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Environment International Mar 2020Polychlorinated naphthalenes are teratogenic environmental contaminants. Mother milk is the most important food for nursing infants. The World Health Organization...
Polychlorinated naphthalenes are teratogenic environmental contaminants. Mother milk is the most important food for nursing infants. The World Health Organization actively promotes breastfeeding for its immunological, psychological, and economic advantages. We firstly measured concentrations of polychlorinated naphthalenes in human milk from 19 provinces in China and estimated their potential health risks to nursing infants and their possible sources. Concentrations ranged from 211.07 to 2497.43 pg/g lipid. The high prevalence of highly toxic hexachlorinated naphthalenes (Hexa-CN66/67) in human milk samples indicated a higher health risk in the sampling areas. Cancer risk posed to nursing infants was not significant, but potential non-carcinogenic adverse health effects were suggested and should be emphasized in some sampling areas. Unintentional emission of polychlorinated naphthalenes from industries that employ thermal processes appears to be the main source for PCNs in human milk in most sampling areas. Correlation analysis also suggested PCNs as impurities in polychlorinated biphenyl mixtures as a previously unrecognized source of polychlorinated naphthalenes in human milk.
Topics: China; Dibenzofurans, Polychlorinated; Environmental Monitoring; Humans; Infant; Milk, Human; Naphthalenes; Polychlorinated Biphenyls; Risk Assessment
PubMed: 31887713
DOI: 10.1016/j.envint.2019.105436 -
Environmental Health Perspectives Mar 2022Miscellaneous cardiovascular risk factors have been defined, but the contribution of environmental pollutants exposure on cardiovascular disease (CVD) remains...
BACKGROUND
Miscellaneous cardiovascular risk factors have been defined, but the contribution of environmental pollutants exposure on cardiovascular disease (CVD) remains underappreciated.
OBJECTIVE
We investigated the potential impact of typical environmental pollutant exposure on atherogenesis and its underlying mechanisms.
METHODS
We used human umbilical vein endothelial cells (HUVECs) and apolipoprotein E knockout () mice to investigate how 2,3,5-trichloro-6-phenyl-[1,4]-benzoquinone (PCB29-pQ, a toxic polychlorinated biphenyl metabolite) affects atherogenesis and identified early biomarkers of CVD associated with PCB29-pQ exposures. Then, we used long noncoding RNAs (lncRNAs) -overexpressing mice and apolipoprotein E/caveolin 1 double-knockout () mice to address the role of these early biomarkers in PCB29-pQ-induced atherogenesis. Plasma samples from patients with coronary heart disease (CHD) were also used to confirm our findings.
RESULTS
Our data indicate that lncRNA bound to via argonaute 2 in PCB29-pQ-challenged HUVECs. Our mRNA sequencing assay identified transforming growth () as a possible target gene of ; sponged and inhibited the binding of to . The effect of PCB29-pQ-induced endothelial injury, vascular inflammation, development of plaques, and atherogenesis in mice was greater with -mediated inhibition, whereas -overexpressing mice and mice showed the opposite effect. Consistently, plasma levels of and were found to be significantly associated individuals diagnosed with CHD.
DISCUSSIONS
These findings demonstrated that a mechanism-based, integrated-omics approach enabled the identification of potentially clinically relevant diagnostic indicators and therapeutic targets of CHD mediated by environmental contaminants using and models of HUVECs and and mice. https://doi.org/10.1289/EHP9833.
