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Description of key information

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 repeated dose toxicity. 
Inhalation exposure to phosphorus tribromide may also be used as an indication of HBr toxicity. PBr3 reacts with moisture in the air and on wet surfaces to produce phosphonic acid and hydrogen bromide gas (HBr). The hydrolysis rate for this reaction is 4 x 10-17 cm2/s. At a relative humidity of 5%, hydrolysis half-life is 810 milliseconds. This decreases to 81 milliseconds at 50% RH, and 41 milliseconds for 100% RH.
HBr is a substance that rapidly undergoes changes in contact with moisture – either in the air or in contact with respiratory or oral tissues. (See Annex VIII Section 9.2.2.1 Hydrolysis). HBr is generally unmeasurable in the body as it changes directly to hydrobromic acid in water forming hydrogen and bromide ions. In air, it may form bromine, but the reaction pathway ultimately ends with the formation of bromide ions (Annex VIII Section 8.8.1 Toxicokinetics assessment). It is generally accepted that bromide is the chemical moiety of concern for long-term assessment of systemic HBr toxicity.

Key value for chemical safety assessment

Additional information

HBr is a highly reactive substance which is well known to cause burns to skin and eyes. It is classified/labelled with the symbols “C” and “Xi” and the risk phrases “R35” and “R37”.

 

Though there are minimal animal repeated dose data on 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 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/m3or 2 ppm). Additional routes of exposure (i.e., oral or dermal) are not considered as appropriate routes for determination of repeated dose toxicity.

Inhalation exposure to phosphorus tribromide may also be used as an indication of HBr toxicity. PBr3 reacts with moisture in the air and on wet surfaces to produce phosphonic acid and hydrogen bromide gas (HBr) according to the following reaction:

PBr3+ 3 H2O → 3 HBr + H3PO3

The hydrolysis rate for this reaction is 4 x 10-17 cm2/s. At a relative humidity of 5%, hydrolysis half-life is 810 milliseconds. This decreases to 81 milliseconds at 50% relative humidity (RH), and 41 milliseconds for 100% RH. As the diffusion of PBr3 vapour is very slow, given the high hydrolysis rate, PBr3 would be expected to travel less than 1 cm from a pool of liquid before reacting. Thus, inhalation exposure to PBr3 can be considered analogous to HBr exposure.

HBr is a substance that rapidly undergoes changes in contact with moisture – either in the air or in contact with respiratory or oral tissues. (See Annex VIII Section 9.2.2.1 Hydrolysis). HBr is generally unmeasurable in the body as it changes directly to hydrobromic acid in water forming hydrogen and bromide ions. In air, it may form bromine, but the reaction pathway ultimately ends with the formation of bromide ions (Annex VIII Section 8.8.1 Toxicokinetics assessment). It is generally accepted that bromide is the chemical moiety of concern for long-term assessment of systemic HBr toxicity. 

 

Sub-acute

Wolfe, R.E.,et al. (1997) reported that in a 28-day study in Fischer 344 rats exposed to phosphorus tribromide (PBr3) (which hydrolyses into HBr and phosphonic acid) for 4 hours per day, five days per week, at dose levels of 0.03, 0.1 or 0.3 mg/L showed no signs of toxic stress, alterations of body weight, or changes in organ weights compared to control animals. Minor serum chemistry and hematology effects were seen in treated animals. Microscopic tissue findings were limited to rats of the 0.3 mg/L group and consisted of mild inflammation of the nasal passages. A concentration of 0.1 mg/L was the no observable adverse effect level (NOAEL) in a 28-day inhalation study.

In a separate 5-day study, Wolfe, R.E.,et al., (1997) reported that five exposures of rats for 4 hours per day to PBr3 causing no deaths or signs of toxic stress at concentrations up to 0.51 mg/L PBr3(equivalent to 0.467 mg/L HBr). Mean body weights decreased in all groups (including control animals) over the 5 exposure days. Weights were statistically lower in the high dose group compared to control on days 3 and 4. Several mean values of serum chemistries and hematology values differed in treated animals compared to control. Increases in serum chloride were thought to be analytical interference by presence of serum bromide. Increased values in calcium and potassium were seen in the high-dose group/ Decreased alkaline phosphatase and creatine kinase values were seen in the high-dose group; and ALT values were increased in the 0.16 and 0.51 mg/L groups. The high-dose group showed gross lesions as irregularly shaped and reddened nares. There were no statistically different absolute or relative organ weights between control and exposed animals. Microscopic lesions were seen in the high dose group in the most anterior segment of the nasal passages. Lesions consisted of suppurative inflammation of the nasal mucosa. One high dose animal had minimal squamous metaplasia of the respiratory epithelium of the trachea. In the mid dose group, one animal had slight inflammation of the anterior nasal mucosa. There were no microscopic lesions in the low dose or control animals.

 

Sub-chronic

In a 90-day repeated inhalation dose study with HCl, summarised by OEHHA (2007), several animals died during the study, although the deaths were not considered to be exposure related. A slight but significant decrease in body weight gain was reported in male and female mice and in male Fischer 344 rats in the high-exposure groups. No effects were noted in hematology, clinical chemistry, or urinalysis. Minimal or mild rhinitis was observed in both strains of rats. Concentration- and time-related lesions were noted in the anterior portion of the nasal cavity of exposed rats. Cheilitis, eosinophilic globules in the nasal epithelium, and accumulation of macrophages in the peripheral tissues were observed in mice of all exposed groups. The 90-day LOAEL derived from the study is 10 ppm for both mice and rats.

Justification for classification or non-classification

HBr is a highly reactive substance which is well known to cause burns to skin and eyes. It is classified/labelled with the symbols “C” and “Xi” and the risk phrases “R35” and “R37”.

HBr is generally unmeasurable in the body as it changes directly to hydrobromic acid in water forming hydrogen and bromide ions. In air, it may form bromine but the reaction pathway ultimately ends with the formation of bromide ions (Annex VIII Section 8.8.1 Toxicokinetics assessment). It is generally accepted that bromide is the chemical moiety of concern for long-term assessment of systemic HBr toxicity.