Acute Exposure Guideline Levels for Selected Airborne Chemicals Volume 16 (2014) / Chapter Skim
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4 Allyl Alcohol1 Acute Exposure Guideline Levels PREFACE Under the authority of the Federal Advisory Committee Act (FACA)
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Allyl Alcohol 181 experience notable discomfort, irritation, or certain asymptomatic, nonsensory effects. However, the effects are not disabling and are transient and reversible upon cessation of exposure.
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182 Acute Exposure Guideline Levels 4- and 8-h AEGL-2 values, respectively. A total uncertainty factor of 30 was applied.
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Allyl Alcohol 183 1. INTRODUCTION Allyl alcohol is a colorless liquid that is a potent sensory irritant.
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184 Acute Exposure Guideline Levels allyl alcohol. Kononenko (1970)
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Allyl Alcohol 185 vaporization and equilibration were allowed before the volunteers entered the room for the static exposure. Volunteers were exposed to allyl alcohol at 0.78, 6.25, 12.5, or 25.0 ppm; whether these concentrations were calculated or measured was not specified.
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186 Acute Exposure Guideline Levels TABLE 4-3 Summary of Sensory Responses to Ally Alcohol During 5-Minute Exposure Olfactory Recognition Ocular Irritation Nasal Irritation Concentration No.
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Allyl Alcohol 187 3.
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188 Acute Exposure Guideline Levels signs of toxicity in rats were lacrimation and tremors, with coma preceding death. Gross necropsy findings in both rats and rabbits (findings not presented separately)
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Allyl Alcohol 189 was not provided)
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190 Acute Exposure Guideline Levels 3.1.3. Mice Union Carbide and Carbon Corporation (1951)
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Allyl Alcohol 191 Labored and noisy breathing and discharge from the nose and mouth were observed within 1 h of exposure. One rabbit convulsed and died after three days of exposure, a second rabbit died after six days of exposure, and the third died after 18 days of exposure.
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192 Acute Exposure Guideline Levels exposure (animals exposed for 4 and 8 h) , 4 h into the exposure (animals exposed for 8 h)
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Allyl Alcohol 193 Groups of five male and five female Crl:CD(SD) rats were exposed by whole body inhalation to allyl alcohol vapor at measured concentrations of 0, 51, 220, or 403 ppm (nominal concentrations were 0, 50, 200, or 400 ppm)
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194 Acute Exposure Guideline Levels the olfactory and respiratory epithelium, chronic inflammation, and goblet cell hyperplasia. For the 8-h exposures, clinical effects were minimal in rats exposed at 10 and 21 ppm; a few animals had reddened limbs and material around the mouth, one rat at each concentration had yellow material around the urogenital area, and one rat in the 21-ppm group had rales/increased respiration (Kirkpatrick 2008)
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TABLE 4-7 Summary of Clinical Signs in Rats Exposed to Ally Alcohol Concentration (ppm) 1h 4h 8h End Point 0 51 220 403 0 22 52 102 0 10 21 52 No.
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TABLE 4-8 Summary of Selected Nasal Histopathologic Findings in Rats Exposed to Ally Alcohola 196 Concentration (ppm) 1h 4h 8h End Point 0 51 220 403 0 22 52 102 0 10 21 52b No.
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Minimal – – – – – – 1 0 – – – 0 Mild – – – – – – 0 2 – – – 0 Moderate – – – – – – 0 0 – – – 2 Metaplasia, olfactory epithelium Total 0 1 0 0 0 0 0 0 0 0 0 1 Mild – 1 – – – – – – – – – 0 Severe, irreversible – 0 – – – – – – – – – 1 a Summary of number of animals with lesion taking into account all six nasal levels; grade for each lesion is the highest grade for any of the six nasal levels. b Results for the rat that died are included.
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198 Acute Exposure Guideline Levels during the last 10 min of exposure. The onset of decreased respiratory rate occurred rapidly, plateaued within 10 min of exposure, and quickly subsided following termination of the exposure.
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Allyl Alcohol 199 3.2.3. Dogs, Guinea Pigs, and Rabbits Torkelson et al.
