External Review Draft Document

March 2015

i

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

information quality guidelines. It has not been formally di sseminated 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

3

4

5



## I MMEDIATELY 

## D ANGEROUS TO 

## L IFE OR 

## H EALTH 

## (IDLH) V ALUE 

## P ROFILE 6

7

8

9



### FOR 10

11

12

13



## B ENZONITRILE 14

15

16

17



## [CAS N O



## . 100-47-0] 18

19

20

21

22

23

24

Department of Health and Human Services 25

Centers for Disease Control and Prevention 26

National Institute for Occupa tional Safety and Health 27

28

29External Review Draft Document

March 2015

ii

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

information quality guidelines. It has not been formally di sseminated 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. 

## D ISCLAIMER 1

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

Safety and Health (NIOSH). In add ition, citations of Web sites extern al to NIOSH do not constitute NIOSH 3

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

responsible for the content of these Web sites. 5

6



## O RDERING 

## I NFORMATION 7

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

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

Telephone: 1-800-CDC-IN FO (1-800-232-4636) 10

TTY: 1-888-232-6348 11

E-mail: cdcinfo@cdc.gov 12

13

or visit the NIOSH Web site at www.cdc.gov/niosh. 14External Review Draft Document

March 2015

iii

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

information quality guidelines. It has not been formally di sseminated 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. 

## Foreword 1

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

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

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

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

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

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

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

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

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

transportation incidents or other uncontrolled-release scenarios). 11

12

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

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

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

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

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

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

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

Preparedness Plans. 20

21

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

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

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

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

scientifically credible IDLH values using available data resources. 26

27

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

scientific basis, toxicologic data and risk assessment appr oach used to derive the ID LH value are summarized to 29

ensure transparency and scientific credibility. 30

31

John Howard, M.D. 32

Director 33

National Institute for Occupa tional Safety and Health 34External Review Draft Document

March 2015

iv

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

information quality guidelines. It has not been formally di sseminated 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. Centers for Disease Control and Prevention 1

2External Review Draft Document

March 2015

v

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

information quality guidelines. It has not been formally di sseminated 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. 

## Content 1

2

FOREWORD

............................................................................................................................... ................................. III 3

ABBREVIATIONS

............................................................................................................................... ........................ VI 4

GLOSSARY

............................................................................................................................... .................................. VII 5

ACKNOWLEDGMENTS

............................................................................................................................... .............. XI 6

1.0 INTRODUCTION

............................................................................................................................... ............... 1 7

1.1 O VERVIEW OF THE IDLH V ALUE FOR B ENZONITRILE

................................................................................................. 1 8

1.2 P URPOSE

............................................................................................................................... ...................................... 1 9

1.3 G ENERAL S UBSTANCE I NFORMATION

......................................................................................................................... 1 10

2.0 ANIMAL TOXICITY DATA

............................................................................................................................. 5 11

3.0 HUMAN DATA

............................................................................................................................... .................. 8 12

4.0 SUMMARY

............................................................................................................................... ......................... 8 13

5.0 REFERENCES

............................................................................................................................... ................. 10 14

15External Review Draft Document

March 2015

vi

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

information quality guidelines. It has not been formally di sseminated 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. 

## Abbreviations 1

2

ACGIH American Conference of Gove rnmental Industrial Hygienists 3

AEGL Acute Exposure Guideline Levels 4

AIHA American Industrial Hygiene Association 5

BMC benchmark concentration 6

BMCL benchmark concentra tion lower confidence limit 7

C ceiling 8

CAS chemical abstract service 9

ERPG Emergency Response Planning Guidelines 10

IDLH immediately dangerous to life or health 11

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

LEL lower explosive limit 13

LOAEL lowest observed adverse effect level 14

mg/m 3 milligram(s) per cubic meter 15

NAC National Advisory Committee 16

NAS National Academy of Sciences 17

NIOSH National Institute for O ccupational Safety and Health 18

NOAEL no observed adverse effect level 19

OSHA Occupational Safety and Health Administration 20

PEL permissible exposure limit 21

ppm parts per million 22

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

rate 24

REL recommended exposure limit 25

SCP Standard Completion Program 26

STEL short term exposure limit 27

TLV threshold limit value 28

TWA time weighted average 29

UEL upper explosive limit 30

WEEL workplace environmental exposure level 31External Review Draft Document

March 2015

vii

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

information quality guidelines. It has not been formally di sseminated 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. 

