Hyaluronan and halogen-induced airway hyperresponsiveness and lung injury.

Chlorine (Cl2 ) and bromine (Br2 ) are produced in large quantities throughout the world and used in the industry and the sanitation of water. These halogens can pose a significant threat to public health when released into the atmosphere during transportation and industrial accidents, or as acts of terrorism. In this review, we discuss the evidence showing that the activity of Cl2 and Br2 , and of products formed by their interaction with biomolecules, fragment high-molecular-weight hyaluronan (HMW-HA), a key component of the interstitial space and present in epithelial cells, to form proinflammatory, low-molecular-weight hyaluronan fragments that increase intracellular calcium (Ca2+ ) and activate RAS homolog family member A (RhoA) in airway smooth muscle and epithelial and microvascular cells. These changes result in airway hyperresponsiveness (AHR) to methacholine and increase epithelial and microvascular permeability. The increase in intracellular Ca2+ is the result of the activation of the calcium-sensing receptor by Cl2 , Br2 , and their by-products. Posthalogen administration of a commercially available form of HMW-HA to mice and to airway cells in vitro reverses the increase of Ca2+ and the activation of RhoA, and restores AHR to near-normal levels of airway function. These data have established the potential of HMW-HA to be a countermeasure against Cl2 and Br2 toxicity.

Vascular permeability disruption explored in the proteomes of mouse lungs and human microvascular cells following acute bromine exposure.

Bromine (Br2) is an organohalide found in nature and is integral to many manufacturing processes. Br2 is toxic to living organisms, and high concentrations can prove fatal. To meet industrial demand, large amounts of purified Br2 are produced, transported, and stored worldwide, providing a multitude of interfaces for potential human exposure through either accidents or terrorism. To identify the key mechanisms associated with acute Br2 exposure, we have surveyed the lung proteomes of C57BL/6 male mice and human lung-derived microvascular endothelial cells (HMECs) at 24 h following exposure to Br2 in concentrations likely to be encountered in the vicinity of industrial accidents. Global discovery proteomics applications combined with systems biology analysis identified robust and highly significant changes in proteins associated with three biological processes: 1) exosome secretion, 2) inflammation, and 3) vascular permeability. We focused on the latter, conducting physiological studies on isolated perfused lungs harvested from mice 24 h after Br2 exposure. These experiments revealed significant increases in the filtration coefficient (Kf) indicating increased permeability of the pulmonary vasculature. Similarly, confluent monolayers of Br2 and Br-lipid-treated HMECs exhibited differential levels of zona occludens-1 that were found to be dissociated from cell wall localization, an increase in phosphorylation and internalization of E-cadherin, as well as increased actin stress fiber formation, all of which are consistent with increased permeability. Taken as a whole, our discovery proteomics and systems analysis workflow, combined with physiological measurements of permeability, revealed both profound and novel biological changes that contribute to our current understanding of Br2 toxicity.

Upregulation of airway smooth muscle calcium-sensing receptor by low-molecular-weight hyaluronan.

We investigated the mechanisms involved in the development of airway hyperresponsiveness (AHR) following exposure of mice to halogens. Male mice (C57BL/6; 20-25 g) exposed to either bromine (Br2) or Cl2 (600 or 400 ppm, respectively, for 30 min) developed AHR 24 h after exposure. Nifedipine (5 mg/kg body wt; an L-type calcium channel blocker), administered subcutaneously after Br2 or Cl2 exposure, produced higher AHR compared with Br2 or Cl2 alone. In contrast, diltiazem (5 mg/kg body wt; a nondihydropyridine L-type calcium channel blocker) decreased AHR to control (air) values. Exposure of immortalized human airway smooth muscle cells (hASMC) to Br2 resulted in membrane potential depolarization (Vm Air: 62 ± 3 mV; 3 h post Br2:-45 ± 5 mV; means ± 1 SE; P < 0.001), increased intracellular [Ca2+]i, and increased expression of the calcium-sensing receptor (Ca-SR) protein. Treatment of hASMC with a siRNA against Ca-SR significantly inhibited the Br2 and nifedipine-induced Vm depolarization and [Ca2+]i increase. Intranasal administration of an antagonist to Ca-SR in mice postexposure to Br2 reversed the effects of Br2 and nifedipine on AHR. Incubation of hASMC with low-molecular-weight hyaluronan (LMW-HA), generated by exposing high-molecular-weight hyaluronan (HMW-HA) to Br2, caused Vm depolarization, [Ca2+]i increase, and Ca-SR expression to a similar extent as exposure to Br2 and Cl2. The addition of HMW-HA to cells or mice exposed to Br2, Cl2, or LMW-HA reversed these effects in vitro and improved AHR in vivo. We conclude that detrimental effects of halogen exposure on AHR are mediated via activation of the Ca-SR by LMW-HA.

