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BACKGROUND: Bisphenol A (BPA; or 4,4'-isopropylidenediphenol) is an endocrine disrupting chemical. It was widely used in a variety of plastic-based manufactured products for several years. The European Food Safety Authority (EFSA) recently reduced the Tolerable Daily Intake (TDI) for BPA by 20,000 times due to concerns about immune-toxicity. OBJECTIVE: We used human biomonitoring (HBM) data to investigate the general level of BPA exposure from 2007 to 2014 of European women aged 18-73 years (n = 4,226) and its determinants. METHODS: Fifteen studies from 12 countries (Austria, Belgium, Denmark, France, Germany, Greece, Israel, Luxembourg, Slovenia, Spain, Sweden, and the United Kingdom) were included in the BPA Study protocol developed within the European Joint Programme HBM4EU. Seventy variables related to the BPA exposure were collected through a rigorous post-harmonization process. Linear mixed regression models were used to investigate the determinants of total urine BPA in the combined population. RESULTS: Total BPA was quantified in 85-100 % of women in 14 out of 15 contributing studies. Only the Austrian PBAT study (Western Europe), which had a limit of quantification 2.5 to 25-fold higher than the other studies (LOQ=2.5 µg/L), found total BPA in less than 5 % of the urine samples analyzed. The geometric mean (GM) of total urine BPA ranged from 0.77 to 2.47 µg/L among the contributing studies. The lowest GM of total BPA was observed in France (Western Europe) from the ELFE subset (GM=0.77 µg/L (0.98 µg/g creatinine), n = 1741), and the highest levels were found in Belgium (Western Europe) and Greece (Southern Europe), from DEMOCOPHES (GM=2.47 µg/L (2.26 µg/g creatinine), n = 129) and HELIX-RHEA (GM=2.47 µg/L (2.44 µg/g creatinine), n = 194) subsets, respectively. One hundred percent of women in 14 out of 15 data collections in this study exceeded the health-based human biomonitoring guidance value for the general population (HBM-GVGenPop) of 0.0115 µg total BPA/L urine derived from the updated EFSA's BPA TDI. Variables related to the measurement of total urine BPA and those related to the main socio-demographic characteristics (age, height, weight, education, smoking status) were collected in almost all studies, while several variables related to BPA exposure factors were not gathered in most of the original studies (consumption of beverages contained in plastic bottles, consumption of canned food or beverages, consumption of food in contact with plastic packaging, use of plastic film or plastic containers for food, having a plastic floor covering in the house, use of thermal paper ). No clear determinants of total urine BPA concentrations among European women were found. A broader range of data planned for collection in the original questionnaires of the contributing studies would have resulted in a more thorough investigation of the determinants of BPA exposure in European women. CONCLUSION: This study highlights the urgent need for action to further reduce exposure to BPA to protect the population, as is already the case in the European Union. The study also underscores the importance of pre-harmonizing HBM design and data for producing comparable data and interpretable results at a European-wide level, and to increase HBM uptake by regulatory agencies.
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BACKGROUND: Phthalates are ubiquitous in the environment. Despite short half-lives, chronic exposure can lead to endocrine disruption. The safety of phthalate substitute DINCH is unclear. OBJECTIVE: To evaluate associations between urinary concentrations of phthalate/DINCH metabolites and body mass index (BMI) z-score among children and adolescents. METHOD: We used Human Biomonitoring for Europe Aligned Studies data from 2876 children (12 studies, 6-12 years, 2014-2021) and 2499 adolescents (10 studies, 12-18 years, 2014-2021) with up to 14 phthalate/DINCH urinary metabolites. We used multilevel linear regression to assess associations between phthalate/DINCH concentrations and BMI z-scores, testing effect modification by sex. In a subset, Bayesian kernel machine regression (BKMR) and quantile-based g-computation assessed important predictors and mixture effects. RESULTS: In children, we found few associations in single pollutant models and no interactions by sex (p-interaction > 0.1). BKMR detected no relevant exposures (posterior inclusion probabilities, PIPs < 0.25), nor joint mixture effect. In adolescent single pollutant analysis, mono-ethyl phthalate (MEP) concentrations were associated with higher BMI z-score in males (ß = 0.08, 95 % CI: 0.001,0.15, per interquartile range increase in ln-transformed concentrations, p-interaction = 0.06). Conversely, mono-isobutyl phthalate (MiBP) was associated with a lower BMI z-score in both sexes (ß = -0.13, 95 % CI: -0.19, -0.07, p-interaction = 0.74), as was sum of di(2-ethylhexyl) phthalate (∑DEHP) metabolites in females only (ß = -0.08, 95 % CI: -0.14, -0.02, p-interaction = 0.01). In BKMR, higher BMI z-scores were predicted by MEP (PIP=0.90) and MBzP (PIP=0.84) in males. Lower BMI z-scores were predicted by MiBP (PIP=0.999), OH-MIDP (PIP=0.88) and OH-MINCH (PIP=0.72) in both sexes, less robustly by DEHP (PIP=0.61) in females. In quantile g-computation, the overall mixture effect was null for males, and trended negative for females (ß = -0.11, 95 % CI: -0.25, 0.03, per joint exposure quantile). CONCLUSION: In this large Europe-wide study, we found age/sex-specific differences between phthalate metabolites and BMI z-score, stronger in adolescents. Longitudinal studies with repeated phthalate measurements are needed.
