PCBs In Humans Research Articles

Determination of hydroxylated polychlorinated biphenyls (OH-PCBs) in human urine in a highly occupationally exposed German cohort: New prospects for urinary biomarkers of PCB exposure

The present study evaluates for the first time the determination of 20 hydroxylated polychlorinated biphenyl (OH-PCB) congeners and their glucuronide and sulfate conjugates in urine as a biomarker of exposure to PCBs in humans. Thereby, a fast, sensitive and selective online solid phase extraction (SPE) method coupled to LC–MS/MS was validated for the determination of OH-PCBs in human urine, being previously successfully developed and applied for the separation and quantitation of OH-PCBs in human plasma. The lowest limit of quantification (LLOQ) ranged from 0.01 to 0.19ngmL−1 and average extraction recoveries from 79 to 125% for all hydroxylated congeners. Within-run precision and between-run precision were between 2 and 17%. Extraction recovery tests were also performed in urine with different creatinine contents (0.52–3.92gL−1) for an estimation of matrix influences and ranged between 69 and 125%. In order to evaluate the applicability of the method, the study was conducted in three different groups, which were distinctly separated as non-exposed to known sources of PCBs (N=21), low-to-moderate PCB-exposed individuals (N=25) and highly occupationally PCB-exposed individuals (N=25), which included workers of a transformer recycling plant, their relatives and workers of surrounding companies from a German cohort. As part of the biomonitoring program HELPcB (Health Effects in High-Level Exposure to polychlorinated biphenyls), urine and blood samples were collected annually from 2010 to 2014. In this way, OH-PCB elimination profile in urine over time, correlations between OH-PCB levels in human plasma and urine, and associations with their parent compounds in plasma of the studied PCB cohort could be also assessed. Tri-chlorinated OH-PCBs were the predominant congeners in urine with concentrations up to 174ngmL−1. High chlorinated OH-PCBs (penta- through hepta-chlorinated OH-PCBs) were also frequently detected in urine samples from non-exposed and occupationally exposed individuals, although levels were in general very low or lower than LLOQ.

Genome-wide association study of plasma levels of polychlorinated biphenyls disclose an association with the CYP2B6 gene in a population-based sample

BackgroundPolychlorinated biphenyls (PCBs) are a group of man-made environmental pollutants which accumulate in humans with adverse health effects. To date, very little effort has been devoted to the study of the metabolism of PCBs on a genome-wide level. ObjectivesHere, we conducted a genome-wide association study (GWAS) to identify genomic regions involved in the metabolism of PCBs. MethodsPlasma levels of 16 PCBs ascertained in a cohort of elderly individuals from Sweden (n=1016) were measured using gas chromatography–high resolution mass spectrophotometry (GC-HRMS). DNA samples were genotyped on the Infinium Omni Express bead microarray, and imputed up to reference panels from the 1000 Genomes Project. Association testing was performed in a linear regression framework under an additive model. ResultsPlasma levels of PCB-99 demonstrated genome-wide significant association with single nucleotide polymorphisms (SNPs) mapping to chromosome 19q13.2. The SNP with the strongest association was rs8109848 (p=3.7×10−13), mapping to an intronic region of CYP2B6. Moreover, when all PCBs were conditioned on PCB-99, further signals were revealed for PCBs -74, -105 and -118, mapping to the same genomic region. The lead SNPs were rs8109848 (p=3.8×10−12) for PCB-118, rs4802104 (p=1.4×10−9) for PCB-74 and rs4803413 (p=2.5×10−9) for PCB-105, all of which map to CYP2B6. ConclusionsIn our study, we found plasma levels of four lower-chlorinated PCBs to be significantly associated with the genetic region mapping to the CYP2B6 locus. These findings show that CYP2B6 is of importance for the metabolism of PCBs in humans, and may help to identify individuals who may be susceptible to PCB toxicity.

