Higher Polychlorinated Biphenyls Research Articles

Associations of polychlorinated biphenyls exposure, lifestyle, and genetic susceptibility with dyslipidemias: Evidence from a general Chinese population

Polychlorinated biphenyls (PCBs) are endocrine-disrupting chemicals that have been associated with various adverse health conditions. Herein we explored the associations of PCBs with dyslipidemia and further assessed the modification effect of genetic susceptibility and lifestyle factors. Six serum PCBs (PCB-28, 101, 118, 138, 153, 180) were determined in 3845 participants from the Wuhan-Zhuhai cohort. Dyslipidemia, including hyper-total cholesterol (HyperTC), hyper-triglyceride (HyperTG), hyper-low density lipoprotein cholesterol (HyperLDL-C), and hypo-high density lipoprotein cholesterol (HypoHDL-C) were determined, and lipid-specific polygenic risk scores (PRS) and healthy lifestyle score were constructed. We found that all six PCB congeners were positively associated with the prevalence of dyslipidemias, and ΣPCB level was associated with HyperTC, HyperTG, and HyperLDL-C in dose-response manners. Compared with the lowest tertiles of ΣPCB, the odds ratios (95% confidence intervals) in the highest tertiles were 1.490 (1.258, 1.765) for HyperTC, 1.957 (1.623, 2.365) for HyperTG, and 1.569 (1.316, 1.873) for HyperLDL-C, respectively. Compared with those with low ΣPCB, healthy lifestyle, and low genetic risk, participants with high ΣPCB, unfavorable lifestyle, and high genetic risk had the highest odds of HyperTC, HyperTG, and HyperLDL-C. Our study provided evidence that high PCB exposure exacerbated the association of genetic risk and unhealthy lifestyle with dyslipidemia.

Unexpectedly high levels and health risks of atmospheric polychlorinated biphenyls in modern mechanical dismantling of obsolete electrical equipment: investigations in a large integrated e-waste dismantling industrial estate

Large industrial estates for electrical and electronic waste (e-waste) mechanical dismantling and recycling are gradually replacing outmoded small factories and intensive domestic workshops for e-waste manual and chemical dismantling. However, the air pollution and health risks of persistent organic pollutants during the modern mechanical processing of e-waste, especially obsolete electrical equipment, still remain unclear. Here, unexpectedly high levels (409.3 ng/m3) and health risks of airborne polychlorinated biphenyls (PCBs) were found during the mechanical processing of obsolete electric equipment or parts in a large integrated dismantling industrial estate, which is comparable to or a dozen times higher than those reported during chemical processing. In contrast, the levels (936.0 pg/m3) and health risks of particulate polybrominated diphenyl ethers (PBDEs) were all lower than those of previous studies. PCB emissions (44.9–3300.5 ng/m3) varied significantly across six mechanical dismantling places specifically treating waste motors, electrical appliances, hardware, transformers, and metals, respectively. The high PCB content and mass processing number of obsolete electrical equipment probably result in the highest PCB emissions from the mechanical dismantling of obsolete motors, followed by waste electrical appliances and metals. The PCB non-cancer and cancer risks associated with inhalation and dermal exposure in different mechanical dismantling places were all above the given potential risk limits. In particular, the health risks of dismantling obsolete motor exceeded the definite risk levels. Little difference in PCB emissions and health risks between working and non-working time suggested the importance of PCB volatilization from most e-waste. Such high PCB emissions and health risks of PCBs undoubtedly posed a severe threat to frontline workers, but fortunately, they decreased significantly with the increasing distance from the industrial estate. We highlight that PCB emissions and associated health risks from obsolete electrical equipment with high PCB content during mechanical dismantling activities should be of great concern.

Investigation of the Relationship between Spontaneous Abortion, Serum Pesticides, and Polychlorinated Biphenyl Levels.