Towards integrating toxicity characterization into environmental studies: case study of bromine in soils.

AbstractPollution from bromine and some of its related compounds is currently unregulated in soil from Russia and other countries, and tools for sound assessment of environmental impacts of bromine contamination are largely missing. Hence, assessing potential implications for humans and ecosystems of bromine soil contamination is urgently needed, which requires the combination of measured soil concentrations from environmental studies and quantified potential toxicity impacts. To address this need, we used data from an experimental study assessing bromine in soils (384 samples) of Tomsk oblast, Russia, starting from measured concentrations obtained by Instrumental Neutron Activation Analysis in an earlier study. From these data, we calculated the bromine mass in soils and used these as starting point to characterize related cumulative impacts on human health and ecosystems in the Tomsk region, using a global scientific consensus model for screening-level comparative toxicity characterization of chemical emissions. Results show that the combination of sampling methodology with toxicity characterization techniques presents a new approach to be used in environmental studies aimed at environmental assessment and analysis of a territory. Our results indicate that it is important to account for substance-specific chemical reaction pathways and transfer processes, as well as to consider region-specific environmental characteristics. Our approach will help complement environmental assessment results with environmental sustainability elements, to consider potential tradeoffs in impacts, related to soil pollution, in support of improved emission and pollution reduction strategies.

Pool Chemical Injuries in Public and Residential Settings - United States, 2008-2017, and New York, 2018.

Pool chemicals are added to water in treated recreational water venues (e.g., pools, hot tubs/spas, and water playgrounds) primarily to protect public health. Pool chemicals inactivate pathogens (e.g., chlorine or bromine), optimize pH (e.g., muriatic acid), and increase water clarity, which helps prevent drowning by enabling detection of distressed swimmers underwater. However, pool chemicals can cause injuries if mishandled. To estimate the annual number of U.S. emergency department (ED) visits for pool chemical injuries, CDC analyzed 2008-2017 data from the National Electronic Injury Surveillance System (NEISS), operated by the U.S. Consumer Product Safety Commission (CPSC). During 2015-2017, pool chemical injuries led to an estimated 13,508 (95% confidence interval [CI] = 9,087-17,929) U.S. ED visits; 36.4% (estimated 4,917 [95% CI = 3,022-6,811]) of patients were aged <18 years. At least 56.3% (estimated 7,601 [95% CI = 4,587-10,615]) of injuries occurred at a residence. Two thirds of the injuries occurred during the period from Memorial Day weekend through Labor Day. This report also describes a toxic chlorine gas incident that occurred at a public pool in New York in 2018. Pool chemical injuries are preventable. CDC's Model Aquatic Health Code (MAHC) is an important resource that operators of public treated recreational water venues (e.g., at hotels, apartment complexes, and waterparks) can use to prevent pool chemical injuries.

The occurrence and transformation behaviors of disinfection byproducts in drinking water distribution systems in rural areas of eastern China.

The occurrence and transformation behaviors of disinfection byproducts (DBPs) were investigated in the finished water and tap water of 14 water treatment plants in rural areas of eastern China. Mammalian cell toxicity data from previous studies were used to evaluate the cytotoxicity of trihalomethanes (THMs), haloacetic acids (HAAs), haloacetonitriles (HANs), trichloronitromethane (TCNM) and the genotoxicity of HAAs, HANs and TCNM. Correlation analysis was conducted to identify the factors that might influence the variability of DBPs. The measured median values were 29.76 µg/L for THMs, 20.47 µg/L for HAAs, 3.98 µg/L for HANs, 0.76 µg/L for haloketones (HKs) and 0.03 µg/L for TCNM. The spatial variability analysis showed that the total concentrations of HAAs and HANs decreased during long hydraulic residence time (HRT) in seven drinking water distribution systems, which could result in reduced mammalian cell cytotoxicity and genotoxicity at consumers' taps. The concentrations of trihalogenated-DBPs were more stable than those of dihalogenated-DBPs and monohalogenated-DBPs during long HRT. Bromine acted as a more efficient substituting agent than chlorine for THMs and dihaloacetonitriles (DHANs) in actual drinking water. The dominant chlorinated-THMs and chlorinated-DHANs would transfer to brominated -THMs and brominated-DHANs when the concentration of bromide ion exceeds 450.67 and 610.25 µg/L, respectively. Correlation analysis indicated that particulate and soluble manganese (Mn) might play critical roles in promoting the production of DBPs in bulk water. Hydraulic disturbance could also result in secondary release of DBPs from loose deposits accumulated on distribution pipe walls.

