Acute Exposure Guideline Levels for Selected Airborne Chemicals Volume 18 (2014) / Chapter Skim
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3 Selected Halogen Fluorides
3 Selected Halogen Fluorides
Pages 66-121
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From page 66... ...
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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1. GENERAL INFORMATION ON SELECTED HALOGEN FLUORIDES In this chapter, the bases of the AEGL values for the following three halogen fluorides are described: chlorine pentafluoride (ClF5)
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Reaction with water is violent, with potential release of bromine, fluorine, hydrogen bromide, and hydrogen fluoride (Dost et al. 1968; NIOSH/OSHA 1992; Teitelbaum 2001)
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. BrF3 is prepared by direct combination of one part bromine with three parts fluorine in a water-cooled copper reactor at temperatures between 15 and 50°C, or by the reaction of bromine fluoride with fluorine (Braker and Mossman 1980)
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From page 70... ...
When the exposure duration was reduced to 30 min, none of the rats died; however, the observation period after exposure was for only 20 h before the rats were killed. The 1-h LC50s for ClF5 and ClF3 in rats were 122 and 299 ppm, respectively.
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1.5. Mechanism of Toxicity The mechanism by which halogen fluorides exert their acute toxicity is by direct irritation and corrosion.
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. TABLE 3-3 Fluoride Content in Bone, Blood Plasma, and Lungs of Rats Exposed to BrF5 (500 ppm for 30 min)
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1.8. Concentration-Exposure Duration Relationship For ClF5, the dose-response curve for lethality is steep.
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For comparison, an n value of 1.3 was used to time scale AEGL values for ClF3 (NRC 2007a) and an n value of 2.0 was used for hydrogen fluoride (NRC 2004)
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No human or animal data on the toxicity of BrF3 were available. AEGL values for this compound were set equal to the AEGLs for the related compound ClF3 (NRC 2007a)
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(0.41 mg/m3) chlorine pentafluoride.
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0.15 ppm 0.15 ppm 0.15 ppm 0.15 ppm 0.15 ppm Slight salivation, slight lacrimation, and slight chromodacryorrhea in rats exposed at 3 ppm for 6 h (DuPont 1955)
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In particular, the following studies would be beneficial: studies of the acute lethality of BrF3 in laboratory animals, studies of ClF5 and BrF5 for exposure durations of 1-8 h, studies of the acute toxicity of BrF5 in species other than rats, and additional data on the concentration-time relationship for BrF5.
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. Examination of the data indicates that the 30- and 60-min lethality data reported in this study exhibited a clear linear concentrationresponse relationship when plotted on a semi-log plot, lending confidence to the calculated LC50 values for these durations.
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In the first two groups of rats exposed
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TABLE 3-9 Acute Lethality in Dogs Exposed to Chlorine Pentafluoride Concentration (ppm) Exposure Duration Mortality 168 15 min 0/4 202 15 min 1/4 300 15 min 2/4 360 15 min 2/4 443 15 min 4/4 102 30 min 1/4 150 30 min 2/4 190 30 min 2/4 223 30 min 3/4 252 30 min 3/4 274 30 min 4/4 63 60 min 0/4 110 60 min 1/4 128 60 min 2/4 143 60 min 4/4 170 60 min 4/4 Source: Adapted from Darmer et al.
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Concentrations were measured with a fluoride ion specific electrode. Lacrimation and nausea were observed almost immediately after onset of exposure and
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reported that "gross and histopathological examination at 28 days postexposure failed to produce any evidence of permanent effects of exposure" in monkeys or any other species; thus, it is difficult to interpret the pathology findings in the various exposure groups. Although mean body weights were not significantly affected following a 28-day observation period, weight gains during this period were depressed.
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MacEwen and Vernot 1973 7 10 min Slight ocular irritation, and no effect on body weight gain or lung wet weight. Mouse 10 60 min Lacrimation and transient effect on body weight.
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30 10 min Mouse 30 10 min Irritation, mild pulmonary congestion observed when killed immediately MacEwen and Vernot 1973 after exposure.
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Mean body weights and body weight gains were unaffected during the 28-day observation period. Gross examination at necropsy revealed no effects in any of the control rats or rats exposed for 10 min.
