Biomonitoring Studies Research Articles

Speciated and Total Urinary Arsenic Levels in Belo Horizonte, the Largest Brazilian City within the Mineral-Rich Region “Iron Quadrangle”

The “Quadrilátero Ferrífero” (Iron Quadrangle) is a mineral-rich province in Brazil, where arsenic anomalies are associated with gold mining and tailings dam failures. Urine samples were randomly collected from residents of Belo Horizonte (BH) city (N = 506 total/138 speciation) and the metropolitan area (N = 35 total/10 speciation), with stratifications in age, female-male and geopolitical regions. Creatinine, acid-digested total arsenic (TAs), and five inorganic and organic arsenic species were measured: arsenobetaine (AsB); arsenous (AsIII) and arsenic (AsV) acids and their dissociation products; monomethylarsonic acid (MMA); and dimethylarsinic acid DMA). Overall, the TAs GM (μg/g creat) of all stratification groups indicated no statistical difference. The TAs geometric mean (GM) of BH was 9.68 [9.17–10.2] μg/g creat, being AsB (43.8%) and DMA (20.7%) the major components. The toxic arsenic (ToxAs) fraction (i.e., AsIII + AsV + MMA + DMA) was 5.23 [4.45–6.15] μg/L. These TAs and ToxAs values are lower than international benchmarks and the Brazilian legislated standard of 35 μg/L for ToxAs. The TAs GM (μg/L) and creatinine were 36% higher for males than for females (p < 0.0001), making TAs GMs comparable, after creatinine correction. Similarly, though the 10–19 age group showed significantly higher ToxAs GM (12.7 [6.49–24.8] μg/L) (p = 0.048) and creatinine (p < 0.001), the ToxAs GM (7.22 [2.92–17.9] μg/g creat), was not statistically different than those from the other age groups. The study, the first one in Brazil, identifies the relative contribution of inorganic and organic arsenic and provides a baseline level for clinical reference and bio-monitoring studies, particularly applicable to both occupational and non-occupational populations in a mineral-rich region.Graphical abstract

Urinary levels of 30 metal/metalloids in the Brazilian southeast population: Findings from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

The assessment of risks associated with environmental exposure to metals/metalloids requires well-established reference values for each population since it varies considerably according to distinct local/regional characteristics. However, very few studies establish baseline values for these elements (essential and toxic) in large population groups, especially in Latin American countries. This study was aimed at establishing urinary reference levels of 30 metals/metalloids: aluminum (Al), antimony (Sb), arsenic (As), barium (Ba), beryllium (Be), cadmium (Cd), cerium (Ce), cesium (Cs), chromium (Cr), cobalt (Co), copper (Cu), lanthanum (La), lead (Pb), lithium (Li), strontium (Sr), manganese (Mn), mercury (Hg), molybdenum (Mo), nickel (Ni), platinum (Pt), rubidium (Rb), selenium (Se), silver (Ag), tin (Sn), tellurium (Te), thallium (Tl), thorium (Th), tungsten (W), uranium (U) and zinc (Zn) in a Brazilian southeast adult population. This pilot study is a cross-sectional analysis conducted with the first wave of the ELSA-Brasil cohort (baseline examination). A total of 996 adults (45.5% men, N = 453, mean age: 50.5, and 54.5% women, N = 543, mean age: 50.6) were included in the study. Sample analyses were performed by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Percentiles (2.5, 10, 25, 50, 75, 95 (CI95%), and 97.5) of each element (μg/g of creatinine) in the study are presented according to sex. Moreover, differences in the mean metal/metalloid urinary levels according to age, education, smoking, and alcohol intake are also presented. Finally, median found values were compared to established values of large human biomonitoring surveys previously conducted in North America and France. This is the first comprehensive and systematic human biomonitoring study that established population reference ranges for 30 (essential and/or toxic elements) in a Brazilian population group.

Exposure to Phthalates in European Children, Adolescents and Adults since 2005: A Harmonized Approach Based on Existing HBM Data in the HBM4EU Initiative.