Occupational and environmental chemical exposure have been associated with adverse reproductive consequences. This study investigates the relationship between spontaneous abortion and blood pesticide and polychlorinated biphenyl (PCB) levels. A survey was conducted, and blood samples were collected from 200 patients, consisting of 100 cases with spontaneous abortion and 100 cases with normal deliveries. A total of 150 different pesticides, including organophosphates, organochlorines, carbamates, and pyrethroids, were screened in the collected blood samples and analyzed quantitatively using Tandem mass spectrometry-specifically in combination with liquid chromatography and gas chromatography-tandem mass spectrometry methods. Eight types of PCBs were analyzed with the gas chromatography-tandem mass spectrometry method. The groups were compared based on these analyses. The mean age of the participants was 28.09 ± 4.94 years. In 59% of the spontaneous abortion group, 5.05 ± 1.97 chemicals were detected in different amounts. (p < 0.05). Analysis of the samples identified the presence of β-Hexachlorocyclohexane (β-HCH), delta-hexachlorocyclohexane (δ HCH), Hexachlorobenzene (HCB), Pentachlorobiphenyl-28 (PCB-28), Pentachlorobiphenyl-52 (PCB-52), o,p'-Dichlorodiphenyldichloroethylene (o,p'-DDE), p,p'-Dichlorodiphenyldichloroethylene (p,p'DDE), o,p'-Dichlorodiphenyldichloroethane (o,p'-DDD), p,p'-Dichlorodiphenyldichloroethane (p,p'-DDD), Pentachlorobiphenyl-118 (PCB-118), Pentachlorobiphenyl-101 (PCB-101), Pentachlorobiphenyl-153 (PCB-153), Pentachlorobiphenyl-138 (PCB-138), Pentachlorobiphenyl-202 (PCB-202), Pentachlorobiphenyl-180 (PCB-180) as well as Fibronil, Buprimate, Acetoclor, Acemiprid, Pentimanthalin, and Triflokystrobin. The spontaneous abortion group had significantly higher exposure to PCB-101, PCB-52, PCB-138, and δ-HCH (p < 0.05). Women included in the study had high pesticide and PCB exposure rates. Many of the blood samples contained multiple pesticides with endocrine-disrupting effects. Higher exposure to organochlorine compounds in the serum was identified in the group with spontaneous abortions.

Concentration levels, spatial variations and exchanges of polychlorinated biphenyls (PCBs) in ambient air, surface water and sediment in Bursa, Türkiye

In this study, ambient air, surface water and sediment samples were simultaneously collected and analyzed for PCBs to investigate their levels, spatial variations and exchanges between these three compartments at different sampling sites for 12 months in Bursa, Türkiye. During the sampling period, a total of 41 PCB concentrations were determined in the ambient air, surface water (dissolved and particle phase) and sediment. Thus, 945.9 ± 491.6 pg/m3 (average ± STD), 53.8 ± 54.7 ng/L, 92.8 ± 59.3 ng/L and 71.4 ± 38.7 ng/g, respectively. The highest concentrations of PCBs in the ambient air and in water particulate phase were measured at the industrial/agricultural sampling site (1308.6 ± 252.1 pg/m3 and 168.7 ± 21.2 ng/L, respectively), ∼ 4–10 times higher than background sites; while the highest concentrations in the sediment and dissolved phase were measured at the urban/agricultural sampling sites (163.8 ± 27.0 ng/L and 145.7 ± 15.3 ng/g, respectively), ∼ 5–20 times higher than background sites. PCB transitions between ambient air-surface water (fA/fW) and surface water-sediment (fW/fS) were investigated by fugacity ratio calculations. According to the fugacity ratios obtained, volatilization from the surface water to the ambient air was observed at all sampling sites (98.7 % of fA/fW ratios are <1.0). Additionally, it has been determined that there is a transport from the surface water to the sediment (100.0 % of fW/fS ratios are higher than 1.0). The flux values in ambient air-surface water and surface water-sediment environments ranged from −1.2 to 1770.6 pg/m2-day and from −225.9 to 0.001 pg/m2-day, respectively. The highest flux values were measured for PCBs with low chlorine content (Mono-, Di-Cl PCBs), while the lowest flux values were measured for the high chlorine content PCBs (Octa-, Nona- and Deca-Cl PCBs). As it was determined in this study that surface waters contaminated by PCBs have the potential to pollute both air and sediments, it will be important to take measures to protect surface waters.

