Chronic bromine intoxication complicated with Fanconi syndrome: A case report.

In this report, we describe a unique case of an 80-year-old woman who developed chronic bromine poisoning due to the prolonged ingestion of over-the-counter (OTC) medication containing bromovalerylurea (BVU), thus leading to the onset of drug-induced partial Fanconi syndrome and resultant osteomalacia. The patient's condition improved following the cessation of bromide intake. This case highlights the potential risks of chronic BVU exposure and the importance of caution regarding the use of OTC medications containing BVU.

Bromine contamination and risk management in terrestrial and aquatic ecosystems.

Bromine (Br) is widely distributed through the lithosphere and hydrosphere, and its chemistry in the environment is affected by natural processes and anthropogenic activities. While the chemistry of Br in the atmosphere has been comprehensively explored, there has never been an overview of the chemistry of Br in soil and aquatic systems. This review synthesizes current knowledge on the sources, geochemistry, health and environmental threats, remediation approaches, and regulatory guidelines pertaining to Br pollution in terrestrial and aquatic environments. Volcanic eruptions, geothermal streams, and seawater are the major natural sources of Br. In soils and sediments, Br undergoes natural cycling between organic and inorganic forms, with bromination reactions occurring both abiotically and through microbial activity. For organisms, Br is a non-essential element; it is passively taken up by plant roots in the form of the Br- anion. Elevated Br- levels can limit plant growth on coastal soils of arid and semi-arid environments. Br is used in the chemical industry to manufacture pesticides, flame retardants, pharmaceuticals, and other products. Anthropogenic sources of organobromine contaminants in the environment are primarily wastewater treatment, fumigants, and flame retardants. When aqueous Br- reacts with oxidants in water treatment plants, it can generate brominated disinfection by-products (DBPs), and exposure to DBPs is linked to adverse human health effects including increased cancer risk. Br- can be removed from aquatic systems using adsorbents, and amelioration of soils containing excess Br- can be achieved by leaching, adding various amendments, or phytoremediation. Developing cost-effective methods for Br- removal from wastewater would help address the problem of toxic brominated DBPs. Other anthropogenic organobromines, such as polybrominated diphenyl ether (PBDE) flame retardants, are persistent, toxic, and bioaccumulative, posing a challenge in environmental remediation. Future research directives for managing Br pollution sustainably in various environmental settings are suggested here.

Comparing different methods for olefin quantification in pygas and plastic pyrolysis oils: Gas chromatography-vacuum ultraviolet detection versus comprehensive gas chromatography versus bromine number titration.

In steam cracking, upstream pyrolysis oil hydroprocessing, and in many downstream processes, olefinic content is key to assess process performance and process safety risk associated with highly exothermic reactions. When looking to plastic pyrolysis oils as a potential feedstock, as well as downstream products such as pyrolysis gasoline (pygas), these materials contain unsaturated hydrocarbons which are not present in fossil feedstocks. Pygas is a product of pyrolysis and exhibits a large number of chemical structural similarities with plastic pyrolysis oils, especially in terms of olefins structure. Quantification of the unsaturation content (olefins and di-olefins) is extremely important in industry, hence the focus of this manuscript. Detailed hydrocarbon analysis with flame ionization detection is inadequate to fully characterize the hydrocarbon composition of such samples, especially when peaks are closely eluting, or even co-eluting. In this study, the gas chromatography coupled to vacuum ultraviolet (GC-VUV) detection method previously described for the analysis of liquid hydrocarbon streams1 and plastic pyrolysis oils2 has been compared with comprehensive gas chromatography (GC × GC) and the industry standard for olefin quantification (i.e., bromine number titration). Although based on different methodologies, a correlation between the olefin content obtained from GC-VUV and the bromine number titration method is hereby presented.

Bromine Substitution Improves the Photothermal Performance of π-Conjugated Phototheranostic Molecules.