Phthalates are mainly used as plasticizers and are associated inter alia with adverse effects on reproductive functions. While more and more national programs in Europe have started monitoring internal exposure to phthalates and its substitute 1,2-Cyclohexanedicarboxylic acid (DINCH), the comparability of results from such existing human biomonitoring (HBM) studies across Europe is challenging. They differ widely in time periods, study samples, degree of geographical coverage, design, analytical methodology, biomarker selection, and analytical quality assurance level. The HBM4EU initiative has gathered existing HBM data of 29 studies from participating countries, covering all European regions and Israel. The data were prepared and aggregated by a harmonized procedure with the aim to describe-as comparably as possible-the EU-wide general population's internal exposure to phthalates from the years 2005 to 2019. Most data were available from Northern (up to 6 studies and up to 13 time points), Western (11; 19), and Eastern Europe (9; 12), e.g., allowing for the investigation of time patterns. While the bandwidth of exposure was generally similar, we still observed regional differences for Butyl benzyl phthalate (BBzP), Di(2-ethylhexyl) phthalate (DEHP), Di-isononyl phthalate (DiNP), and Di-isobutyl phthalate (DiBP) with pronounced decreases over time in Northern and Western Europe, and to a lesser degree in Eastern Europe. Differences between age groups were visible for Di-n-butyl phthalate (DnBP), where children (3 to 5-year olds and 6 to 11-year olds) had lower urinary concentrations than adolescents (12 to 19-year-olds), who in turn had lower urinary concentrations than adults (20 to 39-year-olds). This study is a step towards making internal exposures to phthalates comparable across countries, although standardized data were not available, targeting European data sets harmonized with respect to data formatting and calculation of aggregated data (such as developed within HBM4EU), and highlights further suggestions for improved harmonization in future studies.

HBM4EU feasibility studies: Lessons learned in combining health and human biomonitoring studies

The European Human Biomonitoring Initiative (HBM4EU) is a joint program evaluating humans' exposure to several environmental substances and their potential health effects. One of the main objectives of HBM4EU is to make use of human biomonitoring (HBM) to assess human exposure to chemicals in Europe to better understand the associated health impacts and to improve chemical risk assessment. In parallel to HBM studies, health examination surveys (HESs), nutrition/dietary surveys, and disease specific health surveys are conducted in many European countries. In HESs, information collected by questionnaire(s) is supplemented with physical examinations and analysis of clinical and biological biomarkers in biological samples. HBM and health examination survey (HES) use similar data collection methods and infrastructures hence the feasibility of combining these two is explored in this paper. Within HBM4EU, three feasibility studies (in Finland, Germany, and UK/England) were conducted to evaluate opportunities and obstacles of combining HBM and health studies. In this paper we report lessons learned from these feasibility studies. The Finnish feasibility study called KouBio-KUOPIO study was a new initiative without links to existing studies. The German feasibility study added a HBM module to the first follow-up examination of the LIFE-Adult-Study, a population-based cohort study. The UK feasibility integrates a sustainable HBM module into the Health Survey for England (HSfE), an annual health examination survey. Benefits of combining HBM and HESs include the use of shared infrastructures. Furthermore, participants can receive additional health information from HES, and participation rates tend to be higher due to the potential to obtain personal health information. Preparatory phases including obtaining ethical approval can be time-consuming and complicated. Recruitment of participants and low participation rates are common concerns in survey research and therefore designing user-friendly questionnaires with low participant burden is important. Unexpected events such as the COVID-19 pandemic can cause substantial challenges and delays for such studies. Furthermore, experiences from several countries demonstrated that long-term funding for combined studies can be difficult to obtain. In the future, incorporating HBM modules into existing HESs can provide a feasible and cost-effective method to conduct HBM studies and obtain a wide range of relevant data to support public health policies and research.

The Connections between Mussel Watch for Potentially Toxic Metals and Nexus Seafood-Water-Energy

The previous assessment intends to support the inaugural International Mussel Watch program's use of marine mussels as biomonitors of potentially toxic metals in aquacultural areas has been considered of low novelty even though it is a necessary biomonitoring. When it is looked into the connections between Mussel Watch and Nexus seafood-water-energy, the questions can be raised up because there is apparently no such discussion in the literature. Therefore, the objective of this review is to discuss the connections between Mussel Watch for potentially toxic metals and Nexus seafood-water-energy, based on the topic reported in the literature separately. The current short review can act as a springboard for additional insights to offer fresh perspectives and original suggestions on using marine mussels more effectively in biomonitoring investigations in connections to Nexus seafood-water-energy. Nowadays, the biomonitoring by using Mussel Watch has remained effective and sustainable which further highlighted their importance in pollution monitoring. The likelihood of improved and wider-ranging molluscan uses in environmental monitoring in the future is almost inevitable. However, more research is still needed to address the rising demand in line with sustainable, attainable United Nation Sustainable Development Goals (‘‘Responsible consumption and production’’, and ‘Good Health and Well-beings’). This is surely a major player in the Nexus’s seafood in cycle with water and energy that should be addressed in future biomonitoring studies.

