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i 1

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## I MMEDIATELY 

## D ANGEROUS TO 

## L IFE OR 

## H EALTH 

## (IDLH) V ALUE 

## P ROFILE 7

8

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### FOR 11

12

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## A CRYLONITRILE 14



## [CAS No. 107-13-1] 15

16

17

18

19

Department of Health and Human Services 20

Centers for Disease Control and Prevention 21

National Institute for Occupa tional Safety and Health 22

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ii 

## 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. 14

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iii 

## Foreword 1

2

Chemicals are a ubiquitous component of the modern wo rkplace. 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 envi ronment (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 wo rk 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 concen tration values (IDLH values)” developed by the National 14

Institute for Occupational Safety a nd 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 developi ng Risk Management Plans for non-routine work practices 19

governing operations in high-risk envi ronments (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 Da ngerous to Life or Health Values [NIOSH 2013]. 24

CIB 66 provides 1) an update on the scientific basis a nd risk assessment methodology used to derive IDLH 25

values, 2) the rationale and derivati on 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 acrylonitrile (CAS # 107-13-1). The 29

scientific basis, toxicologic data and risk assessment appr oach used to derive the ID LH value are summarized to 30

ensure transparency and scientific credibility. 31

32

John Howard, M.D. 33

Director 34

National Institute for Occupa tional Safety and Health 35

Centers for Disease Control and Prevention 36

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iv 

## Content 1

Foreword

__________________________________________________________________________________________ iii 2

Abbreviations ________________________________________________________________________________________v 3

Glossary

___________________________________________________________________________________________ vi 4

Acknowledgments

___________________________________________________________________________________ ix 5

1.0 Introduction

_________________________________________________________________________________ 1 6

1.1 Overview of the IDLH Value for Acrylonitrile

_____________________________________________________ 1 7

1.2 Purpose

___________________________________________________________________________________ 1 8

1.3 General Substance Information

_________________________________________________________________ 1 9

2.0 Animal Toxicity Data

__________________________________________________________________________ 4 10

3.0 Human Data

_________________________________________________________________________________ 8 11

4.0 Summary

____________________________________________________________________________________ 8 12

References

________________________________________________________________________________________ 10 13

14

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v 

## 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

°C degree Celsius 9

CAS chemical abstract service 10

CEO cyanoethylene oxide 11

ERPG Emergency Response Planning Guidelines 12

°F degree Fahrenheit 13

IDLH immediately dangerous to life or health 14

LC 50 median lethal concentration 15

LEL lower explosive limit 16

LOAEL lowest observed adverse effect level 17

mg/m 3 milligram(s) per cubic meter 18

NAC National Advisory Committee 19

NAS National Academy of Sciences 20

NIOSH National Institute for O ccupational Safety and Health 21

NOAEL no observed adverse effect level 22

OSHA Occupational Safety and Health Administration 23

PEL permissible exposure limit 24

ppm parts per million 25

RD 50 concentration of a chemical in the air that is estimated to cause a 50% decrease in the respiratory 26

rate 27

REL recommend exposure limit 28

SCP Standard Completion Program 29

STEL short-term exposure limit 30

TLV threshold limit value 31

TWA time weighted average 32

UEL upper explosive limit 33

WEEL workplace environmental exposure level 34

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vi 

## 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. 40

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vii 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. 37

Mode of Action : The sequence of significant events and processes that describes how a substance causes a toxic 38

outcome. Mode of action is distinguished from the more detailed mechanism of action, which implies a more 39

detailed understanding on a molecular level. 40

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viii No Observed Adverse Effect Level (NOAEL) : The highest tested dose or concentration of a substance that has 1

been reported to cause no harmful (adverse) health effects in people or animals. 2

Occupational Exposure Limit (OEL) : Workplace exposure recommendations developed by governmental 3

agencies and non-governmental organizations. OELs are intended to represent the maximum airborne 4

concentrations of a chemical substance below wh ich workplace exposures should not cause adverse health 5

effects. OELs may apply to ceiling, short-term (STELs), or time-weighted average (TWA) limits. 6

Peak Concentration : Highest concentration of a substance record ed during a certain period of observation. 7

Permissible Exposure Limit (PEL) : Occupational exposure limits devel oped by OSHA (29 CFR 1910.1000) or 8