Topics: Animals; Atherosclerosis; Biomarkers; Human Umbilical Vein Endothelial Cells; Humans; Mice; Polychlorinated Biphenyls; RNA, Long Noncoding
PubMed: 35349355
DOI: 10.1289/EHP9833 -
Environmental Research Mar 2021Polychlorinated biphenyls (PCBs) are a public health concern given evidence that they persist and accumulate in the environment and can cause toxic effects in animals... (Review)
Review
Polychlorinated biphenyls (PCBs) are a public health concern given evidence that they persist and accumulate in the environment and can cause toxic effects in animals and humans. However, evaluating adverse effects of PCBs in epidemiologic studies is complicated by the characteristics of PCB exposure. PCBs exist as mixtures in the environment; the mixture changes over time due to degradation, and given physicochemical differences between specific PCB congeners, the mixture that an individual is exposed to (via food, air, or other sources) is likely different from that which can be measured in biological tissues. This is particularly problematic when evaluating toxicity of shorter-lived congeners that may not be measurable by the time biological samples are collected. We review these and other issues that arise when evaluating epidemiologic studies of PCBs and discuss how epidemiology data can still be used to inform both hazard identification and dose-response evaluation.
Topics: Animals; Epidemiologic Studies; Humans; Polychlorinated Biphenyls; Risk Assessment
PubMed: 33385388
DOI: 10.1016/j.envres.2020.110662 -
Environmental Health : a Global Access... Jun 2019Little attention has been paid to neurotoxicants on the risk of dementia. Exposure to known neurotoxicants such as polychlorinated biphenyls (PCBs) and organochlorine...
Exposure to polychlorinated biphenyls and organochlorine pesticides and risk of dementia, Alzheimer's disease and cognitive decline in an older population: a prospective analysis from the Canadian Study of Health and Aging.
BACKGROUND
Little attention has been paid to neurotoxicants on the risk of dementia. Exposure to known neurotoxicants such as polychlorinated biphenyls (PCBs) and organochlorine (OC) pesticides is suspected to have adverse cognitive effects in older populations.
OBJECTIVE
To assess whether plasma concentrations of PCBs and OC pesticides are associated with the risk of cognitive decline, Alzheimer's disease (AD) and of all-cause dementia in the Canadian older population.
METHODS
Analyses were based on data from the Canadian Study of Health and Aging, a 3-phase, 10-year population-based study of individuals aged 65+ years. Analyses included 669 clinically assessed subjects, of which 156 developed dementia including 108 incident cases of AD. Subjects were screened at each phase with the 100-point Modified Mini-Mental State Examination (3MS), a measurement of global cognitive function. Statistical analyses included Cox proportional hazards model when the outcome was dementia or AD, and a repeated-measure mixed model when the outcome was the 3MS score.
RESULTS
No association of PCB and OC pesticides with the risk of dementia and AD was observed. Elevated concentrations of PCB congeners nos 118, 153, 156, 163, and OC pesticides 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (p,p'-DDT) and its metabolite 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE) were significantly associated with cognitive decline as assessed with the 3MS. A posteriori analyses suggested that only p,p'-DDE was significantly related to a higher cognitive decline in time based on the 3MS among incident cases of dementia compared to subjects remaining nondemented.
CONCLUSION
PCB and OC pesticide plasma concentrations were not related to the incident diagnosis of neither dementia, nor AD. Using the 3MS scores as the outcome, higher concentrations of four PCB congeners and two OC pesticides were associated with lower cognitive performances in subjects. The association of p,p'-DDE with cognitive decline in time in incident cases of dementia merits further investigation.
Topics: Aged; Aged, 80 and over; Alzheimer Disease; Canada; Cognitive Dysfunction; Dementia; Female; Humans; Hydrocarbons, Chlorinated; Incidence; Male; Pesticides; Polychlorinated Biphenyls; Prevalence; Prospective Studies; Risk Factors
PubMed: 31200706
DOI: 10.1186/s12940-019-0494-2 -
Applied and Environmental Microbiology Sep 2020Biphenyl dioxygenase (BPDO), which is a Rieske-type oxygenase (RO), catalyzes the initial dioxygenation of biphenyl and some polychlorinated biphenyls (PCBs). In order...