NIR-II fluorescence imaging-guided photothermal therapy (PTT) has been widely investigated due to its great application potential in tumor theranostics. PTT is an effective and non-invasive tumor treatment method that can adapt to tumor hypoxia; nevertheless, simple and effective strategies are still desired to develop new materials with excellent PTT properties to meet clinical requirements. In this work, we developed a bromine-substitution strategy to enhance the PTT of A-D-A'-D-A π-conjugated molecules. The experimental results reveal that bromine substitution can notably enhance the absorptivity (ϵ) and photothermal conversion efficiency (PCE) of the π-conjugated molecules, resulting in the brominated molecules generating two times more heat (ϵ808 nm ×PCE) than their unsubstituted counterpart. We disclose that the enhanced photothermal properties of bromine-substituted π-conjugated molecules are a combined outcome of the heavy-atom effect, enhanced ICT effect, and more intense bromine-mediate intermolecular π-π stacking. Finally, the NIR-II tumor imaging capability and efficient PTT tumor ablation of the brominated π-conjugated materials demonstrate that bromine substitution is a promising strategy for developing future high-performance NIR-II imaging-guided PTT agents.

Insights into the Structure-Capacity of Food Antioxidant Compounds Assessed Using Coulometry.

CDAC (coulometrically determined antioxidant capacity) involves the determination of the antioxidant capacity of individual compounds or their mixtures using constant-current coulometry, with electrogenerated Br2 as the titrant, and biamperometric detection of the endpoint via Br2 excess. CDAC is an accurate, sensitive, rapid, and cheap measurement of the mol electrons (mol e-) transferred in a redox process. In this study, the CDAC of 48 individual antioxidants commonly found in foods has been determined. The molar ratio CDAC (CDACχ, mol e- mol-1) of representative antioxidants is ranked as follows: tannic acid > malvidin-3-O-glucoside ≃ curcumin > quercetin > catechin ≃ ellagic acid > gallic acid > tyrosol > BHT ≃ hydroxytyrosol > chlorogenic acid ≃ ascorbic acid ≃ Trolox®. In many cases, the CDACχ ranking of the flavonoids did not comply with the structural motifs that promote electron or hydrogen atom transfers, known as the Bors criteria. As an accurate esteem of the stoichiometric coefficients for reactions of antioxidants with Br2, the CDACχ provides insights into the structure-activity relationships underlying (electro)chemical reactions. The electrochemical ratio (ER), defined as the antioxidant capacity of individual compounds relative to ascorbic acid, represents a dimensionless nutritional index that can be used to estimate the antioxidant power of any foods on an additive basis.

Bromine-Enhanced Generation and Epoxidation of Ethylene in Tandem CO2 Electrolysis Towards Ethylene Oxide.

The indirect electro-epoxidation of ethylene (C2 H4 ), produced from CO2 electroreduction (CO2 R), holds immense promise for CO2 upcycling to valuable ethylene oxide (EO). However, this process currently has a mediocre Faradaic efficiency (FE) due to sluggish formation and rapid dissociation of active species, as well as reductive deactivation of Cu-based electrocatalysts during the conversion of C2 H4 to EO and CO2 to C2 H4 , respectively. Herein, we report a bromine-induced dual-enhancement strategy designed to concurrently promote both C2 H4 -to-EO and CO2 -to-C2 H4 conversions, thereby improving EO generation, using single-atom Pt on N-doped CNTs (Pt1 /NCNT) and Br- -bearing porous Cu2 O as anode and cathode electrocatalysts, respectively. Physicochemical characterizations including synchrotron X-ray absorption, operando infrared spectroscopy, and quasi in situ Raman spectroscopy/electron paramagnetic resonance with theoretical calculations reveal that the favorable Br2 /HBrO generation over Pt1 /NCNT with optimal intermediate binding facilitates C2 H4 -to-EO conversion with a high FE of 92.2 %, and concomitantly, the Br- with strong nucleophilicity protects active Cu+ species in Cu2 O effectively for improved CO2 -to-C2 H4 conversion with a FE of 66.9 % at 800 mA cm-2 , superior to those in the traditional chloride-mediated case. Consequently, a single-pass FE as high as 41.1 % for CO2 -to-EO conversion can be achieved in a tandem system.

Preclinical studies of a PARP targeted, Meitner-Auger emitting, theranostic radiopharmaceutical for metastatic ovarian cancer.