MSHA (30 CFR 57.5001) for allowable occupational air borne exposure concentr ations. PELs are legally 9

enforceable and may be designated as ceiling, STEL, or TWA limits. 10

11

Point of Departure (POD) : The point on the dose–response curve fro m which dose extrapolation is initiated. 12

This point can be the lower bound on dose for an estim ated incidence or a change in response level from a 13

concentration-response model (BMC), or it can be a NOAEL or LOAEL for an observed effect selected from 14

a dose evaluated in a health e ffects or toxicology study. 15

RD 50 : The statistically determined concentr ation of a substance in the air that is estimated to cause a 50% (one 16

half) decrease in the respiratory rate. 17

Recommended Exposure Limit (REL) : Recommended maximum exposure limit to prevent adverse health 18

effects based on human and animal studies and established for occupational (up to 10-hour shift, 40-hour 19

week) inhalation exposure by NIOSH. RELs may be designated as ceiling, STEL, or TWA limits. 20

Short-Term Exposure Limit (STEL) : A worker’s 15-minute time-weighted average exposure concentration that 21

shall not be exceeded at any time during a work day. 22

Target Organ : Organ in which the toxic injury manifests in terms of dysfunction or overt disease. 23

Threshold Limit Values (TLVs®) : Recommended guidelines for occupa tional exposure to airborne 24

contaminants, published by the American Conference of Governmental Industrial Hygienists (ACGIH). TLVs 25

refer to airborne concentrations of chemical substa nces and represent conditions under which it is believed 26

that nearly all workers may be repeatedly exposed, da y after day, over a working lifetime, without adverse 27

effects. TLVs may be designated as ceiling, short-term (STELs), or 8-hr TWA limits. 28

Time-Weighted Average (TWA) : A worker’s 8-hour (or up to 10-hour) time-weighted average exposure 29

concentration that shall not be exceeded during an 8- hour (or up to 10-hour) work shift of a 40-hour week. 30

The average concentration is weighted to take into ac count the duration of different exposure concentrations. 31

Toxicity : The degree to which a substance is able to ca use an adverse effect on an exposed organism. 32

33

Uncertainty Factors (UFs) : Mathematical adjustments applied to th e POD when developing IDLH values. The 34

UFs for IDLH value derivation are determined by consid ering the study and effect used for the POD, with 35

further modification based on the overall database. 36

Workplace Environmental Exposure Levels (WEELs) : Exposure levels developed by the American Industrial 37

Hygiene Association (AIHA) that provide guidance for protecting most workers from adverse health effects 38

related to occupational chemical expos ures expressed as a TWA or ceiling limit. 39

40

41

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ix 

## 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

Richard B. Schlesinger, Ph.D., Fellow A.T.S., Senior Associate Dean for Academic Affairs and Research 22

Professor of Biology, Dyson College of Arts and Sciences, Pace University 23

24

25

26

27

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1 

## 1.0 Introduction 1



## 1.1 Overview of the IDLH Value for Acrylonitrile 2

3

IDLH Value: 60 ppm 4

5

The IDLH value for acrylonitrile is based on a BMCL 05 for lethality of 1,784 ppm in rats exposed for 30 minutes 6

[Appel et al. 1981]. A composite uncertainty factor of 30 was applied to account for extrapolation from a lethal 7

concentration threshold in animals, interspecies differences and human variability. The IDLH value for 8

acrylonitrile is set at 60 ppm

. 9

10



## 1.2 Purpose 11

12

This IDLH Value Profile presents (1) a brief summary of technical data associated with acute inhalation 13

exposures to acrylonitrile and (2) the rationale behind the Immediately Dangerous to Life or Health (IDLH) value 14

for acrylonitrile. IDLH values are developed based on the scientific rationale and logic outlined in the NIOSH 15

Current Intelligence Bulletin (CIB) 66: Derivation of Imme diately Dangerous to Life or Health (IDLH) values 16

[NIOSH 2013]. As described in CIB 66, NIOSH performs in -depth literature searches to ensure that all relevant 17

data from human and animal studies with acute exposures to the substance are identified. Information included in 18

CIB 66 on the literature search includes pertinent databases, key terms, and guides for evaluating data quality and 19

relevance for the establishment of an IDLH value. The in formation that is identified in the in-depth literature 20

search is evaluated with general consid erations that include description of studies (i.e., species, study protocol, 21

exposure concentration and duration), health endpoint evaluated, and cr itical effect levels (e.g., NOAELs, 22

