Acute Exposure Guideline Levels for Selected Airborne Chemicals Volume 14 (2013) / Chapter Skim
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6 Propargyl Alcohol Acute Exposure Guideline Levels
6 Propargyl Alcohol Acute Exposure Guideline Levels
Pages 176-209
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From page 176... ...
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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From page 177... ...
Although the AEGL values represent threshold concentrations for the general public, including susceptible subpopulations, such as infants, children, the elderly, persons with asthma, and those with other illnesses, it is recognized that individuals, subject to idiosyncratic responses, could experience the effects described at concentrations below the corresponding AEGL. SUMMARY Propargyl alcohol is a moderately volatile, three-carbon acetylenic alcohol with a geranium-like odor.
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Animal data suggest that olfactory and respiratory-tract epithelium are the primary targets of propargyl alcohol and that damage to these tissues is likely instrumental in deaths after a single acute exposure. Studies of repeated exposures to propargyl alcohol (about 90 days)
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HUMAN TOXICITY DATA 2.1. Acute Lethality No data regarding lethality in humans following inhalation exposure to propargyl alcohol were available.
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2.5. Carcinogenicity No human data on the carcinogenic potential of propargyl alcohol were available.
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Gross pathologic examination of the rat revealed evidence of liver toxicity. A 5-day study was also conducted using one cat, one rabbits, four guinea pigs, 10 rats, and 10 mice exposed to propargyl alcohol at about 1,300 ppm for 1 h/day (BASF 1965)
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. Results of clinical chemistry tests and gross pathologic examinations suggested both hepatic and renal damage, although the hepatic damage appeared to be reversible.
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One rabbit died after 45 exposures. Results of clinical chemistry tests and gross pathologic examinations showed both hepatic and renal damage in most of the test animals.
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Rats Groups of six male and six female rats (strain not specified) were exposed to propargyl alcohol at a nominal concentration of 100 ppm (80 ppm by infrared analysis)
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was detected in female rats 3 days after exposure at 32 and 64 ppm; no effect was observed in males until day 23. An increase in blood urea nitrogen (p < 0.01)
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The duration of the post-exposure observation period was not specified. TABLE 6-4 Effects in Fischer Rats after Exposure to Propargyl Alcohol for 13 Weeks Effect 0 ppm 4 ppm 8 ppm 16 ppm 32 ppm 64 ppm Males Olfactory epithelium 0/10 0/10 0/10 0/10 2/10 5/10 necrosis Respiratory epitheliuma Hyperplasia 2/10 6/10 2/10 4/10 8/10 10/10 Squamous metaplasia 0/10 0/10 0/10 0/10 0/10 3/10 Increased kidney/body weight - - - - - p < 0.01 Increased liver weight - - - - - p < 0.01 Increased liver/body weight - - - - p < 0.01 p < 0.01 Females Olfactory epithelium necrosis 0/10 0/10 0/10 0/10 3/10 5/10 Respiratory epitheliuma Hyperplasia 0/10 2/10 2/10 2/10 10/10 10/10 Sqauamous metaplasia 0/10 0/10 0/10 0/10 0/10 8/10 Necrosis 0/10 0/10 0/10 0/10 0/10 2/10 Increased kidney/body weight - - - - - p < 0.01 Increased liver/body weight - - - - - p < 0.01 a Nasal respiratory epithelium.
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3.2.5. Summary of Nonlethal Toxicity in Animals Nonlethal exposure of several laboratory species to propargyl alcohol resulted in agitation and mucous membrane irritation (ocular and nasal epithelial surfaces)
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Repeated exposure of rats to propargyl alcohol at 5.1 ppm for 6 h/day was without effect, but exposure at 24.6 ppm resulted in increased kidney-to-body weight ratio and a decrease in serum cholinesterase activity. Another study reported that repeated exposure of rats to propargyl alcohol at concentrations less than 32 ppm was without notable effect, but decreased serum cholinesterase activity and increased blood urea nitrogen were found at 32 and 64 ppm.
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. Data on nonlethal responses to propargyl alcohol are primarily from repeated exposure studies (about 13 weeks)
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was not great. Results of acute exposure studies showed the respiratory tract to be a primary target in all species tested, and longer-term exposure studies indicated renal and hepatic effects in the all of the tested species.
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6.2. Animal Data Relevant to AEGL-2 In subchronic studies, decreased serum cholinesterase activity was detected in female rats and increased blood urea nitrogen was detected in males and
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However, the available data do not provide definitive evidence of effects from a single acute exposure to propargyl alcohol. Necropsy results from repeat-exposure studies (Dow Chemical Co.
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7.2. Animal Data Relevant to AEGL-3 Several studies conducted in multiple species are available to assess the lethality of inhaled propargyl alcohol after acute and repeated exposures.
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Animal data suggests olfactory and respiratory-tract epithelium are the primary targets of propargyl alcohol and that damage to these tissues is likely instrumental in deaths after a single acute exposures. Studies of repeated exposures to propargyl alcohol (about 90 days)
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Animal data consistently showed the upper respiratory tract to be the primary target of propargyl alcohol, although hepatic and renal effects are suggested by results of repeated exposure studies. AEGL values were derived from points of departure representing data-based estimates of thresholds for each respective AEGL severity level.
