Human biomonitoring: state of the art. Int J Hyg Environ Health
Human biomonitoring (HBM) of dose and biochemical effect nowadays has tremendous utility providing an efficient and cost effective means of measuring human exposure to chemical substances. HBM considers all routes of uptake and all sources which are relevant making it an ideal instrument for risk assessment and risk management. HBM can identify new chemical exposures, trends and changes in exposure, establish distribution of exposure among the general population, identify vulnerable groups and populations with higher exposures and identify environmental risks at specific contaminated sites with relatively low expenditure. The sensitivity of HBM methods moreover enables the elucidation of human metabolism and toxic mechanisms of the pollutants. So, HBM is a tool for scientists as well as for policy makers. Blood and urine are by far the most approved matrices. HBM can be done for most chemical substances which are in the focus of the worldwide discussion of environmental medicine. This especially applies for metals, PAH, phthalates, dioxins, pesticides, as well as for aromatic amines, perfluorinated chemicals, environmental tobacco smoke and volatile organic compounds. Protein adducts, especially Hb-adducts, as surrogates of DNA adducts measuring exposure as well as biochemical effect very specifically and sensitively are a still better means to estimate cancer risk than measuring genotoxic substances and their metabolites in human body fluids. Using very sophisticated but nevertheless routinely applicable analytical procedures Hb-adducts of alkylating agents, aromatic amines and nitro aromatic compounds are determined routinely today. To extend the spectrum of biochemical effect monitoring further methods should be elaborated which put up with cleavage and separation of the adducted protein molecules as a measure of sample preparation. This way all sites of adduction as well as further proteins, like serum albumin could be used for HBM. DNA-adducts indicate the mutagenicity of a chemical substance as well as an elevated cancer risk. DNA-adducts therefore would be ideal parameters for HBM. Though there are very sensitive techniques for DNA adduct monitoring like P32-postlabelling and immunological methods they lack specificity. For elucidating the mechanism of carcinogenesis and for a broad applicability and comparability in epidemiological studies analytical methods must be elaborated which are strictly specific for the chemical structure of the DNA-adduct. Current analytical possibilities however meet their borders. In HBM studies with exposure to genotoxic chemicals especially the measurement of DNA strand breaks in lymphocytes and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in white blood cells has become very popular. However, there is still a lack of well-established dose-response relations between occupational or environmental exposures and the induction of 8-OHdG or formation of strand breaks which limits the applicability of these markers. Most of the biomarkers used in population studies are covered by standard operating procedures (SOPs) as well as by internal and external quality assessment schemes. Therefore, HBM results from the leading laboratories worldwide are analytically reliable and comparable. Newly upcoming substances of environmental relevance like perfluorinated compounds can rapidly be assessed in body fluids because there are very powerful laboratories which are able to elaborate the analytical prerequisites in due time. On the other hand, it is getting more and more difficult for the laboratories to keep up with a progress in instrumental analyses. In spite of this it will pay to reach the ultimate summit of HBM because it is the only way to identify and quantify human exposure and risk, elucidate the mechanism of toxic effects and to ultimately decide if measures have to be taken to reduce exposure. Risk assessment and risk management without HBM lead to wrong risk estimates and cause inadequate measures. In some countries like in USA and in Germany, thousands of inhabitants are regularly investigated with respect to their internal exposure to a broad range of environmentally occurring substances. For the evaluation of HBM results the German HBM Commission elaborates reference- and HBM-values.
Available from: Lara Manyes
- "One of the most important strategies for detecting OTA in individuals and the amount that has been absorbed is through the analysis of biomarkers. Biomarkers enable measurement of the exposure to a toxic agent and any toxic response, as well as the prediction of the likely response; in this sense, two types on biomarkers can be differentiated: i) biomarkers of exposure: those that allow measurement of the compound itself or its metabolites in body fluids; and ii) biomarkers of biochemical effect: corresponding to the measurement after exposure to the compound itself or its metabolites reaching a toxicological significant target (Duarte et al., 2011; Angerer et al., 2007). "
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ABSTRACT: The purposes of this review was to study potential biomarkers of exposure for ochratoxin A (OTA) in biological fluids (blood, urine and breast milk) for the period of 2005-2014, calculate the estimated daily intake (EDI) of OTA by using database consumption for the Spanish population and, finally to correlate OTA levels detected in blood and EDI values calculated from food products. The values of OTA detected in potential biomarkers of exposure for blood, breast milk and urine ranged from 0.15 to 18.0, from 0.002 to 13.1 and, from 0.013 to 0.2 ng/mL, respectively. The calculated EDI for OTA in plasma ranged from 0.15 to 26 ng/kg bw/day, higher than that obtained in urine (0.017-0.4 ng/kg bw/day). All these values are correlated with the range of EDI for OTA calculated from food products: 0.0001-25.2 ng/kg bw/day.
