applied by different European or international organizations were analysed. Examples of such use were identified for a few selected groups of chemicals of concern for human health. In addition, we present the results of a survey, aimed at collecting information from national regulatory risk assessors on their day-to-day RA practices, the use of HBM data, and the obstacles and challenges related to their use. The results evidenced and explained some of the current obstacles of using HBM data in RA. These included the lack of HBM guidance values or biomonitoring equivalents (BEs), limited toxicokinetic information to support the interpretation of HBM data and, in the occupational health and safety (OSH) field, the lack of legal enforcement. Therefore, to support the integration of HBM in regulatory RA, we recommend, on one hand, the elaboration of a EU level guidance on the use of HBM in RA and, on the other hand, the continuation of research efforts to integrate HBM with new RA approaches using in vitro/in silico data and Adverse Outcome Pathways (AOPs).     

Human biomonitoring assessment values: Approaches and data requirements

Human biomonitoring (HBM) data is a very useful metric for assessing human's exposures to chemicals in commerce. To assess the potential health risks associated with the presence of chemicals in blood, urine or other biological matrix requires HBM assessment values. While HBM assessment values based on human exposure–response data remain the most highly valuable and interpretable assessment values, enough data exists for such values for very few chemicals. As a consequence, efforts have been undertaken to derive HBM assessment values in which external dose based guidance values such as tolerable daily intakes have been translated into equivalent biomonitoring levels. The development of HBM values by the German HBM Commission and Biomonitoring Equivalents by Summit Toxicology has resulted in conceptually similar assessment values. The review of the development of these values provided here demonstrates examples and approaches that can be used to broaden the range of chemicals for which such assessment values can be derived. Efforts to date have resulted in the publication of HBM assessment values for more than 80 chemicals, and now provide tools that can be used for the evaluation of HBM data across chemicals and populations.     

Austrian reference values for phthalate metabolite exposure in children/adolescents and adults

Reference values (RV₉₅) are statistically derived values comprising the rounded 95th percentiles within the 95% confidence interval and indicate the upper margin of background exposure to chemical substances in a population at a given time period. Based on representative national human biomonitoring data on several urinary phthalate metabolites in children, adolescents and adults from 2010 to 2011, RV₉₅ were derived for the Austrian population based on a IUPAC guideline and the recommendation of the German Human Biomonitoring Commission. The RV₉₅ (rounded values) for phthalate metabolites in children and adolescents aged 6–15 years are 110?μg/l (confidence interval of 95th population percentile: 83.7–163) for mono-ethyl phthalate (MEP), 45?μg/l (40.9–60.6) for mono-n-butyl phthalate (MnBP), 130?μg/l (126–161) for mono-isobutyl phthalate (MiBP), 25?μg/l (17.8–33.6) for mono-benzyl phthalate (MBzP), 100?μg/l (94.0–126) for the sum of the di(2-ethylhexyl) phthalate (DEHP) metabolites including mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (5OH-MEHP), mono(2-ethyl-5-oxohexyl) phthalate (5oxo-MEHP) and mono(2-ethyl-5-carboxypentyl) phthalate (5cx-MEPP), and 1.5?μg/l (0.64–1.6) for mono-cyclohexyl phthalate (MCHP). In adults aged 18–81 years, RV₉₅ are 440?μg/l (353–636) for MEP, 40?μg/l (33.1–52.1) for MnBP, 110?μg/l (87.3–118) for MiBP, 10?μg/l (7.2–11.8) for MBzP, 50?μg/l (44.6–68.3) for the sum of MEHP, 5OH-MEHP, 5oxo-MEHP and 5cx-MEPP, and 1.5?μg/l (0.95–1.8) for MCHP. For almost all investigated metabolites, children and adolescents exhibit higher RV₉₅ than adults, with the exceptions being MEP and MCHP. Compared to available RV₉₅ for Germany and Canada, Austrian values are lower for all investigated population groups.     