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For the investigation of diseases and other harmful environmental influences (e.g., chemicals) epidemiological studies rely on high quality human samples, among others. Collecting samples and data in the field can pose an enormous challenge to the study team with regard to health protection and occupational safety, especially in the context of a pandemic where there was great uncertainty about the biological risks associated with SARS-CoV-2. The German Environmental Specimen Bank (German ESB) is a key element of environmental and human biomonitoring in Germany with the aim to document and assess trends of human and environmental exposure to chemicals over time and to provide scientific data for policy decision makers. Starting with a pilot study in 1978 human samples are now collected at four sampling locations annually, while sampling is carried out with a highly standardized mobile laboratory since 2013. Due to the corona pandemic 3 of 4 ESB sampling campaigns had to be cancelled in 2020. However, a continuous sampling is crucial to generate current policy relevant data on chemical exposure. Hence, a protection and hygiene concept has been developed including COVID-19 testing with the goal to protect the health of participants and employees during sampling and to meet legal requirements, while sustaining the standardized procedures of sampling and sample preparation. The concept is based on a flexible approach to allow adjustments to changing government regulations and recommendations in the course of the pandemic. By implementing this concept, all samplings were successfully carried out in 2021 & 2022, with the pandemic still ongoing. This paper provides an example of good practice and valuable insights in how to collect human samples during a pandemic.
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COVID-19 , SARS-CoV-2 , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , Alemania/epidemiología , Exposición a Riesgos Ambientales/efectos adversos , Manejo de Especímenes , Monitoreo Biológico/métodos , Monitoreo del Ambiente/métodos , Bancos de Muestras Biológicas , Pandemias , Exposición Profesional/prevención & controlRESUMEN
Phthalates and the substitute plasticizer DINCH belong to the first group of priority substances investigated by the European Human Biomonitoring Initiative (HBM4EU) to answer policy-relevant questions and safeguard an efficient science-to-policy transfer of results. Human internal exposure levels were assessed using two data sets from all European regions and Israel. The first collated existing human biomonitoring (HBM) data (2005-2019). The second consisted of new data generated in the harmonized "HBM4EU Aligned Studies" (2014-2021) on children and teenagers for the ten most relevant phthalates and DINCH, accompanied by a quality assurance/quality control (QA/QC) program for 17 urinary exposure biomarkers. Exposures differed between countries, European regions, age groups and educational levels. Toxicologically derived Human biomonitoring guidance values (HBM-GVs) were exceeded in up to 5% of the participants of the HBM4EU Aligned Studies. A mixture risk assessment (MRA) including five reprotoxic phthalates (DEHP, DnBP, DiBP, BBzP, DiNP) revealed that for about 17% of the children and teenagers, health risks cannot be excluded. Concern about male reproductive health emphasized the need to include other anti-androgenic substances for MRA. Contaminated food and the use of personal care products were identified as relevant exposure determinants paving the way for new regulatory measures. Time trend analyses verified the efficacy of regulations: especially for the highly regulated phthalates exposure dropped significantly, while levels of the substitutes DINCH and DEHTP increased. The HBM4EU e-waste study, however, suggests that workers involved in e-waste management may be exposed to higher levels of restricted phthalates. Exposure-effect association studies indicated the relevance of a range of endpoints. A set of HBM indicators was derived to facilitate and accelerate science-to-policy transfer. Result indicators allow different groups and regions to be easily compared. Impact indicators allow health risks to be directly interpreted. The presented results enable successful science-to-policy transfer and support timely and targeted policy measures.
