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1

2

3

4

5

6 IMMEDIATELY DANGEROUS TO LIFE OR HEALTH (IDLH) VALUE PROFILE

7

8

9

10 FOR

11

12

13

14 BENZONITRILE

15

16

17

18 [CAS NO. 100-47-0] 

19

20

21

22

23

24

25 Department of Health and Human Services 

26 Centers for Disease Control and Prevention 

27 National Institute for Occupational Safety and Health 

28

29
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1 DISCLAIMER

2 Mention of any company or product does not constitute endorsement by the National Institute for Occupational 

3 Safety and Health (NIOSH). In addition, citations of Web sites external to NIOSH do not constitute NIOSH 

4 endorsement of the sponsoring organizations or their programs or products. Furthermore, NIOSH is not 

5 responsible for the content of these Web sites. 

6

7 ORDERING INFORMATION

8 This document is in the public domain and may be freely copied or reprinted. To receive NIOSH documents or 

9 other information about occupational safety and health topics, contact NIOSH at 

10 Telephone: 1-800-CDC-INFO (1-800-232-4636) 

11 TTY: 1-888-232-6348 

12 E-mail: cdcinfo@cdc.gov 

13

14 or visit the NIOSH Web site at www.cdc.gov/niosh. 
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1 Foreword 

2 Chemicals are a ubiquitous component of the modern workplace. Occupational exposures to chemicals have the 

3 potential to adversely affect the health and lives of workers. Acute or short-term exposures to high concentrations 

4 of some airborne chemicals have the ability to quickly overwhelm workers, resulting in a spectrum of undesirable 

5 health outcomes that may inhibit the ability to escape from the exposure environment (e.g., irritation of the eyes 

6 and respiratory tract or cognitive impairment), cause severe irreversible effects (e.g., damage to the respiratory 

7 tract or reproductive toxicity), and in extreme cases, cause death. Airborne concentrations of chemicals capable 

8 of causing such adverse health effects or of impeding escape from high-risk conditions may arise from a variety of 

9 non-routine workplace situations , including special work procedures (e.g., in confined spaces), industrial 

10 accidents (e.g., chemical spills or explosions), and chemical releases into the community (e.g., during 

11 transportation incidents or other uncontrolled-release scenarios). 

12

13 The “immediately dangerous to life or health air concentration values (IDLH values)” developed by the National 

14 Institute for Occupational Safety and Health (NIOSH) characterize these high-risk exposure concentrations and 

15 conditions [NIOSH 2013]. IDLH values are based on a 30-minute exposure duration and have traditionally 

16 served as a key component of the decision logic for the selection of respiratory protection devices [NIOSH 2004]. 

17 Occupational health professionals have employed these values beyond their initial purpose as a component of the 

18 NIOSH Respirator Selection Logic to assist in developing Risk Management Plans for non-routine work practices 

19 governing operations in high-risk environments (e.g., confined spaces) and the development of Emergency 

20 Preparedness Plans. 

21

22 The approach used to derive IDLH values for high priority chemicals is outlined in the NIOSH Current 

23 Intelligence Bulletin (CIB) 66: Derivation of Immediately Dangerous to Life or Health Values [NIOSH 2013]. 

24 CIB 66 provides 1) an update on the scientific basis and risk assessment methodology used to derive IDLH 

25 values, 2) the rationale and derivation process for IDLH values, and 3) a demonstration of the derivation of 

26 scientifically credible IDLH values using available data resources.

27

28 The purpose of this technical report is to present the IDLH value for benzonitrile (CAS # 100-47-0). The 

29 scientific basis, toxicologic data and risk assessment approach used to derive the IDLH value are summarized to 

30 ensure transparency and scientific credibility. 

31 

32 John Howard, M.D. 

33 Director 

34 National Institute for Occupational Safety and Health 
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1 Centers for Disease Control and Prevention 

2 
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1 Content 

2

3 FOREWORD ................................................................................................................................................................ III

4 ABBREVIATIONS .......................................................................................................................................................VI

5 GLOSSARY .................................................................................................................................................................VII

6 ACKNOWLEDGMENTS .............................................................................................................................................XI

7 1.0 INTRODUCTION.............................................................................................................................................. 1

8 1.1 OVERVIEW OF THE IDLH VALUE FOR BENZONITRILE.................................................................................................1

9 1.2 PURPOSE .....................................................................................................................................................................1