Advanced ovarian cancer currently has few therapeutic options. Poly(ADP-ribose) polymerase (PARP) inhibitors bind to nuclear PARP and trap the protein-inhibitor complex to DNA. This work investigates a theranostic PARP inhibitor for targeted radiopharmaceutical therapy of ovarian cancer in vitro and PET imaging of healthy mice in vivo. METHODS: [77Br]RD1 was synthesized and assessed for pharmacokinetics and cytotoxicity in human and murine ovarian cancer cell lines. [76Br]RD1 biodistribution and organ uptake in healthy mice were quantified through longitudinal PET/CT imaging and ex vivo radioactivity measurements. Organ-level dosimetry following [76/77Br]RD1 administration was calculated using RAPID, an in-house platform for absorbed dose in mice, and OLINDA for equivalent and effective dose in human. RESULTS: The maximum specific binding (Bmax), equilibrium dissociation constant (Kd), and nonspecific binding slope (NS) were calculated for each cell line. These values were used to calculate the cell specific activity uptake for cell viability studies. The half maximal effective concentration (EC50) was measured as 0.17 (95 % CI: 0.13-0.24) nM and 0.46 (0.13-0.24) nM for PARP(+) and PARP(-) expressing cell lines, respectively. The EC50 was 0.27 (0.21-0.36) nM and 0.30 (0.22-0.41) nM for BRCA1(-) and BRCA1(+) expressing cell lines, respectively. When measuring the EC50 as a function of cellular activity uptake and nuclear dose, the EC50 ranges from 0.020 to 0.039 Bq/cell and 3.3-9.2 Gy, respectively. Excretion through the hepatobiliary and renal pathways were observed in mice, with liver uptake of 2.3 ± 0.4 %ID/g after 48 h, contributing to estimated absorbed dose values in mice of 19.3 ± 0.3 mGy/MBq and 290 ± 10 mGy/MBq for [77Br]RD1 and [76Br]RD1, respectively. CONCLUSION: [77Br]RD1 cytotoxicity was dependent on PARP expression and independent of BRCA1 status. The in vitro results suggest that [77Br]RD1 cytotoxicity is driven by the targeted Meitner-Auger electron (MAe) radiotherapeutic effect of the agent. Further studies investigating the theranostic potential, organ dose, and tumor uptake of [76/77Br]RD1 are warranted.

Tandem Efficient Bromine Removal and Silver Recovery by Resorcinol-Formaldehyde Resin Nanoparticles.

Halogen wastewater greatly threatens the health of human beings and aquatic organisms due to its severe toxicity, corrosiveness, and volatility. Efficient bromine removal is therefore urgently required, while existing Br2-capture materials often face challenges from limited water stability and possible halogen leaking. We report a facile and efficient aqueous Br2 removal method using submicron resorcinol-formaldehyde (RF) resin nanoparticles (NPs). The abundant aromatic groups dominate the Br2 removal by substitution reactions. An excellent Br2 conversion capacity of 7441 mg gRF-1 was achieved by RF NPs that outperform state-of-the-art materials by ∼2-fold, along with advantages including good water stability, low cost, and easy fabrication. Two recycling-coupled (electrochemical or H2O2-involved) Br2 removal routes further reveal the feasibility of in-depth halogen removal by RF NPs. The brominated resin can be downstream upcycled for silver recovery, realizing the harvesting of precious metal, reducing of heavy-metal pollution, and resource utilization of brominated resin.

Can Pyrolysis Oil Be Used as a Feedstock to Close the Gap in the Circular Economy of Polyolefins?

Plastics are engineering marvels that have found widespread use in all aspects of modern life. However, poor waste management practices and inefficient recycling technologies, along with their extremely high durability, have caused one of the major environmental problems facing humankind: waste plastic pollution. The upcycling of waste plastics to chemical feedstock to produce virgin plastics has emerged as a viable option to mitigate the adverse effects of plastic pollution and close the gap in the circular economy of plastics. Pyrolysis is considered a chemical recycling technology to upcycle waste plastics. Yet, whether pyrolysis as a stand-alone technology can achieve true circularity or not requires further investigation. In this study, we analyzed and critically evaluated whether oil obtained from the non-catalytic pyrolysis of virgin polypropylene (PP) can be used as a feedstock for naphtha crackers to produce olefins, and subsequently polyolefins, without undermining the circular economy and resource efficiency. Two different pyrolysis oils were obtained from a pyrolysis plant and compared with light and heavy naphtha by a combination of physical and chromatographic methods, in accordance with established standards. The results demonstrate that pyrolysis oil consists of mostly cyclic olefins with a bromine number of 85 to 304, whereas light naphtha consists of mostly paraffinic hydrocarbons with a very low olefinic content and a bromine number around 1. Owing to the compositional differences, pyrolysis oil studied herein is completely different than naphtha in terms of hydrocarbon composition and cannot be used as a feedstock for commercial naphtha crackers to produce olefins. The findings are of particular importance to evaluating different chemical recycling opportunities with respect to true circularity and may serve as a benchmark to determine whether liquids obtained from different polyolefin recycling technologies are compatible with existing industrial steam crackers' feedstock.

