Acute Exposure Guideline Levels for Selected Airborne Chemicals Volume 16 (2014) / Chapter Skim
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2 Benzonitrile1 Acute Exposure Guideline Levels PREFACE Under the authority of the Federal Advisory Committee Act (FACA)
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122 Acute Exposure Guideline Levels effects. However, the effects are not disabling and are transient and reversible upon cessation of exposure.
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Benzonitrile 123 the LC50 (lethal concentration, 50% lethality) would be used to extrapolate to a lethal threshold.
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124 Acute Exposure Guideline Levels 1. INTRODUCTION Benzonitrile is produced by vapor-phase catalytic ammoxidation of toluene, dehydrogenation of the Diels-Alder adduct of butadiene and acrylonitrile, or by reaction of benzoic acid with urea at 220-240°C in the presence of a metallic catalyst.
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Benzonitrile 125 2.
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126 Acute Exposure Guideline Levels 3.
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Benzonitrile 127 In an acute oral toxicity study, two male and two female albino Charles River rats were administered undiluted benzonitrile by gavage at single doses of 0.6, 0.9, 1.4, or 2.0 g/kg and observed for 14 days (Industrial Bio-Test 1970)
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128 Acute Exposure Guideline Levels or 3.0 g/kg and observed for 14 days (Industrial Bio-Test 1970)
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Benzonitrile 129 3.6. Summary Animal toxicity data are limited to acute lethality studies in rats, mice, and rabbits.
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130 TABLE 2-3 Summary of Animal Toxicity Data on Benzonitrile Species Concentration or Dose Exposure Duration Effect Reference Inhalation Studies Rat 190 ppm 4h No-observed-effect level Industrial Bio-Test 1970 Rat 900 ppm 1h Irritation of extremities MacEwen and Vernot 1974 Rat 900 ppm 3h Labored breathing, poor coordination MacEwen and Vernot 1974 Rat 900 ppm 4h No mortality (0/6) , decreased weight gain MacEwen and Vernot 1974 Rat 1,900 ppm 4h 30% mortality (3/10)
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Rat 2,350 mg/kg Single gavage LD84 Agaev 1977 Mouse 650 mg/kg Single gavage LD16 Agaev 1977 Mouse 1,400 mg/kg Single gavage LD50 Agaev 1977 Mouse 2,350 mg/kg Single gavage LD84 Agaev 1977 Dermal Studies Rabbit 0.9 g/kg 4h 0% mortality (0/4) ; muscular weakness, Industrial Bio-Test 1970 prostration, salivation, ataxia, tremors, loss of righting reflex Rabbit 1.4 g/kg 24 h 100% mortality (4/4)
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132 Acute Exposure Guideline Levels 4.4. Structure-Activity Relationships Because the acute toxicity of most nitriles is dependent on their ability to undergo cytochrome P450 mediated hydroxylation, on the carbon alpha to the cyano group (α-carbon)
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Benzonitrile 133 5.2. Animal Data Relevant to AEGL-1 No animal data on benzonitrile consistent with the definition of AEGL-1 were available.
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134 Acute Exposure Guideline Levels 7.
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Benzonitrile 135 be described by the equation Cn × t = k, where the exponent n ranges from 0.8 to 3.5 (ten Berge et al.
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136 Acute Exposure Guideline Levels 9. REFERENCES Agaev, F.B.
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Benzonitrile 137 APPENDIX A DERIVATION OF AEGL VALUES FOR BENZONITRILE Derivation of AEGL-1 Values The data on benzonitrile were insufficient for deriving AEGL-1 values. Derivation of AEGL-2 Values In the absence of relevant data to derive AEGL-2 values for benzonitrile, AEGL-3 values were divided by 3 to estimate AEGL-2 values.
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138 Acute Exposure Guideline Levels 10-min AEGL-3: C3 × 0.167 h = 176,242,250 ppm-h C3 = 1,055,342,814 ppm C = 1,018 ppm 1,018 ÷ 30 = 34 ppm 30-min AEGL-3: C3 × 0.5 h = 176,242,250 ppm-h C3 = 352,484,500 ppm C = 706 ppm 706 ÷ 30 = 24 ppm 1-h AEGL-3: C3 × 1 h = 176,242,250 ppm-h C3 = 176,242,250 ppm C = 561 ppm 561 ÷ 30 = 19 ppm 4-h AEGL-3: C1 × 4 h = 890 ppm-h C1 = 223 ppm C = 223 ppm 223 ÷ 30 = 7.4 ppm 8-h AEGL-3: C1 × 8 h = 890 ppm-h C1 = 111 ppm C = 111 ppm 111 ÷ 30 = 3.7 ppm
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Benzonitrile 139 APPENDIX B ACUTE EXPOSURE GUIDELINE LEVELS FOR BENZONITRILE Derivation Summary AEGL-1 VALUES The data on benzonitrile were insufficient for deriving AEGL-1 values.
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140 Acute Exposure Guideline Levels AEGL-3 VALUES Continued Uncertainty factors/Rationale: Total uncertainty factor: 30 Interspecies: 10, even though mortality data suggest that rats and mice have similarly steep dose-response relationships (e.g., similar oral LD16, LD50, and LD84) (Agaev 1977)
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Benzonitrile 141 APPENDIX C CATEGORY PLOT FOR BENZONITRILE FIGURE C-1 Category plot of toxicity data and AEGL values for benzonitrile.
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142 TABLE C-1 Data Used in Category Plot for Benzonitrile 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 11 10 AEGL AEGL-2 7.8 30 AEGL AEGL-2 6.2 60 AEGL AEGL-2 2.5 240 AEGL AEGL-2 1.2 480 AEGL AEGL-3 34 10 AEGL AEGL-3 24 30 AEGL AEGL-3 19 60 AEGL AEGL-3 7.4 240 AEGL AEGL-3 3.7 480 AEGL Industrial Bio-Test 1970 Rat 1 190 240 0 No-observed-effect level MacEwen and Vernot 1974 Rat 1 900 60 1 Irritation of extremities MacEwen and Vernot 1974 Rat 1 900 180 2 Labored breathing, poor coordination MacEwen and Vernot 1974 Rat 1 900 240 2 No mortality (0/6)
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