Associations and Interactions between Heavy Metals with White Blood Cell and Eosinophil Count.

The accumulation of heavy metals in the body has been associated with an elevated immune response. The aim of this study was to investigate the associations among heavy metals and white blood cell (WBC) and eosinophil count in the general population in southern Taiwan. We also explored the interactions and synergetic effects of heavy metals on WBC and eosinophil count. We conducted a health survey in the general population living in southern Taiwan between June 2016 and September 2018. Seven heavy metals were measured: blood lead (Pb), and urine cadmium (Cd), copper (Cu), nickel, arsenic (As), chromium and manganese (Mn). A total of 2,447 participants were enrolled. In multivariable analysis, high concentrations of Pb (log per 1 mg/L; coefficient ß, 0.332; p = 0.005) and Cu (log per 1 µg/dL; coefficient ß, 0.476; p < 0.001) were significantly associated with a high WBC count. In addition, high concentrations of Pb (log per 1 mg/L; coefficient ß, 0.732; p < 0.001), As (log per 1 µg/L; coefficient ß, 0.133; p = 0.015), Cu (log per 1 µg/dL; coefficient ß, 0.181; p = 0.018), and Cd (log per 1 µg/L; coefficient ß, 0.139; p = 0.002) were significantly associated with a high eosinophil count. Further, the effect of interactions between Pb and As (coefficient ß, 0.721; p = 0.029) and Mn and Cu (coefficient ß, 0.482; p = 0.018) on WBC count, and As and Cu (unstandardized coefficient ß, 0.558; p = 0.002) on eosinophil count were statistically significant. In conclusion, the heavy metals Pb, As, Cu, and Cd were associated with WBC and eosinophil count. In addition, synergistic effects of heavy metal poisoning on the association with WBC and eosinophil count were also observed.

Human Biomonitoring (HBM)-I values for perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) - Description, derivation and discussion.

In 2016, the German Human Biomonitoring Commission (HBM-C) published a statement on its decision to develop HBM-I values for Perfluorooctanoic acid (PFOA) and Perfluorooctanesulfonic acid (PFOS) (Bundesgesundheitsbl 2016, 59:1364 DOI 10.1007/s00103-016-2437-1). The HBM-I value corresponds to the concentration of a substance in a human biological material below which no adverse health effects are expected, according to current knowledge and assessment by the HBM-C, and, consequently, there is no need for action. Evidence for associations between PFOA- and PFOS-body burden and health outcomes was found for fertility and pregnancy, weights of newborns at birth, lipid metabolism, immunity, sex hormones and age at puberty/menarche, thyroid hormones, onset of menopause as well as uric acid metabolism. Significant contrasts were reported for human blood plasma concentrations between 1 and 10 ng PFOA/mL, and 1-15 ng PFOS/mL, respectively. Within the reported ranges, the HBM-C has decided to set the HBM-I-values at 2 ng PFOA/mL and 5 ng PFOS/mL blood plasma. The underlying pathomechanisms do not appear to be sufficiently clarified to provide an unambiguous explanation of the effects observed. Consistency of toxicological and epidemiological data has been considered. The available data do not indicate an unequivocal proof of a genotoxicity of PFOA and PFOS.

Human biomonitoring (HBM)-II values for perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) - Description, derivation and discussion.

For evaluation of internal exposure to harmful substances, the Human Biomonitoring Commission of the German Environment Agency (HBM Commission) develops toxicologically justified assessment values (HBM-I and HBM-II). The HBM-I value corresponds to the concentration of a compound in human biological material below which no adverse health effects are expected to occur. Consequently, no action is required when the HBM-I value is not exceeded (HBM-Commission, 1996). In 2016, the HBM Commission developed HBM-I values of 2 ng PFOA/mL and 5 ng PFOS/mL in blood serum or plasma, respectively. A detailed delineation of supporting arguments was published in April 2018 (HBM-Commission, 2018). In contrast to the HBM-I, the HBM-II value corresponds to the concentration in human biological material which, when exceeded, may lead to health impairment which is considered as relevant to exposed individuals (HBM-Commission, 1996, HBM-Commission, 2014). HBM-II VALUES FOR PFOA AND PFOS: On September 17, 2019, the HBM Commission of the German Environment Agency established the following HBM-II values: Women at child-bearing age: 5 ng PFOA/mL blood plasma; 10 ng PFOS/mL blood plasma; All other population groups: 10 ng PFOA/mL blood plasma; 20 ng PFOS/mL blood plasma.