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Salivation, ocular irritation, lacrimation, and rhinorrhea, described by the study authors as "typical ClF5 irritation and discomfort symptoms," were seen during the exposures, with the most severe signs observed in the group exposed for 10 min at 30 ppm. Exposed groups exhibited body weight gains similar to that of the control group.
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From page 88... ...
Salivation, ocular irritation, lacrimation, and rhinorrhea, described by the study authors as "typical ClF5 irritation and discomfort symptoms," were seen during the exposures, with the most severe signs observed in the group exposed for 10 min at 30 ppm. Exposed groups exhibited body weight gains during the first week after exposure.
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From page 89... ...
indicates that toxicologically significant quantities of ClF5 did not reach the lungs at those concentrations. Animals of both groups killed after a 28-day observation period had no alternations in body weight gain or gross pathologic findings in the lungs.
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At gross necropsy, pulmonary congestion was observed in monkeys exposed at 10 ppm for 60 min, and rats had pale livers and kidneys. A second experiment at lower concentrations reported salivation, ocular irritation, lacrimation, and rhinorrhea, but no gross pathologic findings in groups of five rhesus monkeys, eight beagles, 30 rats, and 30 mice exposed to ClF5 at 5 ppm for 60 min, 10 ppm for 30 min, or 30 ppm for 10 min (MacEwen and Vernot 1973)
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Symptoms Gross pathology Other effects Species 10 3 None None No effect on body weight Rats 7 Slight moistening of eyes None No effect on body weight Rats 30 Salivation, ocular irritation, Reversible pulmonary Slight transient weight loss Monkeys, dogs, lacrimation, and rhinorrhea (all congestion and edema (monkeys)
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. The values of the two uncertainty factors are also consistent with those used to derive AEGL values for the related compounds ClF3, HF, and ClO2 (NRC 2004, 2007a,b)
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2.5.2. Animal Data Relevant to AEGL-3 Lethality data on ClF5 were available for the monkey, dog, rat, and mouse (Darmer et al.
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(14 mg/m3) TABLE 3-16 AEGL Values for Chlorine Pentafluoride Exposure Duration Classification 10 min 30 min 1h 4h 8h AEGL-1 NRa NRa NRa NRa NRa (nondisabling)
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TABLE 3-17 Lethality Data from Studies of Rats Exposed to Bromine Trifluoride Concentration (ppm) Exposure Duration Effect 1,000 20 min No deaths (0/10)
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3.3.2. Animal Data Relevant to AEGL-1 No animal data relevant to developing AEGL-1 values for BrF5 were found.
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3.5.2. Animal Data Relevant to AEGL-3 A single study provided lethal and nonlethal concentration-exposure durations for the rat.
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(30 mg/m3) TABLE 3-20 AEGL Values for Bromine Pentafluoride Exposure Duration Classification 10 min 30 min 1h 4h 8h AEGL-1 NRa NRa NRa NRa NRa (nondisabling)
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BROMINE TRIFLUORIDE 4.1. Human Toxicity Data No reliable data on the toxicity of BrF3 in humans were found.
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4.3.2. Animal Data Relevant to AEGL Values No animal data relevant to deriving AEGL-1, AEGL-2, or AEGL-3 values for BrF3 were found.
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1971. The acute toxicity of chlorine pentafluoride.
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2001. Standing Operating Procedures for Developing Acute Exposure Guideline Levels for Hazardous Chemicals.
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Pp. 11-52 in Acute Expo sure Guideline Levels for Selected Airborne Chemicals, Vol.
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FIGURE A-1 LC50 values for chlorine pentafluoride in the rat. Source: Darmer et al.
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1.9 × 1 h = 0.17 ppm-h Uncertainty factors: 3 for interspecies differences 3 for intraspecies variability Modifying factor: 3 to extrapolate from an effect level to a no effect level (4-h and 8-h AEGL-2 values) Calculations: 10-min AEGL-2: 7 ppm ÷ 10 = 0.70 ppm 30-min AEGL-2: (5.078 ppm-min ÷ 30 min)
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Derivation of AEGL-2 Values No human or animal data relevant to deriving AEGL-2 values for BrF5 were available. AEGL-2 values were set equal to those for the related compound, ClF5.