External exposure and bioaccumulation of PCBs in humans living in a contaminated urban environment

Humans are exposed to different mixtures of PCBs depending on the route of exposure. In this study we investigated the potential contribution of inhalation to the overall human exposure to PCBs in an urban area. For this purpose, the mechanistically based, non-steady state bioaccumulation model ACC-HUMAN was applied to predict the PCB body burden in an adult living in the Midwestern United States who eats a typical North American diet and inhales air contaminated with PCBs. Dietary exposure was estimated using measured data for eighteen PCB congeners in different food groups (fish, meat and egg, dairy products). Two scenarios for inhalation exposure were evaluated: one using air concentrations measured in Chicago, and a second using air measurements in a remote area on Lake Michigan, Sleeping Bear Dunes. The model predicted that exposure via inhalation increases the accumulated mass of PCBs in the body by up to 30% for lower chlorinated congeners, while diet is by far the dominant source of exposure for those PCB congeners that accumulate most in humans.

DNA damage associated with PCBs in the whole blood cells of Inuit

Lower chlorinated PCBs can damage DNA directly or via free radical mechanisms. In order to assess the DNA-damaging potential of PCBs in humans, blood samples were collected from Inuit population from Salluit, Northern Canada. Their diet comprises blubber from sea mammals and fatty fish, which accumulate non-biodegradable PCBs at varying levels. The 103 samples thus collected were categorized into low-, medium- and high-PCB exposure groups. A comprehensive 32P-postlabeling adductomics technology, which allows measure differences in DNA adduct profiles of polar and lipophilic adducts between control and exposure groups, was applied to these samples to assess the effect of PCB on DNA damage. The adduct patterns obtained were qualitatively similar to other human tissues studied previously. A range of highly polar to lipophilic subgroups of adducts were detected. The known oxidative lesion, 8-oxodG was predominant. While some individual adducts appear to accumulate with increasing PCB levels, a definitive association could not be made. A possible confounder effect of selenium is discussed.

Evidence for neuropsychological effects of PCBs in environmental studies: Getting better all the time

AbstractThis invited response to the paper by D.V. Cicchetti, A.S. Kaufman, and S.S. Sparrow (CKS), and the responses by the investigative teams of the studies criticized by them, addresses specific errors of logic and interpretation by CKS, and integrates comments made by the study investigators. CKS provide a flawed analysis of the literature on the neuropsychological effects of PCBs identified in epidemiological studies. Arguments regarding the inadequacy of study design and data analysis are for the most part factually in error, unimportant, superceded by later testing or analysis within a study, or if true, would bias results toward the null rather than finding spurious effects. They also fail to differentiate between small effects in an individual and the societal consequences of such effects, and fail to recognize the overall consistency of effects among studies. In fact, the literature is remarkably consistent in documenting adverse consequences of developmental exposure to PCBs in humans. In addition, contrary to assertions by CKS, developmental studies in monkeys documented cognitive effects at body burdens observed in human studies. © 2004 Wiley Periodicals, Inc. Psychol Schs 41: 693–707, 2004.

An input-output balance study for PCBs in humans : Juan, C.-Y. et al. Environmental International, 2002, 28, (3), 203–214

An input-output balance study for PCBs in humans : Juan, C.-Y. et al. Environmental International, 2002, 28, (3), 203–214

The statistical merits of various methods of calculating transfer coefficients between environmental media – development of the ideal formula for data-sets with a log-normal distribution

The statistical treatment of data-sets from environmental pollutant studies in which different measurements are combined to produce averages or comparative factors (e.g., transfer coefficients (TCs), input–output balance values) are considered here, with particular reference to the analysis of data from input–output balance studies of pollutants such as PCBs in animals and humans. Many methods of statistical analysis ignore the fact that all measurements are subject to error, and generally assume that the normal distribution applies to all data-sets, which is commonly inappropriate for environmental (and particularly biological system) data. Considerably different estimations can be obtained by applying different, commonly used, statistical methods, as shown in a simulation study presented here and when applied to data from an input–output balance study of PCBs in humans. Alternative average and combined factor estimators for the treatment of data from these types of studies that give considerable advantages in terms of bias and the ease of assessment of accuracy are proposed.

