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Epidemiology (Cambridge, Mass.) Jul 2021Polychlorinated biphenyls (PCBs), a diverse class of chemicals, are hypothesized mammary carcinogens. We examined plasma levels of 17 PCBs as individual congeners and as...
BACKGROUND
Polychlorinated biphenyls (PCBs), a diverse class of chemicals, are hypothesized mammary carcinogens. We examined plasma levels of 17 PCBs as individual congeners and as a mixture in association with breast cancer using a novel approach based on quantile g-computation.
METHODS
This study included 845 White and 562 Black women who participated in the population-based, case-control Carolina Breast Cancer Study Phase I. Cases (n = 748) were women with a first diagnosis of histologically confirmed, invasive breast cancer residing in 24 counties in central and eastern North Carolina; controls (n = 659) were women without breast cancer from the same counties. PCBs were measured in plasma samples obtained during the study interview. We estimated associations [covariate-adjusted odds ratios (ORs) and 95% confidence intervals (CIs)] between individual PCB congeners and breast cancer using multivariable logistic regression. We assessed PCB mixtures using quantile g-computation and examined effect measure modification by race.
RESULTS
Comparing highest and lowest tertiles of PCBs resulted in ORs of 1.3 (95% CI = 0.95, 1.8) for congener 74, 1.4 (95% CI = 1.0, 1.9) for 99, 1.3 (95% CI = 0.91, 1.8) for 194, and 1.2 (95% CI = 0.90, 1.7) for 201. Among all women, we estimated a joint effect of the PCB mixture with an OR of 1.3 (95% CI = 0.98, 1.6) per tertile change. In race-stratified analyses, associations for tertiles of PCB mixtures were stronger among Black women (OR = 1.5; 95% CI = 1.0, 2.3) than among White women (OR = 1.1; 95% CI = 0.81, 1.6).
CONCLUSION
Our results are consistent with the hypothesis that exposure to PCB mixtures increase the risk of breast cancer, but studies of populations with different exposure profiles are needed.
Topics: Black or African American; Breast Neoplasms; Case-Control Studies; Environmental Pollutants; Female; Humans; North Carolina; Polychlorinated Biphenyls
PubMed: 33788793
DOI: 10.1097/EDE.0000000000001356 -
Environmental Science & Technology Jul 2022Exposure to polychlorinated biphenyls (PCBs) and their hydroxylated metabolites (OH-PCBs) has been implicated in neurodevelopmental disorders. However, the distribution...
Exposure to polychlorinated biphenyls (PCBs) and their hydroxylated metabolites (OH-PCBs) has been implicated in neurodevelopmental disorders. However, the distribution of PCBs and OH-PCBs in the human brain has not been characterized. This study investigated the age-, sex-, and brain region-specific distribution of all 209 PCBs using gaschromatography-tandem mass spectrometry (GC-MS/MS) in neonatal ( = 7) and adult ( = 7) postmortem brain samples. OH-PCB analyses were performed by GC-MS/MS (as methylated derivatives) and, in a subset of samples, by nontarget liquid chromatography high-resolution mass spectrometry (Nt-LCMS). Fourteen higher chlorinated PCB congeners were observed with a detection frequency >50%. Six lower chlorinated PCBs were detected with a detection frequency >10%. Higher chlorinated PCBs were observed with higher levels in samples from adult versus younger donors. PCB congener profiles from adult donors showed more similarities across brain regions and donors than younger donors. We also assess the potential neurotoxicity of the PCB residues in the human brain with neurotoxic equivalency (NEQ) approaches. The median ΣNEQs, calculated for the PCB homologues, were 40-fold higher in older versus younger donors. Importantly, lower chlorinated PCBs made considerable contributions to the neurotoxic potential of PCB residues in some donors. OH-PCBs were identified for the first time in a small number of human brain samples by GC-MS/MS and Nt-LCMS analyses, and all contained four or fewer chlorine.
Topics: Adult; Aged; Brain; Gas Chromatography-Mass Spectrometry; Humans; Hydroxylation; Infant, Newborn; Polychlorinated Biphenyls; Tandem Mass Spectrometry
PubMed: 35658127
DOI: 10.1021/acs.est.2c00581 -
PloS One 2022Iron and steel industries are the major contributors to persistent organic pollutants (POPs). The microbial community present at such sites has the potential to...