10 1.3 GENERAL SUBSTANCE INFORMATION .........................................................................................................................1

11 2.0 ANIMAL TOXICITY DATA............................................................................................................................. 5

12 3.0 HUMAN DATA ................................................................................................................................................. 8

13 4.0 SUMMARY........................................................................................................................................................ 8

14 5.0 REFERENCES ................................................................................................................................................ 10

15
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1 Abbreviations 

2

3 ACGIH American Conference of Governmental Industrial Hygienists 

4 AEGL Acute Exposure Guideline Levels 

5 AIHA American Industrial Hygiene Association 

6 BMC benchmark concentration 

7 BMCL benchmark concentration lower confidence limit 

8 C ceiling 

9 CAS chemical abstract service 

10 ERPG Emergency Response Planning Guidelines 

11 IDLH immediately dangerous to life or health 

12 LCLo lowest concentration of a chemical that caused death in humans or animals 

13 LEL lower explosive limit 

14 LOAEL lowest observed adverse effect level 

mg/m3 15 milligram(s) per cubic meter 

16 NAC National Advisory Committee 

17 NAS National Academy of Sciences 

18 NIOSH National Institute for Occupational Safety and Health 

19 NOAEL no observed adverse effect level 

20 OSHA Occupational Safety and Health Administration 

21 PEL permissible exposure limit 

22 ppm parts per million 

23 RD50 concentration of a chemical in the air that is estimated to cause a 50% decrease in the respiratory 

24 rate 

25 REL recommended exposure limit 

26 SCP Standard Completion Program 

27 STEL short term exposure limit 

28 TLV threshold limit value 

29 TWA time weighted average 

30 UEL upper explosive limit 

31 WEEL workplace environmental exposure level 
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1 Glossary 

2

3 Acute Exposure: Exposure by the oral, dermal, or inhalation route for 24 hours or less. 

4 Acute Exposure Guideline Levels (AEGLs): Threshold exposure limits for the general public applicable to 

5 emergency exposure periods ranging from 10 minutes to 8 hours. AEGL-1, AEGL 2, and AEGL-3 are 

6 developed for five exposure periods (10 and 30 minutes, 1 hour, 4 hours, and 8 hours) and are distinguished 

7 by varying degrees of severity of toxic effects ranging from transient, reversible effects to life-threatening 

8 effects [NAS 2001]. AEGLs are intended to be guideline levels used during rare events or single once-in-a9 lifetime exposures to airborne concentrations of acutely toxic, high-priority chemicals [NAS 2001]. The 

10 threshold exposure limits are designed to protect the general population, including the elderly, children or 

11 other potentially sensitive groups that are generally not considered in the development of workplace exposure 

12 recommendations (additional information available at http://www.epa.gov/oppt/aegl/). 

13 Acute Reference Concentration (RfC): An estimate (with uncertainty spanning perhaps an order of magnitude) 

14 of a continuous inhalation exposure for an acute duration (24 hours or less) of the human population 

15 (including sensitive subgroups) that is likely to be without an appreciable risk of deleterious effects during a 

16 lifetime. It can be derived from a NOAEL, LOAEL, or benchmark concentration, with uncertainty factors 

17 (UFs) generally applied to reflect limitations of the data used. Generally used in USEPA noncancer health 

18 assessments [USEPA 2014]. 

19 Acute Toxicity: Any poisonous effect produced within a short period of time following an exposure, usually 24 

20 to 96 hours. 

21 Adverse Effect: A substance-related biochemical change, functional impairment, or pathologic lesion that affects 

22 the performance of an organ or system or alters the ability to respond to additional environmental challenges. 

23 Benchmark Dose/Concentration (BMD/BMC): A dose or concentration that produces a predetermined change 

24 in response rate of an effect (called the benchmark response, or BMR) compared to background [USEPA 

25 2014] (additional information available at http://www.epa.gov/ncea/bmds/). 

26 Benchmark Response (BMR): A predetermined change in response rate of an effect. Common defaults for the 

27 BMR are 10% or 5%, reflecting study design, data variability, and sensitivity limits used. 

28 BMCL: A statistical lower confidence limit on the concentration at the BMC [USEPA 2014]. 

29 Bolus Exposure: A single, relatively large dose. 

30 Ceiling Value (“C”): U.S. term in occupational exposure indicating the airborne concentration of a potentially 

31 toxic substance that should never be exceeded in a worker’s breathing zone. 