## Glossary 1

2

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

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

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

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

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

effects [NAS 2001]. AEGLs are intended to be guideline le vels used during rare events or single once-in-a8

lifetime exposures to airborne concentrations of acu tely toxic, high-priority chemicals [NAS 2001]. The 9

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

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

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

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

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

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

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

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

assessments [USEPA 2014]. 18

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

to 96 hours. 20

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

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

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

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

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

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

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

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

Bolus Exposure : A single, relatively large dose. 29

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

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

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

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

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

[USEPA 2014]. 35

36

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

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

ECt 50 : A combination of the effective concentration of a s ubstance in the air and the exposure duration that is 39

predicted to cause an effect in 50% (one half) of the experimental test subjects. 40External Review Draft Document

March 2015

viii

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

information quality guidelines. It has not been formally di sseminated 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. Emergency Response Planning Guidelines (ERPGs) : Maximum airborne concentrations below which nearly all 1

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

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

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

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

response to gross manifestations of clinical toxicity. 6

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

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

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

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

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

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

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

specific exposure conditions. 14

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

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

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

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

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

minute exposure duration. 20

LC 01 : The statistically determined concentra tion of a substance in the air that is estimated to cause death in 1% of 21

the test animals. 22

LC 50 : The statistically determined concentr ation of a substance in the air that is estimated to cause death in 50% 23

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

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

percentage of the test animals. 26

27

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

the test animals; median lethal concentration. 29

LD LO : The lowest dose of a substance that causes death, usua lly for a small percentage of the test animals. 30

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

the presence of an ignition source. 32

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

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

death. 35

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

has been reported to cause harmful (adverse) health effects in people or animals. 37External Review Draft Document

March 2015

ix

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

information quality guidelines. It has not been formally di sseminated 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. Mode of Action : The sequence of significant events and processes that describes how a substance causes a toxic 1

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

detailed understanding on a molecular level. 3

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

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

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

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

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

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

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

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

MSHA (30 CFR 57.5001) for allowable occupational air borne exposure concentr ations. PELs are legally 12

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

14

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

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

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

a dose evaluated in a health e ffects or toxicology study. 18

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

half) decrease in the respiratory rate. 20

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

36

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

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

further modification based on the overall database. 39External Review Draft Document

March 2015

x

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

information quality guidelines. It has not been formally di sseminated 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. Workplace Environmental Exposure Levels (WEELs) : Exposure levels developed by the American Industrial 1

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

effects related to occupational chemical exposures expressed as a TWA or ceiling limit. 3External Review Draft Document

March 2015

xi

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

information quality guidelines. It has not been formally di sseminated 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. 

## Acknowledgments 1

2

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

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

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

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

7



### Education and Information Division 8

Devin Baker, M.Ed. 9

Charles L. Geraci, Ph.D. 10

Thomas J. Lentz, Ph.D. 11

Richard Niemeier, Ph.D. 12

Chris Sofge, Ph.D. 13

14

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

technical review of this report. 16

17

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

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

Science, College of Public H ealth, Ohio State University 20

21

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

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

University 24External Review Draft Document

March 2015

1

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

information quality guidelines. It has not been formally di sseminated 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. 

## 1.0 Introduction 1



## 1.1 Overview of the IDLH Value for Benzonitrile 2

3

4

IDLH Value 47 ppm (198 mg/m 3 ) 5

6

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

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

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

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

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

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

animals, animal to human differences, and human variab ility is applied to the con centration of 1,400 ppm, 13

resulting in an IDLH value of 47 ppm

. 14

15



## 1.2 Purpose 16

17

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

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

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

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

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

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

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

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

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

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

LOAELs, LC 50 values). For benzonitrile, the in-depth literatu re search was conducted th rough February 2014. 28

29



## 1.3 General Substance Information 30

31

Chemical: Benzonitrile 32External Review Draft Document

March 2015

2

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

information quality guidelines. It has not been formally di sseminated 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. CAS No: 100-47-0 1

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

Chemical category: Nitriles † 3

4

Structural formula: 5

6

7

8

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

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

Level (AEGL) values for benzonitrile. 11

12

Table 1: Physiochemical Properties of Benzonitrile 13

14

Property Value

Molecular weight 103.12 ‡

Chemical formula C 7 H 5 N

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: o C – Celsius; o F – Fahrenheit; mmHg – millimeter mercury; LEL – lower explosive limit; UEL – upper explosive limit 15

* NLM [2012] 16

† IFA [2012] 17

‡ HSDB [2012] 18

19

20

Table 2: Alternative Exposure Guidelines for Benzonitrile 21

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

Abbreviation: ACGIH – American Conference of Governmental I ndustrial Hygienists; AIHA – Am erican Industrial Hygiene 23

Association; ERPG – Emergency Re sponse Preparedness Guidelines; IDLH – immediatel y dangerous to life or health; NIOSH – Nationa l 24 NExternal Review Draft Document

March 2015

3

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

information quality guidelines. It has not been formally di sseminated 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. Institute for Occupational Safety and Hea lth; OSHA – Occupational Safety and Health Administration; PEL – permissible exposure limit; 1

REL – recommended exposure limit; SCP – Standards Completion Program; WEEL – workplace e nvironmental exposure level 2External Review Draft DocumentMarch 20154This information is distributed solely for the purpose of pre-dissemination peer review under applicable information quality guidelines. It has not beenformally disseminated by the National Institute for Occupational Safety and Health. It does not represent and should not be construed to represent anyagency determination or policy.Table 3: AEGL Values for Benzonitrile12Classification 10-min 30-min 1-hour 4-hour 8-hour End Point[reference]AEGL-1 NR NR NR NR NR Insufficient dataAEGL-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 AEGL-3 valuesAEGL-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 lethal threshold in mice[MacEwen and Vernot 1974]Abbreviation: AEGL – acute exposure guideline levels; mg/m3– milligrams per cubic meter; min – minute; NR – not recommended due to insufficient data; ppm – parts per million3*References: NAS [2014]45External Review Draft Document

March 2015

5

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

information quality guidelines. It has not been formally di sseminated 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. 