Levels of phthalate metabolites in urine among mother-child-pairs - results from the Duisburg birth cohort study, Germany

Phthalates are used ubiquitously and human exposure is widespread. Some phthalates are anti-androgens and have to be regarded as reproductive and developmental toxicants. In the Duisburg birth cohort study we examine the associations between hormonally active environmental agents and child development. Here we report the concentrations of 21 primary and secondary phthalate metabolites from seven low molecular weight (LMW) phthalates (DMP, DEP, BBzP, DiBP, DnBP, DCHP, DnPeP) and five high-molecular weight (HMW) phthalates (DEHP, DiNP, DiDP, DPHP, DnOP) in 208 urine samples from 104 mothers and their school-aged children. Analysis was performed by multidimensional liquid chromatography coupled to tandem mass spectrometry (LC/LC-MS/MS), using internal isotope-labeled standards. In both children and mothers, 18 out of 21 phthalate metabolites were detected above the limits of quantification (between 0.2 and 1.0 μg/l) in nearly all urine samples. Among the LMW phthalates, the excretion level (geometric mean) of the ΣDiBP metabolites was most prominent in children (103.9 μg/l), followed by ΣDnBP (56.5 μg/l), and MEP (39.1 μg/l). In mothers ΣDiBP (66.6 μg/l) was highest, followed by MEP (50.5 μg/l), and ΣDnBP (36.0 μg/l). Among the HMW phthalates, ΣDEHP was highest in children and mothers (55.7/28.9 μg/l). Compared to reference values derived from the German Human Biomonitoring Commission, children's metabolite concentrations were within background levels, whereas for mothers considerably higher exposure to the LMW phthalates DnBP and DiBP, and the HMW phthalate DEHP was detected (MiBP: 10.7%; MnBP: 11.7%; ΣDEHP: 23.3% of the samples were above the reference values). The LMW metabolites from DMP, DiBP, and DnBP, and the HMW metabolites from DEHP and DiNP were correlated between the mothers and children, probably indicating shared exposure in the immediate surrounding environment. Children showed higher excretion levels for most of the secondary metabolites than mothers, confirming previous findings on higher oxidized metabolite levels in children. The LMW metabolites ΣDiBP, ΣDnBP, and MMP, and the HMW metabolites ΣDEHP were negatively associated with children's age. The LMW metabolites ΣDiBP, ΣDnBP, and MBzP were inversely associated with body mass index of the children. The LMW ΣDiBP metabolites revealed a significant association with nicotine metabolites in urine from both children and mothers. Further analyses are ongoing to study long-term phthalate exposure and the associations with puberty outcome in these children.     

Human biomonitoring in Israel: past, present, future

The first human biomonitoring (HBM) studies in Israel in the 1970s and 80s focused on measuring exposure to polychlorinated biphenyls (PCBs) and organochlorine insecticides in the general population and organophosphate pesticides in agricultural workers. In the late 1990 s, a regional human biomonitoring study found differences in blood lead levels in children from Israel, Jordan, and the Palestinian Authority. Taken together with data on time trends in lead emissions in Israel, the study indicated the benefits from phasing out of leaded gasoline. More recently, a pilot study in pregnant women in Jerusalem, conducted in collaboration with the US-CDC, found widespread exposure to phthalates, organophosphate pesticides, and the carbamate bendiocarb. Creatinine-adjusted total dimethyl (DM) metabolite concentrations were between 4 and 6 times higher than populations of pregnant women in the United States. The Israel Ministry of Health is currently collaborating with the Hebrew University of Jerusalem and Al Quds University to study exposures to phthalates and organophosphates in pregnant women in Israel and the Palestinian Authority. The Israel Ministry of Health has also begun the first National Biomonitoring Study to measure exposures to bisphenol A, phthalates, organophosphates, polyaromatic hydrocarbons, the phytoestrogens genistein and daidzein, and cotinine in the Israeli adult population. This study is being carried out in collaboration with the University of Erlangen-Nuremberg in Germany. Until recently, HBM programs in Israel were targeted at selected occupational groups (workers potentially exposed to metals, volatile organic compounds (VOCs), and cholinesterase inhibitors) and naval divers potentially exposed to environmental contaminants. The future of HBM in Israel lies in extending such programs to measuring exposures in representative samples of the general population, increasing international collaboration in this field, developing analytical capacity and expertise, and increasing use of human biomonitoring studies in forming and evaluating environmental health policy.     