Enhancement of nitrogen fixation and diazotrophs by long-term polychlorinated biphenyl contamination in paddy soil

Biological nitrogen fixation (BNF) driven by diazotrophs is a major means of increasing available nitrogen (N) in paddy soil, in addition to anthropogenic fertilization. However, the influence of long-term polychlorinated biphenyl (PCB) contamination on the diazotrophic community and nitrogen fixation in paddy soil is poorly understood. In this study, samples were collected from paddy soil subjected to > 30 years of PCB contamination, and the soil diazotrophic community and N2 fixation rate were evaluated by Illumina MiSeq sequencing and acetylene reduction assays, respectively. The results indicated that high PCB contamination increased diazotrophic abundance and the N2 fixation rate, and altered diazotrophic community structure in the paddy soil. The random forest model demonstrated that the β-diversity of the diazotrophic community was the most significant predictor of the N2 fixation rate. Structure equation modeling identified a specialized keystone diazotrophic ecological cluster, predominated by Bradyrhizobium, Desulfomonile, and Cyanobacteria, as the key driver of N2 fixation. Overall, our findings indicated that long-term PCB contamination enhanced the N2 fixation rate by altering diazotrophic community abundance and structure, which may deepen our understanding of the ecological function of diazotrophs in organic-contaminated soil.

Presence of novel and legacy flame retardants and other pollutants in an e-waste site in China and associated risks

Electrical and Electronic Equipment (EEE) residues and their management have been widely identified as potential sources of plasticizers and flame retardants to the environment, especially in non-formal e-waste facilities. This study evaluates the distribution, partitioning and environmental and human impact of organophosphate esters (OPEs), legacy polychlorinated biphenyls (PCBs), polybromodiphenyl ethers (PBDEs) and organochlorine pesticides (OCPs) in the e-waste recycling area of Baihe Tang village, in the Qingyuan county, Guangdong province, China. A plastic debris lump accumulated in a small pond during years was identified as the main source of pollution with ∑pollutants of 8400 μg/g dw, being OPEs the main contaminants detected, followed by PBDEs. This lump produced the contamination of water, sediments, soils and hen eggs in the surrounding area at high concentrations. Plastic-water and water-sediment partitioning coefficients explained the migration of OPEs to the water body and accumulation in sediments, with a strong dependence according to the KOW. Triphenyl phosphate (TPhP), tricresyl phosphate (TCPs) and high chlorination degree PCBs produced a risk in soils and sediments, considering the lowest predicted no effect concentration, while the presence of PCBs and PBDEs in free range hen eggs exceeded the acceptable daily intake. OCPs were detected at low concentrations in all samples. The presence of organic contaminants in e-waste facilities worldwide is discussed to highlight the need for a strict control of EEE management to minimize environmental and human risks.

A Review of Polychlorinated Biphenyls (PCBs) Pollution in the Air: Where and How Much Are We Exposed to?

Polychlorinated biphenyls (PCBs) were widely used in industrial and commercial applications, until they were banned in the late 1970s as a result of their significant environmental pollution. PCBs in the environment gained scientific interest because of their persistence and the potential threats they pose to humans. Traditionally, human exposure to PCBs was linked to dietary ingestion. Inhalational exposure to these contaminants is often overlooked. This review discusses the occurrence and distribution of PCBs in environmental matrices and their associated health impacts. Severe PCB contamination levels have been reported in e-waste recycling areas. The occurrence of high PCB levels, notably in urban and industrial areas, might result from extensive PCB use and intensive human activity. Furthermore, PCB contamination in the indoor environment is ten-fold higher than outdoors, which may present expose risk for humans through the inhalation of contaminated air or through the ingestion of dust. In such settings, the inhalation route may contribute significantly to PCB exposure. The data on human health effects due to PCB inhalation are scarce. More epidemiological studies should be performed to investigate the inhalation dose and response mechanism and to evaluate the health risks. Further studies should also evaluate the health impact of prolonged low-concentration PCB exposure.

