Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 17 (2014)

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9 Boron Tribromide1 Acute Exposure Guideline Levels PREFACE Under the authority of the Federal Advisory Committee Act (FACA) P.L. 92-463 of 1972, the National Advisory Committee for Acute Exposure Guide- line Levels for Hazardous Substances (NAC/AEGL Committee) has been estab- lished to identify, review, and interpret relevant toxicologic and other scientific data and develop AEGLs for high-priority, acutely toxic chemicals. AEGLs represent threshold exposure limits for the general public and are applicable to emergency exposure periods ranging from 10 minutes (min) to 8 hours (h). Three levels—AEGL-1, AEGL-2, and AEGL-3—are developed for each of five exposure periods (10 and 30 min and 1, 4, and 8 h) and are distin- guished by varying degrees of severity of toxic effects. The three AEGLs are defined as follows: AEGL-1 is the airborne concentration (expressed as parts per million or milligrams per cubic meter [ppm or mg/m3]) of a substance above which it is predicted that the general population, including susceptible individuals, could experience notable discomfort, irritation, or certain asymptomatic, nonsensory 1 This document was prepared by the AEGL Development Team composed of Sylvia Talmage (Oak Ridge National Laboratory), Lisa Ingerman (SRC, Inc.), Chemical Man- ager Robert Benson (National Advisory Committee [NAC] on Acute Exposure Guideline Levels for Hazardous Substances), and Ernest V. Falke (U.S. Environmental Protection Agency). The NAC reviewed and revised the document and AEGLs as deemed neces- sary. Both the document and the AEGL values were then reviewed by the National Re- search Council (NRC) Committee on Acute Exposure Guideline Levels. The NRC com- mittee has concluded that the AEGLs developed in this document are scientifically valid conclusions based on the data reviewed by the NRC and are consistent with the NRC guidelines reports (NRC 1993, 2001). 458 

Boron Tribromide 459 effects. However, the effects are not disabling and are transient and reversible upon cessation of exposure. AEGL-2 is the airborne concentration (expressed as ppm or mg/m3) of a substance above which it is predicted that the general population, including sus- ceptible individuals, could experience irreversible or other serious, long-lasting adverse health effects or an impaired ability to escape. AEGL-3 is the airborne concentration (expressed as ppm or mg/m3) of a substance above which it is predicted that the general population, including sus- ceptible individuals, could experience life-threatening health effects or death. Airborne concentrations below the AEGL-1 represent exposure concentra- tions that could produce mild and progressively increasing but transient and nondisabling odor, taste, and sensory irritation or certain asymptomatic, nonsen- sory effects. With increasing airborne concentrations above each AEGL, there is a progressive increase in the likelihood of occurrence and the severity of effects described for each corresponding AEGL. Although the AEGL values represent threshold concentrations for the general public, including susceptible subpopula- tions, such as infants, children, the elderly, persons with asthma, and those with other illnesses, it is recognized that individuals, subject to idiosyncratic respons- es, could experience the effects described at concentrations below the corre- sponding AEGL. SUMMARY Boron tribromide is a colorless, fuming liquid with a sharp or acrid, irritat- ing odor. It hydrolyzes or decomposes violently in the presence of water or moist air, producing heat, hydrogen bromide, and boric acid. In the presence of water, conversion to hydrogen bromide is complete. Boron tribromide is used as a cata- lyst in the manufacture of diborane, ultrahigh purity boron, and semiconductors. It is an excellent demethylating or dealkylating agent for ethers, particularly in the production of pharmaceuticals. As a Lewis acid catalyst it finds applications in olefin polymerization and in Friedel-Crafts chemistry. Theoretically, one mole of boron tribromide hydrolyzes into three moles of hydrogen bromide. No human or animal data were available to derive AEGL values for boron tribromide, as the reactive nature of boron tribromide precludes toxicity testing. Hydrogen bromide is considered the irritant hydrolysis product as boric acid has been used in topical antiseptic powders and ointments, and dilute solutions are used in eye and mouthwash solutions. On the basis that boron tribromide hydro- lyzes into hydrogen bromide, the AEGL values for boron tribromide were based on the AEGL values for hydrogen bromide. The boron tribromide values were derived by dividing the hydrogen bromide AEGL values by 3. See Chapter 8 for the technical support document on hydrogen bromide. The AEGL values for boron tribromide are presented in Table 9-1. 

