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Polychlorinated biphenyls (PCBs) persist and accumulate in the ecosystem depending upon the degree of chlorination of the biphenyl rings. Airborne PCBs are especially susceptible to oxidative metabolism, yielding mono- and di-hydroxy metabolites. We have previously demonstrated that 4-chlorobiphenyl hydroquinones (4-CB-HQs) acted as cosubstrates for arachidonic acid metabolism by prostaglandin H synthase (PGHS) and resulted in an increase of prostaglandin production in vitro. In the present study, we tested the capability of 4-CB-HQ to act as a co-substrate for PGHS catalysis in vivo. BQ and 4-CB-2′,5′-HQ were administered intratracheally to male Sprague-Dawley rats (2.5 μmol/kg body weight) using nanosized polyamidoamine (PAMAM) dendrimers as carriers. We found that 24 h post application, PGE metabolites in kidney of rats treated with 4-CB-2′,5′-HQ were significantly increased compared to the controls. The increase of PGE metabolites was correlated with increased alveolar macrophages in lung lavage fluid. The elevation of PGE synthesis is of great interest since it plays a crucial role in balancing homeostasis and inflammation where a chronic disturbance may increase risk of cancer. PAMAM dentrimers proved to be an effective transport medium and did not stimulate an inflammatory response themselves. [ABSTRACT FROM AUTHOR]

The health risk of inhalation exposure to polychlorinated biphenyls (PCB) cannot be assessed with high confidence due to the lack of rigorous inhalation studies. One uncertainty rests on exposure regimen, as whole-body exposure systems allow oral PCB intake that confounds the exposure. We conducted contemporaneous PCB inhalation exposures with whole-body and nose-only exposure methods. Female Sprague-Dawley rats were concurrently exposed to vapor-phase PCBs (533 ± 93 µg/m³) generated from PCB11-supplemented Chicago Air Mixture resembling the Chicago airshed, 4 h/day, 6 days/week, for 4 weeks. Congener-specific analysis showed 1.5-fold higher ?PCBs in the lungs of nose-only exposed than the whole-body exposed animals (p = 0.0024). Higher ?PCB concentrations were also found in the sera, livers, brains, and adipose tissue of nose-only exposed animals (1.1-1.5-fold), but these increases were not statistically significant. Congener profiles of five tissue types were dominated by PCB 28/31 and higher-chlorinated congeners in both groups reflecting rapid metabolism of other lower-chlorinated PCBs. No toxicity was seen regarding metabolic enzyme expression, glutathione, or histopathology. However, diminished weight gain and reduced plasma total thyroxine levels were found in both groups compared with controls, after exposure to 76 µg/m³ ?PCBs as adjusted for continuous exposure. Hepatic lipid peroxidation was also elevated in the nose-only group. Our study shows that prolonged nose-only exposure was well-tolerated and eliminated the need for housing animals outside the vivarium, thus was preferred for long-term PCB inhalation studies. [ABSTRACT FROM AUTHOR]

Abstract: Background: The production ban of polychlorinated biphenyl (PCB) technical mixtures has left the erroneous impression that PCBs exist only as legacy pollutants. Some lower-chlorinated PCBs are still being produced and contaminate both indoor and ambient air. Objectives: To inform PCB risk assessment, we characterized lung uptake, distribution, metabolism and excretion of PCB11 as a signature compound for these airborne non-legacy PCBs. Methods: After delivering [14C]PCB11 to the lungs of male rats, radioactivity in 34 major tissues and 5 digestive matter compartments was measured at 12, 25, 50, 100, 200 and 720min postexposure, during which time the excreta and exhaled air were also collected. [14C]PCB11 and metabolites in lung, liver, blood, digestive matter, urine, feces, and adipose tissues were extracted separately to establish the metabolic profile of the disposition. Results: [14C]PCB11 was distributed rapidly to all tissues after 99.8% pulmonary uptake and quickly underwent extensive metabolism. The major tissue deposition of [14C]PCB11 and metabolites translocated from liver, blood and muscle to skin and adipose tissue 200min postexposure, while over 50% of administered dose was discharged via urine and feces within 12h. Elimination of the [14C]PCB11 and metabolites consisted of an initial fast phase (t½ =9–33min) and a slower clearance phase to low concentrations. Phase II metabolites dominated in liver blood and excreta after 25min postexposure. Conclusions: This study shows that PCB11 is completely absorbed after inhalation exposure and is rapidly eliminated from most tissues. Phase II metabolites dominated with a slower elimination rate than the PCB11 or phase I metabolites and thus can best serve as urine biomarkers of exposure. [Copyright &y& Elsevier]

