National Academies Press: OpenBook

Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 16 (2014)

Chapter: 2 Benzonitrile Acute Exposure Guideline Levels

« Previous: 1 Aliphatic Nitriles Acute Exposure Guideline Levels
Suggested Citation:"2 Benzonitrile Acute Exposure Guideline Levels." National Research Council. 2014. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 16. Washington, DC: The National Academies Press. doi: 10.17226/18707.
×

2

Benzonitrile1

Acute Exposure Guideline Levels

PREFACE

Under the authority of the Federal Advisory Committee Act (FACA) P.L. 92-463 of 1972, the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances (NAC/AEGL Committee) has been established to identify, review, and interpret relevant toxicologic and other scientific data and develop AEGLs for high-priority, acutely toxic chemicals.

AEGLs represent threshold exposure limits for the general public and are applicable to emergency exposure periods ranging from 10 minutes (min) to 8 hours (h). Three levels—AEGL-1, AEGL-2, and AEGL-3—are developed for each of five exposure periods (10 and 30 min and 1, 4, and 8 h) and are distinguished by varying degrees of severity of toxic effects. The three AEGLs are defined as follows:

AEGL-1 is the airborne concentration (expressed as parts per million or milligrams per cubic meter [ppm or mg/m3]) of a substance above which it is predicted that the general population, including susceptible individuals, could experience notable discomfort, irritation, or certain asymptomatic, nonsensory

_______________________________

1This document was prepared by the AEGL Development Team composed of Cheryl Bast (Oak Ridge National Laboratory), Gary Diamond (SRC, Inc.), Chemical Manager George Rodgers (National Advisory Committee [NAC] on Acute Exposure Guideline Levels for Hazardous Substances), and Ernest V. Falke (U.S. Environmental Protection Agency). The NAC reviewed and revised the document and AEGLs as deemed necessary. Both the document and the AEGL values were then reviewed by the National Research Council (NRC) Committee on Acute Exposure Guideline Levels. The NRC committee has concluded that the AEGLs developed in this document are scientifically valid conclusions based on the data reviewed by the NRC and are consistent with the NRC guidelines reports (NRC 1993, 2001).

Suggested Citation:"2 Benzonitrile Acute Exposure Guideline Levels." National Research Council. 2014. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 16. Washington, DC: The National Academies Press. doi: 10.17226/18707.
×

effects. However, the effects are not disabling and are transient and reversible upon cessation of exposure.

AEGL-2 is the airborne concentration (expressed as ppm or mg/m3) of a substance above which it is predicted that the general population, including susceptible individuals, could experience irreversible or other serious, long-lasting adverse health effects or an impaired ability to escape.

AEGL-3 is the airborne concentration (expressed as ppm or mg/m3) of a substance above which it is predicted that the general population, including susceptible individuals, could experience life-threatening health effects or death.

Airborne concentrations below the AEGL-1 represent exposure concentrations that could produce mild and progressively increasing but transient and nondisabling odor, taste, and sensory irritation or certain asymptomatic, nonsensory effects. With increasing airborne concentrations above each AEGL, there is a progressive increase in the likelihood of occurrence and the severity of effects described for each corresponding AEGL. 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

Benzonitrile is a colorless liquid at ambient temperature and pressure and has an odor of volatile almond oil. The liquid is irritating to the skin and eyes, and the vapor is irritating to the eyes, nose, and throat (HSDB 2003). Information on the toxicity of benzonitrile in humans is limited to a single case study of a nonlethal dermal and inhalation exposure (HSDB 2003). Symptoms included severe respiratory distress, tonic convulsions, and periods of unconsciousness which lasted for 75 min. The benzonitriles ioxynil (4-hydroxy-3,5-diiodobenzonitrile) and bromoxynil (4-hydroxy-3,5-dibromodobenzonitrile) are uncoupling agents (Ellenhorn 1997); however, the mechanism of toxicity of benzonitrile has not been established. AEGL-1 values are not recommended for benzonitrile because of insufficient data.

Data on benzonitrile were also insufficient for calculating AEGL-2 values. Therefore, values were estimated by dividing the AEGL-3 values by 3. The steepness of the dose-response relationship makes it difficult to discern thresholds for impairment of escape (AEGL-2) and lethality (AEGL-3) from the available data.

A study of mice exposed to benzonitrile at 890 ppm for 2 h was used as the basis of AEGL-3 values. Because one of seven mice died, further adjustment to estimate the lethal threshold was warranted. Typically, a 3-fold reduction of

Suggested Citation:"2 Benzonitrile Acute Exposure Guideline Levels." National Research Council. 2014. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 16. Washington, DC: The National Academies Press. doi: 10.17226/18707.
×

the LC50 (lethal concentration, 50% lethality) would be used to extrapolate to a lethal threshold. However, an LC50 value was not available for benzonitrile. The 2-h study reported 14% mortality, which suggests the test concentration of 890 ppm is below the LC50; therefore, a 2-fold adjustment was applied. The resulting adjusted value of 445 ppm was considered an estimate of the lethality threshold and used as the point of departure for deriving AEGL-3 values. An interspecies uncertainty factor of 10 was applied. Mortality data reported by Agaev (1977) on benzonitrile suggest that rats and mice have similarly steep dose-response relationships (e.g., similar oral LD16, LD50, and LD84), but the reported lack details about the methods, and no data on other species are available. An intraspecies uncertainty factor of 3 was applied to account for sensitive individuals. This value is supported by the steep concentration-response curve for benzonitrile, which implies little individual variability. For example, the steepness of the curve is evident in mice exposed by inhalation to benzonitrile (10% mortality at 890 ppm for 2 h [ct = 1,780 ppm-h] vs. 100% mortality at 700 ppm for 4 h [ct = 2,800 ppm-h]) (MacEwen and Vernot 1974), in rats exposed orally (no mortality at 0.6 g/kg vs. 100% mortality at 2.0 g/kg) (Industrial Bio-Test 1970), and in rabbits exposed dermally (no mortality at 0.9 g/kg vs. 100% mortality at 1.4 g/kg) (Industrial Bio-Test 1970). The total uncertainty factor is 30. The concentration-exposure time relationship for many irritant and systemically acting vapors and gases may be described by the equation Cn × t = k, where the exponent n ranges from 0.8 to 3.5 (ten Berge et al. 1986). Insufficient data were available to derive an empirical value for n. Therefore, time scaling was performed using default values of n = 3 to extrapolate to shorter durations and n = 1 to extrapolate to longer durations to provide AEGL values that are protective of human health (NRC 2001).

