Acute Exposure Guideline Levels for Selected Airborne Chemicals Volume 13 (2012) / Chapter Skim
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1 Boron Trifluoride
1 Boron Trifluoride
Pages 13-58
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From page 13... ...
Both the document and the AEGL values were then reviewed by the National Research Council (NRC) Committee on Acute Exposure Guideline Levels.
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. Acute toxicity studies with dogs, rats, mice, and guinea pigs were available, but exposure concentrations were generally expressed only in terms of nominal concentrations.
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AEGL-1 values are based on a no-effect level for irritation. A group of 10 rats exposed for 4 h to measured concentrations of boron trifluoride at 25 mg/m3 had no abnormal findings, whereas rats exposed to the next higher concentration of 74 mg/m3 had histopathologic changes in the larynx and tracheal bifurcation indicative of irritation (Bowden 2005)
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From page 16... ...
The ether complexes consist of a 1:1 molar ratio of boron trifluoride and either the dimethyl or diethyl ether, and can dissociate under the proper temperature and pressure conditions. A single study was found that evaluated the toxicity of boron trifluoride-dimethyl ether, but it reported only nominal concentrations.
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. TABLE 1-2 Chemical and Physical Data for Boron Trifluoride Parameter Valuea Reference Synonyms Trifluoroborane; boron NIOSH 2011 trifluoride-dimethyl ether (1:1)
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HUMAN TOXICITY DATA 2.1. Acute Lethality No data on lethality in humans following acute inhalation exposure to boron trifluoride were found.
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Groups of 10 rats, 10 mice, and 10 guinea pigs were exposed to nominal concentrations of boron trifluoride (Stokinger and Spiegl 1953)
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For the acute study, groups of five male and five female 9-week-old F344 rats were exposed for 4 h to liquid aerosols of boron trifluoride dihydrate at mean measured concentrations of 0, 1,010, 1,220, 1,320, or 1,540 mg/m3 (animals were exposed to boron trifluoride dihydrate, but the concentrations are based on boron trifluoride) (Hoffman 1981; Rusch et al.
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All 10 rats from the high-concentration group died before the sixth exposure. Clinical signs after two days included mucoid and/or red nasal discharge, dry or moist rales, dried red material around nose or mouth, lacrimation, and yellow anal-genital staining, whereas three control females exhibited mucoid nasal discharge and one control male had mucoid nasal discharge and dry rales (see Table 1-4)
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TABLE 1-4 Clinical Signs in Rats Exposed to Boron Trifluoride for Nine Days Observation 0 mg/m3 24 mg/m3 66 mg/m3 180 mg/m3 Exposure day 2 Number examined 10 10 10 10 Number affected 4 7 7 7 No signs 6 3 3 3 Mucoid nasal discharge 4 5 4 5 Red nasal discharge, dried red 0 2 2 1 material around nose or mouth Dry rales 1 2 2 1 Moist rales 0 1 0 2 Lacrimation 0 0 0 1 Stained anal-genital area 0 2 1 1 Exposure day 5 Number examined 10 10 10 10 Number affected 0 6 10 10 No signs 10 4 0 0 Dead 0 0 0 3 Mucoid nasal discharge 0 0 9 2 Red nasal discharge, dried red 0 6 6 4 material around nose or mouth Dry rales 0 0 3 0 Moist rales 0 2 7 1 Lacrimation 0 0 0 7 Stained anal-genital area 0 1 5 5 Gasping, shallow or labored breathing 0 0 0 3 Poor condition 0 0 0 8 Source: Adapted from Hoffman and Rusch 1982b; Rusch et al.
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3.1.2. Mice Groups of 10 mice, 10 rats, and 10 guinea pigs were exposed to nominal concentrations of boron trifluoride (Stokinger and Spiegl 1953)
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3.1.3. Guinea Pigs A series of experiments was carried out in guinea pigs to investigate the acute toxicity of inhaled boron trifluoride (DuPont Company 1948)
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Dry boron trifluoride gas was metered into the exposure chamber with a stream of nitrogen to prevent loss of the chemical. To determine actual exposure concentrations, air samples were taken from the chamber by drawing chamber air through a fritted glass scrubber containing distilled water.