Biomonitoring of DEET and DCBA in Canadian children following typical protective insect repellent use

N,N-diethyl-m-toluamide (DEET) is an ingredient found in many consumer insect repellents and its use is recommended to Canadians by government agencies, including Health Canada, for protection against insect bites including mosquitos and ticks. The majority of research on DEET exposure and toxicokinetics in humans has focused on adult populations with little information from vulnerable populations, including children. We aimed to fill this knowledge gap by examining real-world exposure data for DEET and its metabolite 3-diethylcarbamoyl benzoic acid (DCBA) in a sample population of Canadian children. We conducted a 24-h observational exposure human biomonitoring study at three overnight summer camps in Ontario, Canada through July and August 2019. Participating children aged 7-13 years provided multiple spot urine samples over a 24-h period and completed a journal to document insect repellent use and factors that could influence absorption of DEET. Children were instructed to use insect repellent as they usually would while attending a summer camp. Exposure was quantified using the information from the participant's journal and the change in the mass of their insect repellent containers over the course of the study. A total of 389 urine samples were collected from 124 children. Among participants using insect repellent, urinary levels of DEET were elevated between 2 and 8h post-application and decreased thereafter but remained qualitatively higher than concentrations in participants who did not use insect repellent on the study day, even at 18-22h post-application. DCBA was the predominant metabolite of DEET exposure in urine. DCBA was elevated between 8 and 14h post-application, and declined thereafter, but not to the level observed among those who did not use insect repellent on the study day. Children who used more insect repellent, or used higher concentration insect repellent (10%-30% DEET) excreted higher levels of DEET and DCBA. Excreted DEET and DCBA accounted for 0.001% (median) and 1.3% (median) of the estimated applied DEET, respectively. Children did not reach an undetectable level of DEET or DCBA in urine, even among those not using insect repellent during the study day, indicating a potentially complex multi-route exposure to insect repellents in a real world scenario. This work provides targeted biomonitoring data for children intentionally using DEET-based insect repellents for normal protective use, and will support the risk re-evaluation of DEET by Health Canada.

Invited Perspective: PFAS in Breast Milk and Infant Formula-It's Time to Start Monitoring.

Invited Perspective: PFAS in Breast Milk and Infant Formula-It's Time to Start Monitoring.

Methods and Strategies for Biomonitoring in Occupational Exposure to Plant Protection Products Containing Glyphosate.

Glyphosate, and the ever growing reliance on its use in agriculture, has been a point of contention for many years. There have been debates regarding the risk and safety of using glyphosate-based herbicides as well as the effects of occupational, accidental, or systematic. Although there have been a number of studies conducted, the biomonitoring of glyphosate poses a series of challenges. Researchers attempting to determine the occupational exposure face questions regarding the most appropriate analytical techniques and sampling procedures. The present review aims to summarize and synthetize the analytical methodologies available and suitable for the purpose of glyphosate biomonitoring studies as well as discuss the advantages and disadvantages of each analytical technique, from the most modern to more well-established and older ones. The most relevant publications that have described analytical methods and published within the last 12 years were studied. Methods were compared, and the advantages and disadvantages of each methods were discussed. A total of 35 manuscripts describing analytical methods for glyphosate determination were summarized and discussed, with the most relevant one being compared. For methods that were not intended for biological samples, we discussed if they could be used for biomonitoring and approaches to adapt these methods for this purpose.