32 Chronic Exposure: Repeated exposure for an extended period of time. Typically exposures are more than 

33 approximately 10% of life span for humans and >90 days to 2 years for laboratory species. 

34 Critical Study: The study that contributes most significantly to the qualitative and quantitative assessment of risk 

35 [USEPA 2014]. 

36

37 Dose: The amount of a substance available for interactions with metabolic processes or biologically significant 

38 receptors after crossing the outer boundary of an organism [USEPA 2014]. 

39 ECt50: A combination of the effective concentration of a substance in the air and the exposure duration that is 

40 predicted to cause an effect in 50% (one half) of the experimental test subjects. 
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1 Emergency Response Planning Guidelines (ERPGs): Maximum airborne concentrations below which nearly all 

2 individuals can be exposed without experiencing health effects for 1-hour exposure. ERPGs are presented in a 

3 tiered fashion with health effects ranging from mild or transient to serious, irreversible, or life threatening 

4 (depending on the tier). ERPGs are developed by the American Industrial Hygiene Association [AIHA 2006]. 

5 Endpoint: An observable or measurable biological event or sign of toxicity ranging from biomarkers of initial 

6 response to gross manifestations of clinical toxicity. 

7 Exposure: Contact made between a chemical, physical, or biological agent and the outer boundary of an 

8 organism. Exposure is quantified as the amount of an agent available at the exchange boundaries of the 

9 organism (e.g., skin, lungs, gut). 

10 Extrapolation: An estimate of the response at a point outside the range of the experimental data, generally 

11 through the use of a mathematical model, although qualitative extrapolation may also be conducted. The 

12 model may then be used to extrapolate to response levels that cannot be directly observed. 

13 Hazard: A potential source of harm. Hazard is distinguished from risk, which is the probability of harm under 

14 specific exposure conditions. 

15 Immediately Dangerous to Life or Health (IDLH) condition: A situation that poses a threat of exposure to 

16 airborne contaminants when that exposure is likely to cause death or immediate or delayed permanent adverse 

17 health effects or prevent escape from such an environment [NIOSH 2004, 2013]. 

18 IDLH value: A maximum (airborne concentration) level above which only a highly reliable breathing apparatus 

19 providing maximum worker protection is permitted [NIOSH 2004, 2013]. IDLH values are based on a 30-

20 minute exposure duration. 

21 LC01: The statistically determined concentration of a substance in the air that is estimated to cause death in 1% of 

22 the test animals. 

23 LC50: The statistically determined concentration of a substance in the air that is estimated to cause death in 50% 

24 (one half) of the test animals; median lethal concentration. 

25 LCLO: The lowest lethal concentration of a substance in the air reported to cause death, usually for a small 

26 percentage of the test animals. 

27

28 LD50: The statistically determined lethal dose of a substance that is estimated to cause death in 50% (one half) of 

29 the test animals; median lethal concentration. 

30 LDLO: The lowest dose of a substance that causes death, usually for a small percentage of the test animals. 

31 LEL: The minimum concentration of a gas or vapor in air, below which propagation of a flame does not occur in 

32 the presence of an ignition source. 

33 Lethality: Pertaining to or causing death; fatal; referring to the deaths resulting from acute toxicity studies. May 

34 also be used in lethality threshold to describe the point of sufficient substance concentration to begin to cause 

35 death. 

36 Lowest Observed Adverse Effect Level (LOAEL): The lowest tested dose or concentration of a substance that 

37 has been reported to cause harmful (adverse) health effects in people or animals. 
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1 Mode of Action: The sequence of significant events and processes that describes how a substance causes a toxic 

2 outcome. Mode of action is distinguished from the more detailed mechanism of action, which implies a more 

3 detailed understanding on a molecular level. 

4 No Observed Adverse Effect Level (NOAEL): The highest tested dose or concentration of a substance that has 

5 been reported to cause no harmful (adverse) health effects in people or animals. 

6 Occupational Exposure Limit (OEL): Workplace exposure recommendations developed by governmental 

7 agencies and non-governmental organizations. OELs are intended to represent the maximum airborne 

8 concentrations of a chemical substance below which workplace exposures should not cause adverse health 

9 effects. OELs may apply to ceiling, short-term (STELs), or time-weighted average (TWA) limits. 

