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.

Mechanisms involved in the neurotoxic effects of environmental toxicants such as polychlorinated biphenyls and brominated flame retardants.

Many toxic substances have been distributed to the environment, some of which have properties that promote accumulation and biomagnification in living organisms. Approximately 1.2 million metric tons of polychlorinated biphenyls (PCBs) have been produced and about 30% have been discharged to the environment. Approximately 200 000 metric tons of brominated flame retardants (BFRs) are produced annually, of which considerable amounts have been spread globally, even to the Polar Regions. Behavioral testing of animals has shown that these compounds may affect learning, memory and fine motor functions. Animals are most sensitive during early development. Several epidemiological studies have shown that PCBs and BFRs may be responsible for similar effects in humans. Of especially concern are possible effects of PCBs and BFRs in mixtures containing the highly neurotoxic methyl mercury. The compounds affect several targets in the nervous system that seem to be interconnected, and may be responsible for the observed behavioral deficits. It was shown early that PCBs affect dopamine and serotonin levels in the brain. Later studies showed that transport mechanisms of these neurotransmitters appear to be particularly sensitive to PCBs. Furthermore, PCBs affect intracellular calcium levels and induce formation of reactive oxygen species both in vivo and in vitro, and reduce cell viability in vitro. Neuroendocrine functions, particularly the thyroid hormone system, are also sensitive to disruption by PCBs and BFRs. Their metabolites, such as hydroxy-metabolites, appear to be particularly potent. We conclude that PCBs are particularly toxic during early development and that the toxic effects are a combination of several factors, including disturbance of calcium homeostasis, oxidative stress, and influence on neurotransmitter transport. Monoaminergic cells appear to be particularly vulnerable.

Bromide intoxication by the combination of bromide-containing over-the-counter drug and dextromethorphan hydrobromide.

A 30-year old woman was presented to the emergency room with marked lethargy and fever. Her physical examination showed an acneiform eruption on the face. Blood biochemistry showed a high chloride level and a negative anion gap. High blood bromide level measurements on an ion-selective electrode was noted later to cause spurious hyperchloremia with a negative anion gap. After receiving saline hydration and diuretic treatment, her serum chloride returned to normal range on hospital day nine. Slow resolution of her mental status occurred over 2 months. Her skin lesions disappeared about 5 months later. In conclusion, in face of an unusual high chloride level and a negative anion gap in a patient of long-term use of over-the-counter (OTC) agents, bromide intoxication should be included in the differential diagnosis.

Bromism from daily over intake of bromide salt.

Bromide intoxication today is an infrequent disease, but preparations containing bromide are still available in nonprescription compounds, on the French market. We report a casewith bromide intoxication due to daily over intake (approximately 20 tablets per day; i.e. total elemental bromide intake approximately 6 g/day) of calcium bromo-galactogluconate (Calcibronat) for 1.5 months. A 30-year-old woman with a long history of psychotropic drug abuse was hospitalized in a psychiatric department for neuropsychological manifestations. She presented a seriously disturbed mental status with confusion, disorientation, auditory and visual hallucinations, and loss of short-time memory. A markedly increased serum bromide level of 1717 mg/L (21.5 mEq/L) measured on the first day after her admission confirmed the diagnosis of chronic bromism suspected based on her symptomatology. During her hospitalization, bromide plasma concentrations were measured and monitored using inductively coupled plasma mass spectrometry, a sensitive and very specific method. After withdrawal of the drug, the symptoms improved within 8 days. Serial bromide concentrations gradually declined throughout nearly 2 months of monitoring, until she was discharged from the hospital. We found an elimination half-life of bromide in blood of approximately of 10 days. This case demonstrates that, while today bromism occurs infrequently, it should still be included in the differential diagnosis of neuropsychiatric symptoms.

Another hot tub hazard. Toxicity secondary to bromine and hydrobromic acid exposure.

We describe the clinical course of two patients who developed acute pneumonitis followed by reactive airways dysfunction syndrome after bathing in a hot tub. Additional findings were present and suggested that exposure to a corrosive agent was responsible. Bromine and hydrobromic acid generated from a widely used water disinfectant were implicated as the underlying cause. Physicians should be alert to the possibility that such exposures may initiate or exacerbate inflammatory pulmonary disease.

Bromide intoxication due to propantheline bromide.

An elderly woman presented with pneumonia and mental status changes and was found to have bromide poisoning due to ingestion of propantheline bromide over a 2-month period. The interference of bromide with serum chloride measurements on an ion-selective electrode resulted in spurious hyperchloremia and was crucial in making the diagnosis. To our knowledge, bromide intoxication due to propantheline bromide has not been reported previously.

Delayed health sequelae of accidental exposure to bromine gas.

The delayed health effects from accidental exposure to bromine vapors in a group of six people were evaluated. During the acute exposure, they had only some respiratory symptoms and skin burns of first to second degree involving small areas. All were treated in one hospital and released within 1-4 d. Six to 8 wk later, some still had health complaints such as cough, shortness of breath, chest tightness, eye irritation, headache, dizziness, fatigue, and memory, sleep, and sexual disturbances, but no objective laboratory or clinical evidence of effects. Mechanisms that might have led to manifestations of such complaints 1-2 mo after the accident are discussed and possible ways to alleviate similar situations are suggested.

[Acute poisoning with bromine vapors of a pharmaceutical plant operator]. / Ostroe otravlenie parami broma u apparatchika khimiko-farmatsevticheskogo zavoda.

A characteristic feature of bromium acute intoxications in levomycetine production is the delayed hemorrhagic component manifestation in the clinical course of toxic bronchitis (on the 20th day after inhaling bromium vapours), and the changes in the heart in the form of myocardial toxic dystrophia, as well as the growing activity of some liver related enzymes, which is indicative of the hepatocyte membrane lesions.

Bromate intoxication: hairdressers' anuria.

A 17-year-old hairdresser developed sodium bromate poisoning after drinking a cup of hair neutralizer in a suicide attempt. She presented 1 week later with anuria, required hemodialysis for 5 days, and subsequently recovered. Sensorineural hearing loss, often a characteristic finding, was absent. Early diagnosis of bromate intoxication requires an appreciation that it commonly occurs in hairdressers, may be accompanied by deafness, and may present with insidious anuria.

Accidental bromine exposure in an urban population: an acute epidemiological assessment.

In November 1984, because of an accident at a chemical plant, the population of a large area in the town of Geneva, Switzerland, was exposed to toxic bromine gas during several hours at concentrations above the short-term exposure limit. We describe the development of the disaster, the reactions of the fire brigade, the police and the first aid services as well as the breakdown of communications that occurred. On-the-spot epidemiological assessment of the exposed area and of the characteristics of the exposure syndrome was combined with the emergency care of 91 self-referred patients that were seen at the University Hospital. Follow-up was obtained one month later. The clinical course was moderate (eyes and upper airways irritation) and self-limiting in all cases. Immediate definition of the exposed population permitted effective follow-up. Such early evaluation could prove to be of crucial importance for managing more serious accidents of a similar nature.