Metagenomic analysis for taxonomic and functional potential of Polyaromatic hydrocarbons (PAHs) and Polychlorinated biphenyl (PCB) degrading bacterial communities in steel industrial soil.
Iron and steel industries are the major contributors to persistent organic pollutants (POPs). The microbial community present at such sites has the potential to remediate these contaminants. The present study highlights the metabolic potential of the resident bacterial community of PAHs and PCB contaminated soil nearby Bhilai steel plant, Chhattisgarh (India). The GC-MS/MS analysis of soil samples MGB-2 (sludge) and MGB-3 (dry soil) resulted in identification of different classes of POPs including PAHs {benzo[a]anthracene (nd; 17.69%), fluorene (15.89%, nd), pyrene (nd; 18.7%), benzo(b)fluoranthene (3.03%, nd), benzo(k)fluoranthene (11.29%; nd), perylene (5.23%; nd)} and PCBs (PCB-15, PCB-95, and PCB-136). Whole-genome metagenomic analysis by Oxford Nanopore GridION Technology revealed predominance of domain bacteria (97.4%; 97.5%) followed by eukaryote (1.4%; 1.5%), archaea (1.2%; 0.9%) and virus (0.02%; 0.04%) in MGB-2 and MGB-3 respectively. Proteobacteria (44.3%; 50.0%) to be the prominent phylum followed by Actinobacteria (22.1%; 19.5%) in MBG-2 and MBG-3, respectively. However, Eukaryota microbial communities showed a predominance of phylum Ascomycota (20.5%; 23.6%), Streptophyta (18.5%, 17.0%) and unclassified (derived from Eukaryota) (12.1%; 12.2%) in MGB-2 and MGB-3. The sample MGB-3 was richer in macronutrients (C, N, P), supporting high microbial diversity than MGB-2. The presence of reads for biphenyl degradation, dioxin degradation, PAH degradation pathways can be further correlated with the presence of PCB and PAH as detected in the MGB-2 and MGB-3 samples. Further, taxonomic vis-à-vis functional analysis identified Burkholderia, Bradyrhizobium, Mycobacterium, and Rhodopseudomonas as the keystone degrader of PAH and PCB. Overall, our results revealed the importance of metagenomic and physicochemical analysis of the contaminated site, which improves the understanding of metabolic potential and adaptation of bacteria growing under POP contaminated environments.
Topics: Bacteria; Polychlorinated Biphenyls; Soil; Soil Pollutants; Steel; Tandem Mass Spectrometry
PubMed: 35486615
DOI: 10.1371/journal.pone.0266808 -
Annals of Human Biology Feb 2023Humans are now exposed to a multitude of chemicals throughout the life course, some of which may affect growth and development owing to their endocrine-like activity. (Review)
Review
Age at menarche and chemical exposure: per- and polyfluoroalkyl substances (PFAS), dichloro-diphenyl-trichloroethane (DDT), dichloro-diphenyl-dichloroethylene (DDE), and polychlorinated biphenyls (PCBs).
CONTEXT
Humans are now exposed to a multitude of chemicals throughout the life course, some of which may affect growth and development owing to their endocrine-like activity.
OBJECTIVE
To assess the relationship of suspect toxicants to maturation, specifically to age at menarche.
METHODS
We conducted two systematic reviews of age at menarche and PFOA, PFOS, PCBs and DDE/DDT based on publications indexed by pubmed.
RESULTS
16 unique reports were identified. Most studies of PFOA and PFOS reported either no association or delays in the age at menarche; only one reported an earlier age. Studies of DDT and DDE were more mixed. Reports on PCBs varied by PCB congener group with an equal number of them reporting delays and no association but one an acceleration. Sources of variation in results include the timing of exposure assessment (prenatal vs. postnatal), level of the toxicant, and sample size. No obvious pattern to the variation in results could be tied to those sources of variation.
CONCLUSION
The absence of consistent evidence from multiple reports of earlier age at menarche suggests that these toxicants may not be responsible for accelerated sexual maturation in girls. However, human populations naturally vary in the variety and levels of exposure, making the comparison of studies difficult. Further, studies vary in methodology, complicating aggregation of results and generalisations.