AEGL values for benzonitrile are presented Table 2-1.

TABLE 2-1 AEGL Values for Benzonitrile


Classification 10 min 30 min 1 h 4 h 8 h End Point (Reference)

AEGL-1 (nondisabling) NRa NRa NRa NRa NRa Insufficient data
AEGL-2 11 ppm 7.8 ppm 6.2 ppm 2.5 ppm 1.2 ppm One-third of
(disabling) (48 mg/m3) (33 mg/m3) (26 mg/m3) (10 mg/m3) (5.2 mg/m3) AEGL-3 values
AEGL-3 34 ppm 24 ppm 19 ppm 7.4 ppm 3.7 ppm Estimated lethal
(lethal) (140 mg/m3) (99 mg/m3) (79 mg/m3) (31 mg/m3) (16 mg/m3) threshold in mice (MacEwen and Vernot 1974)

aNot recommended. Absence of AEGL-1 values does not imply that exposures below AEGL-2 values are without adverse effects.

Suggested Citation:"2 Benzonitrile Acute Exposure Guideline Levels." National Research Council. 2014. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 16. Washington, DC: The National Academies Press. doi: 10.17226/18707.
×

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. It is used as an intermediate for rubber chemicals, and as a solvent for nitrile rubber, lacquers, and resins and polymers. It is also used as an additive in nickel-plating baths, for separating naphthalene and alkylphthalenes from nonaromatics by azeotropic distillation, as a jet fuel additive, in cotton bleaching baths, as a drying additive for acrylic fibers, and in the removal of titanium tetrachloride and vanadium oxytrichloride from silicon tetrachloride (HSDB 2003).

The physical and chemical properties of benzonitrile are presented in Table 2-2.

TABLE 2-2 Physical and Chemical Data on Benzonitrile

Parameter Data Reference
Common name Benzonitrile IPCS 1999
Synonyms Cyanobenzene, benzoic acid nitrile; phenyl cyanide IPCS 1999
CAS registry no. 100-47-0 IPCS 1999
Chemical formula C6H5 (CN) IPCS 1999
Molecular weight 103.1 IPCS 1999
Physical state Colorless liquid HSDB 2003
Melting point -12.8°C IPCS 1999
Boiling point 190.7°C IPCS 1999
Flash Point 75°C IPCS 1999
Density/Specific gravity 1.010 at 25°C/15°C HSDB 2003
Solubility Poor solubility in water; miscible with organic solvents, soluble in alcohol, ether and acetone HSDB 2003
Vapor density 3.6 (air = 1) HSDB 2003
Vapor pressure 0.768 mm Hg at 25°C HSDB 2003
Conversion factors in air 1 ppm = 4.22 mg/m3  
Suggested Citation:"2 Benzonitrile Acute Exposure Guideline Levels." National Research Council. 2014. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 16. Washington, DC: The National Academies Press. doi: 10.17226/18707.
×

2. HUMAN TOXICITY DATA

2.1. Acute Lethality

Information on the toxicity of benzonitrile in humans is limited to a single occupational case study (HSDB 2003). A male worker was accidentally drenched (head and clothing) with benzonitrile. He was subsequently doused with water, but his clothing was not immediately removed. Immediately thereafter the worker collapsed into unconsciousness. He was subsequently bathed to remove dermal exposure, and became responsive for a short period, but exhibited respiratory distress. He then fell into deep unconsciousness and exhibited tonic contractions in the muscles of his arms and face. The tonic muscle contractions were alleviated following treatment with phenobarbitol and sodium thiosulfate. Under supplemental oxygen, he remained unconscious for approximately 75 min and gradually recovered and was released without apparent symptoms the following day. Air concentrations of benzonitrile experienced during the exposure were not reported. Dermal exposure to benzonitrile probably contributed to the absorbed dose.

2.2. Nonlethal Toxicity

An odor threshold of 2.9 × 10-5 mg/L (0.007 ppm) has been reported for benzonitrile (HSDB 2003).

2.3. Developmental and Reproductive Toxicity

Developmental and reproductive studies of acute human exposure to benzonitrile were not available.

2.4. Genotoxicity

Genotoxic studies of acute human exposure to benzonitrile were not available.

2.5. Carcinogenicity

Carcinogenicity studies of human exposure to benzonitrile were not available.

2.6. Summary

No reports regarding lethality, nonlethal toxicity, developmental and reproductive toxicity, genotoxicity, or carcinogenicity on benzonitrile were available.

Suggested Citation:"2 Benzonitrile Acute Exposure Guideline Levels." National Research Council. 2014. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 16. Washington, DC: The National Academies Press. doi: 10.17226/18707.
×

3. ANIMAL TOXICITY DATA

3.1. Acute Lethality

3.1.1. Rats

A group of six male CFE rats was exposed to benzonitrile at 900 ppm (saturated atmosphere) in a 30-L glass exposure chamber for 4 h and observed for 14 days (MacEwen and Vernot 1974). The benzonitrile atmosphere was produced by passing air through a fritted disc bubbler immersed in 200 mL of test material. The airflow through the bubbler was 10 L/min, and 9 min was necessary to achieve 95% saturation in the exposure chamber. The chamber concentration of benzonitrile was continuously analyzed using a total hydrocarbon analyzer initially calibrated with several standard gas bags containing benzonitrile at 450 and 900 ppm in air. Irritation of the extremities was observed during the first hour of exposure, followed by poor coordination and labored breathing after 3 h. Prostration occurred at 3.5 h. Following the 14-day observation period, five of the six rats had weight gain that was below normal (data not presented). No treatment-related deaths occurred; however, microscopic examinations of the rats at the end of the 14-day observation period revealed multifocal areas of lymphoid hyperplasia with macrophage-containing foamy accumulations.