460 Acute Exposure Guideline Levels TABLE 9-1 AEGL Values for Boron Tribromide Classification 10 min 30 min 1h 4h 8h End Pointa AEGL-1 0.33 ppm 0.33 ppm 0.33 ppm 0.33 ppm 0.33 ppm Analogy with (nondisabling) (3.4 (3.4 (3.4 (3.4 (3.4 hydrogen bromide mg/m3) mg/m3) mg/m3) mg/m3 ) mg/m3) AEGL-2 83 ppm 28 ppm 13 ppm 3.3 ppm 1.7 ppm Analogy with (disabling) (850 (290 (130 (34 (17 hydrogen bromide mg/m3) mg/m3) mg/m3) mg/m3) mg/m3) AEGL-3 250 ppm 83 ppm 40 ppm 10 ppm 5 ppm Analogy with (lethal) (2,600 (850 (410 (100 (51 hydrogen bromide mg/m3) mg/m3) mg/m3) mg/m3) mg/m3) a On the basis that one mole of boron tribromide hydrolyzes into three moles of hydrogen bromide, the AEGL values for hydrogen bromide were divided by three. 1. INTRODUCTION Boron tribromide is a colorless, fuming liquid with a sharp or acrid, irritat- ing odor. It hydrolyzes or decomposes in the presence of water or moist air, pro- ducing heat, hydrogen bromide, and boric acid (ACGIH 2001; O’Neil et al. 2006; Krzystowczyk 2007; Ball et al. 2012). Boron tribromide is nonflammable (BOC 1996). However, as a result of the strong Lewis acid properties of bro- mide, the reaction with water is violent and results in risk of explosion. This reactivity, resulting in caustic action at the site of exposure, makes it impossible to determine systemic toxicity. Breakdown to hydrogen bromide in water is complete (Krzystowczyk 2007). Theoretically, three moles of hydrogen bromide are produced from one mole of boron tribromide. Additional chemical and phys- ical properties are listed in Table 9-2. The boron trihalides are important industrial chemicals that are used as Lewis acid catalysts and in chemical vapor deposition processes. As a Lewis acid catalyst, boron tribromide finds applications in olefin polymerization and in Friedel-Crafts chemistry. Boron tribromide is used as a catalyst in the manufac- ture of diborane and ultrahigh purity boron. Boron tribromide is an excellent demethylating or dealkylating agent for ethers in the production of pharmaceuti- cals. The electronics industry uses boron tribromide as a source of boron in pre- deposition processes for doping in the manufacture of semi-conductors (Albe- marle Corporation 2004; HSDB 2013). Boron tribromide is produced on a large scale by the reaction of bromine and granulated boron carbide (Alam et al. 2003). It is commercially available neat or in solution with dichloromethane or hexanes (Doyaguez 2005). Boron tribromide is shipped in 70-kg stainless-steel drums (Albemarle Corporation 2004). 2. HUMAN TOXICITY DATA By analogy with hydrogen bromide, the acrid odor of boron tribromide should be detectable at 2 ppm (Ball et al. 2012). Data were insufficient to set a 

Boron Tribromide 461 level of odor awareness. Boron tribromide is considered irritating to the skin and mucus membranes and corrosive to the eyes (HSDB 2013). No inhalation data on lethal concentrations, developmental or reproductive toxicity, genotoxicity, or carcinogenicity of boron tribromide in humans were found. Data on the breakdown products, hydrogen bromide and boric acid, were available. The Connecticut State Department of Health (unpublished data, 1955) evaluated responses of human subjects to hydrogen bromide vapors. Six volun- teers inhaled hydrogen bromide at 2-6 ppm for durations of several minutes (see Table 9-3). The odor was detectable by all subjects at all concentrations. None of the subjects experienced ocular irritation. Only one subject experienced nasal and throat irritation at 3 ppm. One subject experienced throat irritation at the higher concentrations, and all subjects experienced nasal irritation at 5 and 6 ppm. Although exposure at 5 ppm caused nasal and throat irritation in a majority of the volunteers, the report stated that “it was considered unlikely that noticea- ble disturbances will occur if peak concentrations do not exceed this value for brief periods.” TABLE 9-2 Chemical and Physical Properties of Boron Tribromide Parameter Value References Synonyms Boron bromide; tribromoborane HSDB 2013 CAS registry no. 10294-33-4 HSDB 2013 Chemical formula BBr3 HSDB 2013 Molecular weight 250.57 HSDB 2013 Physical state Liquid HSDB 2013 Boiling point 91.3ºC HSDB 2013 Melting point –46ºC HSDB 2013 Density (water =1) 2.60 g/mL HSDB 2013 Solubility in water Hydrolyzes violently HSDB 2013 Vapor pressure 69 mm Hg at 25ºC Barber et al. 1964; ACGIH 2001 Flammability limits Non-flammable BOC Gases 1996 Conversion factors 1 ppm = 10.25 mg/m3 ACGIH 2001 1 mg/m3 = 0.097 ppm TABLE 9-3 Human Responses to Hydrogen Bromide Vapor Number of Subjects with Response (n = 6) Response 2 ppm 3 ppm 4 ppm 5 ppm 6 ppm Detectable odor 6 6 6 6 6 Nasal irritation 0 1 3 6 6 Throat irritation 0 1 1 1 1 Ocular irritation 0 0 0 0 0 Source: Connecticut State Department of Health, unpublished data, 1955. 