Despite their potential for a variety of applications, copper nanoparticles induce very strong inflammatory responses and cellular toxicity following aerosolized delivery. Coating metallic nanoparticles with polysaccharides, such as biocompatible and antimicrobial chitosan, has the potential to reduce this toxicity. In this study, copper nanoparticles were coated with chitosan using a newly developed and facile method. The presence of coating was confirmed using x-ray photoelectron spectroscopy, rhodamine tagging of chitosan followed by confocal fluorescence imaging of coated particles and observed increases in particle size and zeta potential. Further physical and chemical characteristics were evaluated using dissolution and x-ray diffraction studies. The chitosan coating was shown to significantly reduce the toxicity of copper nanoparticles after 24 and 52 h and the generation of reactive oxygen species as assayed by DHE oxidation after 24 h in vitro. Conversely, inflammatory response, measured using the number of white blood cells, total protein, and cytokines/chemokines in the bronchoalveolar fluid of mice exposed to chitosan coated versus uncoated copper nanoparticles, was shown to increase, as was the concentration of copper ions. These results suggest that coating metal nanoparticles with mucoadhesive polysaccharides (e.g. chitosan) could increase their potential for use in controlled release of copper ions to cells, but will result in a higher inflammatory response if administered via the lung. [ABSTRACT FROM AUTHOR]

Although inhalation of atmospheric polychlorinated biphenyls (PCBs) is the most universal exposure route and has become a substantial concern in urban areas, research is lacking to determine the body burden of inhaled PCBs and consequent health effects. To reflect the Chicago airshed environment and mimic the PCB profile in Chicago air, we generated vapors from a Chicago air mixture (CAM). Sprague-Dawley rats were exposed to the CAM vapor for 1.6 h/day via nose-only inhalation for 4 weeks, 520 ± 10 μg/m3. Congener-specific quantification in tissue and air samples was performed by gas chromatography-tandem mass spectrometry (GC/MS/MS). In contrast to the lower-chlorinated congener-enriched vapor, body tissues mainly contained tri- to hexachlorobiphenyls. Congener profiles varied between vapor and tissues and among different organs. The toxic equivalence (TEQ) and neurotoxic equivalence (NEQ) were also investigated for tissue distribution. We evaluated a variety of end points to catalogue the effects of long-term inhalation exposure, including immune responses, enzyme induction, cellular toxicity, and histopathologic abnormalities. Glutathione oxidized/reduced ratio (GSSG/GSH) was increased in the blood of exposed animals, accompanied by elevation of hematocrit. This study demonstrated that inhalation contributed to the body burden of mostly tri- to hexachlorobiphenyls and produced a distinct profile of congeners in tissue, yet minimal toxicity was found at this exposure dose, estimated at 134 μg/rat. [ABSTRACT FROM AUTHOR]

Despite the continued presence of PCBs in indoor and ambient air, few studies have investigated the inhalation route of exposure. While dietary exposure has declined, inhalation of the semivolatile, lower-chlorinated PCBs has risen in importance. We measured the uptake, distribution, and time course of elimination of inhaled PCB congeners to characterize the pulmonary route after short-term exposure. Vapor-phase PCBs were generated from Aroclor 1242 to a nose-only exposure system and characterized for congener levels and profiles. Rats were exposed via inhalation acutely (2.4 mg/m³ for 2 h) or subacutely (8.2 mg/m³, 2 h × 10 days), after which pulmonary immune responses and PCB tissue levels were measured. Animals acutely exposed were euthanized at 0, 1, 3, 6, and 12 h post exposure to assess the time course of PCB uptake and elimination. Following rapid absorption and distribution, PCBs accumulated in adipose tissue but decayed in other tissues with half-lives increasing in liver (5.6 h) < lung (8.2 h) < brain (8.5 h) < blood (9.7 h). PCB levels were similar in lung, liver, and adipose tissue, lower in brain, and lowest in blood. Inhalation of the airborne PCB mixture contributed significantly to the body burden of lower-chlorinated congeners. Congeners detected in tissue were mostly ortho-substituted ranging from mono- to pentachlorobiphenyls. Selective uptake and elimination led to accumulation of a distinct congener spectrum in tissue. Minimal evidence of toxicity was observed. [ABSTRACT FROM AUTHOR]

