Review

Authors: Yinfeng Wang, Changchang Hu, Tao Fang...

The developmental origins of health and disease concept illustrates that exposure in early life to various factors may affect the offspring's long‑term susceptibility to disease. During development, the nervous system is sensitive and vulnerable to the environmental insults. Polychlorinated biphenyls (PCBs), which are divided into dioxin‑like (DL‑PCBs) and non‑dioxin‑like PCBs (NDL‑PCBs), are synthetic persistent environmental endocrine‑disrupting chemicals. The toxicological mechanisms of DL‑PCBs have been associated with the activation of the aryl hydrocarbon receptor and NDL‑PCBs have been associated with ryanodine receptor‑mediated calcium ion channels, which affect neuronal migration, promote dendritic growth and alter neuronal connectivity. In addition, PCB accumulation in the placenta destroys the fetal placental unit and affects endocrine function, particularly thyroid hormones and the dopaminergic system, leading to neuroendocrine disorders. However, epidemiological investigations have not achieved a consistent result in different study cohorts. The present review summarizes the epidemiological differences and possible mechanisms of the effects of intrauterine PCB exposure on neurological development.

Topics: Environmental Exposure; Environmental Pollutants; Female; Humans; Infant, Newborn; Nervous System; Nervous System Malformations; Polychlorinated Biphenyls; Pregnancy; Prenatal Exposure Delayed Effects

PubMed: 34132363
DOI: 10.3892/ijmm.2021.4983

Review

Authors: David Werner, Sarah E Hale, Upal Ghosh...

Traditional and new relationships of polychlorinated biphenyl (PCB) distribution among the solid phases, the free aqueous phase, and biolipids are comprehensively reviewed using seven well-characterized freshwater and marine sediments polluted with PCBs. The traditional relationship relating free aqueous concentration and biolipid concentration to sediment total organic carbon, compound octanol-water partitioning coefficient, and solid-phase contaminant concentration overestimates measured free aqueous concentrations and biolipid concentrations by mean factors of 8 and 33, respectively. By contrast, relationships based on measured free aqueous phase concentrations or the PCB mass fraction desorbed from sediment provide reasonable predictions of biolipid concentrations. Solid-phase concentration-based predictions perform better when sorption to amorphous organic matter and black carbon (BC) is distinguished. Contrary to previously published relationships, BC sorption appears to be linear for free aqueous PCB-congener concentrations in the picogram to microgram per liter range.

Topics: Geologic Sediments; Polychlorinated Biphenyls; Water Pollutants, Chemical

PubMed: 19961220
DOI: 10.1021/es902325t

Review

Authors: Chelsea A Weitekamp, Rachel M Shaffer, Catheryne Chiang...

From the 1950s to the 1970s, three Superfund sites discharged polychlorinated biphenyl (PCB)-contaminated waste upstream of the Mohawk Nation at Akwesasne, resulting in PCB contamination of groundwater, soil, and sediment in the surrounding area. Given the persistence of PCBs in the environment and in human tissues, there are continued concerns regarding PCB exposures and the potential for adverse health effects in the community. We developed an evidence map of PCB research at Akwesasne in order to characterize the available data and to highlight potential research needs. Human health and exposure biomarker studies were identified from a literature search based on population, exposure, comparator, and outcome (PECO) criteria. Data extracted from references that met the inclusion criteria after full-text review included study characteristics (e.g., sample size, study design, sampling years), details on PCB measurements (e.g., analytical method, number of congeners analyzed, method detection limits), and results (e.g., PCB levels and summary of study conclusions). We identified 33 studies, conducted between 1986 and 2013, that examined PCB exposure characteristics and health effects in residents of the Akwesasne Mohawk Nation. Organizing this literature into an evidence map including information on study cohort, congener groupings, exposure biomarker characteristics, and health effects allowed us to identify research gaps and to suggest future research priorities for the community. We identified current PCB exposure levels and PCB source characterization as major uncertainties, both of which could be addressed by new studies of PCB concentrations in environmental media.

Topics: Cohort Studies; Environmental Exposure; Humans; Indians, North American; Outcome Assessment, Health Care; Polychlorinated Biphenyls

PubMed: 35764106
DOI: 10.1016/j.chemosphere.2022.135454

Review

Authors: Laura M Carlson, Krista Christensen, Sharon K Sagiv...