Biphenyl dioxygenase (BPDO), which is a Rieske-type oxygenase (RO), catalyzes the initial dioxygenation of biphenyl and some polychlorinated biphenyls (PCBs). In order to enhance the degradation ability of BPDO in terms of a broader substrate range, the BphAE, BphAE, and BphAE variants were created from the parent enzymes BphAE, BphAE, and BphAE, respectively, by a substitution at one residue, Ser283Met. The results of steady-state kinetic parameters show that for biphenyl, the / values of BphAE, BphAE, and BphAE were significantly increased compared to those of their parent enzymes. Meanwhile, we determined the steady-state kinetics of BphAEs toward highly chlorinated biphenyls. The results suggested that the Ser283Met substitution enhanced the catalytic activity of BphAEs toward 2,3',4,4'-tetrachlorobiphenyl (2,3',4,4'-CB), 2,2',6,6'-tetrachlorobiphenyl (2,2',6,6'-CB), and 2,3',4,4',5-pentachlorobiphenyl (2,3',4,4',5-CB). We compared the catalytic reactions of BphAE and its variants toward 2,2'-dichlorobiphenyl (2,2'-CB), 2,5-dichlorobiphenyl (2,5-CB), and 2,6-dichlorobiphenyl (2,6-CB). The biochemical data indicate that the Ser283Met substitution alters the orientation of the substrate inside the catalytic site and, thereby, its site of hydroxylation, and this was confirmed by docking experiments. We also assessed the substrate ranges of BphAE and its variants with degradation activity. BphAE and BphAE were clearly improved in oxidizing some of the 3-6-chlorinated biphenyls, which are generally very poorly oxidized by most dioxygenases. Collectively, the present work showed a significant effect of mutation Ser283Met on substrate specificity/regiospecificity in BPDO. These will certainly be meaningful elements for understanding the effect of the residue corresponding to position 283 in other Rieske oxygenase enzymes. The segment from positions 280 to 283 in BphAEs is located at the entrance of the catalytic pocket, and it shows variation in conformation. In previous works, results have suggested but never proved that residue Ser283 of BphAE might play a role in substrate specificity. In the present paper, we found that the Ser283Met substitution significantly increased the specificity of the reaction of BphAE toward biphenyl, 2,3',4,4'-CB, 2,2',6,6'-CB, and 2,3',4,4',5-CB. Meanwhile, the Ser283Met substitution altered the regiospecificity of BphAE toward 2,2'-dichlorobiphenyl and 2,6-dichlorobiphenyl. Additionally, this substitution extended the range of PCBs metabolized by the mutated BphAE. BphAE and BphAE were clearly improved in oxidizing some of the more highly chlorinated biphenyls (3 to 6 chlorines), which are generally very poorly oxidized by most dioxygenases. We used modeled and docked enzymes to identify some of the structural features that explain the new properties of the mutant enzymes. Altogether, the results of this study provide better insights into the mechanisms by which BPDO evolves to change and/or expand its substrate range and its regiospecificity.
Topics: Bacterial Proteins; Burkholderiaceae; Dioxygenases; Genetic Engineering; Mutagenesis, Site-Directed; Polychlorinated Biphenyls
PubMed: 32709719
DOI: 10.1128/AEM.01040-20 -
The Science of the Total Environment Jul 2022Characterization of PCB exposure sources for vulnerable population groups is essential to minimize the health effects of PCB exposure. At the same time, it is important...
Application of a pharmacokinetic model in characterizing sources of polychlorinated biphenyl exposure and determining threshold daily intakes for adverse health effects in infants and toddlers.