Effects of seawater intrusion on the formation of disinfection byproducts in drinking water.

Seawater contains high levels of halides, which can increase the concentrations of bromide and iodide ions in coastal groundwater and surface water sources. Intrusion of seawater alters the chemistry of fresh water leading to the formation of additional brominated and iodinated disinfection byproducts (DBPs), many of which are cyto- and genotoxic to the mammalian cells, and have cancer risks to humans. In this study, effects of seawater intrusion on the formation of trihalomethanes (THMs), and haloacetic acids (HAAs) were investigated by spiking groundwater using 0.0-2.0% seawater (by volume) and liquid chlorine as disinfectant. The concentrations of bromide and iodide ions in groundwater (0.0% seawater) were 42.5 and non-detected (ND) µg/L respectively, which were increased up to 1100 and 2.1 µg/L respectively, following mixing with 2.0% seawater. The regulated THMs (THM4) were increased from 30.4 to 106.3 µg/L while iodinated THMs (I-THMs) were increased from 0.13 to 1.6 µg/L respectively due possibly to molecular substitution and additional pathways of THMs formation. Bromoform was increased from 0.5 to 94.3 µg/L while iodoform was increased from ND to 1.02 µg/L. HAAs were increased from 27.9 to 72.9 µg/L where tribromoacetic acid was increased from 2.0 to 43.7 µg/L. In 0.0% seawater, bromine incorporation factor (BIF) for THM4 and HAAs were 0.077 and 0.050 respectively, which were increased to 0.942 and 0.38 at 2% seawater respectively. For dihalogenated HAAs (X2AA) and trihalogenated HAAs (X3AA), BIF in 0.0% seawater were 0.098 and 0.14 respectively, which were increased to 0.863 and 0.924 for 2.0% seawater respectively. Mixing of 2.0 seawater increased the toxicity of THM4, HAAs and I-THMs by 4.2, 5.9 and 201.8 folds, respectively indicating the importance of reducing seawater intrusion into the freshwater sources. Further, alteration of water sources and/or adaptation of advanced treatment can assist in lowering the risks.

Bromine Radical (Br• and Br2•-) Reactivity with Dissolved Organic Matter and Brominated Organic Byproduct Formation.

Dissolved organic matter (DOM) is a major scavenger of bromine radicals (e.g., Br• and Br2•-) in sunlit surface waters and during oxidative processes used in water treatment. However, the literature lacks quantitative measurements of reaction rate constants between bromine radicals and DOM and lacks information on the extent to which these reactions form brominated organic byproducts. Based on transient kinetic analysis with different fractions and sources of DOM, we determined reaction rate constants for DOM with Br• ranging from <5.0 × 107 to (4.2 ± 1.3) × 108 MC-1 s-1, which are comparable with those of HO• but higher than those with Br2•- (k = (9.0 ± 2.0) × 104 to (12.4 ± 2.1) × 105 MC-1 s-1). Br• and Br2•- attack the aromatic and antioxidant moieties of DOM via the electron transfer mechanism, resulting in Br- release with minimal substitution of bromine into DOM. For example, the total organic bromine was less than 0.25 µM (as Br) at environmentally relevant bromine radicals' exposures of ∼10-9 M·s. The results give robust evidence that the scavenging of bromine radicals by DOM is a crucial step to prevent inorganic bromine radical chemistry from producing free bromine (HOBr/OBr-) and subsequent brominated byproducts.

Exploration of brominated Plastoquinone analogs: Discovery and structure-activity relationships of small antimicrobial lead molecules.