Human Biomonitoring of Selected Hazardous Compounds in Portugal: Part II-Lessons Learned on Mycotoxins.

Human biomonitoring (HBM) data provide information on total exposure regardless of the route and sources of exposure. HBM studies have been applied to quantify human exposure to contaminants and environmental/occupational pollutants by means of determining the parent compounds, their metabolites, or even their reaction products in biological matrices. HBM studies performed among the Portuguese population are dispersed and limited. Thus, to overcome this knowledge gap, this work reviews the published Portuguese HBM information concerning mycotoxins detected in the urine, serum, milk, hair, and nails of different groups of the Portuguese population. This integrative approach to the available HBM data allows us to analyze the main determinants and patterns of exposure of the Portuguese population to the selected hazardous compounds, as well as to assess the potential health risks. We also aimed to identify the main difficulties and challenges of HBM through the analysis of the enrolled studies. Ultimately, this study aims to support national and European policies in promoting human health by summarizing the most important outcomes and lessons learned through the HBM studies carried out in Portugal.

The impact of comet assay data normalization in human biomonitoring studies outcomes.

The comet assay has been extensively used in biomonitoring studies. To avoid intra-experimental variability, the incorporation of assay controls in each work session for data normalization has been suggested by some authors but has never been thoroughly analyzed. The aim of this study was to address the impact of data normalization in the results of a biomonitoring study using different normalization models. Human peripheral blood mononuclear cells (PBMC) from 140 healthy individuals were analyzed using the alkaline and FPG-modified version of the comet assay across seven different work sessions. In addition to negative standards, methyl methanesulfonate (MMS) and Ro 19-8022 plus light treated PBMC, were also included in the assay as positive standards. To verify the impact of data normalization, some demographic, lifestyle and environmental exposure-related variables were selected. Significant associations with independent study variables were observed using normalized comet endpoints, as opposed to raw data. After normalization, levels of DNA strand breaks were significantly higher among males and older individuals (>71 years), while net FPG-sensitive sites were positively related to smoking habits and environmental exposures (i.e. air pollution and bottled water consumption). This study highlights how the normalization strategies can influence the statistical results of a human biomonitoring study and lead to different data interpretations.

Temporal trends and determinants of PFR exposure in the Hokkaido Study.

The phase-out of polybrominated diphenyl ethers (PBDE) flame retardants has led to the rapid increase of alternatives such as phosphate flame retardants and plasticizers (PFRs) in many consumer products. Exposure to these additive chemicals is widespread and potentially harmful to humans and the environment. In the present study, we assessed the exposure to PFRs through the analysis of metabolites in urine collected from 7-year old children from Hokkaido, Japan between 2012 and 2017. This allowed us to investigate temporal and seasonal trends for PFR metabolite concentrations and to study determinants of exposure. Thirteen metabolites of seven PFRs were measured in morning spot urine samples (n = 400). Multiple regression models were used to quantify the yearly increase in metabolite concentrations per sampling year. Information on the demographics, indoor environment and dietary habits of the participants were derived from self-administered questionnaires. PFR metabolite concentrations were comparable to our previous study of school children (7-12 years old). Eight PFR metabolites were detected in >50% of the samples. During the study time period, concentrations of three metabolites increased significantly: bis(1,3-dichloro-2-propyl) phosphate (BDCIPP; 13.3% per year), 1-hydroxy-2-propyl bis(1-chloro-2-propyl) phosphate (BCIPHIPP; 12.9% per year), and 2-ethylhexyl phenyl phosphate (EHPHP; 6.7% per year). We also found seasonality as a determinant for several PFR metabolites, with 2-fold higher levels in summer for BCIPHIPP and BDCIPP. Concentrations were also significantly impacted by ventilation habits. More frequent window opening or use of mechanical ventilation was consistently associated with higher levels of PFR metabolites in children's urine. This is the first study to show that human exposure to PFRs has increased in recent years in Japan, which indicates that further research into this class of chemicals is warranted.

Biomonitoring data on young adults from the Environmental Specimen Bank suggest a decrease in the exposure to the fragrance chemical 7-hydroxycitronellal in Germany from 2000 to 2018.