Toxicological Aspect of Some Selected Medicinal Plant Samples Collected from Djelfa, Algeria Region.

Instrumental neutron activation analysis (INAA) has been used to determine the concentration of some toxic chemical elements in a variety of aromatic plants samples collected from Djelfa region. In the present work, eight medicinal plants were examined, such as Artemisia herba-alba Asso., Artemisia compestris L., Laurus nobilis L., Origanum vulgare L., Mentha spicata L., Rosmarinus officinalis L., Mentha pulegium L., and Pistacia lentiscus L. The levels of toxic elements were compared to their daily total intake; Arsenic was present in all plant species examined, with a concentration ranging from 0.18 to 5.44 µg g- 1. Bromine was also detected in all the medicinal plant species, with high concentrations, compared to arsenic except in the case of Laurus nobilis that has the highest concentration of arsenic. Cerium, cobalt, chromium, and antimony were presented in all plant species. The exactitude of the results was assessed by analyzing the certified reference material of SRM-NIST 1573a and CRM GB07605 (GSV4). These data analysis for this medicinal plant can be useful for therapeutics and pharmaceutical purposes.

Bromine inhalation mimics ischemia-reperfusion cardiomyocyte injury and calpain activation in rats.

Halogens are widely used, highly toxic chemicals that pose a potential threat to humans because of their abundance. Halogens such as bromine (Br2) cause severe pulmonary and systemic injuries; however, the mechanisms of their toxicity are largely unknown. Here, we demonstrated that Br2 and reactive brominated species produced in the lung and released in blood reach the heart and cause acute cardiac ultrastructural damage and dysfunction in rats. Br2-induced cardiac damage was demonstrated by acute (3-24 h) increases in circulating troponin I, heart-type fatty acid-binding protein, and NH2-terminal pro-brain natriuretic peptide. Transmission electron microscopy demonstrated acute (3-24 h) cardiac contraction band necrosis, disruption of z-disks, and mitochondrial swelling and disorganization. Echocardiography and hemodynamic analysis revealed left ventricular (LV) systolic and diastolic dysfunction at 7 days. Plasma and LV tissue had increased levels of brominated fatty acids. 2-Bromohexadecanal (Br-HDA) injected into the LV cavity of a normal rat caused acute LV enlargement with extensive disruption of the sarcomeric architecture and mitochondrial damage. There was extensive infiltration of neutrophils and increased myeloperoxidase levels in the hearts of Br2- or Br2 reactant-exposed rats. Increased bromination of sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) and increased phosphalamban after Br2 inhalation decreased cardiac SERCA activity by 70%. SERCA inactivation was accompanied by increased Ca2+-sensitive LV calpain activity. The calpain-specific inhibitor MDL28170 administered within 1 h after exposure significantly decreased calpain activity and acute mortality. Bromine inhalation and formation of reactive brominated species caused acute cardiac injury and myocardial damage that can lead to heart failure. NEW & NOTEWORTHY The present study defines left ventricular systolic and diastolic dysfunction due to cardiac injury after bromine (Br2) inhalation. A calpain-dependent mechanism was identified as a potential mediator of cardiac ultrastructure damage. This study not only highlights the importance of monitoring acute cardiac symptoms in victims of Br2 exposure but also defines calpains as a potential target to treat Br2-induced toxicity.

Exposure of neonatal mice to bromine impairs their alveolar development and lung function.