462 Acute Exposure Guideline Levels Although the inhalation toxicity of boron oxide and borates is well estab- lished (ATSDR 2010), no information on the inhalation toxicity of boric acid in humans was found. Boric acid is used as an astringent and antiseptic. Borates in general are considered either nonirritating or mild dermal and ocular irritants (Hubbard 1998). Oral exposure to boric acid has low acute toxicity in adults (Hubbard 1998), but there are some reports of fatalities (Jordan and Crissey 1957). Death has occurred from intake of less than 5 g in infants and from 5-20 g in adults (O’Neil et al. 2006). Wong et al. (1964) reported that five of 14 in- fants were killed within 2-3 day after ingesting boric acid; the infants that died consumed 4.6-14 g of the chemical, whereas those that survived consumed 2-4.5 g. Mortality was 70% among infants who were accidentally poisoned with boric acid (Goldbloom and Goldbloom 1953). Boric acid has been held responsible for systemic intoxication after inges- tion, injection, application to damaged skin, or enema (McIntyre and Burke 1937; Brooke and Boggs 1951; Ducey and Williams 1953; Johnstone et al. 1955; Rosen and Haggerty 1956; Jordan and Crissey 1957). There is no evi- dence that boric acid or borates are absorbed through intact skin (Sciarra 1958). Whether the apparent increased susceptibility of infants and children is due to immaturity of the kidneys (which accounts for the primary route of elimination) (Locksley and Sweet 1954) or is related to the relatively high dose on a body weight basis (Young et al. 1949) is not clear. Autopsy is generally unremarkable with deaths occurring several days after exposure, but pancreatic lesions and those in kidneys and brain have been described (McNally and Rust 1928; Val- des-Dapena and Arey 1962). Although seizures can precede death, the hyper- chloremic metabolic acidosis is a characteristic feature (Wong et al. 1964). 3. ANIMAL TOXICITY DATA No data on the lethality, developmental or reproductive effects, genotoxi- city, or chronic toxicity or carcinogenicity of boron tribromide were available. Data on the breakdown products, boric acid and hydrogen bromide were availa- ble. Toxicity data on other hydrogen halides, such as hydrogen chloride and hydrogen fluoride, are also relevant. Inhalation exposure of male Swiss-Webster mice to boric acid aerosol at 300 mg/m3 (approximately 120 ppm), the highest achievable concentration, re- sulted in a decrease in respiratory rate by less than 20%. The effect was attribut- ed to sensory irritation, as there was no indication of pulmonary effects (Krysto- fiak and Schaper 1996). The oral LD50 (lethal dose, 50% lethality) for boric acid in rats is 5 g/kg (O’Neil et al. 2006). Groups of five to eight Fisher 344 rats were exposed by inhalation to hy- drogen chloride or hydrogen bromide at approximately 1,300 ppm for 30 min (Stavert et al. 1991). Animals were placed in body plethysmographs for nose- only exposure. Mortality rates were 6% in the hydrogen-chloride group and 8% in the hydrogen-bromide group. Lesions were confined to the nasal passages. 

Boron Tribromide 463 Moderate to severe fibrinonecrotic rhinitis was observed only in the anterior most region of the nasal passages. The same authors (Kusewitt et al. 1989) ex- posed rats to hydrogen chloride or hydrogen bromide at concentrations of 100- 1,000 ppm for 30 min. No deaths occurred at 1,000 ppm before the animals were killed after 24 h. Lesions were confined to the nasal passages with no damage to the lungs. No further details were reported in the abstract. MacEwen and Vernot (1972) exposed groups of 10 male Sprague-Dawley rats to hydrogen bromide at 2,205-3,822 ppm for 1 h. Groups of 10 ICR-derived mice were exposed at 507-1,163 ppm for 1 h. Mortalities from these exposures are summarized in Table 9-4. The 1-h LC50 for hydrogen bromide in rats was 2,858 ppm (95% confidence limits: 2,481-3,164 ppm), and the 1-h LC50 in mice was 814 ppm (95% confidence limits: 701-947 ppm). Responses in the animals were dose-related, and followed a sequence of nasal and ocular irritation, la- bored breathing, gasping, and convulsions. The fur turned orange-brown during the exposures, and burns were observed on the exposed skin of both species. Barrow et al. (1977) exposed groups of four male Swiss-Webster mice to hydrogen chloride at concentrations of 40, 99, 245, 440, or 943 ppm for 10 min. An RD50 (concentration that reduces the respiratory rate by 50%) of 309 ppm was calculated. At 99 ppm, approximately one-third of the RD50, the decrease in respiratory rate was 25-30%. 4. SPECIAL CONSIDERATIONS 4.1. Metabolism and Disposition Boron tribromide undergoes rapid hydrolysis in the presence of water or moist air, producing heat, hydrogen bromide, and boric acid (ACGIH 2001). No information on the hydrolysis half-life was found, but reaction with water or moisture in the air is rapid and complete (Krzystowczyk 2007). 4.2. Mechanism of Toxicity The mechanism of toxicity of boron tribromide appears to be related to the formation of hydrobromic acid. Hydrogen bromide is a severe irritant to the eyes, skin, and nasal passages; high concentration may penetrate to the lungs resulting in edema and hemorrhage (Kusewitt et al. 1989; Stavert et al. 1991; see Chapter 8). Boric acid is used as an astringent and antiseptic. Orally, it is of low acute toxicity to adult humans. Effects include nausea, vomiting, abdominal pain, diar- rhea, depression of the central nervous system, and convulsions. Death has oc- curred from intakes of less than 5 g in infants and from 5-20 g in adults (ACGIH 2005). In the occupational setting, exposure to airborne boric acid and borax dusts is associated with respiratory and ocular irritation without measurable changes in pulmonary function (ATSDR 2010). No studies were available that describe the mechanism of toxicity of systemic effects. 