10 Peak Concentration: Highest concentration of a substance recorded during a certain period of observation. 

11 Permissible Exposure Limit (PEL): Occupational exposure limits developed by OSHA (29 CFR 1910.1000) or 

12 MSHA (30 CFR 57.5001) for allowable occupational airborne exposure concentrations. PELs are legally 

13 enforceable and may be designated as ceiling, STEL, or TWA limits. 

14

15 Point of Departure (POD): The point on the dose–response curve from which dose extrapolation is initiated. 

16 This point can be the lower bound on dose for an estimated incidence or a change in response level from a 

17 concentration-response model (BMC), or it can be a NOAEL or LOAEL for an observed effect selected from 

18 a dose evaluated in a health effects or toxicology study. 

19 RD50: The statistically determined concentration of a substance in the air that is estimated to cause a 50% (one 

20 half) decrease in the respiratory rate. 

21 Recommended Exposure Limit (REL): Recommended maximum exposure limit to prevent adverse health 

22 effects based on human and animal studies and established for occupational (up to 10-hour shift, 40-hour 

23 week) inhalation exposure by NIOSH. RELs may be designated as ceiling, STEL, or TWA limits. 

24 Short-Term Exposure Limit (STEL): A worker’s 15-minute time-weighted average exposure concentration that 

25 shall not be exceeded at any time during a work day. 

26 Target Organ: Organ in which the toxic injury manifests in terms of dysfunction or overt disease. 

27 Threshold Limit Values (TLVs®): Recommended guidelines for occupational exposure to airborne 

28 contaminants, published by the American Conference of Governmental Industrial Hygienists (ACGIH). TLVs 

29 refer to airborne concentrations of chemical substances and represent conditions under which it is believed 

30 that nearly all workers may be repeatedly exposed, day after day, over a working lifetime, without adverse 

31 effects. TLVs may be designated as ceiling, short-term (STELs), or 8-hr TWA limits. 

32 Time-Weighted Average (TWA): A worker’s 8-hour (or up to 10-hour) time-weighted average exposure 

33 concentration that shall not be exceeded during an 8-hour (or up to 10-hour) work shift of a 40-hour week. 

34 The average concentration is weighted to take into account the duration of different exposure concentrations. 

35 Toxicity: The degree to which a substance is able to cause an adverse effect on an exposed organism. 

36

37 Uncertainty Factors (UFs): Mathematical adjustments applied to the POD when developing IDLH values. The 

38 UFs for IDLH value derivation are determined by considering the study and effect used for the POD, with 

39 further modification based on the overall database. 
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1 Workplace Environmental Exposure Levels (WEELs): Exposure levels developed by the American Industrial 

2 Hygiene Association (AIHA) that provide guidance for protecting most workers from adverse health 

3 effects related to occupational chemical exposures expressed as a TWA or ceiling limit.
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1 Acknowledgments 

2

3 This document was developed by the Education and Information Division (Paul Schulte, Ph.D., Director). G. 

4 Scott Dotson, Ph.D., was the project officer and lead NIOSH author for this technical report. The basis for this 

5 document was a report contracted by NIOSH and prepared by Andrew Maier, Ph.D., Ann Parker, and Lynn 

6 Haber, Ph.D. (Toxicology Excellence for Risk Assessment [TERA]). 

7

8 Education and Information Division 

9 Devin Baker, M.Ed. 

10 Charles L. Geraci, Ph.D. 

11 Thomas J. Lentz, Ph.D. 

12 Richard Niemeier, Ph.D. 

13 Chris Sofge, Ph.D. 

14

15 NIOSH would like to acknowledge the contribution of the following subject matter experts for their critical 

16 technical review of this report. 

17

18 Michael S. Bisesi, Ph.D., R.E.H.S., C.I.H., Senior Associate Dean for Academic Affairs; Director, Center 

19 for Public Health Practice; Interim Chair & Associate Professor, Division of Environmental Health 

20 Science, College of Public Health, Ohio State University 

21

22 Mary A. Fox, Ph.D., Assistant Professor; Co-Director, Risk Sciences and Public Policy Institute; 

23 Department of Health Policy and Management, Bloomberg School of Public Health, Johns Hopkins 

24 University 
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1 1.0 Introduction 

2 1.1 Overview of the IDLH Value for Benzonitrile

3

4

IDLH Value 47 ppm (198 mg/m3 5 )

6

7 Basis for IDLH Value: The IDLH value is based on a lethality study in which all mice exposed to 700 ppm for 

8 4 hours died [MacEwen and Vernot 1974]. The 30-minute duration adjusted concentration is 1,400 ppm. This 

9 value is supported by LOAEL values of 890 ppm and 900 ppm for potential escape impairing effects of poor 

10 coordination and labored breathing observed in mice and rats, respectively, following a 1-hour exposure 

11 [MacEwen and Vernot 1974]. The 30-minute duration adjusted concentrations are 1,121 and 1,134 ppm, 

12 respectively. An uncertainty factor of 30 to account for extrapolation from a concentration that is lethal to 

13 animals, animal to human differences, and human variability is applied to the concentration of 1,400 ppm, 

14 resulting in an IDLH value of 47 ppm. 