7-Hydroxy-3,7-dimethyl-1-octanal, also known as 7-hydroxycitronellal (7-HC, CAS No. 107-75-5) is a synthetic fragrance widely used in cosmetic and hygiene products. Because of its wide spread use and its known sensitizing properties, 7-HC was selected as one of 50 chemicals within the frame of the cooperation project between the German Federal Ministry for the Environment, Nature Conservation and Nuclear Safety (BMU) and the German Chemical Industry Association (VCI) to develop a suitable human biomonitoring (HBM) method in order to assess the exposure of the general population in Germany. Within this scope, the recently published analytical method for urinary 7-hydroxycitronellylic acid (7-HCA), the major metabolite of 7-HC, was applied to 329 24h-urine samples of young adults (20 to 29 years) collected between 2000 and 2018 and stored in the Environmental Specimen Bank (ESB). The widespread exposure to 7-HC as already observed in a pilot study with 40 volunteers could be confirmed with quantifiable concentrations of 7-HCA in all 329 study samples (mean: 14.9 ng/mL; median: 8.1 ng/mL). A significant, chronological decrease in 7-HCA levels was found for the monitored years (2000, 2004, 2008, 2012, 2015, 2018). The most pronounced decline occurred between 2000 and 2004 (means: 34.37 versus 23.31, medians: 20.97 versus 12.49 µg/24h; p < 0.01). On average, females exhibited higher levels of urinary 7-HCA compared to males (29.34 versus 17.21 µg/24h, p < 0.05). Based on the urinary 7-HCA excretion, the daily intake (DI) of 7-HC normalized for body weight (bw) was estimated. Over all sampling years, average DI in females was significantly higher compared to males (0.99 versus 0.46 µg/kg bw/d). Assuming dermal exposure as the main route of 7-HC intake, the mean DIs correspond to <0.1% of the derived no effect level (DNEL) of 1,100 µg/kg bw/d defined by the European Chemical Agency (ECHA). The presented results for the exposure to the widely used fragrance 7-HC in Germany can be substantiated by applying the described methodology to the representative cohort of the launched German Environmental Survey in adults (GerES VI).

Organic contaminants in human breast milk identified by non-targeted analysis.

Understanding the health implications of human exposure to mixtures of chemical contaminants is aided by analytical methods that can screen for a broad range of both expected and unexpected compounds. We performed a proof-of-concept analysis combining human breast milk, a biomonitoring matrix for determining contaminant exposure to mothers and infants, with a non-targeted method based on comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry (GC×GC/TOF-MS). A total of 172 presumably anthropogenic halogenated compounds and non-halogenated cyclic and aromatic compounds were tentatively identified in breast milk from San Diego, California through mass spectral database searches. Forty of the compounds were prioritized for confirmation based on halogenation or 100% frequency of detection, and the identities of 30 were verified using authentic standards. Thirty-four (85%) of the prioritized contaminants are not typically monitored in breast milk surveys, and 31 (77%) are regulated in at least one market worldwide, indicating breast milk may be a useful biomonitoring matrix for non-targeted analysis and the assessment of human exposure to future emerging or undiscovered contaminants.

Survey of Occupational and Environmental Exposure Monitoring Solutions.

INTRODUCTION: Service members are exposed to ambient airborne pollutants that have been linked to adverse health effects; however, capabilities to identify and characterize exposures across multi-domain operations are currently lacking. Occupational and environmental exposure monitoring is problematic because there is not a single simple solution, and current technological limitations suggest that simultaneous deployment of multiple devices may be the most effective near-term strategy. MATERIALS AND METHODS: A broad industry scan of wearable, handheld, or portable occupational and environmental exposure monitoring devices was conducted, and subject matter experts were interviewed about the state of the field. RESULTS: This survey identified limitations including the inability to detect multiple analytes or analyte classes, size and weight, and detection limits, but multiple implementation strategies could be employed to meet a variety of combat needs. Device types could be layered, or specific device types could be deployed in acute toxic exposure environments such as dense urban population centers or subterranean spaces. CONCLUSIONS: Evolving technologies and data management strategies may advance personal exposure monitoring in the future. These new devices and methods will likely supplant current technologies, while still using the programmatic and data framework established with early implementation of current commercial off the shelf devices.

Biomonitoring of pharmacists and nurses at occupational risk from handling antineoplastic agents.

