Acute Exposure Guideline Levels for Selected Airborne Chemicals Volume 16 (2014) / Chapter Skim
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3 Methacrylonitrile1 Acute Exposure Guideline Levels PREFACE Under the authority of the Federal Advisory Committee Act (FACA)
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144 Acute Exposure Guideline Levels effects. However, the effects are not disabling and are transient and reversible upon cessation of exposure.
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Methacrylonitrile 145 threshold for irreversible effects and are considered appropriate given the steep concentration-response curve for methacrylonitrile. A comparison of the 4-h LC50 values for several species suggest that mice and rabbits are more sensitive than rats and guinea pigs (Pozzani et al.
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146 Acute Exposure Guideline Levels 1990)
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Methacrylonitrile 147 TABLE 3-2 Physical and Chemical Properties of Methacrylonitrile Parameter Data Reference Synonyms 2-Methyl-2-propenenitile; methyl Cohrssen 2001 acrylonitrile; isoprene cyanide; isopropenylcarbonitrile; 2-cyano-1 propene; 2-cyanopropene; MAN; MeAN CAS registry no. 126-98-7 Cohrssen 2001 Chemical formula C4H5N Cohrssen 2001 Molecular weight 67.09 Cohrssen 2001 Physical state Colorless liquid Farooqui and Mumtaz 1991 Melting point -35.8°C Farooqui and Mumtaz 1991 Boiling point 90.3°C Farooqui and Mumtaz 1991 Flash point 13°C Farooqui and Mumtaz 1991 Specific gravity 0.800 at 20°C Farooqui and Mumtaz 1991 Solubility 2.5% in water; miscible with Farooqui and Mumtaz 1991; acetone, octane, and toluene Hartung 1994 Vapor density 2.31 (air = 1)
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148 Acute Exposure Guideline Levels TABLE 3-4 Effects in Nine Subjects from Exposure to Methacrylonitrile at 2 ppm for 10 Minutes Odor Eye Nose Throat Time (min) Detection Irritation Tears Irritation Irritation 1 4 2 1 0 0 2 4 1 0 0 1 3 3 0 0 0 1 4 0 0 0 0 0 5 0 0 0 0 0 6 0 0 0 0 0 7 0 0 0 2 0 8 0 1 0 1 0 9 0 0 0 0 0 10 0 0 0 0 0 Source: Pozzani et al.
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Methacrylonitrile 149 2.4. Genotoxicity Genotoxic studies of acute human exposure to methacrylonitrile were not available.
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150 Acute Exposure Guideline Levels observed during exposure. Mild and erratic weight loss was initially observed, but was followed by normal weight gain after the exposure period.
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Methacrylonitrile 151 3.1.2. Mice Pozzani et al.
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152 Acute Exposure Guideline Levels followed by death in 3 h. The investigators also exposed one female mongrel dog to methacrylonitrile at 106 ppm for 7 h.
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Methacrylonitrile 153 3.3. Repeated-Dose Studies 3.3.1.
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154 Acute Exposure Guideline Levels Among animals in the 13-week evaluation group, all males and one female in the 120-mg/kg group and two males in the 60-mg/kg group died during the first week of the study (NTP 2000)
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Methacrylonitrile 155 trol of the hind-limbs were observed in two dogs exposed at 13.5 ppm starting at day 39 of exposure. At necropsy, one of these dogs had histopathologic brain lesions, including demyelination of the corpus callosum.
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156 Acute Exposure Guideline Levels body weight per litter, or morphologic development. A decrease in the percentage of male fetuses per litter was noted in the high-dose group (40% vs 61% in control group; p < 0.05)
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Methacrylonitrile 157 respectively)
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158 TABLE 3-7 Summary of Inhalation Toxicity Data on Methacrylonitrile in Animals Species Concentration (ppm) Exposure Duration Effect Reference Single Exposure Studies Rat 85,500 0.47 min No mortality (0/6)
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Rat 20 7 h/d, 5 d/wk, 9 d No effects Pozzani et al. 1968 Rat 50 7 h/d, 5 d/wk, 9 d No effects Pozzani et al.
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160 Acute Exposure Guideline Levels Male Sprague-Dawley rats administered a single dose of [2-14C] methacrylonitrile at 100 mg/kg in safflower oil retained label in erythrocytes for more than 5 days after dosing (Cavazos et al.
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Methacrylonitrile 161 inated most of the chemical within 5 h. Within 24 h, 36% was exhaled as unchanged methacrylonitrile, 26% was exhaled as carbon dioxide, 17% was exhaled as acetone, and 16% was excreted in the urine as metabolites.
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162 Acute Exposure Guideline Levels preliminary study indicated that hepatic microsomal metabolizing activity for nitriles was at maximum 13 h after oral administration of ethanol at 4.0 g/kg. The glucose control was isocaloric to the ethanol dosage.)