Association of urinary nickel levels with diabetes and fasting blood glucose levels: A nationwide Chinese population-based study

Some epidemiological studies support a relationship between nickel exposure and diabetes in the general population. To address this, we tested the association of nickel exposure with diabetes in 10,890 adults aged ≥ 18 years old from the China National Human Biomonitoring study conducted in 2017–2018. Urinary nickel concentrations and fasting blood glucose (FBG) were measured, and lifestyle and demographic data were collected. Weighted logistic and linear regressions were used to estimate the associations of urinary nickel levels with diabetes prevalence and FBG. Restricted cubic splines (RCS) were used to test for the dose-response relationship. The odd ratio (95% confidence interval [CI]) of diabetes for the highest versus lowest quartiles of urinary nickel concentrations was 1.74 (1.28, 2.36) in the multivariate model (p trend =0.001). Each one-unit increase in log-transformed urinary nickel concentrations was associated with a 0.36 (0.17, 0.55) mmol/L elevation in FBG. The RCS curves showed a monotonically increasing dose-response relationship of urinary nickel with diabetes as well as FBG levels, and then tended to flatten after about 4.75 μg/L of nickel exposure. The nickel-diabetes association was stronger in individuals with lower than those with higher rice consumption (OR: 2.39 vs. 1.72). Our study supports a positive association between nickel exposure and diabetes prevalence in Chinese adults, especially in individuals with lower rice consumption. Further large-scale prospective studies are needed to validate our findings.

Effects of pesticide exposure on oxidative stress and DNA methylation urinary biomarkers in Czech adults and children from the CELSPAC-SPECIMEn cohort

Current-use pesticide (CUP) exposure occurs mainly through diet and environmental application in both agricultural and urban settings. While pesticide exposure has been associated with many adverse health outcomes, the intermediary molecular mechanisms are still not completely elucidated. Among others, their roles in epigenetics (DNA methylation) and DNA damage due to oxidative stress are presumed. Scientific evidence on urinary biomarkers of such body response in general population is limited, especially in children.A total of 440 urine samples (n = 110 parent-child pairs) were collected during the winter and summer seasons in order to describe levels of overall DNA methylation (5-mC, 5-mdC, 5-hmdC, 7-mG, 3-mA) and oxidative stress (8-OHdG) biomarkers and investigate their possible associations with metabolites of pyrethroids (3-PBA, t/c-DCCA), chlorpyrifos (TCPY), and tebuconazole (TEB-OH). Linear mixed-effects models accounting for intraindividual and intrahousehold correlations were utilized. We applied false discovery rate procedure to account for multiplicity and adjusted for potential confounding variables.Higher urinary levels of most biological response biomarkers were measured in winter samples. In adjusted repeated measures models, interquartile range (IQR) increases in pyrethroid metabolites were associated with higher oxidative stress. t/c-DCCA and TCPY were associated with higher urinary levels of cytosine methylation biomarkers (5-mC and/or 5-mdC). The most robust association was observed for tebuconazole metabolite with 3-mA (−15.1% change per IQR increase, 95% CI = −23.6, −5.69) suggesting a role of this pesticide in reduced demethylation processes through possible DNA glycosylase inhibition.Our results indicate an urgent need to extend the range of analyzed environmental chemicals such as azole pesticides (e.g. prothioconazole) in human biomonitoring studies. This is the first study to report urinary DNA methylation biomarkers in children and associations between CUP metabolites and a comprehensive set of biomarkers including methylated and oxidized DNA alterations. Observed associations warrant further large-scale research of these biomarkers and environmental pollutants including CUPs.

Implementing a suspect screening method to assess occupational chemical exposures among US-based hairdressers serving an ethnically diverse clientele: a pilot study.

There are over 700,000 hairdressers in the United States, and it is estimated that >90% are female and 31% are Black or Hispanic/Latina. Racial and ethnic minorities in this workforce may be exposed to a unique mixture of potentially hazardous chemicals from products used and services provided. However, previous biomonitoring studies of hairdressers target a narrow list of compounds and few studies have investigated exposures among minority hairdressers. To assess occupational chemical exposures in a sample of US-based Black and Latina hairdressers serving an ethnically diverse clientele by analyzing urine specimens with a suspect screening method. Post-shift urine samples were collected from a sample of US female hairdressers (n = 23) and office workers (n = 17) and analyzed via reverse-phase liquid chromatography coupled to high-resolution mass spectrometry. Detected compounds were filtered based on peak area differences between groups and matching with a suspect screening list. When possible, compound identities were confirmed with reference standards. Possible exposure sources were evaluated for detected compounds. The developed workflow allowed for the detection of 24 compounds with median peak areas ≥2x greater among hairdressers compared to office workers. Product use categories (PUCs) and harmonized functional uses were searched for these compounds, including confirmed compounds methylparaben, ethylparaben, propylparaben, and 2-naphthol. Most product use categories were associated with "personal use" and included 11 different "hair styling and care" product types (e.g., hair conditioner, hair relaxer). Functional uses for compounds without associated PUCs included fragrance, hair and skin conditioning, hair dyeing, and UV stabilizer. Our suspect screening approach detected several compounds not previously reported in biomonitoring studies of hairdressers. These results will help guide future studies to improve characterization of occupational chemical exposures in this workforce and inform exposure and risk mitigation strategies to reduce potential associated work-related health disparities.