High PCBs mineralization capability of a resuscitated strain Bacillus sp. LS1 and its survival in PCB-contaminated soil

Polychlorinated biphenyl (PCB)-degrading strains resuscitated by resuscitation promoting factor (Rpf) enlarged pure degraders to screen effective bio-inoculants for soil bioaugmentation. In this study, whole-genome analysis and PCB-degrading performance of a resuscitated strain LS1 were investigated. Importantly, the persistence and the physiological response of soil-inoculated LS1 were checked. The results indicate that the Bacillus sp. strain LS1 possessed the potential to degrade polycyclic aromatic compounds. LS1 exhibited better performance in degrading PCBs 18 and 52, but lower PCB 77 degradation capability. At PCBs concentration of 10 mg/L, the degradation efficiencies of PCBs 18, 52 and 77 within 96 h were 62.8 %, 59.6 % and 39.8 %, respectively. Combined the bph genes and metabolites detected, as well as the genes found in the genome, the abilities of LS1 for oxidative dehalogenation and mineralization of PCBs via HOPDA-benzoate-protocatechuate-β-ketoadipate pathway were determined. Notably, LS1 can still maintain survival and culturable state after inoculation into PCB-contaminated soil for 70 days. This is the first report to demonstrate the fate of resuscitated strain when used as soil bio-inoculant, which revealed the necessity and feasibility of using resuscitated strains to enhance bioremediation of PCB-contaminated soils.

Human health risk surveillance of polychlorinated biphenyls in bovine milk from alluvial plain of Punjab, Pakistan.

Punjab is the leading province of Pakistan in the production of bovine milk and its consumption. Rapid industrialization, high energy demand, and the production of waste have increased the risk of polychlorinated biphenyls (PCBs) toxicity in the environment. This research work was designed to assess human dietary exposure of∑PCBs17 congeners through ingestion of buffalo and cow's milk from eight main districts of Punjab, Pakistan. The average concentrations of ∑DL-PCBs (8.74ngg-1 and 14.60ngg-1) and ∑I-PCBs (11.54ngg-1 and 18.68ngg-1) in buffalo and cow milk samples were analyzed, respectively. The PCB-156 was predominantly high congener found in both buffalo (2.84ngg-1) and cow milk (2.86ngg-1). It was found that the highest PCBs in bovine milk samples were observed in close vicinities of urban and industrial areas. The estimated daily consumptions of DL-PCBs and I-PCBs, from buffalo and cow milk, were below the acceptable daily intake for both adults and children. Moreover, hazard quotients (HQ) of the ∑PCBs17 congener value were less than 1.0 in adults and greater in the case of children reflecting the high chances of cancer. Furthermore, comprehensive monitoring for childhood cancer is recommended to establish the relationship in future studies.

Effect of PCBs Extracted from Offshore Sediment of South China Sea (Zhanjiang) on Histological Structure and Inflammation of Zebrafish Intestine

As ubiquitous environmental pollutants, polychlorinated biphenyls (PCBs) can cause significant health risks to various organisms, including humans. Meanwhile, PCBs exhibit various properties such as biological toxicity, high fat solubility, and accumulation in sediments and bioaccumulation in the food chain. In this study, the concentration of PCBs in Zhanjiang offshore sediment and the histopathological changes and the mRNA expression of cytokines in intestines of zebrafish (Danio rerio) exposed to environmentally relevant concentrations of PCBs were investigated. Among the six sites selected, PCB28 was found in the sediments of Lakeside Park (BHP) and Seashore Park (HBP), with concentrations of 35.0 and 27.0 μg/kg, respectively. On the other hand, PCB81 was discovered in the sediments of Jinsha Bay (JSW) with a total amount of 29.0 μg/kg. Adult zebrafish were exposed to different PCB concentrations through water, with control (no PCB exposure), positive control (PCB 81 at 10 μg/L), low (5 μg/L), medium (10 μg/L), and high (15 μg/L) PCB doses. The fish were euthanized on days 1, 3, 5, and 7. The intestinal epithelial cells of the zebrafish exposed to PCB extracts proved the dose-responsive lesions. With the increase of concentration and time (P &lt; 0.05), the relative expression of IL-1β, IL-8, and TNF-α mRNA increased significantly. The results showed that intestinal lesions and inflammation were dependent on exposure dose.