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200 Acute Exposure Guideline Levels icity studies in rats exposed to allyl alcohol by gavage; neither study found significant alterations in malformations or variations in the offspring. A decrease in pup viability index was observed in the offspring of rats administered allyl alcohol at 40 mg/kg/day before mating and through lactation day 3 (males were also exposed before mating)
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Allyl Alcohol 201 tered allyl alcohol at 300 mg/L in drinking water for 106 weeks, or when 20 male Syrian golden hamsters were administered allyl alcohol at 2 mg in corn oil by gavage once a week for 60 weeks (Lijinsky and Reuber 1987)
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TABLE 4-9 Summary of Acute Lethality Data in Laboratory Animals Exposed to Allyl Alcohol 202 Species Concentration (ppm) Exposure Duration Deaths Reference Monkey 1,000 4h 1/1 McCord 1932 Mouse 200 1h 0/10 Union Carbide and Carbon Corporation 1951 Mouse 500 0.5 h 0/10 Union Carbide and Carbon Corporation 1951 500 1h 4/10 Mouse 1,000 1h 6/10 Union Carbide and Carbon Corporation 1951 1,000 2h 8/10 1,000 4h 10/10 Mouse 22,000 10 min 10/10 Shell Chemical Corporation 1957 nd 12,200 2 × 10 min 10/10 (after 2 exposure)
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Rat 10 8h 0/10 Kirkpatrick 2008 21 8h 0/10 52 8h 1/10 Rat 200 1h 0/10 Union Carbide and Carbon Corporation 1951 Rat 1,000 0.5 h 1/6 Union Carbide and Carbon Corporation 1951 1,000 1h 4/6 1,000 2h 6/6 Rat 1,000 1h 4/6 Smyth and Carpenter 1948 Rat 1,000 3h 6/6 (during exposure) McCord 1932 200 2×7h 4/4 (by end of 2nd exposure)
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204 TABLE 4-10 Summary of Acute Nonlethal Inhalation Data in Laboratory Animals Exposed to Allyl Alcohol Species Exposure Duration Concentration (ppm) Effects Reference Mouse 10 min 3.9 RD50 Nielsen et al.
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TABLE 4-11 Summary of Nonlethal Inhalation Data in Laboratory Animals Exposed Repeatedly to Allyl Alcohol Species Exposure Duration Concentration (ppm) Effects Reference Mouse 6 h/d for 4 d 2.4 Histopathologic changes in upper respiratory tract epithelium Zissu 1995 (hyperplasia, inflammatory infiltrates, desquamation)
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206 Acute Exposure Guideline Levels exposed for 9 days or 2 weeks (Zissu 1995)
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Allyl Alcohol 207 Mode-of-action information on allyl alcohol has focused on how the chemical causes periportal necrosis in the liver. It appears that this effect is more apt to occur after oral, intraperitoneal, or intravenous administration; thus, its relevance to effects after acute inhalation exposure is uncertain.
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208 Acute Exposure Guideline Levels parent alcohol is a direct irritant or if conversion to the acrolein metabolite is required to produce irritation. Liver preparations metabolized allyl alcohol to acrolein, acrylic acid, glycidaldehyde, and glyceraldehyde.
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Allyl Alcohol 209 uses the algorithm to predict the potency of a reactive compound, the predicted minimum potency will be less than the observed potency.
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210 Acute Exposure Guideline Levels damage can also be influenced by bacterial infections, as demonstrated in a study reporting that allyl alcohol-treated rats pretreated with bacterial endotoxin experienced enhanced hepatic damage compared with rats given allyl alcohol alone (Sneed et al.
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Allyl Alcohol 211 5.2. Animal Data Relevant to AEGL-1 Exposure to allyl alcohol at 51 ppm for 1 h, at 22 ppm for 4 h, or at 10 ppm for 8 h produced reversible histopathologic changes in the nasal cavity of rats, including degeneration of the olfactory epithelium, chronic inflammation, and goblet cell hyperplasia (Kirkpatrick 2008)
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212 Acute Exposure Guideline Levels TABLE 4-12 AEGL-1 Values for Allyl Alcohol 10 min 30 min 1h 4h 8h 0.090 ppm 0.090 ppm 0.090 ppm 0.090 ppm 0.090 ppm (0.22 mg/m3)
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Allyl Alcohol 213 ppm for 8 h. These values were used as the points-of-departure for the 1-, 4- and 8-h AEGL-2 values, respectively.
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214 Acute Exposure Guideline Levels Carbide and Carbon Corporation 1951)
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Allyl Alcohol 215 8.2. Other Standards and Guidelines Standards and guidance levels for workplace and community exposures to allyl alcohol are presented in Table 4-16.
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216 Acute Exposure Guideline Levels TABLE 4-16 Standards and Guidelines for Allyl Alcohol Exposure Duration Guideline 10 min 15 min 30 min 1h 4h 8h AEGL-1 0.09 ppm – 0.09 ppm 0.09 ppm 0.09 ppm 0.09 ppm (0.22 (0.22 (0.22 (0.22 (0.22 mg/m3)
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Allyl Alcohol 217 d REL-TWA (recommended exposure limit – time-weighted average, National Institute for Occupational Safety and Health [NIOSH 2011]
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218 Acute Exposure Guideline Levels Adams, E.M.
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Allyl Alcohol 219 Dunlap, M.K., and C.H.
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220 Acute Exposure Guideline Levels Kirkpatrick, D.T.
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Allyl Alcohol 221 NRC (National Research Council)
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222 Acute Exposure Guideline Levels Tabershaw, I.R., H.M.D. Utidjian, and B.L.