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They were accidentally killed after exposure to high concentrations of boron trifluoride and nitrogen on the twenty-ninth exposure day. In a third experiment, a group of 10 male and 10 female guinea pigs were exposed to boron trifluoride at a nominal concentration of 8 mg/m3 (average measured concentration of 4 mg/m3)
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at measured concentrations of 9, 25, or 74 mg/m3 (nominal concentrations of 319, 734, and 982 mg/m3, respectively) for 4 h (Bowden 2005)
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Cartilage necrosis Total 0 0 0 1 0 0 0 1 Minimal 0 0 0 1 0 0 0 0 Slight 0 0 0 0 0 0 0 0 Moderate 0 0 0 0 0 0 0 1 Anterior ventral hemorrhage Minimal 0 0 0 0 0 0 0 0 Ventral epithelial hyperplasia Total 0 2 1 0 0 1 0 0 Minimal 0 2 0 0 0 1 0 0 Slight 0 0 1 0 0 0 0 0 Ventral inflammatory-cell Total 1 2 2 1 1 1 0 1 infiltration Minimal 1 1 1 1 1 1 0 1 Slight 0 1 1 0 0 0 0 0 Tracheal bifurcation (24-h postexposure) Loss of cilia Minimal 0 3 2 2 1 3 2 5 Tracheal bifurcation (2-wk postexposure)
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From page 29... ...
To determine actual exposure concentrations, air samples were taken from the chamber during exposure by drawing chamber air through a fritted glass scrubber containing distilled water. Samples were also taken from several areas within the chambers to ensure reasonable distribution of the boron trifluoride.
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Unfortunately, exposure concentrations were not analyzed or clearly defined in most of the reports. Studies which actually measured the exposure concentrations and compared them with nominal concentrations found
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1986 1,180b 4h LC50 Kasparov and Kiriĭ 1972 3,900c 1,400 4h 2/6 died; one 148 min into exposure, DuPont Company 1948 the other within 24 h of exposure 2,100c 750 5.5 h 1/10 died Stokinger and Spiegl 1953 Mouse 3,460b 2h LC50 Kasparov and Kiriĭ 1972 2,100c 750 5.5 h 1/10 died Stokinger and Spiegl 1953 Guinea pig 2,760c 1,000 5 min 2/2 died DuPont Company 1948 720c 260 3h 1/2 died 109b 4h LC50 Kasparov and Kiriĭ 1972 210c 750 5.5 h 10/10 died Stokinger and Spiegl 1953 970c 350 1.4 h 7/10 died 370c 135 10.9 h 1/10 died a Concentration provided in ppm only if the study authors reported concentrations in those units. b Not known if nominal or measured concentrations.
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Rat 2,760c 1,000 1h 2/2 rats survived; pulmonary congestion. DuPont Company 1948 720c 260 3h No clinical signs, no gross or microscopic changes.
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1961 127-128 exposures body or organ weights, or gross or microscopic findings. a Concentration provided in ppm only if the study authors reported the exposure concentrations in those units.
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reported a 2-h LC50 of 3,460 mg/m3 in mice, a 4-h LC50 of 1,180 mg/m3 in rats, and a 4-h LC50 of 109 mg/m3 in guinea pigs (unknown whether exposure concentrations were nominal or measured)
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From page 35... ...
An examination of the toxicity data on inhaled boron trifluoride indicates that acute exposure to a lethal concentration results in effects related to the corrosive, irritant nature of this compound. Findings observed during necropsy of animals exposed once to a lethal concentration of boron trifluoride included: an acute inflammatory reaction of the larynx and upper trachea and slightly edematous lungs with moderate congestion of alveolar wall in one rat and consolidation of the upper part of the lobes of the lungs and pus in the bronchi in another rat (DuPont Company 1948)
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From page 36... ...
A single study was found that addressed the toxicity of boron trifluoride-dimethyl ether, but it reported only nominal concentrations. Because the complex can dissociate to form boron trifluoride, the AEGL values are based on this one chemical species alone.
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In a repeated-exposure experiment, groups of dogs, rats, mice, guinea pigs, and rabbits were exposed to boron trifluoride at nominal concentrations of 74 or 138 mg/m3 (27 or 50 ppm) for 6 h/day, 6 days/week for a total of 30 exposure days.
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TABLE 1-10 Mortality in Laboratory Animals Exposed to Boron Trifluoride Dimethyl Ether for 30 Days Mortality (%) Species 27 ppm (130 mg/m3)
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The histopathologic changes in the larynx included minimal to slight ventral cartilage necrosis, minimal anterior ventral hemorrhage, and an increase in the severity of ventral epithelial hyperplasia and ventral inflammatory cell infiltration. Histopathologic changes in the trachea included an increased incidence of cilia loss (minimal)
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for 10.9 h in mice and rats. Studies that measured exposure concentrations and compared them with nominal concentrations found that actual concentrations ranged from 2.7-56% of nominal (Torkelson et al.
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of 736 mg/m3 and BMCL05 (benchmark concentration, 95% lower confidence limit with 5% response) of 554 mg/m3 were calculated by a log-probit analysis using EPA Benchmark Dose Software version 2.0 (2007)
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The graph in Figure 1-1 plots AEGL values for boron trifluoride along with the existing acute animal toxicity data in terms of the categories assigned to them (see data in Appendix C)
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f [3 mg/m3] a ERPG (emergency response planning guidelines)
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ERPG-3 is the maximum airborne concentration below which it is believed nearly all individuals could be exposed for up to 1 h without experiencing or developing lifethreatening health effects. The ERPG-3 for boron trifluoride is based on animal studies.