15

16 1.2 Purpose 

17

18 This IDLH Value Profile presents (1) a brief summary of technical data associated with acute inhalation 

19 exposures to benzonitrile and (2) the rationale behind the Immediately Dangerous to Life or Health (IDLH) value 

20 for benzonitrile. IDLH values are developed based on the scientific rationale and logic outlined in the NIOSH 

21 Current Intelligence Bulletin (CIB) 66: Derivation of Immediately Dangerous to Life or Health (IDLH) values 

22 [NIOSH 2013]. As described in CIB 66, NIOSH performs in-depth literature searches to ensure that all relevant 

23 data from human and animal studies with acute exposures to the substance are identified. Information included in 

24 CIB 66 on the literature search includes pertinent databases, key terms, and guides for evaluating data quality and 

25 relevance for the establishment of an IDLH value. The information that is identified in the in-depth literature 

26 search is evaluated with general considerations that include description of studies (i.e., species, study protocol, 

27 exposure concentration and duration), health endpoint evaluated, and critical effect levels (e.g., NOAELs, 

28 LOAELs, LC50 values). For benzonitrile, the in-depth literature search was conducted through February 2014. 

29

30 1.3 General Substance Information 

31

32 Chemical: Benzonitrile 
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1 CAS No: 100-47-0 

Synonyms: Cyano-benzene; Phenyl cyanide; Benzoic acid nitrile* 2

Chemical category: Nitriles† 3

4

5 Structural formula: 

6

7

8

9 Table 1 highlights selected physiochemical properties of benzonitrile relevant to IDLH conditions. Table 2 

10 provides alternative exposure guidelines for benzonitrile. Table 3 summarizes the Acute Exposure Guidelines 

11 Level (AEGL) values for benzonitrile. 

12

13 Table 1: Physiochemical Properties of Benzonitrile 

14

Property Value 

Molecular weight 103.12‡

Chemical formula C7H5N 

Description Colorless liquid 

Odor Volatile oil of almond scent

Odor Threshold 2.90 x 10-5 mg/L (0.007 ppm).‡

UEL 12%†

LEL 9%†

Vapor pressure 2 x 10-13 mmHg at 20°C (68°F)‡

Flash point 67°C (152.6°F)†

Ignition temperature 550°C (1022°F)†

Solubility Sparingly soluble in water†

Abbreviation: oC – Celsius; o 15 F – Fahrenheit; mmHg – millimeter mercury; LEL – lower explosive limit; UEL – upper explosive limit * 16 NLM [2012] 

† 17 IFA [2012] 

‡ 18 HSDB [2012] 

19

20

21 Table 2: Alternative Exposure Guidelines for Benzonitrile 

22

Organization Value 

Original SCP IDLH value None 

NIOSH REL Not available 

OSHA PEL Not available 

ACGIH TLV [2014] Not available 

AIHA ERPG [2010] Not available 

AIHA WEEL [2010] Not available 

23 Abbreviation: ACGIH – American Conference of Governmental Industrial Hygienists; AIHA – American Industrial Hygiene 

24 Association; ERPG – Emergency Response Preparedness Guidelines; IDLH – immediately dangerous to life or health; NIOSH – National 

N
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1 Institute for Occupational Safety and Health; OSHA – Occupational Safety and Health Administration; PEL – permissible exposure limit; 

2 REL – recommended exposure limit; SCP – Standards Completion Program; WEEL – workplace environmental exposure level 
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1 Table 3: AEGL Values for Benzonitrile 

2

Classification 10-min 30-min 1-hour 4-hour 8-hour End Point 

[reference] 

AEGL-1 NR NR NR NR NR Insufficient dAEGL-2 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) 

One-third of A

AEGL-3 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) 