Characterization of PCB exposure sources for vulnerable population groups is essential to minimize the health effects of PCB exposure. At the same time, it is important to consolidate the knowledge on threshold intakes of PCBs for infants and toddlers to prevent health effects. We estimated total PCB concentrations from birth to 2 years of age in children from Slovak and Czech populations, which continue to have high PCB concentrations in breast milk. Using a pharmacokinetic (PK) model, we characterized dominant PCB exposure sources and estimated new threshold estimated daily intakes (TEDI) (above which adverse effects cannot be excluded) for postnatal PCB exposure in infants and toddlers. In the PK model, concentrations of seven indicator PCBs in breast milk and cord blood samples from 291 mother-child pairs from the Slovak birth cohort, and 396 breast milk samples from Czech mothers we used, together with their physiological characteristics and PCB concentrations from other exposure sources (food, dust, air). The estimated total PCB concentrations in children's blood at different ages were compared with threshold PCB concentrations of 500, 700 and 1000 ng·g in serum proposed by the French Agency for Food, Environmental and Occupational Health & Safety (ANSES) and the German Environment Agency (UBA), above which possible adverse health effects may be expected. We estimated that up to 20.6% of Slovak children and up to 45.7% of Czech children at two years of age exceeded the threshold value of 700 ng·g in blood. Mean TEDIs leading to values of 500 ng·g in blood for children up to two years ranged between 110 and 220 ng·kg·bw·day, varying according to breastfeeding duration. Breast milk and prenatal exposure contributed to 71%-85% of PCBs exposure at two years of age. In contrast, the contributions of PCBs from dust and indoor air were negligible.
Topics: Breast Feeding; Child, Preschool; Drug-Related Side Effects and Adverse Reactions; Dust; Environmental Pollutants; Female; Humans; Infant; Lipids; Milk, Human; Polychlorinated Biphenyls; Pregnancy
PubMed: 35337869
DOI: 10.1016/j.scitotenv.2022.154734 -
Environmental Research Apr 2021Endometriosis is an estrogen-dependent disease. Endocrine disrupting chemicals (EDCs) and their mixtures may play an etiologic role.
BACKGROUND
Endometriosis is an estrogen-dependent disease. Endocrine disrupting chemicals (EDCs) and their mixtures may play an etiologic role.
OBJECTIVES
We evaluated an adipose-to-serum ratio (ASR) of lipophilic EDCs and their mixtures associated with incident endometriosis.
METHODS
We quantified 13 polychlorinated biphenyl (PCB) congeners, 6 polybrominated diphenyl ether (PBDE) congeners, and 11 organochlorine pesticides (OCPs) in serum and omental fat among women from the ENDO Study (2007-2009) aged 18-44 years diagnosed with (n=190) or without (n=283) surgically-visualized incident endometriosis. Odds ratios (OR) and 95% confidence intervals (CI) between ASR and endometriosis were estimated using logistic regression models adjusted for age (years), body mass index (kg/m), serum cotinine (ng/ml), and breastfeeding conditional on parity. Bayesian hierarchical models (BHM) compared estimated associations for adipose and ASR to serum. Bayesian kernel machine regression (BKMR) estimated change in latent health and 95% posterior intervals (PI) between chemical mixtures and endometriosis.
RESULTS
Select ASR for estrogenic PCBs and OCPs were associated with an increased odds of an endometriosis diagnosis, but not for anti-estrogenic PCBs or PBDEs. Across all chemicals, BHMs generated ORs that were on average 14% (95% PI: 6%, 22%) higher for adipose and 20% (95% PI: 12%, 29%) higher for ASR in comparison to serum. ORs from BHMs were greater for estrogenic PCBs and OCPs, with no differences for PBDEs. BKMR models comparing the 75th to 25th percentile were moderately associated with endometriosis for estrogenic PCBs [adipose 0.27 (95% PI: 0.18, 0.72) and ASR 0.37 (95% PI: 0.06, 0.80)] and OCPs [adipose 0.17 (95% PI: 0.21, 0.56) and ASR 0.26 (95% PI: 0.05, 0.57)], but not for antiestrogenic PCBs and PBDEs.
DISCUSSION
ASR added little insight beyond adipose for lipophilic chemicals. BKMR results supported associations between ASR and adipose estrogenic PCB and OCP mixtures and incident endometriosis. These findings underscore the importance of choice of biospecimen and considering mixtures when assessing exposure-disease relationships.