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Monitoreo Biológico , Contaminantes Ambientales , Ácidos Ftálicos , Plastificantes , Humanos , Ácidos Ftálicos/orina , Plastificantes/análisis , Europa (Continente) , Contaminantes Ambientales/orina , Adolescente , Niño , Exposición a Riesgos Ambientales/análisis , Masculino , Medición de Riesgo , Femenino , Adulto , Monitoreo del Ambiente/métodosRESUMEN
Controlling and minimising background contamination is crucial for maintaining a high quality of samples in human biomonitoring targeting organic chemicals. We assessed the contamination of three previous types and one newly introduced medical-grade type of sample tubes used for storing human body fluids at the German Environmental Specimen Bank. Aqueous extracts from these tubes were analysed by non-targeted liquid chromatography-high resolution mass spectrometry (LC-HRMS) before and after a dedicated cleaning procedure. After peak detection using MZmine, Bayesian hypothesis testing was used to group peaks into those originating either from instrumental and laboratory background contamination, or actual tube contaminants, based on if their peak height was reduced, increased or not affected by the cleaning procedure. For all four tube types 80-90% of the 2475 peaks (1549 in positive and 926 in negative mode) were assigned to laboratory/instrumental background, which we have to consider as potential sample tube contaminants. Among the tube contaminants, results suggest a considerable difference in the contaminant peak inventory and the absolute level of contamination among the different sample tube types. The cleaning procedure did not affect the largest fraction of peaks (50-70%). For the medical grade tubes, the removal of contaminants by the cleaning procedure was strongest compared to the previous tubes, but in all cases a small fraction increased in intensity after cleaning, probably due to a release of oligomers or additives. The identified laboratory background contaminants were mainly semi-volatile polymer additives such as phthalates and phosphate esters. A few compounds could be assigned solely as tube-specific contaminants, such as N,N-dibutylformamide and several constituents of the oligomeric light stabiliser Tinuvin-622. A cleaning procedure before use is an effective way to standardise the used sample tubes and minimises the background contamination, and therefore increases sample quality and therewith analytical results.
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Monitoreo Biológico , Ácidos Ftálicos , Humanos , Cromatografía Liquida/métodos , Teorema de Bayes , Cromatografía Líquida con Espectrometría de Masas , Ácidos Ftálicos/análisisRESUMEN
Little is known about exposure determinants of acrylamide (AA), a genotoxic food-processing contaminant, in Europe. We assessed determinants of AA exposure, measured by urinary mercapturic acids of AA (AAMA) and glycidamide (GAMA), its main metabolite, in 3157 children/adolescents and 1297 adults in the European Human Biomonitoring Initiative. Harmonized individual-level questionnaires data and quality assured measurements of AAMA and GAMA (urine collection: 2014-2021), the short-term validated biomarkers of AA exposure, were obtained from four studies (Italy, France, Germany, and Norway) in children/adolescents (age range: 3-18 years) and six studies (Portugal, Spain, France, Germany, Luxembourg, and Iceland) in adults (age range: 20-45 years). Multivariable-adjusted pooled quantile regressions were employed to assess median differences (ß coefficients) with 95% confidence intervals (95% CI) in AAMA and GAMA (µg/g creatinine) in relation to exposure determinants. Southern European studies had higher AAMA than Northern studies. In children/adolescents, we observed significant lower AA associated with high socioeconomic status (AAMA:ß = - 9.1 µg/g creatinine, 95% CI - 15.8, - 2.4; GAMA: ß = - 3.4 µg/g creatinine, 95% CI - 4.7, - 2.2), living in rural areas (AAMA:ß = - 4.7 µg/g creatinine, 95% CI - 8.6, - 0.8; GAMA:ß = - 1.1 µg/g creatinine, 95% CI - 1.9, - 0.4) and increasing age (AAMA:ß = - 1.9 µg/g creatinine, 95% CI - 2.4, - 1.4; GAMA:ß = - 0.7 µg/g creatinine, 95% CI - 0.8, - 0.6). In adults, higher AAMA was also associated with high consumption of fried potatoes whereas lower AAMA was associated with higher body-mass-index. Based on this large-scale study, several potential determinants of AA exposure were identified in children/adolescents and adults in European countries.
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Acrilamida , Monitoreo Biológico , Adolescente , Humanos , Adulto , Niño , Preescolar , Adulto Joven , Persona de Mediana Edad , Acrilamida/toxicidad , Creatinina , Biomarcadores , Encuestas y CuestionariosRESUMEN
The UV filters octocrylene (OC) and 2-ethylhexyl salicylate (EHS) are commonly used in sunscreens and frequently detected in environmental media. However, knowledge on human exposures is scarce. In this human biomonitoring (HBM) study, we analyzed concentrations of exposure biomarkers specific to OC (CPAA, DOCCA, 5OH-OC) and EHS (5OH-EHS, 5oxo-EHS, 5cx-EPS) in 24-h urine samples (n = 420) from the German Environmental Specimen Bank (ESB). These samples were collected from German students (20-29 years; 30 males/30 females per year) between 1996 and 2020 (4-year intervals; collection in winter). We found continuously increasing OC and EHS exposures (Jonckheere-Terpstra; p < 0.001) documented by very few to no samples with concentrations of the most sensitive biomarkers CPAA and 5cx-EPS above the limit of quantification (LOQ) in 1996 (5 % and 0 %, respectively) and reaching 100 % and 93 % above the LOQ in 2016, with median concentrations of 4.79 and 0.071 µg/L, respectively. In 2020, biomarker concentrations slightly decreased to 3.12 µg/L CPAA (97 %>LOQ) and 0.060 µg/L 5cx-EPS (88 %>LOQ). This general trend was confirmed by the other biomarkers, however at lower detection rates. Based on metabolite excretion in the 24-h urine samples and human toxicokinetic data, we calculated maximum daily intakes (DI) of 17 µg/(kg bw * d) OC and 59 µg/(kg bw * d) EHS. Based on a derived no-effect level (DNEL) of 0.8 mg/(kg bw * d), the OC exposures of individuals in our study did not indicate any health risk. Similarly, for EHS all biomarker concentrations were well below the HBM-I values of 12 µg/L 5OH-EHS and 11 µg/L 5cx-EPS. Our data proves the general applicability of specific OC and EHS metabolites for HBM in the general population and shows clearly increasing exposures. Higher (co-)exposures must be expected in populations with increased sunscreen use such as (summer) vacationers, children and outdoor workers.