Estimated let[MacEwen an

Abbreviation: AEGL – acute exposure guideline levels; mg/m3 3 – milligrams per cubic meter; min – minute; NR – not recommended due to insufficient da* 4 References: NAS [2014] 

5
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1 2.0 Animal Toxicity Data 

2

3 Some of the lethality studies reported non-lethal effects. The MacEwen and Vernot [1974] lethality study 

4 reported non-lethal effects in mice exposed to 890 ppm of benzonitrile for durations ranging from 60 to 120 

5 minutes and rats exposed to 900 ppm for 60 to 240 minutes. Mice showed signs of irritation of the extremities 

6 during the first hour of exposure, followed by poor coordination and labored breathing after 60 to 90 minutes; 

7 these effects could be identified as escape-impairing. The rats showed signs of irritation of extremities, labored 

8 breathing, poor coordination, and decreased weight gain; these effects could also be escape-impairing. Mice 

9 exposed for 4 hours in the same study also had hepatic congestion and sinusoidal dilatation. Industrial Bio-Test 

10 [1970] exposed groups of male (n = 5) and female (n =5) rats to benzonitrile at concentrations of 190 and 1,900 

11 ppm for 4 hours and observed for 14 days. No effects or deaths were reported in animals exposed to 190 ppm. In 

12 the higher treatment group, 3 female rats died after exposure to 1,900 ppm. Two of the animals died 2 hours post 

13 exposure, while the third died 6 days after exposure. NAS [2014] noted that the clinical signs of acute toxicity of 

14 benzonitrile included labored breathing, poor coordination, hypoactivity, salivation, lacrimation, muscular 

15 weakness and dyspnea. 

16

17 Table 4 summarizes the LC data identified in animal studies and provides 30-minute equivalent derived values for 

18 benzonitrile. Table 5 provides non-lethal data reported in animal studies with 30-minute equivalent derived 

19 values. Information in these tables includes species of test animals, toxicological metrics (i.e., LC, NOAEL, 

20 LOAEL), adjusted 30-minute concentration, and the justification for the composite uncertainty factors applied to 

21 calculate the derived values. 

22 
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1 Table 4: Lethal Concentration Data for Benzonitrile2

Reference Species Other 

lethality (ppm) 

LCLo

(ppm) 

Time (min) 

Adjusted 30-min Concentration* 

Composite UncertaintFactor 

MacEwen and Vernot [1974] Mouse 700‡ -- 240 1,400 30± Industrial Bio-Test [1970] Rat 1,900§ -- 240 3,800 30± 

3 Abbreviation: LC – lethal concentration; LCLo – lowest concentration of a chemical that caused death in humans or animals; min – minute

* For exposures other than 30 minutes the ten Berge et al. [1986] relationship is used for duration adjustment (Cn 4 x t = k); no empirically est

5 available, therefore the default values were used, n = 3 for exposures greater than 30 minutes and n = 1 for exposures less than 30 minutes. 6 †The derived value is the result of the adjusted 30-minute concentration divided by the composite uncertainty factor. 

‡ 7 700 ppm reported by MacEwen and Vernot [1974] resulted in 100% mortality. ± 8 Composite uncertainty factor to account for adjustment of LC50 values to LC01 values, use of lethal concentration threshold in animals, inte

9 human variability. 

§ 10 1900 ppm reported by Industrial BioTest [1970] resulted in 30% mortality. 

111213
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1 Table 5: Non-lethal Concentration Data for Benzonitrile2

Reference Species NOAEL 

(ppm) 

LOAEL (ppm) 

Time (min) 

Adjusted 30-min Concentration* 

Composite Uncertainty Factor 

DerivValue(ppm

MacEwen and Vernot [1974] Mouse -- 890 60 1,121 10± 112 MacEwen and Vernot [1974] Rat -- 900 60 1,134 10± 113 

MacEwen and Vernot [1974] Rat -- 900 180 1,635 10± 164 Industrial Bio-Test [1970] Rat 190 -- 240 380 3‡ 127 

34 Abbreviation: NOAEL – no observed adverse effect level; min – minute; LOAEL – lowest observed adverse effect level; ppm – parts per 

* For exposures other than 30 minutes the ten Berge et al. [1986] relationship is used for duration adjustment (Cn 5 x t = k); no empirically est

6 available, therefore the default values were used, n = 3 for exposures greater than 30 minutes and n = 1 for exposures less than 30 minutes. 