Assessing health outcomes associated with exposure to polychlorinated biphenyls (PCBs) is important given their persistent and ubiquitous nature. PCBs are classified as a Group 1 carcinogen, but the full range of potential noncancer health effects from exposure to PCBs has not been systematically summarized and evaluated. We used systematic review methods to identify and screen the literature using combined manual review and machine learning approaches. A protocol was developed that describes the literature search strategy and Populations, Exposures, Comparators, and Outcomes (PECO) criteria used to facilitate subsequent screening and categorization of literature into a systematic evidence map of PCB exposure and noncancer health endpoints across 15 organs/systems. A comprehensive literature search yielded 62,599 records. After electronic prioritization steps, 17,037 studies were manually screened at the title and abstract level. An additional 900 studies identified by experts or supplemental searches were also included. After full-text screening of 3889 references, 1586 studies met the PECO criteria. Relevant study details such as the endpoints assessed, exposure duration, and species were extracted into literature summary tables. This review compiles and organizes the human and mammalian studies from these tables into an evidence map for noncancer health endpoints and PCB mixture exposure to identify areas of robust research as well as areas of uncertainty that would benefit from future investigation. Summary data are available online as interactive visuals with downloadable metadata. Sufficient research is available to inform PCB hazard assessments for most organs/systems, but the amount of data to inform associations with specific endpoints differs. Furthermore, despite many years of research, sparse data exist for inhalation and dermal exposures, which are highly relevant human exposure routes. This evidence map provides a foundation for future systematic reviews and noncancer hazard assessments of PCB mixtures and for strategic planning of research to inform areas of greater uncertainty.

Topics: Animals; Humans; Carcinogens; Mammals; Polychlorinated Biphenyls; Uncertainty

PubMed: 36580985
DOI: 10.1016/j.envres.2022.115148

Authors: Lawrence S Redmond, John A Kaufman, Metrecia L Terrell...

In 1973-74, a polybrominated biphenyl (PBB) flame retardant mixture was shipped to Michigan livestock feed mills in place of a nutritional supplement and contaminated the food supply. Following the accident, the Michigan PBB Registry was established to study the long-term health effects of halogenated compounds and is now led by a community-academic partnership. PBB exposure is associated with altered DNA methylation in sperm, which may lead to adverse birth outcomes in children whose fathers have increased levels of serum PBB or polychlorinated biphenyl (PCB). Paternal PBB and PCB levels of men enrolled in the Michigan PBB Registry (n = 155) were analyzed against matched offspring birthweight and gestational age (n = 336). Birthweight and gestational age were dichotomized at the 25th percentile and 37 weeks, respectively, and paternal PBB and PCB levels were examined as continuous measures and divided into tertiles. Associations of offspring birthweight and gestational age with paternal PBB and PCB serum concentrations were modeled using multivariable linear spline and log-risk regression, adjusting for family clustering, paternal health and lifestyle factors, maternal PBB, and PCB serum concentrations, sex, and offspring gestational age (for birthweight). Fathers in the middle and upper PBB and PCB tertiles had increased risks for lowest quartile birthweight compared to the first tertile, with adjusted risk ratios (aRR) = 1.67 (95% CI: 0.93, 2.99) and aRR = 2.06 (95% CI: 1.12, 3.79) for PBB, and aRR = 1.47 (95% CI: 0.79, 2.75) and aRR = 1.34 (95% CI: 0.70, 2.54) for PCB, respectively. Elevated paternal PBB levels were not associated with an increased risk for preterm birth, while PCB levels were associated with a small, but not significant, decrease in gestational age, β = -0.37 (95% CI: -0.76, 0.03) weeks per log unit increase PCB. The findings suggest that increased paternal PBB and PCB levels negatively impact offspring birthweight, and paternal PCB levels may negatively impact gestational age.

Topics: Birth Weight; Child; Environmental Pollutants; Fathers; Female; Humans; Infant; Infant, Newborn; Male; Polybrominated Biphenyls; Polychlorinated Biphenyls; Premature Birth; Semen

PubMed: 36041536
DOI: 10.1016/j.envres.2022.114215

Authors: Gary S Pittman, Xuting Wang, Michelle R Campbell...