464 Acute Exposure Guideline Levels TABLE 9-4 One-Hour Inhalation Studies of Hydrogen Bromide Species Concentration (ppm) Mortality Ratio Rat 2,205 1/10 2,328 4/10 2,759 4/10 3,253 6/10 3,711 7/10 3,822 10/10 Mouse 507 0/10 875 7/10 1,036 9/10 1,163 10/10 Source: Adapted from McEwen and Vernot 1972. 4.3. Structure-Activity Relationships Because one mole of boron tribromide breaks down into three moles of hydrogen bromide, the toxicity of hydrogen bromide and related hydrogen hal- ides are relevant. On the basis of lethality, hydrogen fluoride is the most toxic, followed by hydrogen bromide and then hydrogen chloride, although the values for hydrogen bromide and hydrogen chloride were similar (MacEwen and Vernot 1972). At sublethal concentrations, the severity and extent of lesions in the upper respiratory tract of rats exposed to hydrogen halides by inhalation were greatest for hydrogen fluoride, followed by hydrogen chloride and then hydrogen bromide. However, the severity and extent of lesions were similar among the three chemicals (Kusewitt et al. 1989; Stavert et al. 1991). The halides chlorine, bromine, and iodine, are exceptionally good leaving groups, readily hydrolyzing to their acid forms in the aqueous environment. The exception is boron trifluoride. The lack of outer orbitals on the fluoride atom re- sults in a shorter and, thus, stronger bond than what is present with the other hal- ides (Krzystowczyk 2007). Toxicity comparisons of the boron trihalides with their breakdown products are summarized in Table 9-5. The 4-h LC50 for boron trifluo- ride in rats is 1.21 mg/L (approximately 436 ppm) (Rusch et al. 1986). The 1-h LC50 for hydrogen fluoride ranges from 966 ppm to 1,395 ppm (Vernot et al. 1977; NRC 2004). The 1-h LC50 for boron trichloride in rats is 2,541 ppm (Vernot et al. 1977). The 1-h LC50 for hydrogen chloride in rats is 3,124 ppm (Vernot et al. 1977). The similarity in toxicity values for boron trifluoride and boron trichloride with the hydrolysis products tends to support limited hydrolysis. 4.4. Other Relevant Information No information on species variability, susceptible populations, or concen- tration-exposure duration relationships for boron tribromide was available. For 

Boron Tribromide 465 hydrogen halides, such as hydrogen fluoride and hydrogen chloride, the mouse is more susceptible than the rat to the lethal effects (NRC 1991). 5. DATA ANALYSIS FOR AEGL-1 5.1. Human Data Relevant to AEGL-1 No human data on boron tribromide relevant to AEGL-1 end points were available. 5.2. Animal Data Relevant to AEGL-1 No animal data on boron tribromide relevant to AEGL-1 end points were available. 5.3. Derivation of AEGL-1 Values No human or animal data on boron tribromide were available to derive AEGL-1 values. On the basis that one mole of boron tribromide hydrolyzes into three moles of hydrogen bromide in moist air, the AEGL-1 values for boron tribromide were derived by dividing the hydrogen bromide AEGL-1 values by 3. See Chapter 8 of this report for how AEGL-1 values were derived for hydrogen bromide. The AEGL-1 values for boron tribromide are presented in Table 9-6, and the calculations are in Appendix A. TABLE 9-5 Comparison of LC50 Values for Boron Trihalides and Acid Halides in Rats Chemical LC50 Value Reference Boron trifluoride 436 ppm (4 h) Rusch et al. 1986 Hydrogen fluoride 500 ppm (4 h)a Vernot et al. 1977 Boron trichloride 2,541 ppm (1 h) Vernot et al. 1977 Hydrogen chloride 3,124 ppm (1 h) Vernot et al. 1977 Boron tribromide No data — Hydrogen bromide 2,858 ppm (1 h) MacEwen and Vernot 1972 a Value was time scaled from 1 h to 4 h using the equation C2 × t = k (NRC 2004). TABLE 9-6 AEGL-1 Values for Boron Tribromide 10 min 30 min 1h 4h 8h 0.33 ppm 0.33 ppm 0.33 ppm 0.33 ppm 0.33 ppm (3.4 mg/m3) (3.4 mg/m3) (3.4 mg/m3) (3.4 mg/m3) (3.4 mg/m3) 