Update of the reference and HBM values derived by the German Human Biomonitoring Commission

In 2007, we reviewed the working principles and working procedures of the German Human Biomonitoring Commission together with the reference values and human biomonitoring (HBM) values derived up to that time. Since then, the Commission has decided to derive additionally HBM I values on the basis of tolerable daily intakes and has used and evaluated this new approach on the metabolites of (2-ethylhexyl) phthalate (DEHP) in urine. Furthermore, the Commission has derived a HBM I value for thallium in urine, has recinded the HBM values for lead in blood, and has updated the HBM values for cadmium in urine. Based on the representative data of the German Environmental Survey on Children from 2003 to 2006 (GerES IV), the Commission has updated the reference values for a large number of environmental pollutants in urine and blood of children in Germany. Since 2007, the Commission has derived new and updated reference values for PFOS and PFOA in human plasma, for thallium in urine, for aromatic amines in urine, for a comprehensive number of phthalate metabolites in urine, and for organochlorine pesticides in human breast milk. Furthermore, the Commission has evaluated background exposure levels for two naphthalene metabolites and acrylamide (using acrylamide-haemoglobin adduct) for the general population. This paper reports the new values, including those already published, in order to provide an updated overview.     

Interpreting human biomonitoring data in a public health risk context using Biomonitoring Equivalents

Human biomonitoring (HBM) has proven an extremely valuable tool for determining which chemicals are getting into people, detecting trends in population exposures over time, and identifying populations with exposures above background. The potential significance of the HBM data in the context of existing toxicology data and risk assessments can be assessed if chemical-specific quantitative screening criteria are available. Such screening criteria would ideally be based on robust datasets relating potential adverse effects to biomarker concentrations in human populations. However, such assessments are data intensive and exist for only a few chemicals. As an interim approach, the concept of Biomonitoring Equivalents (BEs) has been developed. A Biomonitoring Equivalent (BE) is defined as the concentration or range of concentrations of a chemical or its metabolites in a biological medium (blood, urine, or other medium) that is consistent with an existing health-based exposure guidance value such as a Reference Dose (RfD) or Tolerable or Acceptable Daily Intake (TDI or ADI). This paper provides an overview of the derivation of BEs and how BEs can be used to interpret human biomonitoring data in a public health risk context.     

Update of the reference and HBM values derived by the German Human Biomonitoring Commission

In 2007, we reviewed the working principles and working procedures of the German Human Biomonitoring Commission together with the reference values and human biomonitoring (HBM) values derived up to that time. Since then, the Commission has decided to derive additionally HBM I values on the basis of tolerable daily intakes and has used and evaluated this new approach on the metabolites of (2-ethylhexyl) phthalate (DEHP) in urine. Furthermore, the Commission has derived a HBM I value for thallium in urine, has recinded the HBM values for lead in blood, and has updated the HBM values for cadmium in urine. Based on the representative data of the German Environmental Survey on Children from 2003 to 2006 (GerES IV), the Commission has updated the reference values for a large number of environmental pollutants in urine and blood of children in Germany. Since 2007, the Commission has derived new and updated reference values for PFOS and PFOA in human plasma, for thallium in urine, for aromatic amines in urine, for a comprehensive number of phthalate metabolites in urine, and for organochlorine pesticides in human breast milk. Furthermore, the Commission has evaluated background exposure levels for two naphthalene metabolites and acrylamide (using acrylamide-haemoglobin adduct) for the general population. This paper reports the new values, including those already published, in order to provide an updated overview.     