Groups of five male and five female young adult Charles River rats were exposed to benzonitrile at 0.8 or 8 mg/L (190 or 1,900 ppm) in a 70-L Plexiglas inhalation chamber for 4 h and observed for 14 days (Industrial Bio-Test 1970). An aerosol of undiluted benzonitrile was generated with an Ohio Ball-Jet Nebulizer. A stream of clean dry air was passed through the nebulizer and the resulting aerosol stream was mixed with additional dry air to obtain the final desired concentration. The test atmosphere was then introduced into the top of the exposure chamber, dispersed with a baffle plate, and exhausted at the bottom of the chamber. Air flow rates were measured with rotameters connected to the air supply line upstream of the aerosol; temperature and pressure of the test atmosphere were also measured. Average nominal concentrations were calculated by dividing the nebulizer weight loss by the total volume of air used during each exposure. No deaths, clinical signs, or effects on body weight were observed in the 0.8-mg/L group. At necropsy, no gross treatment-related effects were found in this group. Three females died after exposure at 8 mg/L; two deaths occurred 2 h after the end of the exposure period and one occurred on day 6. Six of the eight surviving rats lay prostrate 18 h after exposure; this effect persisted in two animals through day 4 and in one animal through day 6 (when death occurred). No adverse effects on body weight were noted. Necropsy of animals that died on the day of exposure showed minimal pulmonary hyperemia.

Agaev (1977) reported the following lethal concentrations of benzonitrile in white rats: LC84 = 1,071 ppm, LC50 = 929 ppm, and LC16 = 738 ppm. Exposure duration and other experimental details were not reported.

Suggested Citation:"2 Benzonitrile Acute Exposure Guideline Levels." National Research Council. 2014. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 16. Washington, DC: The National Academies Press. doi: 10.17226/18707.
×

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). Dose-related clinical signs included hypoactivity, muscular weakness, ruffled fur, prostration, dyspnea, and lacrimation. Mortality was 0/4 at 0.6 g/kg, 2/4 at 0.9 g/kg, 3/4 at 1.4 g/kg, and 4/4 at 2.0 g/kg. An oral LD50 of 1.0 ± 0.2 g/kg was calculated.

Agaev (1977) reported the following lethal doses for a one-time exposure to a 50% solution of benzonitrile in sunflower oil in white rats: LD84 = 2,350 mg/kg, LD50 = 1,500 mg/kg, and LD16 = 650 mg/kg. No other experimental details were reported.

3.1.2. Mice

Groups of seven or 10 male CF-1 mice were exposed to benzonitrile at target concentrations of 900 ppm (saturated atmosphere) in a 30-L glass exposure chamber for 2 or 4 h and observed for 14 days (MacEwen and Vernot 1974). Measured concentrations were 890 ppm for the 2-h exposure and 700 ppm for the 4-h exposure. The benzonitrile atmosphere was produced by passing air through a fritted disc bubbler immersed in 200 mL of test material. The airflow through the bubbler was 10 L/min, and 9 min was necessary to achieve 95% saturation in the exposure chamber. The benzonitrile chamber concentration was continuously analyzed using a total hydrocarbon analyzer initially calibrated with several standard gas bags containing benzonitrile at 450 and 900 ppm in air. Irritation of the extremities was observed during the first hour of exposure, followed by poor coordination and labored breathing after 60-90 min. Prostration occurred at 2.5 h. All mice in the 4-h group died; three died on the day of exposure (including one during exposure at 3.5 h), three on day 1, and four on day 2. Only one mouse in the 2-h group died on day 2. Congestion accompanied by edema was found in the lungs of both exposure groups at necropsy. Mice exposed for 4 h also had hepatic congestion and sinusoidal dilation.

Agaev (1977) reported the following lethal concentrations for benzonitrile in white mice: LC84 = 595 ppm, LC50 = 429 ppm, and LC16 = 167 ppm. Exposure duration and other experimental details were not reported.

Agaev (1977) reported the following lethal doses for a one-time exposure to a 50% solution of benzonitrile in sunflower oil in white mice: LD84 = 2,350 mg/kg, LD50 = 1,400 mg/kg, and LD16 = 650 mg/kg. No other experimental details were reported.

3.1.3. Rabbits

In an acute dermal toxicity study, two male and two female New Zealand white rabbits were administered undiluted benzonitrile at doses of 0.9, 1.4, 2.0,

Suggested Citation:"2 Benzonitrile Acute Exposure Guideline Levels." National Research Council. 2014. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 16. Washington, DC: The National Academies Press. doi: 10.17226/18707.
×

or 3.0 g/kg and observed for 14 days (Industrial Bio-Test 1970). The test substance was applied to the clipped skin, covered with impervious plastic sheeting, and allowed to remain in contact with the skin for 24 h. The rabbits were fitted with collars to prevent oral ingestion of the benzonitrile. Local skin irritation was characterized as barely perceptible to pale red erythema and slight edema at the end of the 24-h exposure period; the dermal irritation subsided during the first week. Dose-related clinical signs included salivation, muscular weakness, ataxia, prostration, tremors, and loss of righting reflex. Mortality was 0/4 at 0.9 g/kg and 4/4 at 1.4, 2.0, and 3.0 g/kg, suggesting a very steep dose-response curve. An acute dermal LD50 of 1.2 ± 0.1 g/kg was calculated. Necropsy of animals that died from treatment found consolidation of the lungs, watery fluid in the peritoneal cavity, and hyperemia of kidneys.

In an ocular irritation study, 0.1 mL of undiluted benzonitrile was instilled into the right eye of five New Zealand white rabbits; the left eyes served as scoring controls (Industrial Bio-Test 1970). The cornea, iris, and palpebral conjunctiva were graded according to the Draize method after 1 min, after 1, 24, and 72 h, and after 7 days following instillation. Benzonitrile was graded as mildly irritating. Transient iridal and conjunctival irritation (redness grade 2, swelling grade 1, and discharge grade 2) was observed within 1 min after instillation. Irritation peaked at 1 min and subsided over the following 24-72 h.

In a primary skin irritation study, 0.5 mL of undiluted benzonitrile was applied to the shaved abraded or unabraded skin of four New Zealand white rabbits (Industrial Bio-Test 1970). The test sites were covered with gauze and plastic sheeting and remained in place for 24 h. No irritation was found 24- or 72-h post-treatment.

3.2. Nonlethal Toxicity

No nonlethal toxicity studies of benzonitrile in animals were found.

3.3. Developmental and Reproductive Toxicity

Developmental and reproductive toxicity studies of animal exposure to benzonitrile were not available.

3.4. Genotoxicity

Genotoxicity studies of animal exposure to benzonitrile were not available.

3.5. Carcinogenicity

Carcinogenicity studies of animal exposure to benzonitrile were not available.