466 Acute Exposure Guideline Levels 6. DATA ANALYSIS FOR AEGL-2 6.1. Human Data Relevant to AEGL-2 No human data on boron tribromide relevant to AEGL-2 end points were available. 6.2. Animal Data Relevant to AEGL-2 No animal data on boron tribromide relevant to AEGL-2 end points were available. 6.3. Derivation of AEGL-2 Values No human or animal data on boron tribromide were available to derive AEGL-2 values. On the basis that one mole of boron tribromide hydrolyzes into three moles of hydrogen bromide in moist air, the AEGL-2 values for boron tribromide were derived by dividing the hydrogen bromide AEGL-2 values by 3. See Chapter 8 of this report for how AEGL-2 values were derived for hydrogen bromide. The AEGL-2 values for boron tribromide are presented in Table 9-7. 7. DATA ANALYSIS FOR AEGL-3 7.1. Human Data Relevant to AEGL-3 No human data on boron tribromide relevant to AEGL-3 end points were available. 7.2. Animal Data Relevant to AEGL-3 No animal data on boron tribromide relevant to AEGL-3 end points were available. 7.3. Derivation of AEGL-3 Values No human or animal data on boron tribromide were available to derive AEGL-3 values. On the basis that one mole of boron tribromide hydrolyzes to form three moles of hydrogen bromide in moist air, the AEGL-3 values for bo- ron tribromide were derived by dividing the hydrogen bromide AEGL-3 values by three. See Chapter 8 of this report for how AEGL-3 values were derived for hydrogen bromide. AEGL-3 values for boron tribromide are presented in Table 9-8. 

Boron Tribromide 467 TABLE 9-7 AEGL-2 Values for Boron Tribromide 10 min 30 min 1h 4h 8h 83 ppm 28 ppm 13 ppm 3.3 ppm 1.7 ppm (850 mg/m3) (290 mg/m3) (130 mg/m3) (34 mg/m3) (17 mg/m3) TABLE 9-8 AEGL-3 Values for Boron Tribromide 10 min 30 min 1h 4h 8h 250 ppm 83 ppm 40 ppm 10 ppm 5 ppm (2600 mg/m3) (850 mg/m3) (410 mg/m3) (100 mg/m3) (51 mg/m3) The toxicity of boric acid liberated during hydrolysis of boron tribromide was considered. The intake of boric acid at the AEGL-3 values by infants, the most susceptible population, can be calculated. The 8-h AEGL-3 is 51 mg/m3. The breathing rate of a child is 12 m3/day. Boron tribromide is 4.32% boron. Assuming complete uptake of boron from the respiratory tract, the resulting up- take for a child is: 51 mg/m3 × 12 m3/24 h × 8 h × 0.0432 = 8.8 mg of boron potentially absorbed. This value is low when compared with the 2-5 g of boron needed for lethality in a child. 8. SUMMARY OF AEGL VALUES 8.1. AEGL Values and Toxicity End Points AEGL values for boron tribromide are presented in Table 9-9. 8.2. Comparison with Other Standards and Guidelines Workplace guidelines exist for boron tribromide (see Table 9-10). The American Conference of Governmental Industrial Hygienists has established a TLV-ceiling value of 1 ppm for boron tribromide, which is based on analogy with hydrogen bromide (ACGIH 2012, 2001). ACGIH recommends ceiling val- ues for primary irritants with no known chronic effects. The ceiling value is a concentration that should not be exceeded during any part of the working day. The National Institute for Occupational Safety and Health (NIOSH 2011) rec- ommended exposure limit-ceiling and the Netherlands MAC value are also 1 ppm (MSZW 2004). These guidelines are higher than the AEGL-1 value of 0.33 ppm. The ACGIH TLV-ceiling for hydrogen bromide is 2 ppm (ACGIH 2012), and the ACGIH TLV-TWA for boric acid is 2 mg/m3 as inhalable particulate mass (ACGIH 2012). 