## 2.0 Animal Toxicity Data 1

2

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

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

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

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

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

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

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

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

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

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

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

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

weakness and dyspnea. 15

16

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

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

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

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

calculate the derived values. 21

22External Review Draft DocumentMarch 20156This information is distributed solely for the purpose of pre-dissemination peer review under applicable information quality guidelines. It has not beenformally disseminated by the National Institute for Occupational Safety and Health. It does not represent and should not be construed to represent anyagency determination or policy.Table 4: Lethal Concentration Data for Benzonitrile12Reference SpeciesOtherlethality(ppm)LCLo(ppm)Time(min)Adjusted30-minConcentration*CompositeUncertaintyFactorDerivedValue†(ppm)MacEwen and Vernot [1974] Mouse 700‡-- 240 1,400 30±47Industrial Bio-Test [1970] Rat 1,900§-- 240 3,800 30±127Abbreviation:LC – lethal concentration; LCLo– lowest concentration of a chemical that caused death in humans or animals; min – minute; ppm – parts per million3*For exposures other than 30 minutes the ten Berge et al. [1986] relationship is used for duration adjustment (Cnx t = k); no empirically estimated n values were4available, therefore the default values were used, n = 3 for exposures greater than 30 minutes and n = 1 for exposures less than 30 minutes.5†The derived value is the result of the adjusted 30-minute concentration divided by the composite uncertainty factor.6‡700 ppm reported by MacEwen and Vernot [1974] resulted in 100% mortality.7±Composite uncertainty factor to account for adjustment of LC50values to LC01values, use of lethal concentration threshold in animals, interspecies differences and8human variability.9§1900 ppm reported by Industrial BioTest [1970] resulted in 30% mortality.10111213External Review Draft DocumentMarch 20157This information is distributed solely for the purpose of pre-dissemination peer review under applicable information quality guidelines. It has not beenformally disseminated by the National Institute for Occupational Safety and Health. It does not represent and should not be construed to represent anyagency determination or policy.Table 5: Non-lethal Concentration Data for Benzonitrile12Reference Species NOAEL(ppm)LOAEL(ppm)Time(min)Adjusted30-minConcentration*CompositeUncertaintyFactorDerivedValue†(ppm)MacEwen and Vernot [1974] Mouse -- 890 60 1,121 10±112MacEwen and Vernot [1974] Rat -- 900 60 1,134 10±113MacEwen and Vernot [1974] Rat -- 900 180 1,635 10±164Industrial Bio-Test [1970] Rat 190 -- 240 380 3‡1273Abbreviation:NOAEL – no observed adverse effect level; min – minute; LOAEL – lowest observed adverse effect level; ppm – parts per million4*For exposures other than 30 minutes the ten Berge et al. [1986] relationship is used for duration adjustment (Cnx t = k); no empirically estimated n values were5available, 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±Composite uncertainty factor assigned to account for adjusting from a LOAEL to NOAEL, interspecies differences and human variability.8‡Composite uncertainty factor assigned to accountfor interspeciesdifferences and human variability9External Review Draft Document

March 2015

8

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

information quality guidelines. It has not been formally di sseminated 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. 

## 3.0 Human Data 1

2

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

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

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



## 4.0 Summary 6

7

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

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

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

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

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

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

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

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

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

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

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

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

20

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

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

is predicted that the general population, including suscep tible individuals, could experi ence irreversible or other 23

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

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

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

which it is predicted that the gene ral population, including susceptible individuals, could experience life27

threatening health effects or death [NAS 2001, 2014]. The AEGL-3 value for 30-minutes was set at 24 ppm and 28

was based on lethal threshold estimates in mice reported in MacEwan and Vernot [1974]. NIOSH used the same 29External 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 di sseminated 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. study as the basis of the IDLH value of 47 ppm for be nzonitrile. The differences between the AEGL-3 value and 1

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

3External 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 di sseminated 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. 

## 5.0 References 1

2

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

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

5

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

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

8

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

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

Association Press. 11

12

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

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

15

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

hazardous substances. 17

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

March 17, 2014. 19

20

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

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

23

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

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

Aerospace Medical Division, Air Force Systems Command. 26

27

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

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

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

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

32

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

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

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

Washington, DC. [http://www.epa.gov/oppt/aegl/pubs/ali phatic_nitriles_final_volum e_16_2014sf.pdfpdf]. Data 36

accessed: August 1, 2014. 37

38

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

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

National Institute for Occupati onal Safety and Health, DHHS (N IOSH) Publication No. 2005-100. 41

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

43

NIOSH [2013]. NIOSH Current Intelligence Bulletin 66: Deri vation of Immediately Dangero us to Life or Health 44

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

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

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

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

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

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

2014. 5

6

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

accessed: March 17, 2014. 8

9

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

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

12

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

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

15

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

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

18