- "The targeted approach subsequently focuses on specific compounds that have probative value to diagnose subtle changes in metabolism or biochemistry that may indicate an activation of an AOP. These approaches rely on measurements from biological media such as blood, breath, and urine (Angerer et al., 2007; Au, 2007; Paustenbach & Galbraith, 2006; Pleil, 2008, 2012). In fact, the U.S. Centers for Disease Control and Prevention (CDC) have been operating the National Health and Nutrition Examination Survey (NHANES) since 1971 (http:// www.cdc.gov/nchs/nhanes/history.htm). "
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ABSTRACT: Environmental exposure diagnostics use creatinine concentrations in urine aliquots as the internal standard for dilution normalization of all other excreted metabolites when urinary excretion rate data are not available. This is a reasonable approach for healthy adults as creatinine is a human metabolite that is continually produced in skeletal muscles and presumably excreted in the urine at a stable rate. However, creatinine also serves as a biomarker for glomerular filtration rate (efficiency) of the kidneys, so undiagnosed kidney function impairment could affect this commonly applied dilution calculation. The United States Environmental Protection Agency (US EPA) has recently conducted a study that collected approximately 2600 urine samples from 50 healthy adults, aged 19-50 years old, in North Carolina in 2009-2011. Urinary ancillary data (creatinine concentration, total void volume, elapsed time between voids), and participant demographic data (race, gender, height, and body weight) were collected. A representative subset of 280 urine samples from 29 participants was assayed using a new kidney injury panel (KIP). In this article, we investigated the relationships of KIP biomarkers within and between subjects and also calculated their interactions with measured creatinine levels. The aims of this work were to document the analytical methods (procedures, sensitivity, stability, etc.), provide summary statistics for the KIP biomarkers in "healthy" adults without diagnosed disease (distribution, fold range, central tendency, variance), and to develop an understanding as to how urinary creatinine level varies with respect to the individual KIP proteins. Results show that new instrumentation and data reduction methods have sufficient sensitivity to measure KIP levels in nominally healthy urine samples, that linear regression between creatinine concentration and urinary excretion explains only about 68% of variability, that KIP markers are poorly correlated with creatinine (r2 ∼ 0.34), and that statistical outliers of KIP markers are not random, but are clustered within certain subjects. In addition, we interpret these new adverse outcome pathways based in vivo biomarkers for their potential use as intermediary chemicals that may be diagnostic of kidney adverse outcomes to environmental exposure.
Available from: Hermann Fromme
- "For decades, human biomonitoring has been shown to be a versatile tool for the identification and assessment of the general population's exposure to chemicals (Göen et al., 2012). Compared to air-monitoring, which reflects external exposure, biomonitoring focuses on the analysis of metabolites in biological materials and, therefore, it may increase significance for risk assessment (Angerer et al., 2007). Following uptake, MTps are rapidly metabolized to oxidized species which are excreted via urine, mainly in conjugated forms. "
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ABSTRACT: To investigate the assumed association between indoor air pollution with monoterpenes (MTps) and the internal MTp exposure of occupants, a comparative study was performed in daycare centers in two federal states of Germany. Three well-known monoterpenoid air pollutants, viz. α-pinene (αPN), Δ(3)-carene (CRN), and R-limonene (LMN), were measured in indoor air in 45 daycare centers. Additionally, urine samples of 222 children visiting these facilities were collected in the evening after a full-day stay. Altogether 11 MTp metabolites were analyzed in the urine samples using a novel highly sensitive and selective gas chromatographic-tandem-mass spectrometric procedure. The medians (95th percentiles) of the MTp levels in indoor air were 9.1μgm(-3) (94μgm(-3)) for LMN, 2.6μgm(-3) (13μgm(-3)) for αPN, and <1.0μgm(-3) (3.2μgm(-3)) for CRN. None of the day care centers exceeded the German health precaution or hazard guide value. In spite of the low MTp air exposure, the urine analyses revealed an exposure to the three monoterpenes in almost all children. The median levels of MTp metabolites in urine were 0.11mgL(-1) for LMN-8,9-OH, 0.10mgL(-1) for LMN-1,2-OH, 49μgL(-1) for PA, 2.9μgL(-1) for POH, 5.2μgL(-1) for tCAR, and 4.1μgL(-1) for cCAR (LMN metabolites), 7.2μgL(-1) for MYR, 19μgL(-1) for tVER, and 19μgL(-1) for cVER (αPN metabolites), as well as 8.2μgL(-1) for CRN-10-COOH (CRN metabolite). Statistically significant and strong correlations among the urinary metabolites of each MTp were found. Moreover, statistical associations between LMN metabolites and the LMN indoor air levels were revealed. However, the weakness of the associations indicates a considerable impact of other MTp sources, e.g. diet and consumer products, on the internal exposure.
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