Twenty-second Interim Report of the Committee on Acute Exposure Guideline Levels (2013) / Chapter Skim
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Twenty-second Interim Report of the Committee on Acute Exposure Guideline Levels
Twenty-second Interim Report of the Committee on Acute Exposure Guideline Levels
Pages 1-44
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From page 1... ...
In response to that request, the NRC published Guidelines for Developing Community Emergency Exposure Levels for Hazardous Substances in 1993. Subsequently, Standing Operating Procedures for Developing Acute Exposure Guideline Levels for Hazardous Substances was published in 2001; it provided updated procedures, methods, and other guidelines used by the National Advisory Committee (NAC)
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: acrylonitrile, allyl alcohol, boron tribromide, bromine chloride, cadmium, carbon tetrachloride, carbonyl fluoride, cyanide salts, diketene, ethyl benzene, germane, halogen fluorides (chlorine pentafluoride, bromine pentafluoride, and bromine trifluoride) , hexafluoropropylene, hydrogen bromide and hydrogen iodide, methacrylaldehyde, oxygen difluoride, pentaborane, stibine, styrene, tellurium hexafluoride, tetrafluoroethylene, thionyl chloride, and toluene.
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TABLE 2 Summary of Proposed AEGL Values for Allyl Alcohol 10 min 30 min 1h 4h 8h End Point, Derivation Factors AEGL-1 (nondisabling)
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The proposed AEGL-1 values on the basis of the Nielsen study are based on an RD10 (concentration that reduces the respiratory rate by 10%) of 0.27 ppm in mice.
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An updated literature search should be performed, and recent compilations reviewed for relevant information on the mechanism of action of allyl alcohol (see UNEP 2005 and EPA 2009)
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However, the proposed AEGL values must be revised in light of changes to the AEGL values for hydrogen bromide specified later in this report. BROMINE CHLORIDE The committee reviewed the AEGL TSD on bromine chloride that was presented by Heather Carlson-Lynch of SRC, Inc.
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; default time scaling. Abbreviations: BMCL05, benchmark concentration, 95% lower confidence limit with 5% response; UF, uncertainty factor.
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Studies comparing bromine chloride, bromine, and chlorine would also be helpful. CADMIUM The committee reviewed the AEGL TSD on cadmium that was presented by Gary Diamond of SRC, Inc.
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; default time scaling Abbreviations: LC50, lethal concentration, 50% lethality; UF, uncertainty factor. TABLE 6 Summary of Proposed AEGL Values for Carbon Tetrachloride Reviewed by the Committee 10 min 30 min 1h 4h 8h End Point, Derivation Factors AEGL-1 (nondisabling)
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CARBONYL FLUORIDE The committee reviewed the AEGL TSD on carbonyl fluoride that was presented by Julie Klotzbach of SRC, Inc. Table 7 presents a summary of the proposed AEGL values for carbonyl fluoride and their basis.
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CYANIDE SALTS The committee reviewed the AEGL TSD on sodium cyanide, potassium cyanide, and calcium cyanide that was presented by Heather Carlson-Lynch of SRC, Inc. Table 8 presents a summary of the proposed AEGL values for the three cyanide salts and their basis.
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Table 9 presents a summary of the proposed AEGL values for diketene and their basis. The committee agreed with the proposal not to derive AEGL-1 values, and the approach of basing the AEGL-2 values on the AEGL-3 values.
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; default time scaling Abbreviations: BMCL05, benchmark concentration, 95% lower confidence limit with 5% response; NR, not recommended; UF, uncertainty factor. AEGL Specific Comments The committee agreed that the data on diketene were inadequate to derive AEGL-1 value.
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; PBPK model for time scaling Abbreviations: PBPK, physiologically based pharmacokinetic; UF, uncertainty factor. TABLE 11 Summary of Proposed AEGL Values for Germane Reviewed by the Committee End Point, Classification 10 min 30 min 1h 4h 8h Derivation Factors AEGL-1 NR NR NR NR NR Insufficient data (nondisabling)
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All of the other AEGL values were appropriately justified. TABLE 12 Summary of Proposed AEGL Values for Selected Halogen Fluorides Reviewed by the Committee End Point, Classification 10 min 30 min 1h 4h 8h Derivation Factors Chlorine pentafluoride AEGL-1 NR NR NR NR NR Insufficient warning (nondisabling)
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HEXAFLUOROPROPYLENE The committee reviewed the AEGL TSD on hexafluoropropylene that was presented by Heather Carlson-Lynch of SRC, Inc. Table 13 presents a summary of the proposed AEGL values for hexafluoropropylene and their basis.
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; time scaling, n = 1.33 Abbreviations: BMCL05, benchmark concentration, 95% lower confidence limit with 5% response; UF, uncertainty factor. A similar reanalysis of the POD for AEGL-2 values should also be performed.
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For hydrogen bromide, the committee approved the proposed AEGL-1 values, but recommends revisions to how the AEGL-2 and AEGL-3 values were derived. The AEGL values for hydrogen iodide are based on those for hydrogen bromide.