Topics: Adolescent; Adult; Bayes Theorem; Endometriosis; Environmental Pollutants; Female; Halogenated Diphenyl Ethers; Humans; Hydrocarbons, Chlorinated; Persistent Organic Pollutants; Polychlorinated Biphenyls; Pregnancy; Young Adult
PubMed: 33484721
DOI: 10.1016/j.envres.2021.110732 -
Environment International Aug 2015Detailed polychlorinated biphenyl (PCB) signatures and chiral Enantiomer Fractions (EFs) of CB-95, CB-136 and CB-149 were measured for 30 workers at a transformer...
Detailed polychlorinated biphenyl (PCB) signatures and chiral Enantiomer Fractions (EFs) of CB-95, CB-136 and CB-149 were measured for 30 workers at a transformer dismantling plant. This was undertaken to identify sources of exposure and investigate changes to the PCB signature and EFs over different exposure periods. Approximately 1.5 g of serum was extracted and PCB signatures were created through analysis by comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry (GC×GC-TOFMS) and EFs calculated following analysis by gas chromatography with high resolution mass spectrometry (GC-HRMS). A total of 84 PCBs were identified in the serum samples with concentrations of the 7 indicator PCBs ranging from 11-350 ng g(-1) of serum (1.2-39 μg g(-1) lipid). The PCB signatures were interpreted using principal component analysis (PCA) which was able to distinguish workers with background or recent minimal exposure from those with prolonged occupational exposure. Occupationally exposed individuals had a similar PCB profile to Aroclor A1260. However, individuals with prolonged exposure had depleted proportions of several PCB congeners that are susceptible to metabolism (CB-95, CB-101 and CB-151) and elevated proportions of PCBs that are resistant to metabolism (CB-74, CB-153, CB-138 and CB-180). The results also identified a third group of workers with elevated proportions of CB-28, CB-60, CB-66, CB-74, CB-105 and CB-118 who appeared to have been exposed to an additional source of PCBs. The results show near complete removal of the CB-95 E2 enantiomer in some samples, indicating that bioselective metabolism or preferential excretion of one enantiomer occurs in humans. By considering PCB concentrations along with detailed congener specific signatures it was possible to identify different exposure sources, and gain an insight into both the magnitude and duration of exposure.
Topics: Environmental Pollutants; Gas Chromatography-Mass Spectrometry; Humans; Occupational Exposure; Polychlorinated Biphenyls; Principal Component Analysis; Stereoisomerism
PubMed: 25916940
DOI: 10.1016/j.envint.2015.04.006 -
Environmental Health : a Global Access... Feb 2018Polychlorinated biphenyls (PCBs) are persistent organic environmental contaminants and known endocrine-disrupting chemicals (EDCs). Previous studies demonstrated that...
BACKGROUND
Polychlorinated biphenyls (PCBs) are persistent organic environmental contaminants and known endocrine-disrupting chemicals (EDCs). Previous studies demonstrated that developmental exposure to the weakly estrogenic PCB mixture Aroclor 1221 (A1221) in Sprague-Dawley rats altered sexual development, adult reproductive physiology and body weight. The current study tested the hypothesis that prenatal A1221 exposure not only disrupts these endpoints within an exposed individual's (F generation) lifespan, but may also affect subsequent generations (F-F).
METHODS
We treated pregnant female rats on embryonic days (E) 16 and E18 with A1221 (1 mg/kg), estradiol benzoate (50 μg/kg, positive estrogenic control), or vehicle (3% DMSO in sesame oil, negative control). Endpoints related to sexually dimorphic developmental trajectories of reproductive and developmental physiology were measured, and as adults, reproductive endocrine status was assessed, in the F, F, and F generations.