Anniston, Alabama was home to a major polychlorinated biphenyl (PCB) production facility from 1929 until 1971. The Anniston Community Health Survey I and II (ACHS-I 2005-2007, ACHS-II 2013-2014) were conducted to explore the effects of PCB exposures. In this report we examined associations between PCB exposure and DNA methylation in whole blood using EPIC arrays (ACHS-I, n = 518; ACHS-II, n = 299). For both cohorts, 35 PCBs were measured in serum. We modelled methylation versus PCB wet-weight concentrations for: the sum of 35 PCBs, mono-ortho substituted PCBs, di-ortho substituted PCBs, tri/tetra-ortho substituted PCBs, oestrogenic PCBs, and antiestrogenic PCBs. Using robust multivariable linear regression, we adjusted for age, race, sex, smoking, total lipids, and six blood cell-type percentages. We carried out a two-stage analysis; discovery in ACHS-I followed by replication in ACHS-II. In ACHS-I, we identified 28 associations (17 unique CpGs) at p ≤ 6.70E-08 and 369 associations (286 unique CpGs) at FDR p ≤ 5.00E-02. A large proportion of the genes have been observed to interact with PCBs or dioxins in model studies. Among the 28 genome-wide significant CpG/PCB associations, 14 displayed replicated directional effects in ACHS-II; however, only one in ACHS-II was statistically significant at p ≤ 1.70E-04. While we identified many novel CpGs significantly associated with PCB exposures in ACHS-I, the differential methylation was modest and the effect was attenuated seven years later in ACHS-II, suggesting a lack of persistence of the associations between PCB exposures and altered DNA methylation in blood cells.

Topics: Adult; Alabama; CpG Islands; DNA Methylation; Environmental Exposure; Environmental Pollutants; Female; Health Surveys; Humans; Male; Middle Aged; Occupational Exposure; Polychlorinated Biphenyls

PubMed: 31607210
DOI: 10.1080/15592294.2019.1666654

Authors: June T Spector, Anneclaire J De Roos, Cornelia M Ulrich...

BACKGROUND

Polychlorinated biphenyl (PCB) exposure has been associated with non-Hodgkin lymphoma in several studies, and the immune system is a potential mediator.

OBJECTIVES

We analyzed associations of plasma PCBs with immune function measures. We hypothesized that higher plasma PCB concentrations are associated with lower immune function cross-sectionally, and that increases in PCB concentrations over a one year period are associated with decreases in immune function.

METHODS

Plasma PCB concentrations and immune function [natural killer (NK) cell cytotoxicity and PHA-induced T-lymphocyte proliferation (PHA-TLP)] were measured at baseline and one year in 109 postmenopausal overweight women participating in an exercise intervention study in the Seattle, Washington (USA) area. Mixed models, with adjustment for body mass index and other potential confounders, were used to estimate associations of PCBs with immune function cross-sectionally and longitudinally.

RESULTS

Associations of PCBs with immune function measures differed across groups of PCBs (e.g., medium- and high-chlorinated and dioxin-like [mono-ortho-substituted]) and by the time frame for the comparison (cross-sectional vs. longitudinal). Higher concentrations of medium- and high-chlorinated PCBs were associated with higher PHA-TLP cross-sectionally but not longitudinally. The mean decrease in 0.5 µg/mL PHA-TLP/50.0 pmol/g-lipid increase in dioxin-like PCBs over one year was 51.6 (95% confidence interval 2.7, 100.5; P=0.039). There was no association between plasma PCBs and NK cytotoxicity.

CONCLUSIONS

These results do not provide strong evidence of impaired cellular immunity from PCB exposure. Larger longitudinal studies with greater variability in PCB exposures are needed to further examine temporal associations of PCBs with immune function.

Topics: Aged; Cross-Sectional Studies; Environmental Exposure; Female; Humans; Killer Cells, Natural; Longitudinal Studies; Middle Aged; Polychlorinated Biphenyls; Postmenopause; T-Lymphocytes

PubMed: 24721136
DOI: 10.1016/j.envres.2014.03.011

Authors: A L Hinwood, A C Callan, J Heyworth...