Topics: Female; Pregnancy; Humans; Polychlorinated Biphenyls; DDT; Dichloroethylenes; Trichloroethanes; Menarche; Dichlorodiphenyl Dichloroethylene; Fluorocarbons; Environmental Pollutants
PubMed: 37357949
DOI: 10.1080/03014460.2023.2221039 -
Environmental Health Perspectives Mar 2021Polychlorinated biphenyls (PCBs) are signaling disrupting chemicals that exacerbate nonalcoholic steatohepatitis (NASH) in mice. They are epidermal growth factor...
BACKGROUND
Polychlorinated biphenyls (PCBs) are signaling disrupting chemicals that exacerbate nonalcoholic steatohepatitis (NASH) in mice. They are epidermal growth factor receptor (EGFR) inhibitors that enhance hepatic inflammation and fibrosis in mice.
OBJECTIVES
This study tested the hypothesis that epidermal growth factor (EGF) administration can attenuate PCB-related NASH by increasing hepatic EGFR signaling in a mouse model.
METHODS
C57BL/6 male mice were fed a 42% milk fat diet and exposed to Aroclor 1260 () or vehicle for 12 wk. EGF () or vehicle were administered daily for 10 d starting at study week 10. Liver and metabolic phenotyping were performed. The EGF dose was selected based on results of an acute dose-finding study (30 min treatment of EGF at 0.2, 0.02, of via intraperitoneal injection). Hepatic phosphoproteomic analysis was performed using liver tissue from this acute study to understand EGFR's role in liver physiology.
RESULTS
Markers of EGFR signaling were higher in EGF-treated mice. -exposed mice had lower hepatic free fatty acids, inflammation, and fibrosis relative to PCB-only exposed mice. EGF-treated mice had higher plasma lipids, with no improvement in hepatic steatosis, and an association with higher LXR target gene expression and lipogenesis. EGF-treated mice showed more severe hyperglycemia associated with lower adiponectin levels and insulin sensitivity. EGF-treated mice had higher hepatic , NRF2, and AhR target gene expression but lower constitutive androstane receptor and farnesoid X receptor target gene expression. The hepatic EGF-sensitive phosphoproteome demonstrated a role for EGFR signaling in liver homeostasis.
DISCUSSION
These results validated EGFR inhibition as a causal mode of action for PCB-related hepatic inflammation and fibrosis in a mouse model of NASH. However, observed adverse effects may limit the clinical translation of EGF therapy. More data are required to better understand EGFR's underinvestigated roles in liver and environmental health. https://doi.org/10.1289/EHP8222.
Topics: Animals; Epidermal Growth Factor; Liver; Male; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Polychlorinated Biphenyls
PubMed: 33788613
DOI: 10.1289/EHP8222 -
Environment International Jun 2020Polychlorinated biphenyls (PCBs) are infamous industry by-products or additives, and increasing evidences demonstrated that their exposure is associate with adverse...
Polychlorinated biphenyls (PCBs) are infamous industry by-products or additives, and increasing evidences demonstrated that their exposure is associate with adverse effects on human health. Liver, as the dominate site for xenobiotic metabolism, is apt to be the primary target of PCBs insult. Although PCBs' hepatic toxic effects have been extensively studied, however, the biotransformation of PCBs in liver and the toxicities of associated PCB metabolites are neglected at some extent. Thus, we choose 2,3,5-trichloro-6-phenyl-[1,4]-benzoquinone (PCB29-pQ), a surrogate PCB29 metabolite, and evaluated its contribution on hepatotoxicity. In the current study, we discovered PCB29-pQ-induced lipid peroxidation and iron overload both in vivo and in vitro. Further mechanistic research confirmed iron overload is caused by reactive oxygen species (ROS)-driven hepcidin disorder in hepatic cells, and the increase of hepcidin is regulated by the translocation of nuclear factor erythroid 2-related factor 2 (Nrf2).