RE: "A FRAMEWORK FOR DESCRIPTIVE EPIDEMIOLOGY".

Lesko et al. (1) have formulated a framework for descriptive epidemiology that includes key features of a descriptive research question and a checklist of items to include when reporting on descriptive studies. Their focus and the focus of the related article by Fox et al. (2) is health outcomes. These recent publications may have been partially motivated by the abundance of recent research, of variable quality, on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patterns and determinants. While this focus is well-justified and should not be diminished, we argue that there is an equally valid need for attention to descriptive analyses of exposures. The framework proposed by Lesko et al. (1) can be easily adapted and applied to descriptive analyses of exposures. Descriptive analysis of independent variables is particularly relevant to observational studies that are not amenable to emulating a “target trial” (3, 4). Environmental chemicals are one such example. Human biomonitoring studies that describe chemical concentrations in a population can inform risk assessment, contribute to the development of directed acyclic graphs, and help identify vulnerable population subgroups. Rather than report a descriptive estimand such as the risk or rate of an outcome, we report detection frequencies and measures of central tendency and spread. Descriptive analyses of environmental chemicals should include details on the laboratory and statistical methods for handling concentrations below the limit of detection and quantification. Otherwise, all of Lesko et al.’s principles can be applied to this type of exposure.

Approaches to mixture risk assessment of PFASs in the European population based on human hazard and biomonitoring data.

Per- and polyfluoroalkyl substances (PFASs) are a highly persistent, mobile, and bioaccumulative class of chemicals, of which emissions into the environment result in long-lasting contamination with high probability for causing adverse effects to human health and the environment. Within the European Biomonitoring Initiative HBM4EU, samples and data were collected in a harmonized way from human biomonitoring (HBM) studies in Europe to derive current exposure data across a geographic spread. We performed mixture risk assessments based on recent internal exposure data of PFASs in European teenagers generated in the HBM4EU Aligned Studies (dataset with N=1957, sampling years 2014-2021). Mixture risk assessments were performed based on three hazard-based approaches: the Hazard Index (HI) approach, the sum value approach as used by the European Food Safety Authority (EFSA) and the Relative Potency Factor (RPF) approach. The HI approach resulted in the highest risk estimates, followed by the RPF approach and the sum value approach. The assessments indicate that PFAS exposure may result in a health risk in a considerable fraction of individuals in the HBM4EU teenager study sample, thereby confirming the conclusion drawn in the recent EFSA scientific opinion. This study underlines that HBM data are of added value in assessing the health risks of aggregate and cumulative exposure to PFASs, as such data are able to reflect exposure from different sources and via different routes.

Insulin Resistance in Children and the role of Endocrine-Disrupting Chemicals: Taking Stock of the Situation

The prevalence of non-communicable diseases, of which insulin resistance is a major constituent, among the pediatric population is exponentially increasing worldwide; this is causing a significant health burden, making understanding the basis of this phenomenon an issue of primary importance. During the last decades, we also observed that exposure to endocrine-disrupting chemicals is becoming more and more common; this has led researchers to investigate the mechanism of action and define the role of those substances in interfering with human metabolism and hormonal balance, especially at a young age. We reviewed the literature on prospective, epidemiological, and cross-sectional studies that have shown a link between exposure to pesticides, polychlorinated biphenyls, bisphenol A, phthalates, aromatic polycyclic hydrocarbons, or dioxins and insulin resistance; the strength of the associations varies between the substances and human biomonitoring studies have helped in defining the role of these chemicals. The number of prospective studies in children and even in adults is still low and heterogenous, still, evidence that Endocrine disruptors might be involved in the development of insulin resistance and related diseases is accumulating. This review aims to analyze the latest findings linking exposure to endocrine-disrupting chemicals with insulin resistance in children with the perspective of taking a cue for conducting new studies and identifying the most concerning Endocrine disruptors exposures, in order to guide future risk assessment and policy action aimed to limit the negative consequences of endocrine disrupting chemical exposure.