Polychlorinated biphenyls (PCBs) and dioxins are well known for their persistence in the environment. PCBs can be found in the residential environment long after the use of these chemicals in domestic products and industrial processes has ceased. Dioxins have been assessed in Australia as being of very low concentrations. Despite concerns about residential dust as a source of human exposure to persistent chemicals, there has been limited testing of PCBs and dioxins in dust in Australia. As part of an assessment of maternal exposure to a variety of persistent toxic substances, we analysed 30 residential dust samples from a variety of geographical settings for their dioxin and PCB concentrations. PCBs were found in most samples, the median and range concentrations (pg g(-1)) of dominant congeners of PCB were as follows: PCB118 (315; <35.0-29 000), PCB105 (130; 14.0-16 000) and PCB156 (440; <5.00-2800). Dioxin concentrations were generally low with median concentrations for the total sum of dioxin-like polychlorinated dibenzodioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) of 3.75 pg g(-1) each. There was a very high percentage of non-detects. Concentrations of both PCBs and dioxins were low compared with most studies reporting residential dust concentrations internationally. Age of dwelling was the only factor observed to influence both PCB congener concentrations and dioxin isomers in multivariate regression analyses. No other housing or sociodemographic variables, including proximity to industry, were important predictors in multivariate linear regression models.

Topics: Air Pollution, Indoor; Australia; Dioxins; Dust; Female; Humans; Maternal Exposure; Polychlorinated Biphenyls; Pregnancy

PubMed: 25343442
DOI: 10.1039/c4em00383g

Authors: Duo Zhang, Panithi Saktrakulkla, Kristopher Tuttle...

Polychlorinated biphenyls (PCBs) are persistent toxic chemicals with both legacy sources (e.g., Aroclors) and new sources (e.g., unintentional contaminants in some pigments and varnishes). PCB sulfates are derived from further metabolism of hydroxylated PCBs (OH-PCBs), which are oxidative metabolites of PCBs. While OH-PCBs and PCB sulfates are implicated in multiple toxicological effects, studies of PCB sulfates in human serum have been limited by available analytical procedures. We have now developed a method for extraction of PCB sulfates from serum followed by differential analysis with, and without, sulfatase-catalyzed hydrolysis to OH-PCBs. A sulfatase from was purified by affinity chromatography, and it displayed broad specificity for PCB sulfates without contaminant glucuronidase activity. Following sulfatase-catalyzed hydrolysis of the PCB sulfates extracted from serum, the corresponding OH-PCBs were derivatized to methoxy-PCBs and quantitated by GC-MS/MS. In a pooled sample of human serum, we identified 10 PCB sulfates, with three PCB sulfate congeners exhibiting the highest concentrations from 1200 to 3970 pg/g of serum. In conclusion, we have developed a sensitive and specific method for the determination of PCB sulfates in human serum.

Topics: Aroclors; Humans; Hydroxylation; Polychlorinated Biphenyls; Sulfates; Tandem Mass Spectrometry

PubMed: 33502843
DOI: 10.1021/acs.est.0c06983

Review

Authors: A Schecter, J Stanley, K Boggess...

Polychlorinated biphenyls (PCBs) are synthetic chemicals, manufactured in volume from about 1929 to the 1970s. Environmental contamination by PCBs has been documented in various substances, including human tissue. PCBs have been measured in human tissue by a variety of analytical methods. PCB levels have been reported as an approximation of total PCB content expressed in terms of a commercial mixture, by identification and quantification of chromatographic peaks, or by qualitative and quantitative characterization of specific congeners. Until recently, the coplanar mono-ortho- and di-ortho substituted PCBs, which are especially toxic and present in significant concentration in humans from industrial countries, had not been measured in human tissues. Examples of various types of commonly used analyses are presented in general population subjects and in persons who experienced special exposure. In this paper, the usefulness of PCB blood determinations following potential exposure is demonstrated, and their application in health studies is illustrated from a number of case studies. Coplanar PCB, mono-ortho-substituted and di-ortho-substituted PCB levels in human blood are presented and compared with polychlorinated dioxin (PCDD) and polychlorinated dibenzofuran (PCDF) levels in the U.S. population. Dioxin toxic equivalents for the two groups of chemicals are calculated and compared. It is found that mono-ortho-substituted and, to a lesser extent, coplanar PCBs, contribute substantially to dioxin toxic equivalents (TEq) in blood from U.S. adults. Because of substantial PCB contribution to dioxin toxic equivalents, total dioxinlike toxicity can only be determined if dioxins, dibenzofurans, and dioxinlike PCBs are measured.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: 2,4,5-Trichlorophenoxyacetic Acid; 2,4-Dichlorophenoxyacetic Acid; Adipose Tissue; Agent Orange; Defoliants, Chemical; Environmental Exposure; Food Contamination; Humans; Liver; Milk, Human; Occupational Exposure; Oryza; Plant Oils; Polychlorinated Biphenyls; Polychlorinated Dibenzodioxins

PubMed: 8187704
DOI: 10.1289/ehp.94102s1149