Seasonal Air–Sea Exchange Dynamics of Polychlorinated Biphenyls Over the East China Marginal Seas: The Role of Water Masses in a Complex Coastal–Ocean Current System

AbstractContinental marginal seas are key reservoirs of anthropogenic pollutants. Understanding the physical processes controlling the air–sea exchange dynamics of polychlorinated biphenyls (PCBs) in the continental margin seas is crucial to constrain the contribution of PCBs from land and rivers to the ocean; however, the transport and fate of PCBs, and their controlling factors of air–sea exchange in the continental marginal seas still remain poorly understood. Here, we collected atmospheric and surface water samples from the Yellow Sea (YS) and East China Sea (ECS) in summer 2018 and winter 2019, and examined the PCB concentrations. The PCB air–sea gas exchange fluxes showed higher net volatilization in winter, largely due to southward movement of the strengthened Yellow Sea Coastal Current and Yangtze River Diluted Water with high PCB concentrations. Both the dissolved PCB concentrations in seawater and wind speed were the primary factors influencing the PCB air–sea exchange fluxes in winter. By contrast, weak PCB volatilization fluxes occurred when the Taiwan Warm Current with low PCB concentrations dominated in the ECS in summer. In comparison, the accumulation and release of some PCB homologues caused by a green tide in the coastal YS could lead to increased volatilization flux in summer. Our results suggest the transfer of air–sea exchange dynamics of PCBs from a water concentration‐dominated pattern to an environmental parameter‐controlled one due to their decreased land‐based input, and highlight the impact of water mass‐triggered changes (environmental parameters and algal blooms) on the air–sea exchange behavior of PCBs in the continental marginal sea.

PCB exposure is associated with reduction of endosymbionts in riparian spider microbiomes

Microbial communities, including endosymbionts, play diverse and critical roles in host biology and reproduction, but contaminant exposure may cause an imbalance in the microbiome composition with subsequent impacts on host health. Here, we examined whether there was a significant alteration of the microbiome community within two taxa of riparian spiders (Tetragnathidae and Araneidae) from a site with historical polychlorinated biphenyl (PCB) contamination in southern Ontario, Canada. Riparian spiders specialize in the predation of adult aquatic insects and, as such, their contaminant levels closely track those of nearby aquatic ecosystems. DNA from whole spiders from sites with either low or high PCB contamination was extracted, and spider microbiota profiled by partial 16S rRNA gene amplicon sequencing. The most prevalent shift in microbial communities we observed was a large reduction in endosymbionts in spiders at the high PCB site. The abundance of endosymbionts at the high PCB site was 63 % and 98 % lower for tetragnathids and araneids, respectively, than at the low PCB site. Overall, this has potential implications for spider reproductive success and food webs, as riparian spiders are critical gatekeepers of energy and material fluxes at the land-water interface.

Dietary Acid Load, Serum Polychlorinated Biphenyl Levels, and Mortality Following Breast Cancer in the Long Island Breast Cancer Study Project.

