Hydrogen bromide

Endpoint summary

Additional information

Toxicokinetic summary: Hydrogen bromide (HBr)

 

Though there are minimal animal repeated dose data on hydrogen bromide (HBr) available (supporting study provided in Section 8.6.1: 20-day repeated inhalation study in the rat), there are sufficient data available on the analogue substance hydrogen chloride (HCl) (Section 8.6.2; inhalation exposure) to indicate an appropriate level for hazard identification for the main route of exposure (i.e., inhalation). The available data on the analogue HCl have been used for indication of an EU Indicative Occupational Exposure Level value (IOELV) for HBr given in Directive 2000/39/EC (15 minute IOELV limit = 6.7 mg/m3 or 2 ppm). Additional routes of exposure (i.e., oral or dermal) are not considered as appropriate routes for determination of toxicity.

 

HCl vapour or aerosols of hydrochloric acid are readily inhaled. HCl rapidly dissociates into hydrogen and chloride ions. Inhaled HCl is partially neutralized by naturally occurring ammonia gas in the respiratory system, before it reaches the lower respiratory tract. HBr is expected to react in a similar manner.

 

For the endpoint of lethality, the relative toxicities to the rat and mouse follow the order hydrogen fluoride (HF) > HBr > HCl (MacEwen, J.D., and Vernot, E.H., 1972). When considering sublethal concentrations, the severity and extent of lesions to the upper respiratory tract were in the order HF > HCl ≈ HBr, although the severity and extent of lesions were very similar among the three chemicals (Kusewitt, D.F., et al., 1989; Stavert, D.M., et al., 1991).

 

The data also showed that all three chemicals are well scrubbed in the upper respiratory passages.

 

Routes of exposure

HBr is a gas and therefore inhalation exposure is the most relevant route of exposure to humans. It also volatilises easily from solution (hydrobromic acid). Other routes of exposure are minimal due to HBr’s reactivity. HBr can dissociate slowly in air at ambient temperature and pressure to form hydrogen and bromine. In contact with moisture, HBr dissociates to hydrogen and bromide ions.

 

Adsorption, Distribution, Metabolism and Excretion

The toxicokinetics of HBr follow the same route as bromine. The toxicokinetic summary for bromine is given below for reference.

 

MacEwen, J.D., and Vernot, E.H. 1972. Toxic Hazards Research Unit Annual Technical Report: 1972. AMRL TR-72-62, AD 755 358, Aerospace Medical Research Laboratory, Wright-Patterson Air Force Base, OH;33 available from National Technical Information Service, Springfield, VA

 

Kusewitt, D.F., Stavert, D.M., Ripple, G., Mundie, T., and Lehnert, B.E. 1989. Relative acute toxicities in the respiratory tract of inhaled hydrogen fluoride, hydrogen bromide, and hydrogen chloride. Toxicologist 9:36.

 

Stavert, D.M., Archuleta, D.C., Behr, M.J., and Lehnert, B.E. 1991. Relative acute toxicities of hydrogen fluoride, hydrogen chloride, and hydrogen bromide in nose- and pseudomouth-breathing rats. Fundam. Appl. Toxicol. 16:636-655.

 

Toxicokinetic Summary: Bromine

 

Mode of Action

The injurious effects of bromine are generally considered to be similar to those of chlorine (Rom, W.N., and Barkman, H.W., 1983; Broderick, A., and Schwartz, D.A., 1992; Schwartz, D.A., 1987). Due to its potent oxidising action, bromine liberates nascent oxygen or oxygen free radicals from the water present in mucous membranes. Nascent oxygen is a potent oxidizer, capable of producing tissue damage. The extent of the damage is dependent on the dose of bromine and the availability of water to react with it. In addition, the formation of hydrobromic (HBr) and bromic (HBrO₃) acids will result in secondary irritation during the reaction. Contact with the respiratory epithelium produces initial alveolar capillary congestion followed by focal and confluent patches of high-fibrinogen oedematous fluid. The fluid is interstitial at first but can fill the alveoli. Once this occurs, copious frothy, blood-tinged sputum is seen. A granulocyte response may occur several hours after inhalation. Hyaline membrane formation can occur later resulting in clinical deterioration at a time when signs of improvement have occurred. Poor oxygen diffusion, hypoxia and hypercapnia result from development of atelectasis, emphysema and membrane formation. Acute obstructive ventilatory impairment leads to severe hypoxaemia, metabolic acidosis and death usually due to cardiac arrest secondary to the hypoxaemia.