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Allyl Alcohol 223 APPENDIX A DERIVATION OF LC01 VALUES AND TIME-SCALING EXPONENT FOR ALLY ALCOHOL Filename: allyl alcohol for Log Probit Model Date: 13 November 2008 Time: 14:07:13 Sequence No. Concentration (ppm)
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224 Acute Exposure Guideline Levels Variance B 0 0 = 6.8256E+01 Covariance B 0 1= -5.6297E+00 Covariance B 0 2 = -7.5164E+00 Variance B 1 1 = 4.7615E-01 Covariance B 1 2 = 6.0522E-01 Variance B 2 2 = 8.4867E-01 Estimation ratio between regression coefficients of ln(conc) and ln(minutes)
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Allyl Alcohol 225 APPENDIX B DERIVATION OF AEGL VALUES FOR ALLYL ALCOHOL Derivation of AEGL-1 Values Key study: Nielsen, G.D., J.C. Bakbo, and E
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226 Acute Exposure Guideline Levels 30-min AEGL-2: C0.95 × 0.5 h = 42 ppm-h C0.95 = 84 ppm C = 106 ppm 106 ÷ 30 = 3.5 ppm 1-h AEGL-2: 51 ppm ÷ 30 = 1.7 ppm 4-h AEGL-2: 22 ppm ÷ 30 = 0.73 8-h AEGL-2: 10 ppm ÷ 30 = 0.33 Derivation of AEGL-3 Values Key studies: Kirkpatrick, D.T.
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Allyl Alcohol 227 Calculations: 10-min AEGL-3: 2,600 ppm ÷ 30 = 87 ppm 30-min AEGL-3: 820 ppm ÷ 30 = 27 ppm 1-h AEGL-3: 400 ppm ÷ 30 = 13 ppm 4-h AEGL-3: 93 ppm ÷ 30 = 3.1 ppm 8-h AEGL-3: 45 ppm ÷ 30 = 1.5 ppm
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228 Acute Exposure Guideline Levels APPENDIX C ACUTE EXPOSURE GUIDELINE LEVELS FOR ALLY ALCOHOL Derivation Summary AEGL-1 VALUES 10 min 30 min 1h 4h 8h 0.090 ppm 0.090 ppm 0.090 ppm 0.090 ppm 0.090 ppm (0.22 mg/m3)
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Allyl Alcohol 229 Duration Concentration Effects 403 ppm Same as at 220 ppm, plus gasping. 4h 22 ppm Clear red material around mouth.
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230 Acute Exposure Guideline Levels AEGL-3 VALUES Continued Exposure route/Concentrations/Durations: Inhalation, 10-1,000 ppm for 1-8 h Effects: Concentration (ppm) Minutes Exposed Responded Reference 51 60 10 0 Kirkpatrick 2008 220 60 10 0 Kirkpatrick 2008 403 60 10 0 Kirkpatrick 2008 22 240 10 0 Kirkpatrick 2008 52 240 10 0 Kirkpatrick 2008 102 240 10 0 Kirkpatrick 2008 10 480 10 0 Kirkpatrick 2008 21 480 10 0 Kirkpatrick 2008 52 480 10 1 Kirkpatrick 2008 200 60 10 0 Union Carbide and Carbon Corporation 1951 1,000 30 6 1 Union Carbide and Carbon Corporation 1951 1,000 60 6 4 Union Carbide and Carbon Corporation 1951 1,000 120 6 6 Union Carbide and Carbon Corporation 1951 1,000 60 6 4 Smyth and Carpenter 1948 1,000 180 6 6 McCord 1932 638 60 6 0 Kirkpatrick 2008 423 60 6 0 Kirkpatrick 2008 114 240 6 0 Kirkpatrick 2008 52 480 6 0 Kirkpatrick 2008 End point/Concentration/Rationale: Estimated lethality thresholds, LC01s of 2,600 ppm for 10 min, 820 ppm for 30 min, 400 ppm for 1 h, 93 ppm for 4 h, and 45 ppm for 8 h.
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Allyl Alcohol 231 APPENDIX D CATEGORY PLOT FOR ALLYL ALCOHOL A useful way to evaluate AEGL values in the context of empirical data is presented in Figure D-1. For this plot, toxic responses were placed into severity categories.
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232 TABLE D-1 Data Used in Category Plot for Allyl Alcohol Source Species Sex No. of Exposures ppm Minutes Category Comments AEGL-1 0.090 10 AEGL AEGL-1 0.090 30 AEGL AEGL-1 0.090 60 AEGL AEGL-1 0.090 240 AEGL AEGL-1 0.090 480 AEGL AEGL-2 11 10 AEGL AEGL-2 3.5 30 AEGL AEGL-2 1.7 60 AEGL AEGL-2 0.73 240 AEGL AEGL-2 0.33 480 AEGL AEGL-3 87 10 AEGL AEGL-3 27 30 AEGL AEGL-3 13 60 AEGL AEGL-3 3.1 240 AEGL AEGL-3 1.5 480 AEGL Dunlap et al.
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Dunlap et al. 1958 Rat Both 1 150.0 420 3 Dunlap et al.
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234 TABLE D-1 Continued Source Species Sex No. of Exposures ppm Minutes Category Comments McCord 1932 Rat Both 1 420 Mortality (4/4)
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Union Carbide and Carbon Mouse 1 1,000.0 240 3 Mortality (10/10) Corporation 1951 Union Carbide and Carbon Rabbit Both 1 500 120 2 Corporation 1951 Union Carbide and Carbon Rabbits 1 500.0 240 3 Mortality (4/4)
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