The release of reactive oxygen species (ROS) and cytokines by alveolar macrophages has been demonstrated in asbestos-induced pulmonary fibrosis, but the mechanism linking alveolar macrophages to the pathogenesis is not known. The GTPase Rac1 is a second messenger that plays an important role in host defense. In this study, we demonstrate that Rac1 null mice are protected from asbestos-induced pulmonary fibrosis, as determined by histological and biochemical analysis. We hypothe-sized that Rac I induced pulmonary fibrosis via generation of ROS. Asbestos increased TNF-α and ROS in a Rac1-dependent manner. TNF-α was elevated only 1 day after exposure, whereas ROS generation progressively increased in bronchoalveolar lavage cells obtained from wild-type (WT) mice. To determine whether ROS generation contributed to pulmonary fibrosis, we overexpressed catalase in WT monocytes and observed a decrease in ROS generation in vitro. More importantly, administration of catalase to WT mice attenuated the development of fibrosis in vivo. For the first time, these results demonstrate that Rac1 plays a crucial role in asbestos-induced pulmonary fibrosis. Moreover, it suggests that a simple intervention may be useful to prevent progression of the disease. [ABSTRACT FROM AUTHOR]

Polychlorinated biphenyls (PCBs) are linked to cancer, learning disabilities, liver and cardiovascular disease, and diabetes. Older schools often contain high levels of PCBs, and inhalation is a major source of exposure. Technical PCB mixtures, called Aroclors, and individual dioxin-like PCBs impair adipocyte function, which can lead to type II diabetes. To determine how PCB52, a non-dioxin like PCB congener found in school air, affects adipose, adolescent male and female rats were exposed to PCB52 by nose-only inhibition for 4h per day for 28 consecutive days. Transcriptomic analysis of white adipose revealed sex-specific differences in gene expression between PCB52- and sham-exposed males and females. Exposed females showed mitochondrial gene changes, including downregulation of the thermogenic uncoupling gene, Ucp1. Human preadipocytes/adipocytes exposed to PCB52 or its main metabolite, 4-OH-PCB52, also showed reduced norepinephrine-induced UCP1 expression. These findings suggest that PCB52 inhalation disrupts thermogenesis in adipose tissue, potentially contributing to metabolic syndrome., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. CONFLICTS OF INTEREST The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Polybrominated diphenyl ethers (PBDEs) are flame retardants applied as coatings to many consumer products, including household items. PBDEs are released and produce airborne vapors and dusts. Inhalation of particle-phase and/or gas-phase PBDEs is therefore a major route of exposure. In an attempt to mimic realistic airborne exposures, actual uptake, and deposition of particles and vapors, we prepared and characterized particles for future animal exposure studies. To trace the particles in environmental and biological systems, we employed fluoro tagging. We synthesized, characterized, and employed three PBDE congeners, 35, 47, and 99, and five fluoro-substituted PBDEs (F-PBDEs), 17-F5' 25-F5', 28-F3', 35-F5', 47-F3, and 99-F3', for this study. The PBDE congeners were selected because they are commonly found in house dust. For that reason, we coated spherical silica particles of 3 microm and C18 endcapped silica as representative and inert support materials, with 20, 30, and 40% PBDEs. We determined the particle size distributions by aerodynamic particle size spectrometry and the morphology by scanning electron microscopy. The suitability of the fluoro-tagged tracers to mimic their corresponding parent PBDEs was investigated by extraction studies from spiked blood serum. Our study is of fundamental importance to the development of xenobiotic tracers for monitoring routes of human exposure to PBDEs and understanding uptake of PBDEs from particles and vapors.