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Studies that measured the exposure concentrations and compared them with nominal concentrations found that actual concentrations ranged from 2.7-56% of nominal values. Therefore, nominal concentrations of boron trifluoride are unreliable.
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1982. Acute Oral Toxicity Study of Boron Trifluoride Dihydrate.
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2001. Standing Operating Procedures for Developing Acute Exposure Guideline Levels for Hazardous Chemicals.
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2005. Boron Trifluoride Dihydrate Acute (Four-H)
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1986. Inhalation toxicity studies with boron trifluoride.
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50 Acute Exposure Guideline Levels 4-h AEGL-3: C1 × 4 h = 221.6 mg/m3-h C1 = 55.4 mg/m3 C = 55 mg/m3 8-h AEGL-3: C1 × 8 h = 221.6 mg/m3-h C1 = 27.7 mg/m3 C = 28 mg/m3
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Boron Trifluoride 51 APPENDIX B BENCHMARK DOSE CALCULATIONS FOR BORON TRIFLUORIDE Probit Model. (Version: 3.1; Date: 05/16/2008)
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From page 52... ...
Deviance Model (likelihood) Parameters Test DF P-value Full model -19.3675 5 Fitted model -22.3 2 5.86491 3 0.1184 Reduced model -34.2965 1 29.8579 4 <0.0001 AIC: 48.6 Goodness of Fit Scaled Estimated Dose Probability Expected Observed Size Residual 0 0 0 0 10 0 1,010 0.196 1.96 3 10 0.829 1,220 0.5082 5.082 2 10 -1.95 1,320 0.6503 6.503 8 10 0.992 1,540 0.8647 8.647 9 10 0.326 Chi-square = 5.58; DF = 3 P-value = 0.1340 Benchmark Dose Computation Specified effect = 0.01 Risk type = Extra risk Confidence level = 0.95 BMD = 735.755 BMDL = 408.953 Benchmark Dose Computation Specified effect = 0.05 Risk type = Extra risk Confidence level = 0.95 BMD = 852.132 BMDL = 554.475
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Probit 1 0.
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1977 Rat Male 1,100 60 PL Vernot et al. 1977 Rat Female 1,000 60 PL DuPont Company 1948 Rat 3,900 240 PL
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From page 55... ...
Stokinger and Spiegl 1953 Rat 2,100 330 PL Stokinger and Spiegl 1953 Rat 370 654 0 Kasparov and Kiriĭ 1972 Rat 1,180 240 PL Rusch et al. 1986 Rat 1,010 240 PL Rat 1,220 240 PL Rat 1,320 240 PL Rat 1,540 240 PL Stokinger and Spiegl 1953 Mice 2,100 330 PL Mice 370 654 0 Kasparov and Kiriĭ 1972 Mice 3,460 120 PL DuPont Company 1948 Guinea pig 2,760 5 3 DuPont Company 1948 Guinea pig 720 180 PL Stokinger and Spiegl 1953 Guinea pig 2,100 330 3 Stokinger and Spiegl 1953 Guinea pig 970 84 PL Stokinger and Spiegl 1953 Guinea pig 370 654 PL Kasparov and Kiriĭ 1972 Guinea pig 109 240 PL DuPont Company 1948 Dog 1,380 30 1 DuPont Company 1948 Dog 1,380 180 2 DuPont Company 1948 Rat 2,760 60 2 DuPont Company 1948 Rat 720 180 0 Bowden 2005 Rat 9 240 0 Bowden 2005 Rat 25 240 0 Bowden 2005 Rat 74 240 1 a 0 = no effect; 1 = discomfort; 2 = disabling; PL = partially lethal; 3 = lethal.
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Data inadequacies include data addressing acute, nonlethal exposures. AEGL-2 VALUES 10 min 30 min 1h 4h 8h 3 3 3 3 37 mg/m 37 mg/m 29 mg/m 18 mg/m 9.3 mg/m3 Data adequacy: No acute toxicity data relevant to deriving AEGL-2 values were available.
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A limitation of the study was that mortality was observed at all exposure concentrations. Another limiting factor is that other studies addressing mortality after acute exposure did not provide analytic exposure concentrations; therefore, there are no other studies using the same or other species to support the values.
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From page 58... ...
, Braun and LD50 = 0.71 g/kg Killeen 1975e Boron trifluoride Primary dermal 6 rabbits, 0.5 mL, corrosive Eibert 1969 diethyl ether irritation Dermal LD50 Rabbits (6 males, 6 females/group, 2 groups) , LD50 = 1-2 g/kg Eye irritation 6 rabbits, 1.1 mL, corrosive Oral, minimal Rabbits (1 male, lethal dose 1 female/group)
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