LOAELs, LC 50 values). For acrylonitrile, the in-depth literatu re search was conducted th rough February 2014. 23

24



## 1.3 General Substance Information 25

26

Chemical: Acrylonitrile 27

CAS No: 107-13-1 28

Synonyms: 2-Propenenitrile; Cyanoethylene; Vinyl cyanide; Fumigrain; Ventox * 29

Chemical category: Nitriles † 30

Structural formula: 31

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2 1

2

Table 1 highlights selected physiochemical properties of acrylonitrile relevant to IDLH conditions. Table 2 3

provides alternative exposure guidelines for acrylonitril e. Table 3 summarizes the Acute Exposure Guidelines 4

Level (AEGL) values for acrylonitrile. 5

6

Table 1: Physiochemical Properties of Acrylonitrile 7

8

Property Value

Molecular weight 53.06 ‡

Chemical formula C 3 H 3 N

Description Colorless to pale-yellow liquid

Odor Sharp onion-garlic odor

Odor Threshold 1.6 ppm §

UEL 28% *

LEL 2.8% †

Vapor pressure 109 mmHg at 25°C (77°F) ‡

Flash point -5°C (23°F) † - closed cup

Ignition temperature 480°C (896°F) †

Solubility Soluble in water †

Abbreviation: o C – Celsius; o F – Fahrenheit; mmHg – millimeter mercury; LEL – lower explosive limit; UEL – 9

upper explosive limit 10

References: * NLM [2014]; † IFA [2014]; ‡ HSDB [2014]; § AIHA [1989] 11

12

Table 2: Alternative Exposu re Guidelines for Acrylonitrile 13

14

Organization Value

Revised (1994) IDLH value * 85 ppm

NIOSH REL † 1 ppm, TWA cancer; 10 ppm, 15-minute ceiling, skin

OSHA PEL[2014] ^ 2 ppm, TWA; 10 ppm, 15-minute ceiling, skin

ACGIH TLV [2014] ‡ 2 ppm, TWA

AIHA ERPG [2010] + ERPG-1: 10 ppm; ERPG-2: 35 ppm; ERPG-3: 75 ppm

AIHA WEEL [2010] § Not available

Abbreviation: ACGIH – American Conference of Government al Industrial Hygienists; AIHA – American 15

Industrial Hygiene Association; ERPG – Emergency R esponse Preparedness Guidelines; IDLH – immediately 16

dangerous to life or health; NIOSH – National Ins titute for Occupational Safety and Health; OSHA – 17

Occupational Safety and Health Administration; PEL – permissible exposure limit; REL – recommended 18

exposure limit; SCP – Standards Completion Program; TWA – time-weighted average; WEEL – workplace 19

environmental exposure level 20

References: * NIOSH [1994]; ^ OSHA [2014]; † NIOSH [2014]; ‡ ACGIH [2014]; AIHA [2010a]+; §AIHA 21

[2010b] 22

23 

### H 2 

### C

NExternal Review DraftMarch 2015This information is distributed solely for the purpose of pre-dissemination peer review under applicable information quality guidelines. It has not been formally disseminatedby the National Institute for Occupational Safety and Health.It does not represent and should not be construed to represent any agency determination or policy.3Table 3: AEGL Values for Acrylonitrile*12Classification 10-min 30-min 1-hour 4-hour 8-hour End Point[reference]AEGL-1 1.5 ppm(3.3 mg/m3)1.5 ppm(3.3 mg/m3)NR NR NR No-effect level for notable discomfort(ocular irritation) in human subjects,4.6 ppm for 8 hour [Sakurai et al. 1978;Jakubowski et al. 1987].AEGL-2 8.6 ppm(19 mg/m3)3.2 ppm(6.9 mg/m3)1.7 ppm(3.7 mg/m3)0.48 ppm(1.0 mg/m3)0.26 ppm(0.56 mg/m3)No-effect level for fetal toxicity (fetal bodyweight) in rats, 12 ppm for 6 hour[Saillenfait et al. 1993].AEGL-3 130 ppm(280 mg/m3)50 ppm(110 mg/m3)28 ppm(61 mg/m3)9.7 ppm(21 mg/m3)5.2 ppm(11 mg/m3)No-effect level for lethality (30-minute, 1-hour, and 8-hour BMCL05) in rats [Dudleyand Neal 1942; Appel et al. 1981].Abbreviation: AEGL – acute exposure guideline levels; mg/m3– milligrams per cubic meter; min – minute; ppm – parts per million3References: * NAS [2014]4