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TABLE 15 Summary of Proposed AEGL Values for Methacrylaldehyde Reviewed by the Committee 10 min 30 min 1h 4h 8h End Point, Derivation Factors AEGL-1 (nondisabling) 0.20 ppm 0.20 ppm 0.20 ppm 0.20 ppm 0.20 ppm Increased blink frequency in humans (0.60 mg/m3)
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OXYGEN DIFLUORIDE The committee reviewed the AEGL TSD on oxygen difluoride that was presented by Gary Diamond of SRC, Inc. Table 16 presents a summary of the proposed AEGL values for oxygen difluoride and their basis.
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Table 17 presents a summary of the proposed AEGL values for pentaborane and their basis. The committee agreed with the proposal not to derive AEGL-1 values, but recommended that the basis of the AEGL-2 and AEGL-3 values be reanalyzed.
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Furthermore, the proposed AEGL values are 5-50 times higher than most of the other exposure guidelines for pentaborane. The discussion of time scaling to derive AEGL-2 values should note that neurotoxic effects are on the continuum of effects leading to death (e.g., tremors, convulsions, apprehension)
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; total UF = 10 (interspecies = 3, intraspecies = 3) ; default time scaling AEGL-3 (lethal)
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As discussed in the comments on carbonyl fluoride, the argument that a steep concentration-response is an indication of little toxic variation within a population is not appropriate and should be removed. Page 8, Introduction: Provide more current information about the uses of stibine.
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Additional relevant information in other references regarding CNS effects should be included. Some references that refer to activity in red blood cells vs.
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." First, the most "current" citation for the standards and guidelines in this table appears to be from 8 years ago, with some references being even older. Second, a number of other occupational exposure limits (OELs)
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Relevant References The following are several references that should be included or expanded upon in the updated TSD. Other relevant information should be sought through an updated literature search.
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2011. Nineteenth Interim Report of the Committee on Acute Exposure Guideline Levels, Part A
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Table 19 presents a summary of the proposed AEGL values for styrene and their basis. The committee agreed with the proposed AEGL-1 values, and recommended a few adjustments to how the AEGL-2 and AEGL-3 values were derived.
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; time scaling, n = 1.2 Abbreviations: BMCL05, benchmark concentration, 95% lower confidence limit with 5% response; CNS, central nervous system; NOAEL, no observed adverse effect level; UF, uncertainty factor. TABLE 20 Summary of Proposed AEGL Values for Tellurium Hexafluoride Reviewed by the Committee 10 min 30 min 1h 4h 8h End Point, Derivation Factors AEGL-1 (nondisabling)
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TETRAFLUOROETHYLENE The committee reviewed the AEGL TSD on tetrafluoroethylene that was presented by Heather Carlson-Lynch of SRC, Inc. Table 21 presents a summary of the proposed AEGL values for tetrafluoroethylene and their basis.
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Table 22 presents a summary of the proposed AEGL values for thionyl chloride and their basis. The committee agreed with the approach to deriving the AEGL values, but recommends that additional information be considered to determine whether alternate derivations might be more appropriate or whether slight adjustments to the calculations might be made before the TSD is finalized.
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; default time scaling Abbreviations: BMCL05, benchmark concentration, 95% lower confidence limit with 5% response; NR, not recommended; UF, uncertainty factor. AEGL Specific Comments The committee agreed with the proposal not to recommend AEGL-1 values for thionyl chloride.
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. Page 6, lines 42-44: The justification for deriving AEGL-2 values by dividing AEGL-3 values by 3 should make it clear that this is a general approach for chemicals with a steep concentration-response curve for lethality and not because of data specific to thionyl chloride.
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From page 35... ...
That report was dismissed because the concentration appeared inconsistent with their rat data. However, because of thionyl chloride's rapid hydrolysis, the toxicity results reflected exposure to sulfur dioxide and hydrogen chloride; only 11 ppm was measured at the highest test concentration, whereas concentrations of sulfur dioxide and hydrogen chloride were calculated to be 661 ppm and 1,322 ppm, respectively.
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data. Provide context for higher toxicity at lower relative humidity as outlined in previous comments (less hydrolysis in ambient air prior to inhalation resulting in deeper deposition of thionyl chloride in the lung, where hydrolysis to sulfur dioxide and hydrogen chloride produces greater direct contact effects of those corrosive irritants with local tissue compared with the result when hydrolysis products are inhaled at the outset)
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In light of the revisions, ensure that appropriate data and assumptions underlie the AEGL-3 values, and present the correct nonlethal toxicity data. Discuss the data underlying the AEGL-2 values for sulfur dioxide and hydrogen chloride to provide supporting context for the AEGL-2 values for thionyl chloride.
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Provide context for gender differences in humans with respect to the hydrolysis products of thionyl chloride, notably sulfur dioxide in exercising asthmatics. Page 28, lines 25-26; and page 33, summary table (UFs/rationale row)
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; total UF = 3 (intraspecies) ; PBPK model for time scaling AEGL-3 (lethal)
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and Thionyl Chloride Using an Environmental Wind Tunnel.
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1962. Acute thionyl chloride poisoning [in Italian]
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1993. Thionyl Chloride: Acute Vapor Inhalation Toxicity Study in Rats.
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2001. Standing Operating Procedures for Developing Acute Exposure Guideline Levels for Hazardous Chemicals.
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1991. Relative acute toxicities of hydrogen fluoride, hydrogen chloride, and hydrogen bromide in nose- and pseudo-mouth-breathing rats.
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