The halogen bromine (Br2) is used extensively in industry and stored and transported in large quantities. Its accidental or malicious release into the atmosphere has resulted in significant casualties. The pathophysiology of Br2-induced lung injury has been studied in adult animals, but the consequences of Br2 exposure to the developing lung are completely unknown. We exposed neonatal mouse littermates on postnatal day 3 (P3) to either Br2 at 400 ppm for 30 min (400/30), to Br2 at 600 ppm for 30 min (600/30), or to room air, then returned them to their dams and observed until P14. Mice exposed to Br2 had decreased survival (S) and had decreased weight (W) at P14 in the 400/30 group (S = 63.5%, W = 6.67 ± 0.08) and in the 600/30 group (S = 36.1%, W = 5.13 ± 0.67) as compared with air breathing mice (S = 100%, W = 7.96 ± 0.30). Alveolar development was impaired, as evidenced by increased mean linear intercept at P14. At P14, Br2 exposed mice also exhibited a decrease of arterial partial pressure of oxygen, decreased quasi-static lung compliance, as well as increased alpha smooth muscle actin mRNA and protein and increased mRNA for IL-1ß, IL-6, CXCL1, and TNFα. Global gene expression, evaluated by RNA sequencing and Ingenuity Pathway Analysis, revealed persistent abnormalities in gene expression profiles at P14 involving pathways of "formation of lung" and "pulmonary development." The data indicate that Br2 inhalation injury early in life results in severe lung developmental consequences, wherein persistent inflammation and global altered developmental gene expression are likely mechanistic contributors.

Mechanisms and Treatment of Halogen Inhalation-Induced Pulmonary and Systemic Injuries in Pregnant Mice.

Inhalation of oxidant gases has been implicated in adverse outcomes in pregnancy, but animal models to address mechanisms and studies to identify potential pregnancy-specific therapies are lacking. Herein, we show that inhalation of bromine at 600 parts per million for 30 minutes by pregnant mice on the 15th day of embryonic development results in significantly lower survival after 96 hours than an identical level of exposure in nonpregnant mice. On the 19th embryonic day, bromine-exposed pregnant mice have increased systemic blood pressure, abnormal placental development, severe fetal growth restriction, systemic inflammation, increased levels of circulating antiangiogenic short fms-like tyrosine kinase-1, and evidence of pulmonary and cardiac injury. Treatment with tadalafil, an inhibitor of type 5 phosphodiesterase, by oral gavage 1 hour post-exposure and then once daily thereafter, attenuated systemic blood pressures, decreased inflammation, ameliorated pulmonary and cardiac injury, and improved maternal survival (from 36% to 80%) and fetal growth. These pathological changes resemble those seen in preeclampsia. Nonpregnant mice did not exhibit any of these pathological changes and were not affected by tadalafil. These findings suggest that pregnant women exposed to bromine may require particular attention and monitoring for signs of preeclampsia-like symptoms.

Measuring nitrate reductase activity from human and rodent tongues.

Reduction of salivary nitrate to nitrite by oral microbes expressing nitrate-reductase has emerged as a crucial pathway in systemic NO homeostasis in humans and other mammals. Selective depletion of oral microbes prevents dietary nitrate-dependent lowering of blood pressure, inhibition of platelet aggregation and ischemic injury. To date, most studies interrogate enterosalivary nitrate reduction by following changes in saliva or plasma nitrite and NO-signaling (functional) end points. Little is known about whether, and if so how, nitrate-reductase enzymatic activity per se (i.e. independent of nitrate levels) is a variable and may account for any individual to individual variation. Here, we describe a minimally invasive protocol that allows for NR activity determination from human, rat and mouse tongue scrapes/swabs. We validate this method using selective application of antiseptic agents to the distal tongue surface which decreased NR activity by >80% and show that bacterial number is a significant variable in measured NR activities between males and females. Also, we show that NR activity is >80% lower in smokers (humans) and after bromine gas exposure (mice), suggesting that exposure to inhaled reactive substances inhibit NR activity identifying a potentially new mechanism by which environmental toxicants promote dysfunction in NO-bioavailability. The described method will facilitate studies testing whether NR specific activity is a variable in different pathophysiologic settings, and in turn how this activity modulates enterosalivary nitrate-reduction.

Role of heme in bromine-induced lung injury.

Bromine (Br2 ) gas inhalation poses an environmental and occupational hazard resulting in high morbidity and mortality. In this review, we underline the acute lung pathology (within 24 h of exposure) and potential therapeutic interventions that may be utilized to mitigate Br2 -induced human toxicity. We discuss our latest published data, which suggest that an increase in heme-dependent tissue injury underlies the pathogenesis of Br2 toxicity. Our study was based on previous findings that demonstrated that Br2 upregulates the heme-degrading enzyme heme oxygenase-1 (HO-1), which converts toxic heme into bilverdin. Interestingly, following Br2 inhalation, heme levels were indeed elevated in bronchoalveolar lavage fluid, plasma, and whole lung tissue in C57BL/6 mice. High heme levels correlated with increased lung oxidative stress, lung inflammation, respiratory acidosis, lung edema, higher airway resistance, and mortality. However, therapeutic reduction of heme levels, by either scavenging with hemopexin or degradation by HO-1, improved lung function and survival. Therefore, heme attenuation may prove a useful adjuvant therapy to treat patients after Br2 exposure.