In the fight with the antimicrobial resistance, our continuous effort to find quinone analogs with higher inhibitory activity has previously led us to the promising Plastoquinone analogs. The 1,4-quinone moiety substituted with alkoxy substituent(s) plays an important role in the field of antimicrobial and anticancer drug discovery and development. Thus, an extensive series of 1,4-quinones, substituted in different positions with a variety of alkoxy substituents, has been designed, synthesized, and evaluated for their antimicrobial activity. Here, we describe the synthesis of brominated Plastoquinone analogs (BrPQ1-15) based on the dimethyl-1,4-quinone scaffold by employing two different paths. We also present here the in vitro antimicrobial activity of these analogs (BrPQ1-15) against a panel of pathogenic organisms. These studies resulted in several new selective antibacterial inhibitors and gave valuable insights into the structure-activity relationships. Among all the analogs studied, two analogs BrPQ1 with a methoxy substituent and BrPQ14 with a cyclic dioxy stand out as the most promising antibacterial molecules against Staphylococcus aureus and Staphylococcus epidermidis. Afterwards, two analogs were selected for a further investigation for biofilm evaluation. Finally, molecular docking studies for BrPQ1 and BrPQ14 with probable target S. aureus PNPase (5XEX) and predictive ADMET studies were also carried out.

Toxicity of Ozonated Wastewater to HepG2 Cells: Taking Full Account of Nonvolatile, Volatile, and Inorganic Byproducts.

Wastewater ozonation forms various toxic byproducts, such as aldehydes, bromate, and organic bromine. However, there is currently no clear understanding of the overall toxicity changes in ozonated wastewater because pretreatment with solid phase extraction cannot retain inorganic bromate and volatile aldehydes, yet contributions of known ozonation byproducts to toxicity are unknown. Moreover, compared with bromate, organic bromine did not receive widespread attention. This study evaluated the toxicity of ozonated wastewater by taking aldehydes, bromate, and organic bromine into consideration. In the absence of bromide, formaldehyde contributed 96-97% cytotoxicity and 92-95% genotoxicity to HepG2 cells among the detected known byproducts, while acetaldehyde, propionaldehyde, and glyoxal had little toxicity. Both formaldehyde and dibromoacetonitrile drove toxicity among the known byproducts when bromide was present. Toxicity assays in HepG2 cells showed that when secondary effluents contained no bromide, the cytotoxicity of the nonvolatile organic fraction (NVOF) was reduced by 56-70%, and genotoxicity was completely removed after ozonation. However, the formed aldehydes (volatile organic fraction, VOF) led to increased overall toxicity. In the presence of bromide, compared with the secondary effluent, ozonation increased the cytotoxicity of the NVOFBr from 3.4-4.0 mg phenol/L to 10.3-13.9 mg phenol/L, possibly due to the formation of organic bromine. In addition, considering the toxicity of VOFBr (VOF in the presence of bromide, including aldehydes, tribromomethane, etc.), the overall cytotoxicity and genotoxicity became much higher than those of the secondary effluent. Although bromate had a limited impact on cytotoxicity and genotoxicity, it caused an increase in oxidative stress in HepG2 cells. Therefore, when taking full account of nonvolatile, volatile, and inorganic fractions, ozonation generally increases the toxicity of wastewater.

Behavioral and Neuronal Effects of Inhaled Bromine Gas: Oxidative Brain Stem Damage.

The risk of accidental bromine (Br2) exposure to the public has increased due to its enhanced industrial use. Inhaled Br2 damages the lungs and the heart; however, adverse effects on the brain are unknown. In this study, we examined the neurological effects of inhaled Br2 in Sprague Dawley rats. Rats were exposed to Br2 (600 ppm for 45 min) and transferred to room air and cage behavior, and levels of glial fibrillary acidic protein (GFAP) in plasma were examined at various time intervals. Bromine exposure resulted in abnormal cage behavior such as head hitting, biting and aggression, hypervigilance, and hyperactivity. An increase in plasma GFAP and brain 4-hydroxynonenal (4-HNE) content also was observed in the exposed animals. Acute and delayed sympathetic nervous system activation was also evaluated by assessing the expression of catecholamine biosynthesizing enzymes, tryptophan hydroxylase (TrpH1 and TrpH2), and tyrosine hydroxylase (TyrH), along with an assessment of catecholamines and their metabolites. TyrH was found to be increased in a time-dependent manner. TrpH1 and TrpH2 were significantly decreased upon Br2 exposure in the brainstem. The neurotransmitter content evaluation indicated an increase in 5-HT and dopamine at early timepoints after exposure; however, other metabolites were not significantly altered. Taken together, our results predict brain damage and autonomic dysfunction upon Br2 exposure.

A Radiobrominated Tyrosine Kinase Inhibitor for EGFR with L858R/T790M Mutations in Lung Carcinoma.