468 Acute Exposure Guideline Levels TABLE 9-9 AEGL Values for Boron Tribromide Exposure Duration Classification 10 min 30 min 1h 4h 8h AEGL-1 0.33 ppm 0.33 ppm 0.33 ppm 0.33 ppm 0.33 ppm (nondisabling) (3.4 mg/m3) (3.4 mg/m3) (3.4 mg/m3) (3.4 mg/m3) (3.4 mg/m3) AEGL-2 83 ppm 28 ppm 13 ppm 3.3 ppm 1.7 ppm (disabling) (850 mg/m3) (290 mg/m3) (130 mg/m3) (34 mg/m3) (17 mg/m3) AEGL-3 250 ppm 83 ppm 40 ppm 10 ppm 5 ppm (lethal) (2600 mg/m3) (850 mg/m3) (410 mg/m3) (100 mg/m3) (51 mg/m3) TABLE 9-10 Standards and Guidelines for Boron Tribromide Exposure Duration Guideline 10 min 30 min 1h 4h 8h AEGL-1 0.33 ppm 0.33 ppm 0.33 ppm 0.33 ppm 0.33 ppm AEGL-2 83 ppm 28 ppm 13 ppm 3.3 ppm 1.7 ppm AEGL-3 250 ppm 83 ppm 40 ppm 10 ppm 5 ppm TLV-C (ACGIH)a 1 ppm 1 ppm 1 ppm 1 ppm 1 ppm b REL-C (NIOSH) 1 ppm 1 ppm 1 ppm 1 ppm 1 ppm MAC (The – – – – 10 mg/m3 Netherlands)c 1 ppm a TLV-C (threshold limit value – ceiling, American Conference of Governmental Indus- trial Hygienists) (ACGIH 2012) is a concentration that should not be exceeded during the working day. b REL-C (recommended exposure limit – ceiling, National Institute for Occupational Safety and Health) (NIOSH 2011) is defined analogous to the ACGIH TLV-ceiling. c MAC (maximaal aanvaarde concentratie [maximal accepted concentration], Dutch Ex- pert Committee for Occupational Standards, The Netherlands) (MSZW 2004) is defined analogous to the ACGIH TLV-TWA. 8.3. Data Adequacy and Research Needs The reactive nature of boron tribromide precludes toxicity testing. In the absence of empirical data on boron tribromide, and on the basis that one mole of boron tribromide theoretically hydrolyzes into three moles of hydrogen bromide, the AEGL values for boron tribromide were based on those for hydrogen bro- mide. The database for hydrogen bromide was combined with the more robust data base for the related chemical, hydrogen chloride. 9. REFERENCES ACGIH (American Conference of Governmental Industrial Hygienists). 2001. Documen- tation of the Threshold Limit Values and Biological Exposure Indices: Boron tri- bromide. American Conference of Governmental Industrial Hygienists, Cincinnati, OH. 

Boron Tribromide 469 ACGIH (American Conference of Governmental Industrial Hygienists). 2005. Documen- tation of the Threshold Limit Values and Biological Exposure Indices: Borate compounds, inorganic. ACGIH, Cincinnati, OH. ACGIH (American Conference of Governmental Industrial Hygienists). 2012. 2012 Threshold Limit Values and Biological Exposure Indices Based on the Documen- tation of the TLVs for Chemical Substances and Physical Agents and BEIs. ACGIH, Cincinnati, OH. Alam, F., F. Evans, G. Mani, and J.R. Papcun. 2003. Boron halides. Pp. 138-168 in Kirk- Othmer Encyclopedia of Chemical Technology, Vol. 4. New York: John Wiley & Sons, Inc. Albemarle Corporation. 2004. Boron tribromide (chemical data sheet). Baton Rouge, LA: Albemarle Corporation. ATSDR (Agency for Toxic Substances and Disease Registry). 2010. Toxicological Pro- file for Boron. U.S. Department of Health and Human Services, Public Health Ser- vice, Agency for Toxic Substances and Disease Registry, Atlanta, GA[online]. Available: http://www.atsdr.cdc.gov/toxprofiles/tp26.pdf [accessed Apr. 9, 2014]. Ball, R.W., M.C. Harass, and B.D. Culver. 2012. Boron tribromide. Pp. 885 - 933 in Pat- ty’s Toxicology, 6th Ed., Vol. 1, E. Bingham, and B. Cohrssen, eds. New York: Wiley. Barber, W.F., C.F. Boynton, and P.E. Gallagher. 1964. Physical properties of boron tri- bromide. J. Chem. Eng. Data 9(1):137-138. Barrow, C.S., Y. Alarie, M. Warrick, and M.F. Stock. 1977. Comparison of the sensory irritation response in mice to chlorine and hydrogen chloride. Arch. Environ. Health 32(2):68-76. BOC (British Oxygen Company) Gases. 1996. BOC Gases: Boron tribromide. Material Safety Data Sheet. London, UK: BOC. Brooke, C., and T. Boggs. 1951. Boric acid poisoning: Report of a case and review of the literature. AMA Am. J. Dis. Child. 82(4):465-472. Doyaguez, E.G. 2005. Boron tribromide. Synlett 10:1636-1637. Ducey, J., and D.B. Williams. 1953. Transcutaneous absorption of boric acid. J. Pediatr. 43(6):644-651. Goldbloom, R.B., and A. Goldbloom. 1953. Boric acid poisoning: Report of four cases and a review of 109 cases from the world literature. J. Pediatr. 43(6):631-643. HSDB (Hazardous Substances Data Bank). 2013. Boron Tribromide (CAS Reg. No. 10294-33-4). TOXNET, Specialized Information Services, U.S. National Library of Medicine, Bethesda, MD [online]. Available: http://toxnet.nlm.nih.gov/cgi-bin/ sis/htmlgen?HSDB [accessed Jan. 8, 2013]. Hubbard, S.A. 1998. Comparative toxicity of borates. Biol. Trace Elem. Res. 66(1- 3):343-357. Johnstone, D.E., N. Basila, and J. Glaser. 1955. Study of boric acid absorption in infants from use of baby powder. J. Pediatr. 46(2):160-167. Jordan, J.W., and J.T. Crissey. 1957. Boric acid poisoning: A report of a fatal adult case from cutaneous use. A critical evaluation of the use of this drug in dermatologic practice. AMA Arch. Dermatol. 75(5):720-728. Krystofiak, S.P., and M.M. Schaper. 1996. Prediction of an occupational exposure limit for a mixture on the basis of its components: Application to metalworking fluids. Am. Ind. Health Assoc. J. 57(3):239-244. Krzystowczyk, N. 2007. Letter to Dr. George Rusch, AEGL Committee Chairman, from Dr. Niomi Krzystowczyk, Director, Corporate Product Stewardship, Albemarle Corporation, Baton Rouge, LA, Dated June 18, 2007. 

