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      Measurement and Comparison of Organic Compound Concentrations in Plasma, Whole Blood, and Dried Blood Spot Samples

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          Abstract

          The preferred sampling medium for measuring human exposures of persistent organic compounds (POPs) is blood, and relevant sample types include whole blood, plasma, and dried blood spots (DBS). Because information regarding the performance and comparability of measurements across these sample types is limited, it is difficult to compare across studies. This study evaluates the performance of POP measurements in plasma, whole blood and DBS, and presents the distribution coefficients needed to convert concentrations among the three sample types. Blood samples were collected from adult volunteers, along with demographic and smoking information, and analyzed by GC/MS for organochlorine pesticides (OCPs), chlorinated hydrocarbons (CHCs), polychlorinated biphenyls (PCBs), and brominated diphenyl ethers (PBDEs). Regression models were used to evaluate the relationships between the sample types and possible effects of personal covariates. Distribution coefficients also were calculated using physically-based models. Across all compounds, concentrations in plasma were consistently the highest; concentrations in whole blood and DBS samples were comparable. Distribution coefficients for plasma to whole blood concentrations ranged from 1.74 to 2.26 for pesticides/CHCs, averaged 1.69 ± 0.06 for the PCBs, and averaged 1.65 ± 0.03 for the PBDEs. Regression models closely fit most chemicals ( R 2 > 0.80), and whole blood and DBS samples generally showed very good agreement. Distribution coefficients estimated using biologically-based models were near one and did not explain the observed distribution. Among the study population, median concentrations of several pesticides/CHCs and PBDEs exceeded levels reported in the 2007–2008 National Health and Nutrition Examination Survey, while levels of other OCPs and PBDEs were comparable or lower. Race and smoking status appeared to slightly affect plasma/blood concentration ratios for several POPs. The experimentally-determined distribution coefficients can be used to compare POP exposures across studies using different types of blood-based matrices.

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          Chlorinated hydrocarbon levels in human serum: effects of fasting and feeding.

          Twenty healthy adult humans had serum samples drawn on four occasions within a 24-hr period: after a 12 hr overnight fast, 4-5 hr after a high fat breakfast, at midafternoon, and the next morning after another 12 hr fast. Nonfasting samples had 22% to 29% higher mean concentrations (p less than 0.05) than did fasting samples for polychlorinated biphenyls (PCBs, 4.81 vs 3.74 ng/g serum wt), hexachlorobenzene (HCB, 0.163 vs 0.134 ng/g serum wt), and p,p'-dichlorodiphenyl-dichloroethylene (p,p'-DDE, 6.74 vs 5.37 ng/g serum wt) measured by electron capture gas liquid chromatography. Total serum lipids were estimated from measurements of total cholesterol, free cholesterol, triglycerides, and phospholipids and were 20% higher in nonfasting samples than in fasting samples (7.05 g/L vs 5.86 g/L). When PCBs, HCB, and p,p'-DDE concentrations were corrected by total serum lipids, results from fasting and non-fasting samples were not statistically different. Because of the differences in these chlorinated hydrocarbon concentrations observed with different sample collection regimens, meaningful comparison of analytical results requires standardizing collection procedures or correcting by total serum lipid levels.
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            German Environmental Survey 1998 (GerES III): environmental pollutants in blood of the German population.

            The German Environmental Survey was conducted for the third time in 1998 (GerES III). The probability sample of about 4800 subjects was selected to be representative for the German population with regard to region (East-/West-Germany), community size, age (18 to 69 years) and gender. Blood samples were taken from each study participant and questionnaires were used to get exposure-related information. Cadmium, lead, mercury, hexachlorobenzene (HCB), hexachlorocyclohexane (alpha-HCH, beta-HCH, gamma-HCH), 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p, p'-DDE) and polychlorinated biphenyls (PCB-138, PCB-153, PCB-180) were analysed in whole blood to document the extent, distribution, and determinants of exposure of the general population to these substances. The geometric means of Cd, Pb, and Hg in blood amounted to 0.44, 31, and 0.58 microgram/l, respectively. Smokers showed a Cadmium level of 1.1 micrograms/l and non-smokers a level of 0.28 microgram/l. The geometric mean of lead was higher in the blood of males than of females (36 micrograms/l vs. 26 micrograms/l). The concentration of mercury in blood depends on fish consumption and the number of teeth with amalgam fillings. The mean concentrations of HCB and p, p'-DDE in blood were 0.44 microgram/l and 1.6 micrograms/l, respectively. In East-Germany (the former GDR) the DDE concentration in blood was more than twice as high as in West-Germany. Geometric means for PCB were 0.42, 0.68 and 0.44 microgram/l for PCB-138, PCB-153, and PCB-180, respectively. A marked increase of HCB, DDE and PCB levels with age could be observed. alpha-HCH and gamma-HCH could be detected in 1.7% and 5.2% of the samples only. beta-HCH was quantified in 34% of the samples with a 95th percentile of 0.5 microgram/l.
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              Sources of variability in biomarker concentrations.

              Human biomonitoring has become a primary tool for chemical exposure characterization in a wide variety of contexts: population monitoring and characterization at a national level, assessment and description of cohort exposures, and individual exposure assessments in the context of epidemiological research into potential adverse health effects of chemical exposures. The accurate use of biomonitoring as an exposure characterization tool requires understanding of factors, apart from external exposure level, that influence variation in biomarker concentrations. This review provides an overview of factors that might influence inter- and intraindividual variation in biomarker concentrations apart from external exposure magnitude. These factors include characteristics of the specific chemical of interest, characteristics of the likely route(s) and frequency of exposure, and physiological characteristics of the biomonitoring matrix (typically, blood or urine). Intraindividual variation in biomarker concentrations may be markedly affected by the relationship between the elimination half-life and the intervals between exposure events, as well as by variation in characteristics of the biomonitored media such as blood lipid content or urinary flow rate. Variation across individuals may occur due to differences in time of sampling relative to exposure events, physiological differences influencing urinary flow or creatinine excretion rates or blood characteristics, and interindividual differences in metabolic rate or other factors influencing the absorption or excretion rate of a compound. Awareness of these factors can assist researchers in improving the design and interpretation of biomonitoring studies.
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                Author and article information

                Contributors
                Journal
                Front Genet
                Front Genet
                Front. Genet.
                Frontiers in Genetics
                Frontiers Media S.A.
                1664-8021
                21 April 2016
                2016
                : 7
                : 64
                Affiliations
                Department of Environmental Health Sciences, University of Michigan Ann Arbor, MI, USA
                Author notes

                Edited by: Douglas Mark Ruden, Wayne State University, USA

                Reviewed by: Paul Stemmer, Wayne State University, USA; Abdu Adem, United Arab Emirates University, UAE

                *Correspondence: Stuart A. Batterman stuartb@ 123456umich.edu

                This article was submitted to Toxicogenomics, a section of the journal Frontiers in Genetics

                Article
                10.3389/fgene.2016.00064
                4838759
                27148360
                ad5592c5-ee41-4fcd-b7ca-9df141b4a656
                Copyright © 2016 Batterman, Chernyak and Su.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 03 February 2016
                : 04 April 2016
                Page count
                Figures: 2, Tables: 3, Equations: 1, References: 26, Pages: 11, Words: 7987
                Categories
                Genetics
                Original Research

                Genetics
                persistent organic compounds,distribution coefficient,plasma,whole blood,dried blood spots

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