Adsorption

Bromine is a gas and therefore inhalation exposure is the most relevant route of exposure to humans (IPCS, 1999). Other routes of exposure are minimal.

Following inhalation, bromine is absorbed by the lungs and the physical characteristics of bromine determine the depth and site of penetration into the lung tissue and therefore the rate of absorption. Bromine deposition in the lungs is primarily determined by the water solubility of bromine. Bromine is relatively more water soluble than chlorine and thus tends to produce effects on the upper respiratory tract (Broderick, A., and Schwartz, D.A., 1992). However, inhalation of high concentrations, e.g., in confined spaces, may also cause marked irritant effects on the lower airways (IPCS, 1999).

No data could be located regarding the absorption of bromine vapoursviathe ocular or dermal routes of exposure.

Following ingestion, bromine liquid is rapidly and completely absorbed from the intestine by passive paracellular transport. Bromine crosses blood cell membranes in an electrically neutral form (HC, 1996).

Distribution

Bromine is distributed widely into various tissues and mainly into the extracellular fluid of the body (HC, 1996).

Metabolism

The reactivity of bromine in biological systems makes it difficult to study the pharmacokinetics and to separate the effects of the bromine from those of the bromine compounds and metabolites.

There are no data regarding the metabolism of inhaled bromine, however bromine has been known to quickly form bromide in living tissue. Bromide is partitioned in the body similarly to chloride and acts by replacing chloride. Bromide is a CNS depressant and its adverse effects are as a result of overdoses, however, due to the extreme irritant nature of bromine, the duration of exposure is severely limited, reducing any likely body burden of bromide (HC, 1996).

No data could be located regarding the biological half-life of inhaled bromine. The biological half-life of ingested bromine has been reported to be between 12 and 30 days in humans (Sticht, G., and Kaferstein, H., 1988; IPCS, 1999). The biological half-life in rats is markedly shorter, being approximately 3 days.

Bromine reacts with water resulting in the formation of hydrobromous acid, which slowly decomposes to hydrogen bromide and O₂(EPA, 2009). The mechanism of action of bromine is by liberation of nascent oxygen or oxygen free radicals from the water present in mucous membranes. It is the nascent oxygen, a potent oxidiser, which is responsible for bromine-induced tissue damage (Sticht, G., and Kaferstein, H., 1988; HSDB, 2007; IPCS, 1999).

Excretion

No data could be located regarding excretion of bromine from the body. It is likely that excretion of any systemically absorbed bromine will be as bromide ion via urine.

References

Broderick, A., and Schwartz, D.A. (1992) Halogen Gases, Ammonia, and Phosgene. In: Sullivan JB and Krieger GR, Eds. Hazardous Materials Toxicology. Baltimore, Williams & Wilkins, 791-796.

EPA (2009). Bromine. Interim Acute Exposure Guidelines Levels (AEGLs) 2009 EPA; Washingon DC.

HC (1996). Health Council of the, Bromine – Health-based Reassessment of Administrative occupational Exposure Limits. 1996. 143.4-143.16.

HSDB (2007). Bromine. Hazardous Substances Data Base, 2007.

IPCS (1999). International Programme on Chemical Safety (IPCS), Bromine. poisons Information Monograph PIM 080 1999 WHO.

Rom, W.N., and Barkman, H.W. (1983) Respiratory Irritants. In: Rom WN, ed. Environmental and Occupational Medicine. Little, Brown and Company, 273-283.

Schwartz, D.A. (1987) Acute Inhalation Injury. Occupational Medicine: State of the Art Reviews 297-318.

Sticht, G., and Kaferstein, H. (1988) Bromine. In: Seiler, H., Sigel, H., Sigel, A., eds. Handbook on Toxicity of Inorganic Compounds. New York, Marcel Dekker Inc., 143-154.