Suggested Citation:"2 Benzonitrile Acute Exposure Guideline Levels." National Research Council. 2014. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 16. Washington, DC: The National Academies Press. doi: 10.17226/18707.
×

3.6. Summary

Animal toxicity data are limited to acute lethality studies in rats, mice, and rabbits. The data suggest that mice are more sensitive than rats to the effects of benzonitrile administered by inhalation; however, oral lethality data suggest that mice and rats have similar sensitivities. Clinical signs included labored breathing, poor coordination, hypoactivity, salivation, lacrimation, muscular weakness, and dyspnea. No developmental and reproductive, genotoxicity, or carcinogenicity data on benzonitrile were available. Animal data on benzonitrile are summarized in Table 2-3.

4. SPECIAL CONSIDERATIONS

4.1. Metabolism

Hydrogen cyanide is not a metabolite of benzonitrile. The major metabolic pathway for benzonitrile is aromatic hydroxylation to cyanophenols. A small amount of the cyanophenol may then be hydrolyzed to benzoic acid. In rabbits, 50% of an orally administered dose of benzonitrile at 150 mg/kg was conjugated to cyanophenols, and 10% was excreted as benzoic acid. In rats, the in vivo microsomal hydroxylation of deuterated benzonitrile yielded primarily 4-hydroxybenzonitrile with 41% retention of deuterium (HSDB 2003). Although not documented, the structure of benzonitrile suggests that formation of an epoxide intermediate may occur; this may account for the hepatotoxicity observed in mice at necropsy by MacEwen and Vernot (1974).

4.2. Mechanism of Toxicity

No information regarding the mechanism of toxicity of benzonitrile was found. The benzonitriles, ioxynil (4-hydroxy-3,5-diiodobenzonitrile) and bromoxynil (4-hydroxy-3,5-dibromodobenzonitrile), are uncoupling agents (Ellenhorn 1997); however, the mechanism of toxicity of benzonitrile has not been established.

4.3. Concurrent Exposure Issues

Tanii and Hashimoto (1984) studied the acute toxicity and effect of carbon tetrachloride on the metabolism of 20 nitriles, including benzonitrile, in male ddY mice. All of the test nitriles liberated cyanide in vivo and in vitro except for benzonitrile. Groups of 10 male ddY mice were dosed orally with either carbon tetrachloride or olive oil, and then treated with the nitrile 24 h later. Pretreatment with carbon tetrachloride clearly enhanced the toxicity of benzonitrile (100% mortality with carbon tetrachloride vs. no mortality with olive oil). However, pretreatment with carbon tetrachloride either reduced or had little effect on the toxicity of nitriles that metabolically liberate cyanide.

Suggested Citation:"2 Benzonitrile Acute Exposure Guideline Levels." National Research Council. 2014. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 16. Washington, DC: The National Academies Press. doi: 10.17226/18707.
×

TABLE 2-3 Summary of Animal Toxicity Data on Benzonitrile


Species Concentration or Dose Exposure Duration Effect Reference

Inhalation Studies
Rat 190 ppm 4 h No-observed-effect level Industrial Bio-Test 1970
Rat 900 ppm 1 h Irritation of extremities MacEwen and Vernot 1974
Rat 900 ppm 3 h Labored breathing, poor coordination MacEwen and Vernot 1974
Rat 900 ppm 4 h No mortality (0/6), decreased weight gain MacEwen and Vernot 1974
Rat 1,900 ppm 4 h 30% mortality (3/10); two died after 2 h, one died on day 6 post-exposure Industrial Bio-Test 1970
Mouse 700 ppm 4 h 100% mortality (10/10) MacEwen and Vernot 1974
Mouse 890 ppm 2 h 14% mortality (1/7) MacEwen and Vernot 1974

Oral Studies

Rat 0.6 g/kg Single gavage No mortality (0/4); hypoactivity, ruffled Industrial Bio-Test 1970
fur, muscular weakness, prostration, dyspnea, lacrimation
Rat 0.9 g/kg Single gavage 50% mortality (2/4); hypoactivity, ruffled fur, muscular weakness, prostration, dyspnea, lacrimation Industrial Bio-Test 1970
Rat 1.4 g/kg Single gavage 75% mortality (3/4); hypoactivity, ruffled fur, muscular weakness, prostration, dyspnea, lacrimation Industrial Bio-Test 1970
Rat 2.0 g/kg Single gavage 100% mortality (4/4); hypoactivity, ruffled fur, muscular weakness, prostration, dyspnea, lacrimation Industrial Bio-Test 1970
Rat 650 mg/kg Single gavage LD16 Agaev 1977
Rat 1,500 mg/kg Single gavage LD50 Agaev 1977
Suggested Citation:"2 Benzonitrile Acute Exposure Guideline Levels." National Research Council. 2014. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 16. Washington, DC: The National Academies Press. doi: 10.17226/18707.
×
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 4 h 0% mortality (0/4); muscular weakness, prostration, salivation, ataxia, tremors, loss of righting reflex Industrial Bio-Test 1970
Rabbit 1.4 g/kg 24 h 100% mortality (4/4); muscular weakness, prostration, salivation, ataxia, tremors, loss of righting reflex Industrial Bio-Test 1970
Rabbit 2.0 g/kg 24 h 100% mortality (4/4); muscular weakness, prostration, salivation, ataxia, tremors, loss of righting reflex Industrial Bio-Test 1970
Rabbit 3.0 g/kg 24 h 100% mortality (4/4); muscular weakness, prostration, salivation, ataxia, tremors, loss of righting reflex Industrial Bio-Test 1970

Suggested Citation:"2 Benzonitrile Acute Exposure Guideline Levels." National Research Council. 2014. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 16. Washington, DC: The National Academies Press. doi: 10.17226/18707.
×

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), and because the hydroxylation is a radical-based reaction, acute toxicity of nitriles is related to the structural features that influence α-carbon radical stability. Generally, nitriles that are metabolized most quickly or easily at the α-carbon are more toxic than nitriles metabolized more slowly at the α-carbon. Thus, the toxicity pattern, in decreasing order, with regard to the type of α-carbon radical formed following α-hydrogen abstraction is benzylic ≈ 3° > 2° > 1°. The presence of a hydroxy or a substituted or unsubstituted amino group on the α-carbon increases toxicity, and the presence of these moieties at other carbon positions decreases acute toxicity (DeVito 1996). Benzonitrile is not metabolized to cyanide in vivo or in vitro (Tanii and Hashimoto 1984).