Methods for the analysis of PCBs in human food, faeces and serum

A method was developed to determine trace concentrations of a range of individual PCB congeners in biological samples (serum, food and faeces) using GC-MS, to prepare a mass balance of PCBs in humans. A simple method for the analysis of PCBs in human serum, which excluded an extraction step, was first employed. Results indicated that the recoveries of 13C 12 PCB spikes were variable. A soxhlet extraction step was added and was found to be efficient and reproducible. A quality control routine and method validation results are presented. In batch tests of the methods presented it was found that the serum analysis method gave within batch mean 13C 12 spike recoveries of 98 – 120% and standard deviations between 6 and 20%. The food/faeces analysis method gave within-batch mean 13C 12 spike recoveries of 88 – 100%, and within batch standard deviations between 4 and 12%. The batch to batch mean recovery for serum analysis was 100%, with an RSD of 9% for high spikes and 10% for low spikes. For food/faeces analysis the batch to batch average recovery was 110%, with an RSD of 5% for high spikes and 9% for low spikes.

Uncertainty in estimated half-lives of PCBS in humans: impact on exposure assessment

Estimates of the half-lives of PCBs in humans derived from successive body burden measurements are reviewed and found to vary widely whether based on congener-specific or aggregate data. Variability due to differences in physiological processes among individuals and in congener properties is to be expected, but does not appear to be a complete explanation. Very short half-lives (i.e. < 1 year) are unlikely for those congeners most frequently found in human blood because the exposures required to sustain observed body burdens are too large to be easily explained. Very long half-lives (> 10 years) may be artifacts of confounding by ongoing exposures (a common effect at low body burdens) and are also suspect. The loss of significant quantities of PCBs from the blood of occupationally exposed persons with half-lives of 2–6 years is comparatively well documented (i.e. has been observed in studies with relatively large numbers of subjects and high initial body burdens). Therefore, very long half-lives must be limited to subsets of congeners or of populations if they occur at all. The impact of the use of fixed estimates of half-lives drawn from the tails of the observed range on the evaluation of regulatory standards is shown to be substantial.

Developmental Neurotoxicity of PCBs in Humans: What Do We Know and Where Do We Go From Here?

The potential neurotoxicity of PCBs was first recognized in 1968 when a number of Japanese people became ill after ingesting rice oil that was contaminated with PCBs during the manufacturing process (Yusho). Later a similar exposure occurred in Taiwan (YuCheng). Children born to Taiwanese mothers who consumed PCB-contaminated rice oil were followed and a number of developmental abnormalities, including lower body weight and height, higher activity levels, greater incidence of behavior problems, and lower IQ scores, were observed. However, interpretation of these findings is complicated by the fact that there did not appear to be any relationship between available indices of exposure and severity of effects, and by the fact that the PCBs to which the Taiwanese were exposed contained unusually high concentrations of dibenzofurans, which are many times more toxic than PCBs, and may have been responsible for some or all of the observed effects. Since the Yusho and YuCheng episodes, several studies have been initiated to study the neurobehavioral effects of exposure to the lower levels of PCBs present in the environment. The two studies published to date have yielded conflicting results. Jacobson, Jacobson, and colleagues reported that in utero PCB exposure was associated with decreased birth weight and head circumference, shorter gestation, and several adverse outcomes on the Brazelton Neonatal Assessment Battery. Later they reported that the body weight deficits associated with prenatal PCB exposure were still present at 5 months and 4 years of age. Deficits in memory function were observed at 7 months and 4 years. Rogan, Gladen, and colleagues did not find any evidence of decreased birth weight or head circumference. Nor did they find any evidence of deficits in memory function. However, they did observe some similar effects on the Brazelton Neonatal Assessment Battery. They also observed a small delay in psychomotor development in the most highly PCB-exposed children, but the effect did not persist beyond 2 years of age. A number of methodological concerns have been raised about the Jacobson study, including issues related to exposure assessment, sample selection, and control of potential confounding variables. However, it is not clear that these shortcomings can explain the discrepancies between their findings and those of Rogan and Gladen. Other possible explanations include differences in exposure levels or PCB congener patterns between the two cohorts, differences in sociodemographic variables between the two cohorts, or other problems inherent in trying to detect subtle neuropsychological deficits at exposure levels that are near the threshold for effects. Hopefully, several new studies that are currently underway will help to resolve the uncertainties regarding the risks of perinatal PCB exposure that have been created by the conflicting results of these early studies.