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Monitoreo Biológico , Contaminantes Ambientales , Masculino , Niño , Femenino , Humanos , Alemania , Protectores Solares/análisis , Biomarcadores/orina , Monitoreo del Ambiente , Exposición a Riesgos Ambientales/análisis , Contaminantes Ambientales/orinaRESUMEN
Early puberty has been found to be associated with adverse health outcomes such as metabolic and cardiovascular diseases and hormone-dependent cancers. The decrease in age at menarche observed during the past decades has been linked to an increased exposure to endocrine-disrupting compounds (EDCs). Evidence for the association between PFAS and phthalate exposure and menarche onset, however, is inconsistent. We studied the association between PFAS and phthalate/DINCH exposure and age at menarche using data of 514 teenagers (12 to 18 years) from four aligned studies of the Human Biomonitoring for Europe initiative (HBM4EU): Riksmaten Adolescents 2016-2017 (Sweden), PCB cohort (follow-up; Slovakia), GerES V-sub (Germany), and FLEHS IV (Belgium). PFAS concentrations were measured in blood, and phthalate/DINCH concentrations in urine. We assessed the role of each individual pollutant within the context of the others, by using different multi-pollutant approaches, adjusting for age, age- and sex-standardized body mass index z-score and household educational level. Exposure to di(2-ethylhexyl) phthalate (DEHP), especially mono(2-ethyl-5-hydroxyhexyl) phthalate (5OH-MEHP), was associated with an earlier age at menarche, with estimates per interquartile fold change in 5OH-MEHP ranging from -0.34 to -0.12 years in the different models. Findings from this study indicated associations between age at menarche and some specific EDCs at concentrations detected in the general European population, but due to the study design (menarche onset preceded the chemical measurements), caution is needed in the interpretation of causality.
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HBM reference values, in contrast to toxicologically derived values, are statistically derived values that provide information on the exposure of the population. The exceedance frequency (if applicable for individual population groups) is often a first assessment standard for the local exposure situation for municipalities. More than 25 years have passed since the German Human Biomonitoring Commission (HBMC) formulated the first recommendations for the derivation of population-based reference values (HBM reference values, RV95) for substance concentrations based on HBM studies. A fundamental revision is timely, for several reasons. There have been considerable advances in relevant statistical methods, which meant that previously time-consuming and inaccessible procedures and calculations are now widely available. Furthermore, not all steps for the derivation of HBM reference values were clearly elaborated in the first recommendations. With this revision we intended to achieve a rigorous standardization of the entire process of deriving HBM reference values, also to realise a higher degree of transparency. In accordance with established international practice, it is recommended to use the 95th percentile of the reference distribution as the HBM reference value. To this end, the empirical 95th percentile of a suitable sample should be rounded, ensuring that the rounded value is within the two-sided 95% confidence interval of the percentile. All estimates should be based on distribution-free methods, and the confidence interval should be estimated using a bootstrap approach, if possible, according to the BCa ("bias-corrected and accelerated bootstrap"). A minimum sample size of 80 observations is considered necessary. The entire procedure ensures that the derived HBM reference value is robust against at least two extreme values and can also be used for underlying mixed distributions. If it is known in advance that certain subgroups (different age groups, smokers, etc.) show differing internal exposures, it is recommended that group-specific HBM reference values should be derived. Especially when the sample sizes for individual subgroups are too small, individual datasets with potential outliers can be excluded in advance to homogenize the reference value population. In the second part, new HBM reference values based on data of the German Environmental Survey for Children and Adolescents (GerES V, 2014-2017) were derived in accordance with the revised recommendations. The GerES V is the most recent population-representative monitoring of human exposure to pollutants in Germany on children and adolescents aged 3-17 years (N = 2294). RV95 for GerES V are reported for four subgroups (males/females and 3-11/12-17 years) for 108 different substances including phthalates and alternative plasticisers, metals, organochlorine pesticides, polychlorinated biphenyls (PCB), per- and polyfluoroalkyl substances (PFAS), parabens, aprotic solvents, chlorophenols, polycyclic aromatic hydrocarbons (PAH) and UV filter, in total 135 biomarkers. Algorithms implemented in R were used for the statistics and the determination of the HBM reference values. To facilitate a quality control of the study data, the corresponding R source code is given, together with graphical representations of results. The HBM reference values listed in this article replace earlier RV95 values derived by the HBMC for children and adolescents from data of precedent GerES studies (e.g. published in Apel et al., 2017).