† 7 The derived value is the result of the adjusted 30-minute concentration divided by the composite uncertainty factor. ± 8 Composite uncertainty factor assigned to account for adjusting from a LOAEL to NOAEL, interspecies differences and human variability. 

9 ‡Composite uncertainty factor assigned to account for interspecies differences and human variability 
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1 3.0 Human Data 

2

3 No relevant human studies were located. Snyder [1990] included a report of an occupational accident where a 

4 worker was drenched in benzonitrile. The worker experienced severe respiratory distress, convulsions and periods 

5 of unconsciousness. No additional information about the exposure scenario or magnitude was provided. 

6 4.0 Summary 

7

8 No human data were available to serve as the basis of the IDLH value for benzonitrile. Animal data are available 

9 that include description of lethality and non-lethal effects in rodents. MacEwan and Vernot [1974] reported 100% 

10 lethality in mice exposed to 700 ppm for 4 hours; this serves as the basis of the IDLH value for benzonitrile. A 

11 30-minute duration equivalent concentration was calculated at 1,400 ppm. Rats and mice experience poor 

12 coordination and labored breathing after a 1-hour exposure period to 890 and 900 ppm, respectively [MacEwen 

13 and Vernot 1974]. The LOAEL value of 890 ppm was duration adjusted to a 30-minute exposure concentration, 

14 resulting in a value of 1,121 ppm. The similarity of the duration-adjusted values for lethality at 1,400 ppm and 

15 non-lethal effects at 1,121 ppm reflects either a steep concentration–response curve or uncertainties with the 

16 duration extrapolation. The IDLH value is based on 100% lethality in mice exposed to 700 ppm for 4 hours 

17 [MacEwen and Vernot 1974]. Application of an uncertainty factor of 30 to the adjusted 30-minute concentration 

18 of 1,400 ppm to account for extrapolation from a concentration that is lethal to animals, animal to human 

19 differences, and human variability, yields an IDLH value for benzonitrile of 47 ppm. 

20

21 It should be noted that the IDLH value for benzonitrile differs by more than an order of magnitude from the 

22 AEGL-2 30-minute value, which is intended to represent an airborne concentration of a substance above which it 

23 is predicted that the general population, including susceptible individuals, could experience irreversible or other 

24 serious, long-lasting adverse health effects or an impaired ability to escape [NAS 2001]. Data to calculate an 

25 AEGL-2 value for benzonitrile were deemed insufficient resulting in the establishment of an AEGL-2 equal to 1/3 

26 of the calculated AEGL-3 value, which is intended to represent an airborne concentration of a substance above 

27 which it is predicted that the general population, including susceptible individuals, could experience life28 threatening health effects or death [NAS 2001, 2014]. The AEGL-3 value for 30-minutes was set at 24 ppm and 

29 was based on lethal threshold estimates in mice reported in MacEwan and Vernot [1974]. NIOSH used the same 
External Review Draft Document 

 March 2015 

9

This information is distributed solely for the purpose of pre-dissemination peer review under applicable 

information quality guidelines. It has not been formally disseminated by the National Institute for Occupational 

Safety and Health. It does not represent and should not be construed to represent any agency determination or 

policy. 

1 study as the basis of the IDLH value of 47 ppm for benzonitrile. The differences between the AEGL-3 value and 

2 IDLH value can be attributed to the alternative critical endpoint and duration adjustments. 

3
External Review Draft Document 

 March 2015 

10

This information is distributed solely for the purpose of pre-dissemination peer review under applicable 

information quality guidelines. It has not been formally disseminated by the National Institute for Occupational 

Safety and Health. It does not represent and should not be construed to represent any agency determination or 

policy. 

1 5.0 References 

2

3 ACGIH (American Conference of Governmental Industrial Hygienists) [2014]. Annual TLVs® (Threshold Limit 

4 Values) and BEIs® (Biological Exposure Indices) booklet. Cincinnati, OH: ACGIH Signature Publications. 

5

6 AIHA (American Industrial Hygiene Association) [2009]. AIHA Emergency Response Planning (ERP) 

7 Committee procedures and responsibilities. Fairfax, VA: American Industrial Hygiene Association. 

8

9 AIHA (American Industrial Hygiene Association) [2010]. Emergency response planning guidelines (ERPG) and 

10 workplace environmental exposure levels (WEEL) handbook. Fairfax, VA: American Industrial Hygiene 

11 Association Press. 

12

13 HSDB [2014]. Hazardous Substances Data Bank [http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?HSDB] CAS No. 

14 100-47-0. Date accessed: August 1, 2012. 