The Association between the Bisphenols Residues in Amniotic Fluid and Fetal Abnormalities in Polish Pregnant Women—Its Potential Clinical Application

The present study aimed to investigate the relationship between the concentrations of bisphenols residues in the amniotic fluid (AF) samples collected during amniocentesis and fetal chromosomal abnormalities in pregnant women. A total of 33 pregnant Polish women aged between 24 and 44 years, and screened to detect high risk for chromosomal defects in the first trimester, were included in this study. Samples were collected from these patients during routine diagnostic and treatment procedures at mid-gestation. The concentrations of various bisphenols residues in the samples were determined by liquid chromatography coupled with triple quadrupole tandem mass spectrometry (LC-ESI-QqQ-MS/MS). Residues of eight analytes (BPS, BPF, BPA, BPAF, BADGE, BADGE•2H2O, BADGE•H2O•HCl and BADGE•2HCl) were detected in amniotic fluid samples in the range 0.69 ng/mL to 3.38 ng/mL. Fetuses with chromosomal abnormalities showed a slightly higher frequency of occurrence of selected bisphenols residues in the AF samples collected between 15-26 weeks of pregnancies. Finally, the proposed method was applied in the simultaneous determination of several endocrine-disrupting chemicals from bisphenol group in 33 human AF samples. BADGE•H2O•HCl has been identified in the AF samples taken from women older than average in the examined group. The number of detected compounds has been significant for the following analytes: BPS, BPAF, BADGE•H2O•HCl and BADGE. The proposed method may be an attractive alternative for application in large-scale human biomonitoring studies.

Exposure to ionizing radiations and changes in blood cells and interleukin-6 in radiation workers.

Long-term exposure to ionizing radiation (IR) can cause dire health consequences even less than the dose limits. Previous biomonitoring studies have focused more on complete blood counts (CBCs), with non-coherent results. In this study, we aimed to investigate the association between exposure to IR and cytokine interleukin-6 (IL-6) along with hematological parameters in Tabriz megacity's radiation workers. In this hospital-based study, blood samples were taken from 33 radiation workers (exposed group) and 34 non-radiation workers (control group) in 4 hospitals. Absorbed radiation dose was measured by a personal film badge dosimeter in radiation workers. The studied biomarkers and all of the selected covariates were measured and analyzed using adjusted multiple linear regression models. The exposed doses for all radiation workers were under the dose limits (overall mean = 1.18mSv/year). However, there was a significant association between exposure to ionizing radiation and IL-6 (49.78 vs 36.17; t = 2.4; p = 0.02) and eosinophils (0.17 vs 0.14; t = 2.02; p = 0.049). The difference between the mean of the other biomarkers in radiation workers was not statistically significant compared to the control group. This study demonstrated that long-term exposure to ionizing radiation, even under the dose limits, is related to a significantly increased level of some blood biomarkers (Il-6 and eosinophil) that, in turn, can cause subsequent health effects such as cancer.

Isomer-Specific Serum Concentrations of Perfluorooctane Sulfonic Acid among U.S. Adults: Results from the National Health and Nutrition Examination Survey (NHANES) and the Study of Women's Health Across the Nation Multi-Pollutant Study (SWAN-MPS).

Electrochemical fluorination manufacture of perfluorooctane sulfonic acid (PFOS), one of the most studied per- and polyfluoroalkyl substances, produces mixtures of linear and branched isomers, but little is known about human exposure to linear or branched PFOS isomers. We examined determinants affecting isomer-specific patterns of PFOS in serum in two adult populations in the United States, the National Health and Nutrition Examination Survey (NHANES) and the Study of Women's Health Across the Nation Multi-Pollutant Study (SWAN-MPS). After adjusting for demographic variables, fish consumption (in both populations), a glomerular filtration rate above 90 mL/min/1.73 m2 (observed in NHANES; not tested in SWAN-MPS), premenopausal status (only observed in SWAN-MPS), and less consumption of processed food (observed in SWAN-MPS; not tested in NHANES) were associated with a higher proportion of linear PFOS. Non-Hispanic Black and Asian participants were likely to have a higher proportion of linear PFOS than non-Hispanic White participants in both populations. Our findings suggest that isomer-specific patterns of PFOS serum concentrations in humans vary depending on population characteristics that affect PFOS exposure and excretion. Consideration of specific PFOS isomers in future human biomonitoring and epidemiologic studies can provide useful insight to better understand PFOS exposure.