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Monitoreo del Ambiente , Contaminantes Ambientales , Humanos , Niño , Masculino , Femenino , Adolescente , Monitoreo del Ambiente/métodos , Valores de Referencia , Monitoreo Biológico , Contaminantes Ambientales/análisis , Alemania , Exposición a Riesgos Ambientales/análisisRESUMEN
BACKGROUND: Seafood is a major source of vital nutrients for optimal fetal growth, but at the same time is the main source of exposure to methylmercury (MeHg), an established neurodevelopmental toxicant. Pregnant women must be provided with dietary advice so as to include safely fish in their diet for nutrition and mercury control. The aim of this work is to present the design of a multicentre randomized control trial (RCT), which combines human biomonitoring (HBM) with dietary interventions using seafood consumption advice to pregnant women for MeHg control, and to collect information about other possible sources of exposure to mercury. It also presents the materials developed for the implementation of the study and the characteristics of the study participants, which were self-reported in the first trimester of pregnancy. METHODS: The "HBM4EU-MOM" RCT was performed in the frame of the European Human Biomonitoring Initiative (HBM4EU) in five coastal, high fish-consuming European countries (Cyprus, Greece, Spain, Portugal and Iceland). According to the study design, pregnant women (≥120/country, ≤20 weeks gestational age) provided a hair sample for total mercury assessment (THg) and personal information relevant to the study (e.g., lifestyle, pregnancy status, diet before and during the pregnancy, information on seafood and factors related to possible non-dietary exposures to mercury) during the first trimester of pregnancy. After sampling, participants were randomly assigned to "control" (habitual practices) or "intervention" (received the harmonized HBM4EU-MOM dietary advice for fish consumption during the pregnancy and were encouraged to follow it). Around child delivery, participants provided a second hair sample and completed another tailored questionnaire. RESULTS: A total of 654 women aged 18-45 years were recruited in 2021 in the five countries, primarily through their health-care providers. The pre-pregnancy BMI of the participants ranged from underweight to obese, but was on average within the healthy range. For 73% of the women, the pregnancy was planned. 26% of the women were active smokers before the pregnancy and 8% continued to smoke during the pregnancy, while 33% were passive smokers before pregnancy and 23% remained passively exposed during the pregnancy. 53% of the women self-reported making dietary changes for their pregnancy, with 74% of these women reporting making the changes upon learning of their pregnancy. Of the 43% who did not change their diet for the pregnancy, 74% reported that their diet was already balanced, 6% found it difficult to make changes and 2% were unsure of what changes to make. Seafood consumption did not change significantly before and during the first trimester of pregnancy (overall average â¼8 times per month), with the highest frequency reported in Portugal (≥15 times per month), followed by Spain (≥7 times per month). During the first-trimester of pregnancy, 89% of the Portuguese women, 85% of the Spanish women and <50% of Greek, Cypriot and Icelandic women reported that they had consumed big oily fish. Relevant to non-dietary exposure sources, most participants (>90%) were unaware of safe procedures for handling spillage from broken thermometers and energy-saving lamps, though >22% experienced such an incident (>1 year ago). 26% of the women had dental amalgams. â¼1% had amalgams placed and â¼2% had amalgams removed during peri-pregnancy. 28% had their hair dyed in the past 3 months and 40% had body tattoos. 8% engaged with gardening involving fertilizers/pesticides and 19% with hobbies involving paints/pigments/dyes. CONCLUSIONS: The study design materials were fit for the purposes of harmonization and quality-assurance. The harmonized information collected from pregnant women suggests that it is important to raise the awareness of women of reproductive age and pregnant women about how to safely include fish in their diet and to empower them to make proper decisions for nutrition and control of MeHg, as well as other chemical exposures.