Dietary acid load (DAL) may be associated with all-cause mortality (ACM) and breast cancer-specific mortality (BCM), and these associations may be modified by serum polychlorinated biphenyl (PCB) levels. Participants included 519 women diagnosed with first primary in situ or invasive breast cancer in 1996/1997 with available lipid-corrected PCB data. After a median of 17 years, there were 217 deaths (73 BCM). Potential renal acid load (PRAL) and net endogenous acid production (NEAP) scores calculated from a baseline food frequency questionnaire estimated DAL. Cox regression estimated covariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between PRAL and NEAP with mortality. We evaluated effect measure modification by total serum PCB levels (>median vs. ≤median). PRAL quartile 4 versus quartile 1 was associated with an ACM HR of 1.31 (95%CI = 0.90–1.92). In the upper median of PCBs, ACM HRs were 1.43 (95%CI = 0.96–2.11) and 1.40 (95%CI = 0.94–2.07) for PRAL and NEAP upper medians, respectively. In the lower median of PCBs, the upper median of NEAP was inversely associated with BCM (HR = 0.40, 95%CI = 0.19–0.85). DAL may be associated with increased risk of all-cause mortality following breast cancer among women with high total serum PCB levels, but inversely associated with breast cancer mortality among women with low PCB levels.

Upregulation of CCL7, CCL20, CXCL2, IL-1β, IL-6 and MMP-9 in Skin Samples of PCB Exposed Individuals—A Preliminary Study

Polychlorinated biphenyls (PCBs) are well known immunotoxic and carcinogenic compounds. Although cutaneous symptoms are the hallmark of exposure to these compounds, exact pathophysiologic mechanisms are not well understood. We took skin biopsies from moderately high PCB exposed workers (n = 25) after an informed consent and investigated the expression of immunological markers such as CCL-7, CCL-20, CXCL2, IL-1β and IL-6, as well as the matrix metalloproteinase MMP-9, EPGN and NRF2 by RT-qPCR, and compared expression levels with plasma PCB levels. Statistical analyses showed a significant correlation between CCL-20, CXCL2, IL-6, IL-1β, CCL-7 and MMP-9 and PCB serum levels. EPGN and NRF2 were not correlated to PCB levels in the blood. We found a significant correlation of genes involved in autoimmune, auto-inflammatory and carcinogenesis in skin samples of PCB exposed individuals with elevated plasma PCB levels. Confirmation of these findings needs to be performed in bigger study groups and larger gen-sets, including multiple housekeeping genes. Further study needs to be performed to see whether a chronical exposure to these and similar compounds can cause higher incidence of malignancies and inflammatory disease.

Accumulation of polychlorinated biphenyls (PCB) associated with bottom sediments in larvae of Chironomus riparius Meigen

Patterns of bioaccumulation of polychlorinated biphenyls (PCBs) by chironomid larvae (Chironomus riparius Meigen) were studied under laboratory conditions. Larvae were maintained for 20 days, separately in two batches of natural bottom sediments sampled from Rybinsk Reservoir (Russia), each differing in PCB content (425.6 μg / kg or 24.8 μg / kg dry weight, respectively). The study revealed that chironomid larvae accumulated PCBs at levels comparable to the PCB content measured in sediments from each exposure. The bioaccumulation coefficient (1.11 and 1.59, respectively, as per dry weight for compared sediment batches) depended directly on the sum PCB content in sediments. At high sediment PCB content, the ratios of homologous groups of PCBs in larvae and sediment were identical and corresponded to the Aroclor 1254 congeners profile; at lower PCB content, pronounced differences were revealed. In larvae, the ratios of 3, 4, 5, and 6CB homologues were evenly distributed at levels of 20–34 %, while the 4CB homologues prevailed (47 %) in sediments. The content of the latter compounds in larvae was lower than in sediments, and higher for the other homologous groups. The study indicates selective bioaccumulation of various homologous groups of PCBs under conditions of low sediment PCB content.

Concentration-dependent enantioselective accumulation of chiral polychlorinated biphenyls in Nelumbo nucifera Gaertn. root from contaminative sediment.