Activating double mutations L858R/T790M in the epidermal growth factor receptor (EGFR) region are often observed as the cause of resistance to tyrosine kinase inhibitors (TKIs). Third-generation EGFR-TKIs, such as osimertinib and rociletinib (CO-1686), was developed to target such resistance mutations. The detection of activating L858R/T790M mutations is necessary to select sensitive patients for therapy. Hence, we aimed to develop novel radiobromine-labeled CO-1686 as a positron emission tomography (PET) imaging probe for detecting EGFR L858R/T790M mutations. Nonradioactive brominated-CO1686 (BrCO1686) was synthesized by the condensation of N-(3-[{2-chloro-5-(trifluoromethyl)pyrimidin-4-yl}amino]-5-bromophenyl) acrylamide with the corresponding substituted 1-(4-[4-amino-3-methoxyphenyl]piperazine-1-yl)ethan-1-one. The radiobrominated [77Br]BrCO1686 was prepared through bromodestannylation of the corresponding tributylstannylated precursor with [77Br]bromide and N-chlorosuccinimide. Although we aimed to provide a novel PET imaging probe, 77Br was used as an alternative radionuclide for 76Br. We fundamentally evaluated the potency of [77Br]BrCO1686 as a molecular probe for detecting EGFR L858R/T790M using human non-small-cell lung cancer (NSCLC) cell lines: H1975 (EGFR L858R/T790M), H3255 (EGFR L858R), and H441 (wild-type EGFR). The BrCO1686 showed high cytotoxicity toward H1975 (IC50 0.18 ± 0.06 µM) comparable to that of CO-1686 (IC50 0.14 ± 0.05 µM). In cell uptake experiments, the level of accumulation of [77Br]BrCO1686 in H1975 was significantly higher than those in H3255 and H441 upon 4 h of incubation. The radioactivity of [77Br]BrCO1686 (136.3% dose/mg protein) was significantly reduced to 56.9% dose/mg protein by the pretreatment with an excess CO-1686. These results indicate that the binding site of the radiotracers should be identical to that of CO-1686. The in vivo accumulation of radioactivity of [77Br]BrCO1686 in H1975 tumor (4.51 ± 0.17) was higher than that in H441 tumor (3.71 ± 0.13) 1 h postinjection. Our results suggested that [77Br]BrCO1686 has specificity toward NSCLC cells with double mutations EGFR L858R/T790M compared to those in EGFR L858R and wild-type EGFR. However, the in vivo accumulation of radioactivity in the targeted tumor needs to be optimized by structural modification.

[The potential of using the underground mineral waters of the Moscow region in the organization of medical rehabilitation and medical tourism]. / Potentsial ispol'zovaniya podzemnykh mineral'nykh vod Moskovskogo regiona v organizatsii meditsinskoi reabilitatsii i lechebnogo turizma.

Moscow in modern borders is the largest metropolitan area in the country with a fairly high and unevenly distributed population density. This predetermines the need to address environmental regulation of urbanization in order to create the most comfortable living conditions for the population. Health care and the maintenance of health of all age groups are the leading role in the list of the most important tasks to ensure the social well-being of citizens. In the bowels of the Moscow region there are natural therapeutic resources: low-mineralized (M 3-5 g/l) sulfate sodium-magnesium-calcium drinking mineral water and chloride sodium bromine brine. The article presents the characteristics of the natural therapeutic resources of the Moscow region, the area of their therapeutic use, justified the possibility of wider use based on the available scientific data on the effect on the body of these waters and their analogues. All this provides an opportunity to achieve the main goal of medical resortology - the use of mineral water as a means of therapy, rehabilitation and prevention of most existing human diseases.

Halogen gas exposure: toxic effects on the parturient.

The elemental halogens include chlorine, bromine, and phosgene. Halogen gas can be directly weaponized and employed in warfare or terrorism. Industrial stockpiles or halogen transport can provide targets for terrorist attack as well as an origin for accidental release creating a risk for potential mass-casualty incidents. Pregnant and post-partum women represent a substantial and vulnerable subset of the population who may be at particular risk during an attack or accidental exposure. We review the effects of halogen exposure on the parturient with a focus on bromine toxicity. Bromine is the most extensively studied agent in the context of pregnancy and to-date murine models form the basis for the majority of current knowledge. Pregnancy potentiates the acute lung injury after halogen exposure. In addition, halogen exposure precipitates a preeclamptic-like syndrome in mice. This phenotype is characterized by systemic and pulmonary hypertension, endothelial dysfunction, decreased cardiac output, placental injury and fetal growth restriction. This constellation contributes to increased maternal and fetal mortality observed after bromine exposure. Angiogenic imbalance is noted with overexpression of the soluble fms-like tyrosine kinase-1 (sFlt-1) form of the vascular endothelial growth factor receptor 1 reminiscent of human preeclampsia. Additional research is needed to further explore the effect of halogen gas exposure in pregnancy and to develop therapeutic interventions to mitigate risk to this unique population.