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Mercurio , Compuestos de Metilmercurio , Animales , Femenino , Humanos , Embarazo , Dieta , Europa (Continente) , Contaminación de Alimentos/análisis , Mercurio/análisis , Compuestos de Metilmercurio/análisis , Estudios Multicéntricos como Asunto , Mujeres Embarazadas , Ensayos Clínicos Controlados Aleatorios como Asunto , Alimentos Marinos/análisis , Adolescente , Adulto Joven , Adulto , Persona de Mediana EdadRESUMEN
The environmental impact on health is an inevitable by-product of human activity. Environmental health sciences is a multidisciplinary field addressing complex issues on how people are exposed to hazardous chemicals that can potentially affect adversely the health of present and future generations. Exposure sciences and environmental epidemiology are becoming increasingly data-driven and their efficiency and effectiveness can significantly improve by implementing the FAIR (findable, accessible, interoperable, reusable) principles for scientific data management and stewardship. This will enable data integration, interoperability and (re)use while also facilitating the use of new and powerful analytical tools such as artificial intelligence and machine learning in the benefit of public health policy, and research, development and innovation (RDI). Early research planning is critical to ensuring data is FAIR at the outset. This entails a well-informed and planned strategy concerning the identification of appropriate data and metadata to be gathered, along with established procedures for their collection, documentation, and management. Furthermore, suitable approaches must be implemented to evaluate and ensure the quality of the data. Therefore, the 'Europe Regional Chapter of the International Society of Exposure Science' (ISES Europe) human biomonitoring working group (ISES Europe HBM WG) proposes the development of a FAIR Environment and health registry (FAIREHR) (hereafter FAIREHR). FAIR Environment and health registry offers preregistration of studies on exposure sciences and environmental epidemiology using HBM (as a starting point) across all areas of environmental and occupational health globally. The registry is proposed to receive a dedicated web-based interface, to be electronically searchable and to be available to all relevant data providers, users and stakeholders. Planned Human biomonitoring studies would ideally be registered before formal recruitment of study participants. The resulting FAIREHR would contain public records of metadata such as study design, data management, an audit trail of major changes to planned methods, details of when the study will be completed, and links to resulting publications and data repositories when provided by the authors. The FAIREHR would function as an integrated platform designed to cater to the needs of scientists, companies, publishers, and policymakers by providing user-friendly features. The implementation of FAIREHR is expected to yield significant benefits in terms of enabling more effective utilization of human biomonitoring (HBM) data.
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The mycotoxin deoxynivalenol (DON) is a frequently found contaminant in cereals and cereal-based products. As a German contribution to the European Joint Programme HBM4EU, we analysed the total DON concentration (tDON) in 24-h urine samples from the German Environmental Specimen Bank (ESB). In total, 360 samples collected in 1996, 2001, 2006, 2011, 2016, and 2021 from young adults in Muenster (Germany), were measured by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) after enzymatic deconjugation of the glucuronide metabolites. tDON was found in concentrations above the lower limit of quantification (0.3 µg/L) in 99% of the samples. Medians of the measured concentrations and the daily excretion were 4.3 µg/L and 7.9 µg/24 h, respectively. For only nine participants, urinary tDON concentrations exceeded the provisional Human biomonitoring guidance value (HBM GV) of 23 µg/L. Urinary tDON concentrations were significantly higher for male participants. However, 24-h excretion values normalized to the participant's body weight did not exhibit any significant difference between males and females and the magnitude remained unchanged over the sampling years with exception of the sampling year 2001. Daily intakes were estimated from excretion values. Exceedance of the tolerable daily intake (TDI) of 1 µg/kg bw per day was observed for less than 1% of all participants. TDI exceedances were only present in the sampling year 2001 and not in more recent sampling years while exceedance of the HBM guidance value was also observed in 2011 and 2021.
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Micotoxinas , Tricotecenos , Femenino , Adulto Joven , Humanos , Masculino , Monitoreo Biológico , Espectrometría de Masas en Tándem , Tricotecenos/orina , Micotoxinas/orina , Exposición a Riesgos Ambientales/análisisRESUMEN
Most countries have acknowledged the importance of assessing and quantifying their population's internal exposure from chemicals in air, water, soil, food and other consumer products due to the potential health and economic impact. Human biomonitoring (HBM) is a valuable tool which can be used to quantify such exposures and effects. Results from HBM studies can also contribute to improving public health by providing evidence of individuals' internal chemical exposure as well as data to understand the burden of disease and associated costs thereby stimulating the development and implementation of evidence-based policy. To have a holistic view on HBM data utilisation, a multi-case research approach was used to explore the use of HBM data to support national chemical regulations, protect public health and raise awareness among countries participating in the HBM4EU project. The Human Biomonitoring for Europe (HBM4EU) Initiative (https://www.hbm4eu.eu/) is a collaborative effort involving 30 countries, the European Environment Agency (EEA) and the European Commission (contracting authority) to harmonise procedures across Europe and advance research into the understanding of the health impacts of environmental chemical exposure. One of the aims of the project was to use HBM data to support evidence based chemical policy and make this information timely and directly available for policy makers and all partners. The main data source for this article was the narratives collected from 27 countries within the HBM4EU project. The countries (self-selection) were grouped into 3 categories in terms of HBM data usage either for public awareness, policy support or for the establishment HBM programme. Narratives were analysed/summarised using guidelines and templates that focused on ministries involved in or advocating for HBM; steps required to engage policy makers; barriers, drivers and opportunities in developing a HBM programme. The narratives reported the use of HBM data either for raising awareness or addressing environmental/public health issues and policy development. The ministries of Health and Environment were reported to be the most prominent entities advocating for HBM, the involvement of several authorities/institutions in the national hubs was also cited to create an avenue to interact, discuss and gain the attention of policy makers. Participating in European projects and the general population interest in HBM studies were seen as drivers and opportunities in developing HBM programmes. A key barrier that was cited by countries for establishing and sustaining national HBM programmes was funding which is mainly due to the high costs associated with the collection and chemical analysis of human samples. Although challenges and barriers still exist, most countries within Europe were already conversant with the benefits and opportunities of HBM. This article offers important insights into factors associated with the utilisation of HBM data for policy support and public awareness.