Evaluation of Biomonitoring Data from the CDC National Exposure Report in a Risk Assessment Context: Perspectives across Chemicals

Background: Biomonitoring data reported in the National Report on Human Exposure to Environmental Chemicals [NER; Centers for Disease Control and Prevention (2012)] provide information on the presence and concentrations of > 400 chemicals in human blood and urine. Biomonitoring Equivalents (BEs) and other risk assessment–based values now allow interpretation of these biomonitoring data in a public health risk context.Objectives: We compared the measured biomarker concentrations in the NER with BEs and similar risk assessment values to provide an across-chemical risk assessment perspective on the measured levels for approximately 130 analytes in the NER.Methods: We identified available risk assessment–based biomarker screening values, including BEs and Human Biomonitoring-I (HBM-I) values from the German Human Biomonitoring Commission. Geometric mean and 95th percentile population biomarker concentrations from the NER were compared to the available screening values to generate chemical-specific hazard quotients (HQs) or cancer risk estimates.Conclusions: Most analytes in the NER show HQ values of < 1; however, some (including acrylamide, dioxin-like chemicals, benzene, xylene, several metals, di-2(ethylhexyl)phthalate, and some legacy organochlorine pesticides) approach or exceed HQ values of 1 or cancer risks of > 1 × 10^–4 at the geometric mean or 95th percentile, suggesting exposure levels may exceed published human health benchmarks. This analysis provides for the first time a means for examining population biomonitoring data for multiple environmental chemicals in the context of the risk assessments for those chemicals. The results of these comparisons can be used to focus more detailed chemical-specific examination of the data and inform priorities for chemical risk management and research.     

Biomonitoring of phthalate metabolites in the Canadian population through the Canadian Health Measures Survey (2007–2009)

Human exposure to phthalates occurs through multiple sources and pathways. In the Canadian Health Measures Survey 2007–2009, 11 phthalate metabolites, namely, MMP, MEP, MnBP, MBzP, MCHP, MCPP, MEHP, MEOHP, MEHHP, MnOP, and MiNP were measured in urine samples of 6–49 year old survey respondents (n = 3236). The phthalate metabolites biomonitoring data from this nationally-representative Canadian survey are presented here. The metabolites MEP, MnBP, MBzP, MCPP, MEHP, MEOHP and MEHHP were detected in >90% of Canadians while MMP, MCHP, MnOP and MiNP were detected in <20% of the Canadian population. Step-wise regression analyses were carried out to identify important predictors of volumetric concentrations (μg/L) of the metabolites in the general population. Individual multiple regression models with covariates age, sex, creatinine, fasting status, and the interaction terms age × creatinine, age × sex and fasting status × creatinine were constructed for MEP, MnBP, MBzP, MCPP, MEHP, MEOHP and MEHHP. The least square geometric mean (LSGM) estimates for volumetric concentration (μg/L) of the metabolites derived from respective regression models were used to assess the patterns in the metabolite concentrations among population sub-groups. The results indicate that children had significantly higher urinary concentrations of MnBP, MBzP, MEHP, MEHHP, MEOHP and MCPP than adolescents and adults. Moreover, MEP, MBzP, MnBP and MEOHP concentrations in females were significantly higher than in males. We observed that fasting status significantly affects the concentrations of MEHP, MEHHP, MEOHP, and MCPP metabolites analyzed in this study. Moreover, our results indicate that the sampling time could affect the DEHP metabolite concentrations in the general Canadian population.     

German Environmental Survey 1998 (GerES III): environmental pollutants in the urine of the German population

The German Environmental Survey (GerES) is a cross-sectional probability study to determine the exposure of the general population to environmental contaminants. The study was repeated for the third time in 1998 (GerES III). Again, a stratified random procedure was used to select the study population taking into account the parameters gender, age, community size and place of residence (West- or East-Germany). A total of 4822 persons between 18 and 69 years of age from 120 localities participated in GerES III. Human biomonitoring comprised the determination of arsenic, cadmium, mercury, metabolites of polycyclic aromatic hydrocarbons (PAH), pentachlorophenol (PCP), other chlorophenols, precious metals (gold, platinum, iridium), nicotine, and cotinine in urine.     