OBJECTIVE: The objective of this study was to evaluate the frequency of genetic lesions in pharmacists and nurses who prepare and/or handle antineoplastic agents and to evaluate whether there are traces of contaminants in the urine of these professionals. METHODS: A total of 59 professionals participated in the study, of which 10 were non-exposed professionals (controls), 25 were pharmacists, and 24 were nurses. KEY FINDINGS: There was a significant increase in genetic damage in lymphocytes and cells of the oral mucosa in both pharmacists and nurses. The levels of cyclophosphamide and ifosfamide were also increased in the urine samples from those individuals. CONCLUSIONS: These results demonstrate the growing need for genetic biomonitoring and biomonitoring of trace antineoplastic agents in the urine of health professionals who prepare and/or handle antineoplastic agents.

Can Fish and Cell Phones Teach Us about Our Health?

Biologging is a scientific endeavor that studies the environment and animals within it by outfitting the latter with sensors of their dynamics as they roam freely in their natural habitats. As wearable technologies advance for the monitoring of human health, it may be instructive to reflect on the successes and failures of biologging in field biology over the past few decades. Several lessons may be of value. Physiological sensors can "encode" for a wider number of states than the one explicitly targeted, although the limits of this are debatable. The combination of orthogonal sensors turns out to be critical to delivering a high value data set. Sensor fusion and engineering for longevity are also important for success. This Perspective highlights successful strategies for biologging that hold promise for human health monitoring.

Association between serum heavy metals and prostate cancer risk - A multiple metal analysis.

BACKGROUND: Prostate cancer is one of the most prevalent cancers in men. Exposure to heavy metals and their association with prostate cancer risk has been studied extensively, but combined effects remain largely inconclusive. OBJECTIVES: To elucidate the association between serum concentrations of heavy metals and prostate cancer risk. METHODS: Inductively coupled plasma mass spectrometry (ICP-MS) was used to determine the concentrations of a panel of 10 heavy metals (Mn, Cu, Zn, As, Se, Sb, Co, Cu, Cd and Pb) in serum samples of 141 cases and 114 controls in the Singapore Prostate Cancer Study. Linear probit regression models were used to estimate risk differences (RDs) and 95% confidence intervals (CIs) for the associations between log-centered serum metal concentrations and prostate cancer risk with adjustment for potential confounders. Bayesian kernel machine regression (BKMR) models were used to account for nonlinear, interactive, and joint metal effects. RESULTS: Using probit regression, four heavy metals (As, Zn, Mn, Sb) were significantly and positively associated with prostate cancer risk in the unadjusted models. Using BKMR analysis, both As and Zn had positive risk differences on prostate cancer risk when all other metals were held fixed at the 25th and 50th percentiles (RD, 25th percentile: As: 0.15, Zn: 0.19, RD, 50th percentile: As: 0.45, Zn: 0.37). In addition, the overall mixture risk difference was positive and the 95% credible intervals did not include 0 when all metals in the mixture were jointly above their 55th percentile, as compared to when all metals were below their median values. CONCLUSIONS: In summary, we found positive associations between the serum levels of As and Zn and prostate cancer risk on the risk difference scale using BKMR models. The overall mixture effect was also associated with increased prostate cancer risk. Future studies are warranted to validate these findings in prospective studies.

Potential biomonitoring of atmospheric carbon dioxide in Coffea arabica leaves using near-infrared spectroscopy and partial least squares discriminant analysis.

The potencial of Coffea arabica leaves as bioindicators of atmospheric carbon dioxide (CO2) was evaluated in a free-air carbon dioxide enrichment (FACE) experiment by using near-infrared reflectance (NIR) spectroscopy for direct analysis and partial least squares discriminant analysis (PLS-DA). A supervised classification model was built and validated from the spectra of coffee leaves grown under elevated and current CO2 levels. PLS-DA allowed correct test set classification of 92% of the elevated-CO2 level leaves and 100% of the current-CO2 level leaves. The spectral bands accounting for the discrimination of the elevated-CO2 leaves were at 1657 and 1698 nm, as indicated by the variable importance in the projection (VIP) score together with the regression coefficients. Seven months after suspension of enriched CO2, returning to current-CO2 levels, new spectral measurements were made and subjected to PLS-DA analysis. The predictive model correctly classified all leaves as grown under current-CO2 levels. The fingerprints suggest that after suspension of elevated-CO2, the spectral changes observed previously disappeared. The recovery could be triggered by two reasons: the relief of the stress stimulus or the perception of a return of favorable conditions. In addition, the results demonstrate that NIR spectroscopy can provide a rapid, nondestructive, and environmentally friendly method for biomonitoring leaves suffering environmental modification. Finally, C. arabica leaves associated with NIR and mathematical models have the potential to become a good biomonitoring system.