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Monitoreo Biológico , Monitoreo del Ambiente , Humanos , Monitoreo del Ambiente/métodos , Salud Pública , Exposición a Riesgos Ambientales/análisis , Formulación de PolíticasRESUMEN
Chemical mixture risk assessment has, in the past, primarily focused on exposures quantified in the external environment. Assessing health risks using human biomonitoring (HBM) data provides information on the internal concentration, from which a dose can be derived, of chemicals to which human populations are exposed. This study describes a proof of concept for conducting mixture risk assessment with HBM data, using the population-representative German Environmental Survey (GerES) V as a case study. We first attempted to identify groups of correlated biomarkers (also known as 'communities', reflecting co-occurrence patterns of chemicals) using a network analysis approach (n = 515 individuals) on 51 chemical substances in urine. The underlying question is whether the combined body burden of multiple chemicals is of potential health concern. If so, subsequent questions are which chemicals and which co-occurrence patterns are driving the potential health risks. To address this, a biomonitoring hazard index was developed by summing over hazard quotients, where each biomarker concentration was weighted (divided) by the associated HBM health-based guidance value (HBM-HBGV, HBM value or equivalent). Altogether, for 17 out of the 51 substances, health-based guidance values were available. If the hazard index was higher than 1, then the community was considered of potential health concern and should be evaluated further. Overall, seven communities were identified in the GerES V data. Of the five mixture communities where a hazard index was calculated, the highest hazard community contained N-Acetyl-S-(2-carbamoyl-ethyl)cysteine (AAMA), but this was the only biomarker for which a guidance value was available. Of the other four communities, one included the phthalate metabolites mono-isobutyl phthalate (MiBP) and mono-n-butyl phthalate (MnBP) with high hazard quotients, which led to hazard indices that exceed the value of one in 5.8% of the participants included in the GerES V study. This biological index method can put forward communities of co-occurrence patterns of chemicals on a population level that need further assessment in toxicology or health effects studies. Future mixture risk assessment using HBM data will benefit from additional HBM health-based guidance values based on population studies. Additionally, accounting for different biomonitoring matrices would provide a wider range of exposures. Future hazard index analyses could also take a common mode of action approach, rather than the more agnostic and non-specific approach we have taken in this proof of concept.
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Background: In environmental health research, sex and gender are not yet adequately considered. There is a need to improve data collection in population-based environmental health studies by comprehensively surveying sex/gender-related aspects according to gender theoretical concepts. Thus, within the joint project INGER we developed a multidimensional sex/gender concept which we aimed to operationalize and to test the operationalization for feasibility. Methods: In an iterative process, we created questionnaire modules which quantitatively captured the requirements of the INGER sex/gender concept. We deployed it in the KORA cohort (Cooperative Health Research in the Region of Augsburg, Germany) in 2019 and evaluated response and missing rates. Results: The individual sex/gender self-concept was surveyed via a two-step approach that asked for sex assigned at birth and the current sex/gender identity. Additionally, we used existing tools to query internalized sex/gender roles and externalized sex/gender expressions. Adapted to the KORA population, we asked for discrimination experiences and care and household activities contributing to explain structural sex/gender relations. Further intersectionality-related social categories (e.g., socio-economic position), lifestyle and psychosocial factors were covered through data available in KORA. We could not identify appropriate tools to assess the true biological sex, sexual orientation and ethnic/cultural identity, which have yet to be developed or improved. The response-rate was 71%, the evaluation of 3,743 questionnaires showed a low missing rate. Prevalence of marginalized groups regarding sex/gender identity and definable by experiences of discrimination was very low. Conclusion: We have shown how the multidimensional INGER sex/gender concept can be operationalized according to an European and North American understanding of sex/gender for use in quantitative research. The questionnaire modules proved feasible in an epidemiologic cohort study. Being a balancing act between theoretical concepts and its quantitative implementation our operationalization paves the way for an adequate consideration of sex/gender in environmental health research.