470 Acute Exposure Guideline Levels Kusewitt, D.F., D.M. Stavert, G. Ripple, T. Mundie, and B.E. Lehnert. 1989. Relative acute toxicities in the respiratory tract of inhaled hydrogen fluoride, hydrogen bromide, and hydrogen chloride. Toxicologist 9:36 [Abstract 144]. Locksley, H.B., and W.H. Sweet. 1954. Tissue distribution of boron compounds in rela- tion to neutron-capture therapy of cancer. Proc. Soc. Exp. Biol. Med. 86(1):56-63. MacEwen, J.D., and E.H. Vernot. 1972. Acute inhalation toxicity of hydrogen bromide. Pp. 62-66 in 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. [online]. Available: http://www.dtic.mil/dtic/tr/full text/u2/755358.pdf [accessed Apr. 9, 2014]. McIntyre, A.R., and J.C. Burke. 1937. Intravenous boric acid poisoning in man. J. Phar- macol. Exp. Ther. 60:112-113. McNally, W.D., and C.A. Rust. 1928. The distribution of boric acid in human organs in six deaths due to boric acid poisoning. J. Am. Med. Assoc. 90(5):382-383. MSZW (Ministerie van Sociale Zaken en Werkgelegenheid). 2004. Nationale MAC-lijst 2004: Boriumtribromide. Den Haag: SDU Uitgevers [online]. Available: http:// www.lasrook.net/lasrookNL/maclijst2004.htm [accessed Apr. 9, 2014]. NIOSH (National Institute of Occupational Safety and Health). 2011. Pocket Guide to Chemical Hazards: Boron tribromide. National Institute for Occupational Safety and Health [online]. Available: http://www.cdc.gov/niosh/npg/npgd0061.html [ac- cessed January 2013]. NRC (National Research Council). 1991. Hydrogen chloride. Pp. 37-51 in Permissible Exposure Levels and Emergency Exposure Guidance Levels for Selected Airborne Contaminants. Washington, DC: National Academy Press. NRC (National Research Council). 1993. Guidelines for Developing Community Emer- gency Exposure Levels for Hazardous Substances. Washington, DC: National Academy Press. NRC (National Research Council). 2001. Standing Operating Procedures for Developing Acute Exposure Guideline Levels for Hazardous Chemicals. Washington, DC: Na- tional Academy Press. NRC (National Research Council). 2004. Hydrogen chloride; Hydrogen fluoride. Pp. 77- 197 in Acute Exposure Guideline Levels for Selected Airborne Chemicals, Vol. 4. Washington, DC: The National Academies Press. O’Neil, M.J., P.E. Heckelman, C.B. Koch, and K.J. Roman, eds. 2006. Boron tribromide. P. 220 in The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologi- cals, 14th Ed. Whitehouse Station, NJ: Merck. Rosen, F.S., and R.J. Haggerty. 1956. Fatal poisoning from topical use of boric acid powder. N. Engl. J. Med. 255(11):530-531. Rusch, G.M., G.M. Hoffman, R.F. McConnell, and W.E. Rinehart. 1986. Inhalation tox- icity studies with boron trifluoride. Toxicol. Appl. Pharmacol. 83(1):69-78. Sciarra, J.J. 1958. A selective review of boric acid toxicity. J. Am. Pharm. Assoc. 19(8):494-495. Stavert, D.M., D.C. Archuleta, M.J. Behr, and B.E. Lehnert. 1991. Relative acute toxici- ties of hydrogen fluoride, hydrogen chloride, and hydrogen bromide in nose- and pseudo-mouth-breathing rats. Fundam. Appl. Toxicol. 16(4):636-655. Valdes-Dapena, M.A., and J.B. Arey. 1962. Boric acid poisoning: Three fatal cases with pancreatic inclusions and a review of the literature. J. Pediatr. 61(4):531-546. Vernot, E.H., J.D. MacEwen, C.C. Haun, and E.R. Kinkead. 1977. Acute toxicity and skin corrosion data for some organic and inorganic compounds and aqueous solu- tions. Toxicol. Appl. Pharmacol. 42(2):417-432. 