Topics: Benzoquinones; Hepatocytes; Hepcidins; Humans; Iron Overload; Polychlorinated Biphenyls; Quinones
PubMed: 32278200
DOI: 10.1016/j.envint.2020.105701 -
Dioxin-like compound exposures and DNA methylation in the Anniston Community Health Survey Phase II.The Science of the Total Environment Nov 2020The Anniston Community Health Survey (ACHS-I) was initially conducted from 2005 to 2007 to assess polychlorinated biphenyl (PCB) exposures in Anniston, Alabama...
The Anniston Community Health Survey (ACHS-I) was initially conducted from 2005 to 2007 to assess polychlorinated biphenyl (PCB) exposures in Anniston, Alabama residents. In 2014, a follow-up study (ACHS-II) was conducted to measure the same PCBs as in ACHS-I and additional compounds e.g., polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and dioxin-like non-ortho (cPCBs) substituted PCBs. In this epigenome-wide association study (EWAS), we examined the associations between PCDD, PCDF, and PCB exposures and DNA methylation. Whole blood DNA methylation was measured using Illumina EPIC arrays (n=292). We modeled lipid-adjusted toxic equivalencies (TEQs) for: ΣDioxins (sum of 28 PCDDs, PCDFs, cPCBs, and mPCBs), PCDDs, PCDFs, cPCBs, and mPCBs using robust multivariable linear regression adjusting for age, race, sex, smoking, bisulfite conversion batch, and estimated percentages of six blood cell types. Among all exposures we identified 10 genome-wide (Bonferroni p≤6.74E-08) and 116 FDR (p≤5.00E-02) significant associations representing 10 and 113 unique CpGs, respectively. Of the 10 genome-wide associations, seven (70%) occurred in the PCDDs and four (40%) of these associations had an absolute differential methylation ≥1.00%, based on the methylation difference between the highest and lowest exposure quartiles. Most of the associations (six, 60%) represented hypomethylation changes. Of the 10 unique CpGs, eight (80%) were in genes shown to be associated with dioxins and/or PCBs based on data from the 2019 Comparative Toxicogenomics Database. In this study, we have identified a set of CpGs in blood DNA that may be particularly susceptible to dioxin, furan, and dioxin-like PCB exposures.
Topics: Alabama; Benzofurans; DNA Methylation; Dibenzofurans, Polychlorinated; Dioxins; Follow-Up Studies; Polychlorinated Biphenyls; Public Health; Surveys and Questionnaires
PubMed: 32629249
DOI: 10.1016/j.scitotenv.2020.140424 -
Chemosphere Aug 2017It has been previously been shown by our lab and others that persistent organic pollutants, such as polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers...
It has been previously been shown by our lab and others that persistent organic pollutants, such as polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs), are contaminants in milk produced for human consumption. To further this research we determined the concentration of 21 PCB and 14 PBDE congeners in livestock serum, mainly bovine, across California. Congeners were extracted from serum using solid phase extraction (SPE), cleaned up by silica cartridge and quantified using gas chromatography-triple quadruple mass spectrometry. We detected significant differences among species and the production class of cattle (beef or dairy). The sum of all 21 PCB congeners (ΣPCBs) in caprine and ovine sera had a mean value of 9.26 and 9.13 ng/mL, respectively, compared to 3.98 ng/mL in bovine sera. The mean value for the sum of all 14 PBDE congeners (ΣPBDEs) in caprine and ovine sera was 2.82 and 2.39 ng/mL, respectively, compared to 0.91 ng/mL in bovine sera. Mean ΣPCBs in dairy cattle was 5.92 ng/mL compared to 2.70 ng/mL in beef cattle. Mean ΣPBDEs in dairy cattle was 1.33 ng/mL compared to 0.70 ng/mL in beef cattle. There were no regional differences in the ΣPCBs or ΣPBDEs in cattle distributed across California. These results highlight the fact that livestock are still being exposed to these pollutants yet little is known about where this exposure may be coming from.
Topics: Animals; California; Cattle; Environmental Pollutants; Gas Chromatography-Mass Spectrometry; Goats; Halogenated Diphenyl Ethers; Humans; Milk; Polybrominated Biphenyls; Polychlorinated Biphenyls; Sheep; Solid Phase Extraction
PubMed: 28426942
DOI: 10.1016/j.chemosphere.2017.04.059 -
International Journal of Hygiene and... Jan 2023Applications of polychlorinated biphenyls (PCBs) in buildings and their persistence in indoor environments have led to cases of current and highly elevated exposure in...