Different congeners of PCBs/PCDFs may have contributed to different health outcomes in the Yucheng cohort

SCHANTZ discussed at length the Yucheng cohort in her review article on developmental neurotoxicity of PCBs in humans in this issue (2) and raised the question concerning the dose-response relationship between serum levels of PCBs and neuropsychological outcomes. Although the Yucheng children have been consistently shown to have mild deficits on both cognitive and behavioral assessments, relationship between available indices of exposure (e.g., child’s serum PCB level, maternal serum PCB level, severity of physical symptomatology) and the neuropsychological outcomes appeared to be lacking. This lack of relationship is likely due to the fact that we did not have the information on the most relevant congeners that produced the health effects studied.

Comments on “Developmental neurotoxicity of PCBs in humans: What do we know and where do we go from here?”

Comments on “Developmental neurotoxicity of PCBs in humans: What do we know and where do we go from here?”

Epidemiologic perspective of the developmental neurotoxicity of PCBs in humans

Epidemiologic perspective of the developmental neurotoxicity of PCBs in humans

Critical issues for research on the neurobehavioral effects of PCBs in humans

Critical issues for research on the neurobehavioral effects of PCBs in humans

Changes in PCB serum concentrations among capacitor manufacturing workers

To assess the elimination of PCBs in humans, PCB concentrations in serum from 165 capacitor manufacturing workers were measured twice within a 46-month interval (March 1976-December 1979). Use of PCBs at the facility was entirely eliminated in 1977. PCB congeners with lower chlorination (LPCBs--mainly tri- and tetrachlorobiphenyls) had decreased in concentration, with six of the LPCB 7 peaks observed by packed column GC showing average reductions of 25-90%. Higher chlorinated PCBs did not decrease significantly as a whole, although three of the six constituent congener peaks showed some decline (15-25%). As expected, decreases in PCB congener concentrations were associated with chlorine substitution configurations known to be amenable to metabolism.

Use and Replaceability of Polychlorinated Biphenyls

Research ArticleOpen AccessUse and replaceability of polychlorinated biphenyls. M G Broadhurst M G Broadhurst Search for more papers by this author Published:1 October 1972https://doi.org/10.1289/ehp.720281Cited by:21AboutSectionsPDF ToolsDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InReddit FiguresReferencesRelatedDetailsCited By Brown K, Minegishi T, Cummiskey C, Fragala M, Hartman R and MacIntosh D (2015) PCB remediation in schools: a review, Environmental Science and Pollution Research, 10.1007/s11356-015-4689-y, 23:3, (1986-1997), Online publication date: 1-Feb-2016. Huang J, Hui Y, Matsumura T, Yu G, Deng S, Yamauchi M, Wu C and Yamazaki N (2013) Detailed analysis of PCBs and PCDD/Fs impurities in a dielectric oil sample (ASKAREL Nr 1740) from an imported transformer in China, Frontiers of Environmental Science & Engineering, 10.1007/s11783-013-0527-y, 8:2, (195-204), Online publication date: 1-Apr-2014. 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