Boron Tribromide 471 Wong, L.C., M.D. Heimbach, D.R. Truscott, and B.D. Duncan. 1964. Boric acid poison- ing: Report on 11 cases. Can. Med. Assoc. J. 90:1018-1023. Young, E.G., R.P. Smith, and O.C. MacIntosh. 1949. Boric acid as a poison. Report of six accidental deaths in infants. Can. Med. Assoc. J. 61(5):447-450. 

472 Acute Exposure Guideline Levels APPENDIX A DERIVATION OF AEGL VALUES FOR BORON TRIBROMIDE Derivation of AEGL-1 Values Inadequate data were available on boron tribromide, so AEGL-1 values were based on the AEGL-1 values for hydrogen bromide. Calculation: On the basis that one mole of boron tribromide hydrolyzes into three moles of hydrogen bromide, the hydrogen bromide AEGL-1 value was divided by 3. For all AEGL-1 durations: 1 ppm ÷ 3 = 0.33 ppm Derivation of AEGL-2 Values Inadequate data were available on boron tribromide, so AEGL-2 values were based on the AEGL-2 values for hydrogen bromide. Calculation: On the basis that one mole of boron tribromide hydrolyzes into three moles of hydrogen bromide, the hydrogen bromide AEGL-2 values were divided by 3. 10-min AEGL-2: 250 ppm ÷ 3 = 83 ppm 30-min AEGL-2: 83 ppm ÷ 3 = 28 ppm 1-h AEGL-2: 40 ppm ÷ 3 = 13 ppm 4-h AEGL-2 10 ppm ÷ 3 = 3.3 ppm 8-h AEGL-2: 5 ppm ÷ 3 = 1.7 ppm Derivation of AEGL-3 Values Inadequate data were available on boron tribromide, so AEGL-3 values were based on the AEGL-3 values for hydrogen bromide. Calculation: On the basis that one mole of boron tribromide hydrolyzes into three moles of hydrogen bromide, the hydrogen bromide AEGL-3 values were divided by 3. 10-min AEGL-3: 740 ppm ÷ 3 = 250 ppm 30-min AEGL-3: 250 ppm ÷ 3 = 83 ppm 

Boron Tribromide 473 1-h AEGL-3 120 ppm ÷ 3 = 40 ppm 4-h AEGL-3: 31 ppm ÷ 3 = 10 ppm 8-h AEGL-3: 15 ppm ÷ 3 = 5 ppm 

474 Acute Exposure Guideline Levels APPENDIX B ACUTE EXPOSURE GUIDELINE LEVELS FOR BORON TRIBROMIDE Derivation Summary AEGL-1 VALUES 10min 30 min 1h 4h 8h 0.33 ppm 0.33 ppm 0.33 ppm 0.33 ppm 0.33 ppm Data adequacy: Inadequate data were available on boron tribromide, so values were based on the AEGL-1 values for hydrogen bromide. On the basis that one mole of boron tribromide hydrolyzes into three moles of hydrogen bromide, the hydrogen bromide AEGL-1 values were divided by 3. AEGL-2 VALUES 10 min 30 min 1h 4h 8h 83 ppm 28 ppm 13 ppm 3.3 ppm 1.7 ppm Data adequacy: Inadequate data were available on boron tribromide, so values were based on the AEGL-2 values for hydrogen bromide. On the basis that one mole of boron tribromide hydrolyzes into three moles of hydrogen bromide, the hydrogen bromide AEGL-2 values were divided by 3. AEGL-3 VALUES 10 min 30 min 1h 4h 8h 250 ppm 83 ppm 40 ppm 10 ppm 5 ppm Data adequacy: Inadequate data were available on boron tribromide, so values were based on the AEGL-3 values for hydrogen bromide. On the basis that one mole of boron tribromide hydrolyzes into three moles of hydrogen bromide, the hydrogen bromide AEGL-3 values were divided by 3.