RESULTS
Significant effects of transgenerational EDCs were found for body weight and serum hormones. The A1221 descendants had significantly higher body weight in the F-maternal lineage throughout postnatal development, and in F-maternal lineage animals after weaning. In females, generation- and lineage-specific effects of exposure were found for serum progesterone and estradiol. Specifically, serum progesterone concentrations were lower in F-A1221 females, and higher in F-A1221 females, compared to their respective F- and F-vehicle counterparts. Serum estradiol concentrations were higher in F-A1221 than F-vehicle females. Reproductive and adrenal organ weights, birth outcomes, sex ratio, and estrous cycles, were unaffected. It is notable that effects of A1221 were only sometimes mirrored by the estrogenic control, EB, indicating that the mechanism of action of A1221 was likely via non-estrogenic pathways.
CONCLUSIONS
PCBs caused body weight and hormonal effects in rats that were not observed in the directly exposed F offspring, but emerged in F and F generations. Furthermore, most effects were in the maternal lineage; this may relate to the timing of exposure of the F fetuses at E16 and 18, when germline (the future F generation) epigenetic changes diverge in the sexes. These results showing transgenerational effects of EDCs have implications for humans, as we are now in the 3rd generation since the Chemical Revolution of the mid-twentieth century, and even banned chemicals such as PCBs have a persistent imprint on the health of our descendants.
Topics: Animals; Aroclors; Endocrine Disruptors; Environmental Pollutants; Female; Male; Rats; Rats, Sprague-Dawley; Reproduction; Sexual Maturation
PubMed: 29458364
DOI: 10.1186/s12940-018-0362-5 -
Toxicological Sciences : An Official... Feb 2016Polychlorinated biphenyls (PCBs) are environmental pollutants associated with non-alcoholic-steatohepatitis (NASH), diabetes, and obesity. We previously demonstrated...
Polychlorinated biphenyls (PCBs) are environmental pollutants associated with non-alcoholic-steatohepatitis (NASH), diabetes, and obesity. We previously demonstrated that the PCB mixture, Aroclor 1260, induced steatohepatitis and activated nuclear receptors in a diet-induced obesity mouse model. This study aims to evaluate PCB interactions with the pregnane-xenobiotic receptor (Pxr: Nr1i2) and constitutive androstane receptor (Car: Nr1i3) in NASH. Wild type C57Bl/6 (WT), Pxr(-/-) and Car(-/-) mice were fed the high fat diet (42% milk fat) and exposed to a single dose of Aroclor 1260 (20 mg/kg) in this 12-week study. Metabolic phenotyping and analysis of serum, liver, and adipose was performed. Steatohepatitis was pathologically similar in all Aroclor-exposed groups, while Pxr(-/-) mice displayed higher basal pro-inflammatory cytokine levels. Pxr repressed Car expression as evident by increased basal Car/Cyp2b10 expression in Pxr(-/-) mice. Both Pxr(-/-) and Car(-/-) mice showed decreased basal respiratory exchange rate (RER) consistent with preferential lipid metabolism. Aroclor increased RER and carbohydrate metabolism, associated with increased light cycle activity in both knockouts, and decreased food consumption in the Car(-/-) mice. Aroclor exposure improved insulin sensitivity in WT mice but not glucose tolerance. The Aroclor-exposed, Pxr(-/-) mice displayed increased gluconeogenic gene expression. Lipid-oxidative gene expression was higher in WT and Pxr(-/-) mice although RER was not changed, suggesting PCB-mediated mitochondrial dysfunction. Therefore, Pxr and Car regulated inflammation, behavior, and energy metabolism in PCB-mediated NASH. Future studies should address the 'off-target' effects of PCBs in steatohepatitis.
Topics: Animals; Behavior, Animal; Body Composition; Constitutive Androstane Receptor; Energy Metabolism; Glucose; Inflammation; Lipid Metabolism; Male; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Polychlorinated Biphenyls; Pregnane X Receptor; Pulmonary Gas Exchange; Receptors, Cytoplasmic and Nuclear; Receptors, Steroid
PubMed: 26612838
DOI: 10.1093/toxsci/kfv250