Applications of polychlorinated biphenyls (PCBs) in buildings and their persistence in indoor environments have led to cases of current and highly elevated exposure in humans, despite the global cease of production decades ago. Personal exposure to PCBs was assessed among residents in a social housing estate in Denmark containing both contaminated (n = 67) and non-contaminated (n = 23) apartments. Samples and estimated daily intakes (EDIs) were assessed for 15 PCB congeners, and body burden, which was limited by the dietary data availability, was compared across 7 indicator PCBs, with its sum (PCB) often applied in European regulation of PCBs. Median PCB EDI across measured pathways for exposed residents was 101 ng· (kg bodyweight)· day, with the majority of exposure (60%) coming from inhalation of contaminated indoor air. Calculated from both PCBs measured in indoor air and on hand wipes, dermal absorption estimates showed comparable results and served as a secondary exposure pathway, accounting for 35% of personal exposure and considering selected assumptions and sources of physical-chemical parameters. Estimates revealed that diet was the primary PCB source among the reference group, accounting for over 75% of the PCB EDI across exposure routes. When evaluating overall EDIs across the two study groups and including dietary estimates, PCB exposure among exposed residents was around 10 times higher than the reference group. Solely within the exposed population, pathway-specific body burdens were calculated to account for exposure across years of residence in contaminated apartments, where lower chlorinated PCBs were dominant in indoor air. Among these dominant congeners, estimated body burdens of PCB-28 and -52 were significantly correlated with measured serum (r = 0.49, 0.45; p < 0.001). This study demonstrates that inhalation and dermal absorption serve as dominant exposure pathways for residents of apartments contaminated with predominantly lower chlorinated PCBs and suggest that predictions of body burden from indoor environment measurements may be comparable to measured serum PCBs.
Topics: Humans; Polychlorinated Biphenyls; Body Burden; Air Pollution; Body Weight; Hand
PubMed: 36395656
DOI: 10.1016/j.ijheh.2022.114056 -
Environmental Health and Preventive... Jan 2015The incidences of childhood allergies have been increasing in recent years in many parts of the world. The development of allergic disorders is attributed to a complex... (Review)
Review
The incidences of childhood allergies have been increasing in recent years in many parts of the world. The development of allergic disorders is attributed to a complex series of interactions between individuals' genetic backgrounds and their immune and psychoneurotic responses to environmental factors. Among the various possible environmental causes of childhood allergies, the early exposure of developing infants to air pollutants and the presence of persistent chemical pollutants such as pesticides have been suggested most frequently. Therefore, it is very important to obtain epidemiological evidence of direct associations between clearly defined adverse health effects and exposure to low levels of pollutants. However, there are no useful biomarkers for assessing such associations. Thus, we planned to establish reliable health-related biomarkers that could be used to investigate these relationships in children. The serum concentrations of several sub-types of polychlorinated biphenyl (PCB) congeners were found to be significantly correlated with interleukin (IL)-8 mRNA expression among asthmatic children. In addition, IL-22 mRNA expression was found to be particularly useful for detecting the effects of environmental pollutants, especially PCB congeners, in a sub-population of vulnerable children who exhibited positive immunoglobulin E (IgE) responses to milk or egg. Furthermore, we detected significant differences in IL-22 mRNA expression between the IgE-negative non-asthmatic subjects and the asthmatic children who exhibited positive IgE reactions toward egg or milk. In conclusion, IL-8 and IL-22 mRNA expressions could be useful biomarkers for detecting sub-populations of children who are particularly vulnerable to the adverse health effects of environmental pollutants, especially PCBs.
Topics: Animals; Asthma; Biomarkers; Child, Preschool; Environmental Exposure; Humans; Hypersensitivity; Immunoglobulin E; Infant; Interleukin-8; Interleukins; Japan; Milk; Molecular Epidemiology; Polychlorinated Biphenyls; RNA, Messenger; Real-Time Polymerase Chain Reaction; Interleukin-22
PubMed: 25344634
DOI: 10.1007/s12199-014-0419-1