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From page 196... ...
Results of animal studies in several species were sufficient for identifying the adverse effects of exposure to propargyl alcohol vapor and for identifying points of departure for AEGLs development. Few data were available to definitively assess the exposure response-exposure duration relationship for propargyl alcohol, especially for identifying a threshold for innocuous effects.
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2001. Standing Operating Procedures for Developing Acute Exposure Guideline Levels for Hazardous Chemicals.
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1995. Histological changes in the respiratory tract of mice exposed to ten fami lies of airborne chemicals.
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:207-213. Critical effect: No histologic changes in the respiratory tract of mice exposed to propargyl alcohol at 25.3 ppm for 6 h/day for 4 days (Zissu 1995)
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Uncertainty factors: 3 for interspecies differences; data from several species indicated quantitatively and qualitatively similar responses to propargyl alcohol. 3 for intraspecies variability; responses to direct-contact irritants are not expected to vary by an order of magnitude among individuals.
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No lethality reported in repeated exposure studies (90 days) of rats exposed to propargyl alcohol at concentrations as high as 80 ppm (Dow Chemical Co.
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202 Acute Exposure Guideline Levels 3 for intraspecies variability; responses to direct-contact irritants are not expected to vary by an order of magnitude among individuals. No evidence that deaths resulting from single acute exposures involved systemic toxicity or solvent narcosis.
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End point/Concentration/Rationale: 25.3 ppm for 6 h considered a no-observedadverse-effect level Uncertainty factors/Rationale: Total uncertainty factor: 10 Interspecies: 3, data on several species indicate quantitatively and qualitatively similar responses to propargyl alcohol Intraspecies: 3, responses to direct-contact irritants are not expected to vary by an order of magnitude among individuals. Modifying factor: None Animal-to-human dosimetric adjustment: None Time scaling: None.
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From page 204... ...
Uncertainty factors/Rationale: Total uncertainty factor: 10 Interspecies: 3, data on several species indicate quantitatively and qualitatively similar responses to propargyl alcohol Intraspecies: 3, histopathologic effects are likely due to direct-contact irritation, which is not expected to vary by an order of magnitude among individuals. Modifying factor: None Animal-to-human dosimetric adjustment: None Time scaling: Cn × t = k; data were inadequate for deriving an empirical value for n, so default values of n = 3 when extrapolating to shorter durations and n = 1 when extrapolating to longer durations were used.
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Data in multiple species allowed for interspecies comparisons.
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of Source Species Sex Exposures ppm Minutes Category Comments NAC/AEGL-1 2.5 10 AEGL NAC/AEGL-1 2.5 30 AEGL NAC/AEGL-1 2.5 60 AEGL NAC/AEGL-1 2.5 240 AEGL NAC/AEGL-1 2.5 480 AEGL NAC/AEGL-2 20 10 AEGL NAC/AEGL-2 20 30 AEGL NAC/AEGL-2 16 60 AEGL NAC/AEGL-2 10 240 AEGL NAC/AEGL-2 6.6 480 AEGL NAC/AEGL-3 130 10 AEGL NAC/AEGL-3 91 30 AEGL NAC/AEGL-3 72 60 AEGL NAC/AEGL-3 29 240 AEGL NAC/AEGL-3 14 480 AEGL (Continued)
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Mouse 1 88 360 1 Histopathologic changes in olfactory and respiratory epithelium (Zissu 1995) Mouse 1 25 360 0 Histopathologic changes in olfactory and respiratory epithelium (Zissu 1995)
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208 Acute Exposure Guideline Levels APPENDIX D BENCHMARK CONCENTRATION ANALYSIS FOR PROPARGYL ALCOHOL Stasenkova and Kochetkova, 1966; Propargyl alcohol; 2-h exposure; lethality study in mice. Probit Model (Version: 2.8; Date: 02/20/2007)
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Propargyl Alcohol 209 Parameter Estimates 95.0% Wald Confidence Interval Variable Estimate Standard error Lower confidence limit Upper confidence limit Background 0.0252266 0.0247475 -0.0232776 0.0737309 Intercept -45.4309 21.7571 -88.074 -2.78782 Slope 6.70209 3.21983 0.391333 13.0128 Goodness of Fit Scaled Estimated Dose probability Expected Observed Size Residual 219.0000 0.0252 0.505 1 20 0.707 655.0000 0.0490 0.980 1 20 0.020 875.0000 0.5012 10.023 10 20 -0.010 1500.0000 0.9998 19.997 20 20 0.058 0.0000 0.0252 0.505 0 20 -0.719 Chi-square = 1.02 d.f. = 2 P-value = 0.6003 Benchmark Dose Computation Specified effect = 0.05 Risk Type = Extra risk Confidence level = 0.95 BMC = 687.589 BMCL05 = 572.737 Probit Model with 0.95 Confidence Level Probit 1 BMD Lower Bound 0.8 Fraction Affected 0.6 0.4 0.2 0 BMDL BMD 0 200 400 600 800 1000 1200 1400 dose FIGURE B-1 Probit model with 0.95 confidence level.
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