A dynamic system for delivering controlled bromine and chlorine vapor exposures to weanling swine skin.

CONTEXT: Assessing the hazards of accidental exposure to toxic industrial chemical (TIC) vapors and evaluating therapeutic compounds or treatment regimens require the development of appropriate animal models. OBJECTIVE: The objective of this project was to develop an exposure system for delivering controlled vapor concentrations of TICs to the skin of anesthetized weanling pigs. Injury levels targeted for study were superficial dermal (SD) and deep dermal (DD) skin lesions as defined histopathologically. MATERIALS AND METHODS: The exposure system was capable of simultaneously delivering chlorine or bromine vapor to four, 3-cm diameter exposure cups placed over skin between the axillary and inguinal areas of the ventral abdomen. Vapor concentrations were generated by mixing saturated bromine or chlorine vapor with either dried dilution air or nitrogen. RESULTS: Bromine exposure concentrations ranged from 6.5 × 10(-4) to 1.03 g/L, and exposure durations ranged from 1 to 45 min. A 7-min skin exposure to bromine vapors at 0.59 g/L was sufficient to produce SD injuries, while a 17-min exposure produced a DD injury. Chlorine exposure concentrations ranged from 1.0 to 2.9 g/L (saturated vapor concentration) for exposures ranging from 3 to 90 min. Saturated chlorine vapor challenges for up to 30 min did not induce significant dermal injuries, whereas saturated chlorine vapor with wetted material on the skin surface for 30-60 min induced SD injuries. DD chlorine injuries could not be induced with this system. CONCLUSION: The vapor exposure system described in this study provides a means for safely regulating, quantifying and delivering TIC vapors to the skin of weanling swine as a model to evaluate therapeutic treatments.

Comparative antioxidant status in freshwater fish Carassius auratus exposed to six current-use brominated flame retardants: a combined experimental and theoretical study.

Decabromodiphenyl ether (BDE-209) and several non-polybrominated diphenyl ether (PBDE) brominated flame retardants (BFRs), such as tetrabromobisphenol A (TBBPA), hexabromocyclododecane (HBCD), decabromodiphenyl ethane (DBDPE), hexabromobenzene (HBB) and pentabromotoluene (PBT), are persistent halogenated contaminants ubiquitously detected in aquatic systems. However, data on comparative toxicological effects of these BFRs are lacking for fish. In this study, a combined experimental and theoretical approach was used to compare and analyze the effects of these BFRs on biochemical biomarkers in liver of Carassius auratus injected intraperitoneally with different doses (10 and 100mg/kg) for 7, 14 and 30 days. Oxidative stress was evoked evidently for the prolonged exposure, represented by the significantly altered indices (superoxide dismutase, catalase, glutathione peroxidase, reduced glutathione, and malondialdehyde). The integrated biomarker response (IBR) index ranked biotoxicity as: PBT>HBB>HBCD>TBBPA>BDE-209>DBDPE. Quantum chemical calculations (electronic parameters, frontier molecular orbitals, and Wiberg bond order) were performed for theoretical analysis. Notably, some descriptors were correlated with the toxicity order, probably implying the existence of a potential structure-activity relationship when more BFRs were included. Besides, theoretical calculations also provided some valuable information regarding the molecular characteristics and metabolic pathways of these current-use BFRs, which may facilitate the understanding on their environmental behavior and fate. Overall, this study adopted a combined experimental and theoretical method for the toxicological determination and analysis of the BFRs, which may also be considered in future ecotoxicological studies.

Assessment of heavy metal content and DNA damage in Hypsiboas faber (anuran amphibian) in coal open-casting mine.

The aims of the study were to determine the heavy metal content in the tissues of Hypsiboas faber from a coal mining area and to compare the DNA damage in the blood cells of these animals with that of animals living in an unpolluted area. The heavy metal content was detected according to the technique of Particle-Induced X-ray Emission (PIXE) and the DNA damage was assessed by the Comet assay. Our results reveal that the specimens of H. faber collected from the coal mining area exhibited elements of order Fe>Cu>Al>Zn>Rb>Mn>Br, independently of the organ. The values of Comet assay parameters (DNA damage index and DNA damage frequency) were significantly higher in specimens collected from the coal mining area than in the reference animals. Our study concludes that the coal mining residues are genotoxic to amphibians and may have adverse effects on soil, water, vegetation and wild animals.