15

16 IFA (Institut für Arbeitsschutz der Deutschen Gesetzlichen Unfallversicherung) [2014]. GESTIS: database on 

17 hazardous substances. 

18 [http://gestis-en.itrust.de/nxt/gateway.dll?f=templates&fn=default.htm&vid=gestiseng:sdbeng]. Date accessed: 

19 March 17, 2014. 

20

21 Industrial Bio-Test [1970]. Acute toxicity studies on benzonitrile. Report to Velsicol Chemical Corporation. P.O. 

22 No. C12670, IBT Nn. A8792. OTS0571101. EPA Document No. 88-920009445. 

23

24 MacEwen JD, Vernot EH [1974]. Acute inhalation toxicity of benzonitrile. Toxic Hazards Research Unit Annual 

25 Technical Report, pp. 77–80. Wright-Patterson Air Force Base, OH: Aerospace Medical Research Laboratory, 

26 Aerospace Medical Division, Air Force Systems Command. 

27

28 NAS (National Academy of Science) [2001]. Standing operating procedures for developing Acute Exposure 

29 Guidelines Levels for hazardous chemicals. NAS, National Research Council (NRC), Committee on Toxicology, 

30 Subcommittee on Acute Exposure Guideline Levels. National Academy Press: Washington, DC. IBSN: 0-309-

31 07553-X. [http://www.epa.gov/oppt/aegl/pubs/sop.pdf]. Date accessed: March 17, 2014. 

32

33 NAS (National Academies of Science) [2014]. Acute Exposure Guideline Levels (AEGLs) for selected airborne 

34 chemicals - Volume: 16. Appendix 2 - Benzonitrile (CAS Reg. No. 107-13-1). NAS, National Research Council, 

35 Committee on Toxicology, Subcommittee on Acute Exposure Guideline Levels National Academy Press: 

36 Washington, DC. [http://www.epa.gov/oppt/aegl/pubs/aliphatic_nitriles_final_volume_16_2014sf.pdfpdf]. Data 

37 accessed: August 1, 2014. 

38

39 NIOSH (National Institute for Occupational Safety and Health) [2004]. NIOSH respirator selection logic. 

40 Cincinnati, OH: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, 

41 National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 2005-100. 

42 [http://www.cdc.gov/niosh/docs/2005-100/pdfs/2005-100.pdf]. Date accessed: March 17, 2014. 

43

44 NIOSH [2013]. NIOSH Current Intelligence Bulletin 66: Derivation of Immediately Dangerous to Life or Health 

45 (IDLH) values. Cincinnati, OH: U.S. Department of Health and Human Services, Centers for Disease Control and 

46 Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 2014-100. 

47 [http://www.cdc.gov/niosh/docs/2014-100/pdfs/2014-100.pdf]. Date accessed: March 17, 2014. 
External Review Draft Document 

 March 2015 

11

This information is distributed solely for the purpose of pre-dissemination peer review under applicable 

information quality guidelines. It has not been formally disseminated by the National Institute for Occupational 

Safety and Health. It does not represent and should not be construed to represent any agency determination or 

policy. 

1

2 NIOSH [2014]. NIOSH pocket guide to chemical hazards. Cincinnati, OH: U.S. Department of Health and 

3 Human Services, Centers for Disease Control and Prevention, National Institute for Occupational Safety and 

4 Health, DHHS (NIOSH) Publication No. 2005-149. [http://www.cdc.gov/niosh/npg/]. Date accessed: March 17, 

5 2014. 

6

7 NLM (National Library of Medicine) [2014]. ChemIDplus lite . [http://chem.sis.nlm.nih.gov/chemidplus/]. Date 

8 accessed: March 17, 2014. 

9

Synder R [1990]. Ethel Browning's toxicity and metabolism of industrial solvents. 2nd 10 Ed. Volume II: Nitrogen 

11 and phosphorus solvents. Amsterdam-New York-Oxford: Elsevier. 

12

13 ten Berge WF, Zwart A, Appelman LM [1986]. Concentration-time mortality response relationship of irritant and 

14 systematically acting vapors and gases. J Haz Mat 13:301–309. 

15

16 USEPA (U.S. Environmental Protection Agency) [2014]. Integrated Risk Information System (IRIS). 

17 [http://www.epa.gov/iris/]. Date accessed: March 17, 2014. 

18