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.

Association of Trajectory of Cardiovascular Health Score and Incident Cardiovascular Disease.

Importance: The American Heart Association 2020 Strategic Impact Goals target an improvement in overall cardiovascular health, as assessed by 7 health metrics (smoking, body weight, physical activity, diet, plasma glucose level, plasma cholesterol level, and blood pressure). Objective: To examine whether trajectories of overall cardiovascular health over time, as assessed by the cardiovascular health score (CHS) in 2006, 2008, and 2010, are associated with subsequent risk of CVD. Design, Setting, and Participants: The Kailuan study is a prospective, population-based study that began in 2006. The cohort included 74 701 Chinese adults free of myocardial infarction, stroke, and cancer in or before 2010. In the present study, CHS trajectories were developed from 2006 to 2010 to predict CVD risk from 2010 to 2015. Data analysis was performed from January 1, 2006, to December 31, 2015. Exposures: The CHS trajectories during 2006-2010 were identified using latent mixture models. Main Outcomes and Measures: Incident CVD events (myocardial infarction and stroke) during 2010-2015 were confirmed by review of medical records. The CHS trajectories were determined using 7 cardiovascular health metrics scored as poor (0 points), intermediate (1 point), and ideal (2 points); total score ranges from 0 (worst) to 14 (best). Based on the baseline CHS and patterns over time, 5 trajectories were categorized (low-stable, moderate-increasing, moderate-decreasing, high-stable I, and high-stable II). Results: Of the 74 701 adults included in the study (mean [SD] age at baseline, 49.6 [11.8] years), 58 216 (77.9%) were men and 16 485 (22.1%) were women. Five CHS trajectories were identified from 2006 to 2010: low-stable (n = 4393; range, 4.6-5.2), moderate-increasing (n = 4643; mean increase from 5.4 to 7.8), moderate-decreasing (n = 14 853; mean decrease from 7.4 to 6.3), high-stable I (n = 36 352; range, 8.8-9.0), and high-stable II (n = 14 461; range, 10.9-11.0). During 5 years of follow-up, 1852 incident CVD cases were identified. Relative to the low-stable trajectory, the high-stable II trajectory was associated with a lower subsequent risk of CVD (adjusted hazard ratio, 0.21; 95% CI, 0.16-0.26, after adjusting for age, sex, educational level, income, occupation, alcohol intake, and serum high-sensitivity C-reactive protein concentration at baseline). Conclusions and Relevance: Cardiovascular health trajectories may be associated with subsequent CVD risk.

Internal exposure of young German adults to di(2-propylheptyl) phthalate (DPHP): Trends in 24-h urine samples from the German Environmental Specimen Bank 1999-2017.

Di(2-propylheptyl) phthalate (DPHP) is used as a substitute for high molecular weight phthalates like di(2-ethylhexyl) phthalate (DEHP) which were subjected to authorization under REACh in 2015. An earlier study on the time trend of exposure in human 24-h urine samples from the German Environmental Specimen Bank has revealed that metabolites of DPHP emerged in 2009 and 2012 (Schütze et al., 2015). In order to better assess a potential trend and the present state of exposure to DPHP, we now measured 180 urine samples from the German Environmental Specimen Bank, 60 per year, collected in 2011, 2014 and 2017, randomized and blinded before analysis. Together with the previously analyzed samples, data for a total of 480 samples covering 19 years from 1999 to 2017 was thus generated. We were able to show that DPHP exposure of the studied population, university students from Münster (Northwestern Germany), has remained essentially constant since 2011, after a rapid increase starting around 2009. Even so, urinary metabolite concentrations were always in the low ppb or sub-ppb range, indicating that DPHP exposure of the general population is substantially lower than for other modern plasticizers, and far below levels currently regarded as critical. DPHP is a plasticizer which is mostly used in non-sensitive applications with little probability of close contact to humans. Still, we observed how temporal trends of DPHP exposure largely follow trends of DPHP consumption in the Western European market. Our results hence demonstrate the potential of biomonitoring to sensitively detect the effects of industrial product strategy on the environment, even when biomarkers are present only at trace level.