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Uncertainty factors: 3 for interspecies differences 3 for intraspecies variability Time scaling: Cn × t = k; default values of n = 3 for extrapolating to shorter durations and n = 1 for extrapolating to longer durations (NRC 2001)
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10-min AEGL-2: 8.1 ppm 30-min AEGL-2: 3.5 ppm 1-h AEGL-2: 2.0 ppm 4-h AEGL-2: 0.70 ppm 8-h AEGL-2: 0.41 ppm Derivation of AEGL-3 Values No human or animal data were available on BrF3. AEGL-3 values were set equal to those for the related compound, ClF3 (see NRC 2007a)
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Selected Halogen Fluorides 109 1-h AEGL-3: 21 ppm 4-h AEGL-3: 7.3 ppm 8-h AEGL-3: 7.3 ppm
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110 Accute Exposure Guideline Levels AP PPENDIX C CATEGORY C PLOTS P FOR SELECTED S H HALOGEN FLU UORIDES Chlorin ne Pentafluoriide FIGUR RE C-1 Category y plot of toxicity y data and AEGL L values for chloorine pentafluoridde.
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63 60 2 Severe signs of irritation. 122 60 SL LC50 (Continued)
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1972 Rat 175 15 SL 10% mortality. 163 30 2 Severe signs of irritation.
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Selecteed Halogen Flu uorides 1113 FIGUR RE C-2 Category y plot of toxicity y data and AEGL L values for brom mine pentafluoride. TABLE E C-2 Data Useed in Category Plot P for Chlorinne Pentafluoridee Source Species ppm Time (min)
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The values of the two uncertainty factors are consistent with those used to derive AEGL values for the related compounds ClF3, HF, and ClO2 (NRC 2004, 2007a,b)
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. ClF5 and related compounds exert toxicity via direct irritation and corrosive action on the respiratory tissues.
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AEGL-2 Values for Bromine Pentafluoride 10 min 30 min 1h 4h 8h 0.70 ppm 0.39 ppm 0.17 ppm 0.082 ppm 0.057 ppm Data adequacy: No human or animal data relevant to deriving AEGL-2 values for BrF5 were available. Therefore, AEGL-2 values were set equal to those for the related compound ClF5.
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Derivation Summary for Bromine Trifluoride AEGL-1 Values for Bromine Trifluoride 10 min 30 min 1h 4h 8h 0.12 ppm 0.12 ppm 0.12 ppm 0.12 ppm 0.12 ppm Data adequacy: No human or animal data relevant for deriving AEGL-1 values for BrF3 were available. AEGL-1 values were set equal to those for the related compound ClF3 (see NRC 2007a)
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AEGL-3 Values for Bromine Trifluoride 10 min 30 min 1h 4h 8h 84 ppm 36 ppm 21 ppm 7.3 ppm 7.3 ppm Data adequacy: No human or animal data relevant for deriving AEGL-3 values for BrF3 were available. AEGL-3 values were set equal to those for the related compound ClF3 (see NRC 2007a)
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From page 119... ...
Uncertainty factors/Rationale: Total uncertainty factor: 10 Interspecies: 3 – The dog is a sensitive species for nasal irritation and provides a good model for humans. Dogs exposed to 1.17 ppm showed obvious lacrimation after 3 h yet rats showed no effects at the same concentration for 6 h.
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From page 120... ...
Modifying factor: Not applicable Animal to Human Dosimetric Adjustment: Insufficient data. Time scaling: Cn × t = k where n = 1.3; based on the time-concentration relationship for LC50 values in monkeys, rats, and mice for exposure durations of 13.5-222 min (Horn and Weir 1955; MacEwen and Vernot 1970; Dost et al.
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From page 121... ...
Time scaling: Cn × t = k where n = 1.3; based on the time-concentration relationship for LC50 values in monkeys, rats, and mice for exposure durations of 13.5-222 min (Horn and Weir 1955; MacEwen and Vernot 1970; Dost et al.
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