Study of the transference rules for bromine in waste printed circuit boards during microwave-induced pyrolysis.

The production of waste printed circuit boards (WPCBs) has drawn increasing global concern, especially because the high bromine (Br) content (5-15%) places obstacles in the way of simple disposal techniques. Microwave-induced pyrolysis of WPCBs provides a promising way to dispose of these hazardous and resource-filled wastes. The transference rules for Br during microwave-induced pyrolysis have been investigated experimentally. It was found that the microwave energy could be used more efficiently to accelerate the heating rate and improve the final pyrolysis temperature by adding some activated carbon (AC) as microwave absorbents. The high temperature and rapid pyrolysis process promoted the yields of gaseous products and the decomposition of brominated compounds into hydrogen bromide and then benefited the capture of Br and the debromination of byproducts. The application of a calcium carbonate (CaCO3) layer overhead led to over 95% debromination of the liquid products and over 50% capture of the total Br. It can be concluded that the presented method is suitable for the control of Br transference in the recycling of WPCBs. This method can also be extended to the disposal of the electronic scraps.

An assessment of transcriptional changes in porcine skin exposed to bromine vapor.

Bromine is an industrial chemical that can cause severe cutaneous burns. This study was a preliminary investigation into the effect of cutaneous exposure to bromine vapor using a weanling swine burn model and microarray analysis. Ventral abdominal sites were exposed to a mean calculated bromine vapor concentration of 0.69 g L(-1) for 10 or 20 min. At 48 h postexposure, total RNA from skin samples was isolated, processed, and hybridized to Affymetrix GeneChip Porcine Genome Arrays. Expression analysis revealed that bromine vapor exposure for 10 or 20 min promoted similar transcriptional changes in the number of significantly modulated probe sets. A minimum of 83% of the probe sets was similar for both exposure times. Ingenuity pathways analysis revealed eight common biological functions among the top 10 functions of each experimental group, in which 30 genes were commonly shared among 19 significantly altered signaling pathways. Transcripts encoding heme oxygenase 1, interleukin-1ß, interleukin 2 receptor gamma chain, and plasminogen activator inhibitor-1 were identified as common potential therapeutic targets for Phase II/III clinical trial or FDA-approved drugs. The present study is an initial assessment of the transcriptional responses to cutaneous bromine vapor exposure identifying molecular networks and genes that could serve as targets for developing therapeutics for bromine-induced skin injury.

Temporal effects in porcine skin following bromine vapor exposure.

Bromine is an industrial chemical that causes severe cutaneous burns. When selecting or developing effective treatments for bromine burns, it is important to understand the molecular mechanisms of tissue damage and wound healing. This study investigated the effect of cutaneous bromine vapor exposure on gene expression using a weanling swine burn model by microarray analysis. Ventral abdominal sites were exposed to a mean calculated bromine vapor concentration of 0.51 g/L for 7 or 17 min. At 6 h, 48 h, and 7 days post-exposure, total RNA from skin samples was isolated, processed, and analyzed with Affymetrix GeneChip® Porcine Genome Arrays (N = 3 per experimental group). Differences in gene expression were observed with respect to exposure duration and sampling time. Ingenuity Pathways Analysis (IPA) revealed four common biological functions (cancer, cellular movement, cell-to-cell signaling and interaction, and tissue development) among the top ten functions of each experimental group, while canonical pathway analysis revealed 9 genes (ARG2, CCR1, HMOX1, ATF2, IL-8, TIMP1, ESR1, HSPAIL, and SELE) that were commonly shared among four significantly altered signaling pathways. Among these, the transcripts encoding HMOX1 and ESR1 were identified using IPA as common potential therapeutic targets for Phase II/III clinical trial or FDA-approved drugs. The present study describes the transcriptional responses to cutaneous bromine vapor exposure identifying molecular networks and genes that could serve as targets for developing therapeutics for bromine-induced skin injury.

Bromine--the red cloud approaching.

Bromine is a strong and prevalent irritating agent that can spread both as liquid and as fumes. It has a characteristic reddish-brown color. The mainstay of the medical management is supportive and symptomatic therapy that should be given as soon as possible to prevent further damage. Medical personnel, especially the emergency department staff, should be familiar with its health effects, including the safety precautions needed when caring for casualties following such an exposure.