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Methacrylonitrile 163 ministered dose of methacrylonitrile may be metabolized via the epoxide intermediate, data suggest that the methacrylonitrile-derived epoxide is broken down and eliminated more efficiently that the acrylonitrile-derived epoxide intermediate. This is supported by the observation of greater exhalation of carbon dioxide by animals treated with methacrylonitrile compared with those treated with acrylonitrile.
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164 Acute Exposure Guideline Levels 5.
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Methacrylonitrile 165 6.3. Derivation of AEGL-2 Values No inhalation data on methacrylonitrile consistent with the definition of AEGL-2 are available.
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166 Acute Exposure Guideline Levels 7.3. Derivation of AEGL-3 Values A comparison of the 4-h LC50 values for the various species tested by Pozzani et al.
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Methacrylonitrile 167 8.
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168 Acute Exposure Guideline Levels 8.3. Data Adequacy and Research Needs Human data on methacrylonitrile are limited to one experimental study.
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Methacrylonitrile 169 Washington, DC, by DuPont, Wilmington, DE, with Cover Letter Dated October 15, 1992. EPA Document No.
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170 Acute Exposure Guideline Levels NIOSH (National Institute for Occupational Safety and Health)
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Methacrylonitrile 171 Younger Laboratories.
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172 Acute Exposure Guideline Levels APPENDIX A DERIVATION OF AEGL VALUES FOR METHYACRYLONITRILE Derivation of AEGL-1 Values AEGL-1 values are not recommended due to the poor warning properties of methacrylonitrile. However, absence of AEGL-1 values does not imply that exposures below the AEGL-2 values are without adverse effects.
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Methacrylonitrile 173 10-min AEGL-3: Set equal to the 30-min AEGL-3 value of 3.9 ppm 30-min AEGL-3: C3 × 0.5 h = 30,581 ppm-h C3 = 61,162 ppm C = 39.4 ppm 39.4 ÷ 10 = 3.9 ppm 1-h AEGL-3: C3 × 1 h = 30,581 ppm-h C3 = 30,581 ppm C = 31.3 ppm 31.3 ÷ 10 = 3.1 ppm 4-h AEGL-3: C × 4 h = 78.8 ppm-h C = 19.7 ppm 19.7 ÷ 10 = 2.0 ppm 8-h AEGL-3: C1 × 8 h = 78.8 ppm-h C1 = 9.9 ppm C = 9.9 ppm 9.9 ÷ 10 = 0.99 ppm
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174 Acute Exposure Guideline Levels APPENDIX B ACUTE EXPOSURE GUIDELINE LEVELS FOR METHACRYLONITRILE Derivation Summary AEGL-1 VALUES AEGL-1 values are not recommended due to the poor warning properties of methacrylonitrile. However, absence of AEGL-1 values does not imply that exposures below the AEGL-2 values are without adverse effects.
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Methacrylonitrile 175 Animal-to-human dosimetric adjustment: Insufficient data Time scaling: Cn × t = k, where default values of n = 3 for extrapolation to shorter durations and n = 1 for extrapolation to longer durations were used to calculate AEGL values that are protective of human health (NRC 2001)
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176 Accute Exposure Guideline Levels AP PPENDIX C CATEGO ORY PLOT FOR F METHAC CRYLONITR RILE FIGUR RE C-1 Category y plot of toxicity y data and AEGL L values for methhacrylonitrile.
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TABLE C-1 Data Used in Category Plot for Methacrylonitrile Source Species Sex No. Exposures ppm Minutes Category Comments AEGL-1 NR 10 AEGL AEGL-1 NR 30 AEGL AEGL-1 NR 60 AEGL AEGL-1 NR 240 AEGL AEGL-1 NR 480 AEGL AEGL-2 1.3 10 AEGL AEGL-2 1.3 30 AEGL AEGL-2 1.0 60 AEGL AEGL-2 0.67 240 AEGL AEGL-2 0.33 480 AEGL AEGL-3 3.7 10 AEGL AEGL-3 3.7 30 AEGL AEGL-3 3.1 60 AEGL AEGL-3 2.0 240 AEGL AEGL-3 0.99 480 AEGL Pozzani et al.
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178 TABLE C-1 Continued Source Species Sex No. Exposures ppm Minutes Category Comments Younger Labs 1969 Rat Males 1 625 240 SL Mortality (2/10)
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DuPont 1968b Dog Females 1 40 420 0 No mortality Dog Females 1 87.5 420 3 100% mortality Pozzani et al. 1968 Guinea pig 1 52.5 240 0 Rabbit 1 19.7 240 0 Mouse 1 19.7 240 0 Saillenfait et al.
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