Chlorine and Bromine Isotope Analysis of Polychlorinated Biphenyls and Polybrominated Diphenyl Ethers Using Gas Chromatography-Quadrupole Mass Spectrometry.

A compound-specific chlorine/bromine isotope analysis (Cl-/Br-CSIA) method was developed using gas chromatography-quadrupole mass spectrometry for polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs), which are toxic to human health and are frequently detected in various abiotic and biotic media. For PCB congeners, the molecular ion method for a concentration of 0.5-10.0 ppm, a dwell time of 20-100 ms, a relative EM voltage of 200 V, an electric current of 34 µA, and an ionization energy of 70 eV was determined as the most suitable scheme, which obtained standard deviations (SDs) of chlorine isotope ratios ranging from 0.00008 to 0.00068. As for the PBDE congeners, the lowest SDs, ranging from 0.00050 to 0.00172, were determined using the top four ion method with a concentration of 5-10 ppm and a dwell time of 20-50 ms. Both the chlorine and bromine isotope ratios showed strong concentration dependencies. Therefore, external standardization or detecting chlorine and bromine isotope ratios at a uniform concentration level is necessary to eliminate the concentration effect. In addition, 13C-correction is critical to remove interference from carbon isotopes. This newly developed Cl-/Br-CSIA method successfully determined the chlorine/bromine isotope ratios of PCBs/PBDEs in technical mixtures and traced the chlorine/bromine isotope ratio variations of PCBs/PBDEs in photodegradation experiments, thereby suggesting that it is a promising tool for assessing the sources and transformation processes of PCBs and PDBEs in the environment.

Halogen exposure injury in the developing lung.

Owing to a high-volume industrial usage of the halogens chlorine (Cl2 ) and bromine (Br2 ), they are stored and transported in abundance, creating a risk for accidental or malicious release to human populations. Despite extensive efforts to understand the mechanisms of toxicity upon halogen exposure and to develop specific treatments that could be used to treat exposed individuals or large populations, until recently, there has been little to no effort to determine whether there are specific features and or the mechanisms of halogen exposure injury in newborns or children. We established a model of neonatal halogen exposure and published our initial findings. In this review, we aim to contrast and compare the findings in neonatal mice exposed to Br2 with the findings published on adult mice exposed to Br2 and the neonatal murine models of bronchopulmonary dysplasia. Despite remarkable similarities across these models in overall alveolar architecture, there are distinct functional and apparent mechanistic differences that are characteristic of each model. Understanding the mechanistic and functional features that are characteristic of the injury process in neonatal mice exposed to halogens will allow us to develop countermeasures that are appropriate for, and effective in, this unique population.

Circulating and tissue biomarkers as predictors of bromine gas inhalation.

The threat from deliberate or accidental exposure to halogen gases is increasing, as is their industrial applications and use as chemical warfare agents. Biomarkers that can identify halogen exposure, diagnose victims of exposure or predict injury severity, and enable appropriate treatment are lacking. We conducted these studies to determine and validate biomarkers of bromine (Br2 ) toxicity and correlate the symptoms and the extent of cardiopulmonary injuries. Unanesthetized rats were exposed to Br2 and monitored noninvasively for clinical scores and pulse oximetry. Animals were euthanized and grouped at various time intervals to assess brominated fatty acid (BFA) content in the plasma, lung, and heart using mass spectrometry. Bronchoalveolar lavage fluid (BALF) protein content was used to assess pulmonary injury. Cardiac troponin I (cTnI) was assessed in the plasma to evaluate cardiac injury. The blood, lung, and cardiac tissue BFA content significantly correlated with the clinical scores, tissue oxygenation, heart rate, and cardiopulmonary injury parameters. Total (free + esterified) bromostearic acid levels correlated with lung injury, as indicated by BALF protein content, and free bromostearic acid levels correlated with plasma cTnI levels. Thus, BFAs and cardiac injury biomarkers can identify Br2 exposure and predict the severity of organ damage.