Application of human biomonitoring (HBM) of chemical exposure in the characterisation of health risks under REACH

REACH requires health risk management for workers and the general population and introduced the concept of Derived No-Effect Level (DNEL). DNELs must be derived for all substances that are classified as hazardous. In analogy to other health-risk based guidance values, such as reference doses (RfDs) and tolerable daily intakes (TDIs), risk to health is considered negligible if the actual exposure is less than the DNEL. Exposure assessment is relatively simple for occupational situations but more complex for the general public, in which exposure may occur via multiple pathways, routes, and media. For such complex or partially defined exposure scenarios, human biomonitoring (HBM) gives a snapshot of the internal or absorbed dose of a chemical and is often the most reliable exposure assessment methodology. For human risk management, HBM data can be interpreted using the recently developed concept of Biomonitoring Equivalents (BEs). Basically, a BE translates an established reference value into a biomarker concentration using toxicokinetic data. If the results of an exposure assessment using HBM indicate that the levels measured are below the DNEL-based BE (BE(DNEL)), it would indicate that the combined exposure via all potential exposure routes is unlikely to pose a risk to human health and that health risk management measures might not be needed. Hence, BEs do not challenge existing risk assessments but rather build upon them to help risk management, the ultimate goal of any risk assessment. A challenge in implementing this approach forms the limited availability of toxicokinetic information for many substances. However, methodologies such as generic physiologically based toxicokinetic models, which allow estimation of biomarker concentrations based on physicochemical properties, are being developed for less data-rich chemicals. Acceptance of the use of BE by regulatory authorities will allow initial screening of population exposure to chemicals to identify those chemicals requiring more detailed risk and exposure assessment, assisting in priority setting and ultimately leading to improved product stewardship and risk management.     

Urinary levels of eight phthalate metabolites and bisphenol A in mother–child pairs from two Spanish locations

Exposure to some phthalate diesters and bisphenol A in the general population is a cause of increasing concern because of their potential adverse effects on the reproductive and endocrine systems and their broad presence in foodstuff and consumer products. The aims of this work are to assess patterns of exposure to phthalates and bisphenol A in a pilot sample of Spanish mothers and their children, and to provide basic information to address priorities in future Spanish surveys/research. Urinary levels of eight phthalate metabolites and bisphenol A have been measured in samples from 120 mother–child pairs in one rural and one urban location in central Spain, recruited as part of the European project DEMOCOPHES. More than 96% of the participants were exposed to all the compounds studied here with generally higher levels in children than their mothers. The sum of secondary DEHP metabolites gave a GM of 33.3 μg/g creatinine (95% CI 30.2–36.6) for mothers and 63.0 μg/g creatinine (95% CI 56.8–69.8) for children. Mono-ethyl phthalate (MEP) was the metabolite with the highest levels, with geometric means (GM) of 150.8 μg/g creatinine (95% CI 124.0–183.5) for mothers and 198.9 μg/g creatinine (95% CI 165.2–239.6) for children. Bisphenol A urinary levels were relatively low with geometric means of 2.0 μg/g (95% CI 1.6–2.4) for mothers and 2.01 μg/g (95% CI 1.7–2.4) for children. Personal care products like body lotions and fragrances showed associations with MEHP, MEP, MnBP and cx-MiNP and canteen food with MBzP and bisphenol A. Exposure of mothers and their children are correlated, except for MEP. As phthalates and bisphenol A are non-persistent chemicals, a daily, intermittent exposure of the population is taking place.     