4.5. Species Differences

One study of inhalation exposure to benzonitrile suggests that rats are more resistant than mice to its lethal effects (MacEwen and Vernot 1974). Another study of the oral lethality of benzonitrile suggests that mice and rats have similar sensitivities (Agaev 1977), but details of the study methods were lacking.

4.6. Concentration-Exposure Duration Relationship

The concentration-exposure time relationship for many irritant and systemically-acting vapors and gases may be described by the equation Cn × t = k, where the exponent n ranges from 0.8 to 3.5 (ten Berge et al. 1986). Data were inadequate to derive an empirical value of n for benzonitrile. To obtain conservative and protective AEGL values in the absence of a chemical-specific scaling exponent, temporal scaling was performed using default values of n = 3 when extrapolating to shorter durations and n = 1 when extrapolating to longer durations.

5. RATIONALE FOR AEGL-1

5.1. Human Data Relevant to AEGL-1

No human data on benzonitrile consistent with the definition of AEGL-1 were available.

Suggested Citation:"2 Benzonitrile Acute Exposure Guideline Levels." National Research Council. 2014. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 16. Washington, DC: The National Academies Press. doi: 10.17226/18707.
×

5.2. Animal Data Relevant to AEGL-1

No animal data on benzonitrile consistent with the definition of AEGL-1 were available.

5.3. Derivation of AEGL-1 Values

Data on benzonitrile are insufficient to derive AEGL-1 values; therefore, AEGL-1 values are not recommended. Absence of AEGL-1 values does not imply that exposures below AEGL-2 values are without adverse effects.

6. RATIONALE FOR AEGL-2

6.1. Human Data Relevant to AEGL-2

No human data on benzonitrile consistent with the definition of AEGL-2 were available.

6.2. Animal Data Relevant to AEGL-2

Studies conducted in rats and mice show steep dose-response relationships which makes it difficult to discern thresholds for AEGL-2 and AEGL-3 effects from the sparse data (MacEwen and Vernot 1974). For example, in mice, exposure to benzonitrile at 890 for 2 h (Cn × t = 1,780 ppm-h) resulted in 14% (1/7) mortality whereas exposure at 700 ppm for 4 h (2,800 ppm-h) resulted in 100% mortality, with prostration occurring at 2.5 h and 10% (1/10) mortality at 3.5 h. In rats, exposure at 900 ppm for 3 h (2,700 ppm-h) resulted in labored breathing and impaired coordination; however, an additional 30 min of exposure at 900 ppm resulted in prostration, but no deaths in rats.

6.3. Derivation of AEGL-2 Values

Given the steepness of the dose-response relationship and uncertainty in distinguishing the threshold for AEGL-2 and AEGL-3 effects, AEGL-2 values were derived based on a 3-fold reduction of the AEGL-3 values. The AEGL-2 values for benzonitrile are presented in Table 2-4, and the calculations for these AEGL-2 values are presented in Appendix A.

TABLE 2-4 AEGL-2 Values for Benzonitrile


10 min 30 min 1 h 4 h 8 h

11 ppm 7.8 ppm 6.2 ppm 2.5 ppm 1.2 ppm
(48 mg/m3) (33 mg/m3) (26 mg/m3) (10 mg/m3) (5.2 mg/m3)

Suggested Citation:"2 Benzonitrile Acute Exposure Guideline Levels." National Research Council. 2014. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 16. Washington, DC: The National Academies Press. doi: 10.17226/18707.
×

7. RATIONALE FOR AEGL-3

7.1. Human Data Relevant to AEGL-3

No human data on benzonitrile consistent with the definition of AEGL-3 were available.

7.2. Animal Data Relevant to AEGL-3

Animal data on benzonitrile consistent with the definition of AEGL-3 are sparse. No deaths were observed in rats exposed to benzonitrile at 190 ppm for 4 h (Industrial Bio-Test 1970) or at 900 ppm for 4 h (MacEwen and Vernot 1974). One of 10 mice died when exposed at 890 ppm for 2 h (MacEwen and Vernot 1974).

7.3. Derivation of AEGL-3 Values

The available data offer two options for deriving the AEGL-3 value. One option is to use the 3.5-h exposure at 900 ppm that resulted in prostration but no deaths in rats as the point of departure. The second option is to base the AEGL-3 values on the 2-h exposure at 890 ppm that resulted in 14% (1/7) mortality in mice. The second option was chosen because it results in lower AEGL-3 values. Because some lethality in mice was observed at 890 ppm, the concentration was adjusted to estimate the lethal threshold. Typically, a 3-fold reduction of the LC50 would be used to extrapolate to a lethality threshold. However, an LC50 value for benzonitrile is not available. The 2-h study reported 14% mortality, which suggests the test concentration of 890 ppm is below the LC50; therefore, a 2-fold adjustment was applied. The resulting adjusted value of 445 ppm was considered an estimate of the lethality threshold and used as the point of departure for deriving AEGL-3 values.

An interspecies uncertainty factor of 10 was applied. Mortality data reported by Agaev (1977) on benzonitrile suggest that rats and mice have similarly steep dose-response relationships (e.g., similar oral LD16, LD50, and LD84), but the reported lack details about the methods, and no data on other species are available. An intraspecies uncertainty factor of 3 was applied to account for sensitive individuals. Application of this value, rather than a default of 10, is supported by the steep concentration-response curve for benzonitrile, which implies little individual variability. For example, the steepness of the curve is evident in mice exposed by inhalation to benzonitrile (10% mortality at 890 ppm for 2 h [ct = 1,780 ppm-h] vs. 100% mortality at 700 ppm for 4 h [ct = 2,800 ppm-h]) (MacEwen and Vernot 1974), in rats exposed orally (no mortality at 0.6 g/kg vs. 100% mortality at 2.0 g/kg) (Industrial Bio-Test 1970), and in rabbits exposed dermally (no mortality at 0.9 g/kg vs. 100% mortality at 1.4 g/kg) (Industrial Bio-Test 1970). The total uncertainty factor is 30. The concentration-exposure time relationship for many irritant and systemically acting vapors and gases may

Suggested Citation:"2 Benzonitrile Acute Exposure Guideline Levels." National Research Council. 2014. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 16. Washington, DC: The National Academies Press. doi: 10.17226/18707.
×

be described by the equation Cn × t = k, where the exponent n ranges from 0.8 to 3.5 (ten Berge et al. 1986). Insufficient data were available to derive an empirical value for n. Therefore, time scaling was performed using default values of n = 3 to extrapolate to shorter durations and n = 1 to extrapolate to longer durations to provide AEGL values that are protective of human health (NRC 2001). AEGL-3 values for benzonitrile are presented in Table 2-5, and the calculations are presented in Appendix A.