Lysmeral Exposure in Children and Adolescences Participating in the German Environmental Survey (2012-2015): Integrating Sex/Gender into Analysis.

Comprehensive consideration of the biological and social diversities of sex and gender as well as their interdependencies is mostly missing in human biomonitoring (HBM) studies. Using the INGER sex/gender concept as theoretical background, we analyzed differences in exposure to lysmeral, a compound commonly found as a fragrance in cosmetics, personal care, and household products, in 2294 children and adolescents in Germany using decision tree, regression, and mediation analysis. The variables "sex assigned at birth" and "age", as well as well as use of personal care products and fabric conditioner proved to have the highest explanatory value. Mediating effects of behaviour associated with societal gender expectations were observed, as the use of cosmetics correlated highly with lysmeral metabolites concentrations in girls between 6 and 17 years, with the strongest effect in adolescents between 14 and 17 years old. In the youngest age group (3-5 years) boys showed higher concentration of the metabolite tert-butylbenzoic acid (TBBA) compared to girls of the same age but only if TBBA urine concentrations were normalized on creatinine. Our study offers the first retrospective sex/gender assessment of HBM data. It demonstrates the possibilities to rethink and broaden sex/gender analysis in existing HBM-studies and highlights the need for inclusion of new sex/gender concepts in the design of new studies.

Exposure Levels of Pyrethroids, Chlorpyrifos and Glyphosate in EU-An Overview of Human Biomonitoring Studies Published since 2000.

Currently used pesticides are rapidly metabolised and excreted, primarily in urine, and urinary concentrations of pesticides/metabolites are therefore useful biomarkers for the integrated exposure from all sources. Pyrethroid insecticides, the organophosphate insecticide chlorpyrifos, and the herbicide glyphosate, were among the prioritised substances in the HBM4EU project and comparable human biomonitoring (HBM)-data were obtained from the HBM4EU Aligned Studies. The aim of this review was to supplement these data by presenting additional HBM studies of the priority pesticides across the HBM4EU partner countries published since 2000. We identified relevant studies (44 for pyrethroids, 23 for chlorpyrifos, 24 for glyphosate) by literature search using PubMed and Web of Science. Most studies were from the Western and Southern part of the EU and data were lacking from more than half of the HBM4EU-partner countries. Many studies were regional with relatively small sample size and few studies address residential and occupational exposure. Variation in urine sampling, analytical methods, and reporting of the HBM-data hampered the comparability of the results across studies. Despite these shortcomings, a widespread exposure to these substances in the general EU population with marked geographical differences was indicated. The findings emphasise the need for harmonisation of methods and reporting in future studies as initiated during HBM4EU.

Prioritization of mixtures of neurotoxic chemicals for biomonitoring using high-throughput toxicokinetics and mixture toxicity modeling

Modern society continues to pollute the environment with larger quantities of chemicals that have also become more structurally and functionally diverse. Risk assessment of chemicals can hardly keep up with the sheer numbers that lead to complex mixtures of increasing chemical diversity including new chemicals, substitution products on top of still abundant legacy compounds. Fortunately, over the last years computational tools have helped us to identify and prioritize chemicals of concern. These include toxicokinetic models to predict exposure to chemicals as well as new approach methodologies such as in-vitro bioassays to address toxicodynamic effects. Combined, they allow for a prediction of mixtures and their respective effects and help overcome the lack of data we face for many chemicals. In this study we propose a high-throughput approach using experimental and predicted exposure, toxicokinetic and toxicodynamic data to simulate mixtures, to which a virtual population is exposed to and predict their mixture effects. The general workflow is adaptable for any type of toxicity, but we demonstrated its applicability with a case study on neurotoxicity. If no experimental data for neurotoxicity were available, we used baseline toxicity predictions as a surrogate. Baseline toxicity is the minimal toxicity any chemical has and might underestimate the true contribution to the mixture effect but many neurotoxicants are not by orders of magnitude more potent than baseline toxicity. Therefore, including baseline-toxic effects in mixture simulations yields a more realistic picture than excluding them in mixture simulations. This workflow did not only correctly identify and prioritize known chemicals of concern like benzothiazoles, organochlorine pesticides and plasticizers but we were also able to identify new potential neurotoxicants that we recommend to include in future biomonitoring studies and if found in humans, to also include in neurotoxicity screening.