Time trend of exposure to the phthalate plasticizer substitute DINCH in Germany from 1999 to 2017: Biomonitoring data on young adults from the Environmental Specimen Bank (ESB)

DINCH (cyclohexane-1,2-dicarboxylic acid-diisononyl ester) is a phthalate plasticizer substitute introduced into the market in 2002. It is increasingly used especially in the production of toys, food contact materials and medical devices. In this measurement campaign on 24-h urine samples of young adults (20–29 years) from the German Environmental Specimen Bank (ESB) collected in 2010, 2011, 2013, 2015 and 2017 (in total 300 samples, 60 samples/year) we analyzed three specific, oxidized DINCH metabolites (OH-MINCH: cyclohexane-1,2-dicarboxylic acid-mono(hydroxy-isononyl) ester; cx-MINCH: cyclohexane-1,2-dicarboxylic acid-mono(carboxy-isooctyl) ester, oxo-MINCH: cyclohexane-1,2-dicarboxylic acid-mono(oxo-isononyl) ester). We merged these data with earlier data of the ESB from the years 1999–2012 and are now able to report levels and time trends of internal DINCH exposure from 1999 to 2017.After first detections of the major oxidized DINCH metabolite OH-MINCH in 2006 (6.7%) detection rates rapidly increased to 43.3% in 2009, 80% in 2010 and 98.3% in 2011 and 2012. From the year 2013 on we could detect OH-MINCH in every urine sample analyzed. The median concentrations of OH-MINCH rapidly increased from 0.15 μg/L in 2010 to twice the concentration in 2011 (0.31 μg/L) with further increases in 2013 (0.37 μg/L), 2015 (0.59 μg/L) and 2017 (0.70 μg/L). Similar increases, albeit at lower detection rates and concentration levels, could be observed for cx-MINCH and oxo-MINCH. All metabolites strongly correlate with each other.For the ESB study population, DINCH exposures are still far below health based guidance values such as the German Human Biomonitoring Value (HBM-I; 4,500 μg/L for the sum of OH-MINCH and cx-MINCH) or the tolerable daily intake (TDI) of EFSA (1 mg/kg bw/d). The median daily DINCH intake (DI) calculated for 2017 was 0.23 μg/kg bw/d, thus 4,310-times lower than the TDI. The maximum DI calculated for one individual in 2012 (42.60 μg/kg bw/d) was a factor of more than 20 below the TDI.The ongoing increase in DINCH exposure needs to be closely monitored in the future, including populations with potentially higher exposures such as children. This close monitoring will enable timely exposure and risk reduction measures if exposures reached critical levels, or if new toxicological data lead to lower health based guidance values. DINCH belongs to the European Human Biomonitoring Initiative (HBM4EU) priority substances for which policy relevant questions still have to be answered.     

Reassessment of critical lead effects by the German Human Biomonitoring Commission results in suspension of the human biomonitoring values (HBM I and HBM II) for lead in blood of children and adults

In Germany, the Human Biomonitoring Commission of the Federal Environment Agency continuously assesses environmental pollutants to derive human biomonitoring (HBM) and reference values. HBM values are derived on the basis of toxicological, epidemiological studies or toxicokinetic extrapolation which provides a concentration of a substance or its metabolites corresponding to tolerable intake doses. Two levels are defined: HBM I and HBM II. In 1996, the Commission set a HBM I of 100 μg/l for lead in blood of children ≤12 years and females of a reproductive age and a HBM I of 150 μg/l for the other persons. In the light of findings from epidemiological studies on effects below 100 μg/l, the Commission reevaluated and confirmed the assessment from 1996 in 2002. Meanwhile the general decline in lead pollution has allowed recent studies to include more cohorts with blood lead levels predominantly below 100 μg/l. These data confirm that lead's critical effect, particularly on the developing organism and during early childhood, concerns the nervous system and that negative correlations between blood lead levels and relevant variables (cognitive function, behaviour) occur at blood lead levels below 100 μg/l. The new data also support the possible persistence of lead-induced effects into adulthood. It is not possible to indicate thresholds. Concerning the estimation of the size of the effects, recent studies suggest that lead's influence on development is comparable with other factors influencing development. Furthermore inorganic lead and compounds were classified by IARC in group 2A (probably carcinogenic to humans) and by the German Research Foundation (MAK Commission) in category 2 (to be regarded as human carcinogen). We conclude that any setting of an “effect threshold” for blood lead levels would be arbitrary and therefore unjustified. As a consequence the Commission suspends the HBM values for lead in blood of children and adults.