8. SUMMARY OF AEGL VALUES

8.1. AEGL Values and Toxicity End Points

AEGL values for benzonitrile are presented in Table 2-6. AEGL-1 values are not recommended due to insufficient data. AEGL-2 values were estimated by dividing the corresponding AEGL-3 values by 3, and AEGL-3 values were based on lethality data from studies of mice.

8.2. Other Standards and Guidelines

No other standards and guidelines for short-term exposures to benzonitrile were found.

8.3. Data Adequacy and Research Needs

No human data on benzonitrile were found and animal data were sparse. AEGL-1 values were not derived. AEGL-2 and AEGL-3 values were derived; however, it was necessary to apply a modifying factor, partly because of the sparse data base.

TABLE 2-5 AEGL-3 Values for Benzonitrile


10 min 30 min 1 h 4 h 8 h

34 ppm 24 ppm 19 ppm 7.4 ppm 3.7 ppm
(140 mg/m3) (99 mg/m3) (79 mg/m3) (31 mg/m3) (16 mg/m3)

TABLE 2-6 AEGL-3 Values for Benzonitrile


Classification 10 min 30 min 1 h 4 h 8 h

AEGL-1 NRa NRa NRa NRa NRa
(nondisabling)
AEGL-2 11 ppm 7.8 ppm 6.2 ppm 2.5 ppm 1.2 ppm
(disabling) (48 mg/m3) (33 mg/m3) (26 mg/m3) (10 mg/m3) (5.2 mg/m3)
AEGL-3 34 ppm 24 ppm 19 ppm 7.4 ppm 3.7 ppm
(lethal) (140 m /m3) (99 m /m3) (79 m /m3) (31 m /m3) (16 m /m3)

aNot recommended. Absence of AEGL-1 values does not imply that exposures below AEGL-2 values are without adverse effects.

Suggested Citation:"2 Benzonitrile Acute Exposure Guideline Levels." National Research Council. 2014. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 16. Washington, DC: The National Academies Press. doi: 10.17226/18707.
×

9. REFERENCES

Agaev, F.B. 1977. Experimental basis of the maximum allowable concentration of benzonitrile in the air of the workplace [in Russian]. Gig. Tr. Prof. Zabol. (6):34-37.

DeVito, S.C. 1996. Designing safer nitriles. Pp. 194-223 in Designing Safer Chemicals, S.C. DeVito, and R.L. Garrett, eds. American Chemical Society Symposium Series Vol. 640. Washington, DC: American Chemical Society.

Ellenhorn, M.J. 1997. Ellenhorn's Medical Toxicology: Diagnosis and Treatment of Human Poisoning, 2nd Ed., M.J. Ellenhorn, S. Schonwald, G. Ordog, and J. Wasserberger, eds. Baltimore, MD: Williams and Wilkins.

HSDB (Hazardous Substances Data Bank). 2003. Benzonitrile (CAS Reg. No. 100-47-0). TOXNET Specialized Information Services, U.S. National Library of Medicine, Bethesda, MD [online]. Available: http://toxnet.nlm.nih.gov/ [accessed June 5, 2013].

Industrial Bio-Test. 1970. Acute Toxicity Studies on Benzonitrile. Report to Velsicol Chemical Corporation, by Industrial Bio-Test Laboratories, Inc., Northbrook, IL. Submitted to EPA, by Sherwin-Williams Company, Washington, DC with Cover Letter Dated September 9, 1992. EPA Document No. 88-920009445. Microfiche No. OTS0571101.

IPCS (International Programme on Chemical Safety). 1999. Benzonitrile (CAS Reg. No. 100-47-0). International Chemical Safety Card No. 1103 [online]. Available: http://www.inchem.org/documents/icsc/icsc/eics1103.htm [accessed Feb. 4, 2014].

MacEwen, J.D. and E.H. Vernot. 1974. Acute inhalation toxicity of benzonitrile. Pp. 77-80 in Toxic Hazards Research Unit Annual Technical Report: 1974. AMRL-TR-74-78. ADA011559. Aerospace Medical Research Laboratory, Aerospace Medical Division, Air Force Systems Command, Wright-Patterson Air Force Base, OH.

NRC (National Research Council). 1993. Guidelines for Developing Community Emergency Exposure Levels for Hazardous Substances. Washington, DC: National Academy Press.

NRC (National Resource Council). 2001. Standing Operating Procedures for Developing Acute Exposure Guideline Levels for Hazardous Chemicals. Washington, DC: National Academy Press.

Tanii, H., and K. Hashimoto. 1984. Studies on the mechanism of acute toxicity of nitriles in mice. Arch. Toxicol. 55(1):47-54.

ten Berge, W.F., A. Zwart, and L.M. Appelman. 1986. Concentration-time mortality response relationship of irritant and systemically acting vapours and gases. J. Hazard. Mater. 13(1):301-309.

Suggested Citation:"2 Benzonitrile Acute Exposure Guideline Levels." National Research Council. 2014. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 16. Washington, DC: The National Academies Press. doi: 10.17226/18707.
×

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.

 
10-min AEGL-2: 34 ppm ÷ 3 = 11 ppm
 
30-min AEGL-2: 24 ppm ÷ 3 = 7.8 ppm
 
1-h AEGL-2: 19 ppm ÷ 3 = 6.2 ppm
 
4-h AEGL-2: 7.4 ppm ÷ 3 = 2.5 ppm
 
8-h AEGL-2: 3.7 ppm ÷ 3 = 1.2 ppm
 
Derivation of AEGL-3 Values
 
Key study: MacEwen, J.D., and E.H. Vernot. 1974. Acute inhalation toxicity of benzonitrile. Pp. 77-80 in Toxic Hazards Research Unit Annual Technical Report: 1974. Aerospace Medical Research Laboratory, Aerospace Medical Division, Air Force Systems Command, Wright-Patterson Air Force Base, OH.
 