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Identidad de Género , Autoimagen , Recién Nacido , Humanos , Masculino , Femenino , Estudios de Cohortes , Proyectos de Investigación , Encuestas y CuestionariosRESUMEN
The European Human Biomonitoring Initiative (HBM4EU) ran from 2017 to 2022 with the aim of advancing and harmonizing human biomonitoring in Europe. More than 40,000 analyses were performed on human samples in different human biomonitoring studies in HBM4EU, addressing the chemical exposure of the general population, temporal developments, occupational exposure and a public health intervention on mercury in populations with high fish consumption. The analyses covered 15 priority groups of organic chemicals and metals and were carried out by a network of laboratories meeting the requirements of a comprehensive quality assurance and control system. The coordination of the chemical analyses included establishing contacts between sample owners and qualified laboratories and monitoring the progress of the chemical analyses during the analytical phase, also addressing status and consequences of Covid-19 measures. Other challenges were related to the novelty and complexity of HBM4EU, including administrative and financial matters and implementation of standardized procedures. Many individual contacts were necessary in the initial phase of HBM4EU. However, there is a potential to develop more streamlined and standardized communication and coordination in the analytical phase of a consolidated European HBM programme.
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COVID-19 , Exposición Profesional , Humanos , Monitoreo Biológico , Exposición a Riesgos Ambientales/análisis , Monitoreo del Ambiente/métodos , Exposición Profesional/análisis , Europa (Continente)RESUMEN
4-methylbenzylidene camphor (4-MBC) is used as a UV-B filter in cosmetics. Two oxidized metabolites of 4-MBC - 3-(4-carboxybenzylidene)camphor (cx-MBC) and 3-(4-carboxybenzylidene)-6-hydroxycamphor (cx-MBC-OH) - were analyzed in 250 24-h urine samples from young adults in Germany. The samples were from the German Environmental Specimen Bank (ESB) and represented exposure in the years 1995, 2005, 2010, 2015 and 2019. A UHPLC-MS/MS method enabled the sensitive determination of both metabolites, with limits of quantification at 0.15 µg L-1 (cx-MBC) and 0.30 µg L-1 (cx-MBC-OH), respectively. A temporal trend of the internal exposure to 4-MBC was clearly noticeable. The metabolite cx-MBC was frequently quantifiable at the beginning of the period: in 70% of the samples in 1995, and 56% in 2005. After 2005, urinary concentrations and detection rates of cx-MBC dropped to reach very low levels. In 2015 and 2019, the detection rate was only 2% and 0%, respectively. A similar trend was observed for cx-MBC-OH, though overall, this metabolite was detected less often and at lower concentration levels than cx-MBC. Nowadays, measurable levels of urinary 4-MBC metabolites are an extremely rare occurrence in Germany. These trends are consistent with the history of 4-MBC use by the cosmetic industry. The highest measured individual concentration of 16.20 µg L-1 (in a sample of the year 2005) was still more than 30 times below the health-based guidance value (HBM-I). An investigation of the ratios between both metabolites uncovered several features of the 4-MBC metabolism which have been essentially overlooked until now. In particular, stereochemical aspects should be explored in future studies. As urine was collected in autumn/winter in Northwestern Germany, the 4-MBC metabolites measured probably do not arise from sunscreen products in a narrow sense. They rather may reveal the use of other skin care products containing 4-MBC for UV protection as an added feature.
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Alcanfor , Espectrometría de Masas en Tándem , Humanos , Adulto Joven , Alcanfor/orina , Protectores Solares , AlemaniaRESUMEN
Per- and polyfluoroalkyl substances (PFASs) were one of the priority substance groups selected which have been investigated under the ambitious European Joint programme HBM4EU (2017-2022). In order to answer policy relevant questions concerning exposure and health effects of PFASs in Europe several activities were developed under HBM4EU namely i) synthesis of HBM data generated in Europe prior to HBM4EU by developing new platforms, ii) development of a Quality Assurance/Quality Control Program covering 12 biomarkers of PFASs, iii) aligned and harmonized human biomonitoring studies of PFASs. In addition, some cohort studies (on mother-child exposure, occupational exposure to hexavalent chromium) were initiated, and literature researches on risk assessment of mixtures of PFAS, health effects and effect biomarkers were performed. The HBM4EU Aligned Studies have generated internal exposure reference levels for 12 PFASs in 1957 European teenagers aged 12-18 years. The results showed that serum levels of 14.3% of the teenagers exceeded 6.9 µg/L PFASs, which corresponds to the EFSA guideline value for a tolerable weekly intake (TWI) of 4.4 ng/kg for some of the investigated PFASs (PFOA, PFOS, PFNA and PFHxS). In Northern and Western Europe, 24% of teenagers exceeded this level. The most relevant sources of exposure identified were drinking water and some foods (fish, eggs, offal and locally produced foods). HBM4EU occupational studies also revealed very high levels of PFASs exposure in workers (P95: 192 µg/L in chrome plating facilities), highlighting the importance of monitoring PFASs exposure in specific workplaces. In addition, environmental contaminated hotspots causing high exposure to the population were identified. In conclusion, the frequent and high PFASs exposure evidenced by HBM4EU strongly suggests the need to take all possible measures to prevent further contamination of the European population, in addition to adopting remediation measures in hotspot areas, to protect human health and the environment. HBM4EU findings also support the restriction of the whole group of PFASs. Further, research and definition for additional toxicological dose-effect relationship values for more PFASs compounds is needed.