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4 

## 2.0 Animal Toxicity Data 1

2

Following acute inhalation exposure to acrylonitrile, the most reported effect is ocular and respiratory irritation, 3

with convulsions and tremors occurring at higher concentra tions. The mechanism by which irritation is caused is 4

unknown. Central nervous system (CNS) effects are like ly a result of the metabolism of acrylonitrile to the 5

cyanide metabolite, cyanoethylene oxide (CEO). While early seizures are likely due to cyanide formation 6

metabolism of acrylonitrile, the later severe clonic convul sions prior to death are speculated to be due to 7

acrylonitrile itself [Ghanayem et al. 1991; Nerland et al . 1989; Benz and Nerland 2005]. Following the formation 8

of cyanide, it is detoxified to thiocyanate via a r hodanese-mediated pathway. Rhodanese is a mitochondrial 9

enzyme and identified as meditating one of the primary path ways for the detoxification of cyanide [Cipollone et 10

al. 2008]. 11

12

There are notable species differences in the metabolis m of acrylonitrile. Dogs are more susceptible to 13

acrylonitrile than other species following inhalation expos ures [Dudley and Neal 1942]. For example, inhalation 14

exposures to 65 or 100 ppm acrylonitrile for 4 hours caused effects including coma and death in dogs, while 15

exposures to acrylonitrile at airborne concentrations between 65 to 100 ppm exposures for 4 hours caused 16

minimal irritation and respiratory change in monkeys, cat s or rabbits. Higher airborne concentrations in species 17

more tolerant did lead to coma, convulsions and death. This difference in toxic susceptibility is thought to be due 18

to dogs having lower levels of a rhodanese [Drawbaugh and Marrs 1987]. 19

20

In a lethality study, the LC 50 value of rats exposed to acrylonitrile for 4 hours was calculated to be 333 ppm; 21

deaths occurred within 2-4 hours [Haskell Laboratories 194 2]. Reported effects included irregular respiration, 22

hyperemia, lacrimation, tremors, c onvulsions and death. Dudley and Neal [1942] investigated the effects of 23

single acute exposure to acrylonitrile in rats, dogs, cats, monkeys, rabbits and guinea pigs. The reported effects 24

varied between species and exposure scena rios (i.e., exposure duration and con centration). For example, female 25

monkeys treated at 65 ppm for 4 hours experienced sli ght increased respiratory rates. In comparison, dogs 26

exposed at 65 ppm for 4 hours exhibited severe salivati on, weakness, comas and 50% mortality. At 315 ppm 27

acrylonitrile for 4 hours, rats experienced marked effect s and 25% mortality during exposure. Rats treated with 28

665 ppm acrylonitrile for 30 minutes had moderate transito ry effects of ocular and nasal irritation with no 29

mortality reported [Dudley and Neal 1942]. In a study of rats exposed to 1080 pp m for 1 hour, there were no 30

deaths, but clinical signs of toxicity included rapid shallow breathing, decreased activity, salivation, lacrimation 31

[Vernon et al. 1990]. Three of ten animals became comato se, but all of the rats recovered within 5 minutes of 32

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5 exposure termination. Species differences in metabolism can be observed between rodent s and humans. Rats and 1

mice are reported to form CEO at greater rates than humans [Roberts et al. 1991]. Humans also detoxify CEO 2

more efficiently than do rodents [Kedderis et al. 1995]. However, evaluation of metabolism and physiologically 3

based pharmacokinetic modeling results suggest that rats are better than mice as an animal model of human 4

acrylonitrile inhalation exposure [Appel et al. 1981; NAS 2014]. 5

6

Table 4 summarizes the LC data identified in animal st udies and provides 30-minute equivalent derived values for 7

acrylonitrile. Table 5 provides non-lethal data reported in animal studies with 30-minute equivalent derived 8

values. Information in these tables includes species of test animals, toxicological metrics (i.e., LC, BMCL, 9