Toxicity end point: Estimated 2-h lethality threshold in mice of 445 ppm
 
Time scaling: Cn × t = k (default values of n = 3 for extrapolating to shorter durations and n =1 for extrapolating to longer durations)
(445 ppm)3 × 2 h = 176,242,250 ppm-h
(445 ppm)1 × 2 h = 890 ppm-h
 
Uncertainty factors: 10 for interspecies differences
3 for intraspecies variability
 
Modifying factor: None
 
Suggested Citation:"2 Benzonitrile Acute Exposure Guideline Levels." National Research Council. 2014. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 16. Washington, DC: The National Academies Press. doi: 10.17226/18707.
×
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

Suggested Citation:"2 Benzonitrile Acute Exposure Guideline Levels." National Research Council. 2014. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 16. Washington, DC: The National Academies Press. doi: 10.17226/18707.
×

APPENDIX B

ACUTE EXPOSURE GUIDELINE LEVELS FOR BENZONITRILE

Derivation Summary

AEGL-1 VALUES

The data on benzonitrile were insufficient for deriving AEGL-1 values.

AEGL-2 VALUES

10 min 30 min 1 h 4 h 8 h
11 ppm
(48 mg/m3)
7.8 ppm
(33 mg/m3)
6.2 ppm
(26 mg/m3)
2.5 ppm
(10 mg/m3)
1.2 ppm
(5.2 mg/m3)
Data adequacy: In the absence of specific data on benzonitrile to determine AEGL-2 values, estimates were made by dividing the AEGL-3 values by 3. These values are considered estimates of the threshold for impaired ability to escape and are considered appropriate given the steep concentration-response curve for benzonitrile.

AEGL-3 VALUES

10 min 30 min 1 h 4 h 8 h
34 ppm
(140 mg/m3)
24 ppm
(99 mg/m3)
19 ppm
(79 mg/m3)
7.4 ppm
(31 mg/m3)
3.7 ppm
(16 mg/m3)
Key reference: MacEwen, J.D., and E.H. Vernot. 1974. Acute inhalation toxicity of benzonitrile. Pp. 77-80 in Toxic Hazards Research Unit Annual Technical Report: 1974. Aerospace Medical Research Laboratory, Aerospace Medical Division, Air Force Systems Command, Wright-Patterson Air Force Base, OH.
Test species/Strain/Number: Mouse, CF-1, 7 or 10 males/group
Exposure route/Concentrations/Durations: Inhalation, 700 ppm for 4 h or 890 ppm for 2 h
Effects:
700 ppm for 4 h: 100% mortality (10/10)
890 ppm for 2 h: 14% mortality (1/7)
End point/Concentration/Rationale: Estimated lethality threshold of 445 ppm. Typically, a 3-fold reduction of the LC50 would be used to estimate a lethal threshold. However, an LC50 value for benzonitrile was not available. The 2-h exposure to benzonitrile at 890 ppm resulted in 14% lethality, which suggests this concentration is below the LC50; therefore, a 2-fold adjustment was applied to estimate a 2-h lethality threshold of 445 ppm.
Suggested Citation:"2 Benzonitrile Acute Exposure Guideline Levels." National Research Council. 2014. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 16. Washington, DC: The National Academies Press. doi: 10.17226/18707.
×
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), details of the study methods are lacking and no data on other species are available.
Intraspecies: 3, because steep concentration-response curves imply little individual variability. The steepness of the curve is evident in mice exposed by inhalation to benzonitrile (10% mortality at 890 ppm for 2 h [ct = 1,780 ppm-h] vs. 100% mortality at 700 ppm for 4 h [ct = 2,800 ppm-h]) (MacEwen and Vernot 1974), in rats exposed orally (no mortality at 0.6 g/kg vs. 100% mortality at 2.0 g/kg) (Industrial Bio-Test 1970), and in rabbits exposed dermally (no mortality at 0.9 g/kg vs. 100% mortality at 1.4 g/kg) (Industrial Bio-Test 1970).
Animal-to-human dosimetric adjustment: Insufficient data
Time scaling: Cn × t = k; default values of n = 3 to extrapolate to shorter durations (10 min, 30 min, and 1 h) and n = 1 to extrapolate to longer durations (4 and 8 h) to provide AEGL values that would be protective of human health (NRC 2001).
Data adequacy: Sparse data set.

Suggested Citation:"2 Benzonitrile Acute Exposure Guideline Levels." National Research Council. 2014. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 16. Washington, DC: The National Academies Press. doi: 10.17226/18707.
×

APPENDIX C

CATEGORY PLOT FOR BENZONITRILE

image

FIGURE C-1 Category plot of toxicity data and AEGL values for benzonitrile.

Suggested Citation:"2 Benzonitrile Acute Exposure Guideline Levels." National Research Council. 2014. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 16. Washington, DC: The National Academies Press. doi: 10.17226/18707.
×

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), decreased weight gain
Industrial Bio-Test 1970 Rat 1 1,900 240 SL 30% mortality (3/10)
MacEwen and Vernot 1974 Mouse 1 700 240 3 100% mortality (10/10)
MacEwen and Vernot 1974 Mouse 1 890 120 SL 14% mortality (1/7)

For category: 0 = no effect, 1 = discomfort, 2 = disabling, SL = some lethality, 3 = lethal