Nelumbo nucifera Gaertn. (lotus) roots were collected from contaminated sediments which were artificially adding different concentrations of chiral polychlorinated biphenyls (PCBs) to investigate the effect of concentration on the accumulation characteristics and chiral signatures of PCBs in lotus root during its growth period of 150 days. Under high PCB exposure concentration, the biota-sediment accumulation factors (BSAFs) of PCBs 91, 95, and 136 in the lotus root were up to 0.25-0.46 and 8.10-10.5 times higher than those under low-exposure concentration (0.024-0.052). The BSAFs of PCBs 149, 176, and 183 under high-exposure concentration were up to 0.24-0.44, while they were undetected at low concentration. The significant difference observed in the BSAFs based on different concentrations indicates that the lotus root accumulation efficiency toward chiral PCBs increases with the contaminate concentration. Although the (-)-enantiomers of PCBs 91, 95, and 136 wereall preferentially accumulated in lotus root under two exposure concentrations, the extent of the preferential accumulation of (-)-PCB 95 decreased with increasing exposure concentration throughout the whole growth period (30-150 days). In addition, the (-)-enantiomers of PCBs 91 and 136 also showed the same tendency during most of the growth period. Conclusively, the exposure concentrations are an important influence factor on the enantioselective accumulation of chiral PCBs in lotus root.

Metabolic activation and toxicological evaluation of polychlorinated biphenyls in Drosophila melanogaster

Degradation of polychlorinated biphenyls (PCBs) is initiated by cytochrome P450 (CYP) enzymes and includes PCB oxidation to OH-metabolites, which often display a higher toxicity than their parental compounds. In search of an animal model reflecting PCB metabolism and toxicity, we tested Drosophila melanogaster, a well-known model system for genetics and human disease. Feeding Drosophila with lower chlorinated (LC) PCB congeners 28, 52 or 101 resulted in the detection of a human-like pattern of respective OH-metabolites in fly lysates. Feeding flies high PCB 28 concentrations caused lethality. Thus we silenced selected CYPs via RNA interference and analyzed the effect on PCB 28-derived metabolite formation by assaying 3-OH-2′,4,4′-trichlorobiphenyl (3-OHCB 28) and 3′-OH-4′,4,6′-trichlorobiphenyl (3′-OHCB 28) in fly lysates. We identified several drosophila CYPs (dCYPs) whose knockdown reduced PCB 28-derived OH-metabolites and suppressed PCB 28 induced lethality including dCYP1A2. Following in vitro analysis using a liver-like CYP-cocktail, containing human orthologues of dCYP1A2, we confirm human CYP1A2 as a PCB 28 metabolizing enzyme. PCB 28-induced mortality in flies was accompanied by locomotor impairment, a common phenotype of neurodegenerative disorders. Along this line, we show PCB 28-initiated caspase activation in differentiated fly neurons. This suggested the loss of neurons through apoptosis. Our findings in flies are congruent with observation in human exposed to high PCB levels. In plasma samples of PCB exposed humans, levels of the neurofilament light chain increase after LC-PCB exposure, indicating neuronal damage. In summary our findings demonstrate parallels between Drosophila and the human systems with respect to CYP mediated metabolism and PCB mediated neurotoxicity.

Prenatal environmental exposures and associations with teen births.

Background:Children’s prenatal exposure to multiple environmental chemicals may contribute to subsequent deficits in impulse control, predisposing them to risk-taking.Objective:Our goal was to investigate associations between prenatal exposure mixtures and risk of teen birth, a manifestation of high-risk sexual activity, among 5,865 girls (1st generation) born in southeast Massachusetts from 1992-1998.Methods:Exposures included prenatal modeled polychlorinated biphenyls (PCBs), ρ,ρ′-dichlorodiphenyl dichloroethylene (DDE), hexachlorobenzene (HCB), lead (Pb), and mercury (Hg). We fit adjusted generalized additive models with multivariable smooths of exposure mixtures, 1st generation infant’s birth year, and maternal age at 1st generation birth. Predicted odds ratios (ORs) for teen birth were mapped as a function of joint exposures. We also conducted sensitivity analyses among 1st generation girls with measured exposure biomarkers (n=371).Results:The highest teen birth risk was associated with a mixture of high prenatal HCB, Hg, Pb, and PCB, but low DDE exposure, with similar associations in sensitivity analyses. The highest OR predicted for girls born in 1995 to mothers of median age (26 years) was at the 95th percentile of the HCB and PCB exposure distributions (OR=3.09; 95% confidence interval: 0.29, 32.4). Additionally, girls born earlier in the study period or to teen mothers were at increased risk of teen birth.Significance:Prenatal environmental chemical exposures and sociodemographic characteristics may interact to substantially increase risk of teen births.