Suggested Citation:"2 Benzonitrile Acute Exposure Guideline Levels." National Research Council. 2014. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 16. Washington, DC: The National Academies Press. doi: 10.17226/18707.
×
Page 121
Suggested Citation:"2 Benzonitrile Acute Exposure Guideline Levels." National Research Council. 2014. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 16. Washington, DC: The National Academies Press. doi: 10.17226/18707.
×
Page 122
Suggested Citation:"2 Benzonitrile Acute Exposure Guideline Levels." National Research Council. 2014. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 16. Washington, DC: The National Academies Press. doi: 10.17226/18707.
×
Page 123
Suggested Citation:"2 Benzonitrile Acute Exposure Guideline Levels." National Research Council. 2014. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 16. Washington, DC: The National Academies Press. doi: 10.17226/18707.
×
Page 124
Suggested Citation:"2 Benzonitrile Acute Exposure Guideline Levels." National Research Council. 2014. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 16. Washington, DC: The National Academies Press. doi: 10.17226/18707.
×
Page 125
Suggested Citation:"2 Benzonitrile Acute Exposure Guideline Levels." National Research Council. 2014. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 16. Washington, DC: The National Academies Press. doi: 10.17226/18707.
×
Page 126
Suggested Citation:"2 Benzonitrile Acute Exposure Guideline Levels." National Research Council. 2014. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 16. Washington, DC: The National Academies Press. doi: 10.17226/18707.
×
Page 127
Suggested Citation:"2 Benzonitrile Acute Exposure Guideline Levels." National Research Council. 2014. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 16. Washington, DC: The National Academies Press. doi: 10.17226/18707.
×
Page 128
Suggested Citation:"2 Benzonitrile Acute Exposure Guideline Levels." National Research Council. 2014. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 16. Washington, DC: The National Academies Press. doi: 10.17226/18707.
×
Page 129
Suggested Citation:"2 Benzonitrile Acute Exposure Guideline Levels." National Research Council. 2014. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 16. Washington, DC: The National Academies Press. doi: 10.17226/18707.
×
Page 130
Suggested Citation:"2 Benzonitrile Acute Exposure Guideline Levels." National Research Council. 2014. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 16. Washington, DC: The National Academies Press. doi: 10.17226/18707.
×
Page 131
Suggested Citation:"2 Benzonitrile Acute Exposure Guideline Levels." National Research Council. 2014. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 16. Washington, DC: The National Academies Press. doi: 10.17226/18707.
×
Page 132
Suggested Citation:"2 Benzonitrile Acute Exposure Guideline Levels." National Research Council. 2014. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 16. Washington, DC: The National Academies Press. doi: 10.17226/18707.
×
Page 133
Suggested Citation:"2 Benzonitrile Acute Exposure Guideline Levels." National Research Council. 2014. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 16. Washington, DC: The National Academies Press. doi: 10.17226/18707.
×
Page 134
Suggested Citation:"2 Benzonitrile Acute Exposure Guideline Levels." National Research Council. 2014. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 16. Washington, DC: The National Academies Press. doi: 10.17226/18707.
×
Page 135
Suggested Citation:"2 Benzonitrile Acute Exposure Guideline Levels." National Research Council. 2014. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 16. Washington, DC: The National Academies Press. doi: 10.17226/18707.
×
Page 136
Suggested Citation:"2 Benzonitrile Acute Exposure Guideline Levels." National Research Council. 2014. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 16. Washington, DC: The National Academies Press. doi: 10.17226/18707.
×
Page 137
Suggested Citation:"2 Benzonitrile Acute Exposure Guideline Levels." National Research Council. 2014. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 16. Washington, DC: The National Academies Press. doi: 10.17226/18707.
×
Page 138
Suggested Citation:"2 Benzonitrile Acute Exposure Guideline Levels." National Research Council. 2014. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 16. Washington, DC: The National Academies Press. doi: 10.17226/18707.
×
Page 139
Suggested Citation:"2 Benzonitrile Acute Exposure Guideline Levels." National Research Council. 2014. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 16. Washington, DC: The National Academies Press. doi: 10.17226/18707.
×
Page 140
Suggested Citation:"2 Benzonitrile Acute Exposure Guideline Levels." National Research Council. 2014. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 16. Washington, DC: The National Academies Press. doi: 10.17226/18707.
×
Page 141
Suggested Citation:"2 Benzonitrile Acute Exposure Guideline Levels." National Research Council. 2014. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 16. Washington, DC: The National Academies Press. doi: 10.17226/18707.
×
Page 142
Next: 3 Methacrylonitrile Acute Exposure Guideline Levels »
Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 16 Get This Book
×
Buy Paperback | $72.00 Buy Ebook | $59.99
MyNAP members save 10% online.
Login or Register to save!
Download Free PDF

Extremely hazardous substances can be released accidentally as a result of chemical spills, industrial explosions, fires, or accidents involving railroad cars and trucks transporting EHSs. Workers and residents in communities surrounding industrial facilities where these substances are manufactured, used, or stored and in communities along the nation's railways and highways are potentially at risk of being exposed to airborne extremely hazardous substances during accidental releases or intentional releases by terrorists. Pursuant to the Superfund Amendments and Reauthorization Act of 1986, the U.S. Environmental Protection Agency has identified approximately 400 extremely hazardous substances on the basis of acute lethality data in rodents.

Acute Exposure Guideline Levels for Selected Airborne Chemicals, Volume 16 identifies, reviews, and interprets relevant toxicologic and other scientific data for selected aliphatic nitriles, benzonitrile, methacrylonitrile, allyl alcohol, hydrogen selenide, ketene, and tear gasin order to develop acute exposure guideline levels (AEGLs) for these high-priority, acutely toxic chemicals.

AEGLs represent threshold exposure limits (exposure levels below which adverse health effects are not likely to occur) for the general public and are applicable to emergency exposures ranging from 10 minutes (min) to 8 h. Three levels - AEGL-1, AEGL-2, and AEGL-3 - are developed for each of five exposure periods (10 min, 30 min, 1 h, 4 h, and 8 h) and are distinguished by varying degrees of severity of toxic effects. This report will inform planning, response, and prevention in the community, the workplace, transportation, the military, and the remediation of Superfund sites.

  1. ×

    Welcome to OpenBook!

    You're looking at OpenBook, NAP.edu's online reading room since 1999. Based on feedback from you, our users, we've made some improvements that make it easier than ever to read thousands of publications on our website.

    Do you want to take a quick tour of the OpenBook's features?

    No Thanks Take a Tour »
  2. ×

    Show this book's table of contents, where you can jump to any chapter by name.

    « Back Next »
  3. ×

    ...or use these buttons to go back to the previous chapter or skip to the next one.

    « Back Next »
  4. ×

    Jump up to the previous page or down to the next one. Also, you can type in a page number and press Enter to go directly to that page in the book.

    « Back Next »
  5. ×

    Switch between the Original Pages, where you can read the report as it appeared in print, and Text Pages for the web version, where you can highlight and search the text.

    « Back Next »
  6. ×

    To search the entire text of this book, type in your search term here and press Enter.

    « Back Next »
  7. ×

    Share a link to this book page on your preferred social network or via email.

    « Back Next »
  8. ×

    View our suggested citation for this chapter.

    « Back Next »
  9. ×

    Ready to take your reading offline? Click here to buy this book in print or download it as a free PDF, if available.

    « Back Next »
Stay Connected!