Partitioning, Translocation Pathways and Environmental Risk Evaluation of Selected Polychlorinated Biphenyls and Pesticides

Degradation-resistant chemical contaminants of health concern such as dichlorodiphenyltrichloroethane (DDT) pesticides and polychlorinated biphenyls (PCBs) in the environment are redistributed between different environmental compartments, where they partition between biotic heterotrophic routes and abiotic features (water and immobile soil components). Their fate and the potential risk they pose is a function of translocation, interaction, environmental behavior, and bio-translation/activities. In this study, the partitioning, translocation, bio-translation pathways of 3-DDT and 6-PCB congeners in dosed soils cultured root and leaf vegetables were investigated to predict their soil–vegetable mobility, depuration, and exposure risk. Results showed that PCB_110 and PCB_180 were the least and highest PCBs concentrated in both the leaf and root vegetables. The variations in the 3-DDT and 6-PCB concentrations in the leaf and root vegetables may be attributed to differences in their solubility and partitioning. Total residual mass fraction 3-DDT taken up by the leaf and root vegetables indicated time-dependent preferentiality in pesticide-type vascular tissue translocation to the vegetables. Mann–Whitney non-parametric test showed evidence of spatial variations in levels of the 3-DDT and 6-PCBs across the farmland; however, the variations in the distribution were not significant (PFML1–FML6 <<Pstat). Risk factors for 3-PCBs and 3-DDT tend to 1(f < 1.0), while that for PCBs_149, 153, and _180 were far less than 0.4 (<1.0). It is therefore uncertain that any immediate health risks could arise from exposure to vegetables containing such congener levels. Continuous exposure to an extrapolated estimate of 25% vegetable population has a 20 ± 10% probability of leading to undesirable chronic effects.

Gut Microbiome Critically Impacts PCB-induced Changes in Metabolic Fingerprints and the Hepatic Transcriptome in Mice.

Polychlorinated biphenyls (PCBs) are ubiquitously detected and have been linked to metabolic diseases. Gut microbiome is recognized as a critical regulator of disease susceptibility; however, little is known how PCBs and gut microbiome interact to modulate hepatic xenobiotic and intermediary metabolism. We hypothesized the gut microbiome regulates PCB-mediated changes in the metabolic fingerprints and hepatic transcriptome. Ninety-day-old female conventional and germ-free mice were orally exposed to the Fox River Mixture (synthetic PCB mixture, 6 or 30 mg/kg) or corn oil (vehicle control, 10 ml/kg), once daily for 3 consecutive days. RNA-seq was conducted in liver, and endogenous metabolites were measured in liver and serum by LC-MS. Prototypical target genes of aryl hydrocarbon receptor, pregnane X receptor, and constitutive androstane receptor were more readily upregulated by PCBs in conventional conditions, indicating PCBs, to the hepatic transcriptome, act partly through the gut microbiome. In a gut microbiome-dependent manner, xenobiotic, and steroid metabolism pathways were upregulated, whereas response to misfolded proteins-related pathways was downregulated by PCBs. At the high PCB dose, NADP, and arginine appear to interact with drug-metabolizing enzymes (ie, Cyp1-3 family), which are highly correlated with Ruminiclostridium and Roseburia, providing a novel explanation of gut-liver interaction from PCB-exposure. Utilizing the Library of Integrated Network-based Cellular Signatures L1000 database, therapeutics targeting anti-inflammatory and endoplasmic reticulum stress pathways are predicted to be remedies that can mitigate PCB toxicity. Our findings demonstrate that habitation of the gut microbiota drives PCB-mediated hepatic responses. Our study adds knowledge of physiological response differences from PCB exposure and considerations for further investigations for gut microbiome-dependent therapeutics.