NOAEL, LOAEL), adjusted 30-minute concentration, and th e justification for the composite uncertainty factors 10

applied to calculate the derived values. 11External Review DraftMarch 2015This information is distributed solely for the purpose of pre-dissemination peer review under applicable information quality guidelines. It has not been formally disseminatedby the National Institute for Occupational Safety and Health.It does not represent and should not be construed to represent any agency determination or policy.6Table 4: Lethal Concentration Data for Acrylonitrile12Reference SpeciesLC50(ppm)BMCL05(ppm)Time(min)Adjusted30-minConcentration*(ppm)CompositeUncertaintyFactorDerivedValue†(ppm)Haskell Laboratory [1942, 1968] Rat 333 -- 240 2,205 30‡ 74Dudley and Neal [1942] Rat -- 1,024 60 1,924 30‡ 64WIL Research Laboratories [2005] Rat 946 -- 240 6,264 30‡ 209Appel et al. [1981]+Rat -- 1,784 30 1,784 30‡ 603Abbreviation:LC – lethal concentration; LC50– median lethal concentration; BMCL05– benchmark concentration lower-boundconfidence limit that corresponds with4the estimated 95% lower confidence bound on the concentration associated with a 5% increased lethality response above controls;min – minute; ppm – parts per million5*For exposures other than 30 minutes the ten Berge et al. [1986] relationship is used for duration adjustment (Cnx t = k); ten Berge et al. [1986] provided an empirically6estimated n =1.1 for all time-scaling.7†The derived value is the result of the adjusted 30-minute LC value divided by the composite uncertainty factor.8‡Composite uncertainty factor to account for the use of lethal concentration threshold in animals,interspecies differences andhuman variability.9+Identified study is the primary basisof the IDLH value for acrylonitrile.10111213External Review DraftMarch 2015This information is distributed solely for the purpose of pre-dissemination peer review under applicable information quality guidelines. It has not been formally disseminatedby the National Institute for Occupational Safety and Health.It does not represent and should not be construed to represent any agency determination or policy.7Table 5: Non-lethal Concentration Data for Acrylonitrile12Reference SpeciesNOAEL(ppm)LOAEL(ppm)Time(min)Adjusted30-minConcentration*CompositeUncertaintyFactorDerivedValue†(ppm)Dudley and Neal [1942] Monkey 65 -- 240 430 3‡ 143Dudley and Neal [1942] Dog 65 240 430 10± 43Dudley and Neal [1942] Rat 665 -- 30 665 3‡ 222Vernon et al. [1990] Rat -- 1,080 60 2,028 10±203Wilson et al. [1948] Humans -- 100 45 145 1 145Jakubowksi et al. [1987] Humans 4.5 -- 480 56 1 56Abbreviation:NOAEL – no observed adverse effect level; min – minute; LOAEL – lowest observed adverse effect level; ppm – parts per million3*For exposures other than 30 minutes the ten Berge et al. [1986] relationship is used for duration adjustment (Cn x t = k); tenBerge et al. [1986] provided an empirically4estimated n =1.1 for all time-scaling.5†The derived value is the result of the adjusted 30-min value divided by the composite uncertainty factor.6‡Composite uncertainty factor assigned to accountfor interspeciesdifferences and human variability.7±Composite uncertainty factor assigned to account for adjusting from a LOAEL to NOAEL, interspecies differences and human variability.8

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8 

## 3.0 Human Data 1

2

Case studies of fatal acute exposures to airborne acrylonitr ile are reported. However, because concentrations and 3

exposure durations were not indicated, no adequate qu antitative data for human lethality are available. 4

Quantitative data are available, however, for non-lethal i nhalation exposure to acrylonitrile. Workers exposed to 5

16-100 ppm acrylonitrile for 20-45 minutes were reporte d to experience dull headaches, nasal and ocular 6

irritation, discomfort in the chest, nervousness and irr itability [Wilson et al. 1948]. These mild effects were 7

reversible upon removal from exposure a nd are not considered escape-impairing. In another study, exposure to 8

4.6 ppm acrylonitrile for 8 hours resulted in no reported si gns or symptoms of toxicity [Jakubowski et al. 1987]. 9

NAS [2014] cited a personal communication reporting that o ccupational exposure to 12-15 ppm resulted in ocular 10

irritation and headache. These effects were not considered escape-impairing. 11

12

NAS [2014] noted various inhalation cancer assessment s for acrylonitrile, and IARC downgraded acrylonitrile 13

from category 2A - Probably carcinogenic to humans to 2B - Possibly Carcinogenic to Humans , noting that data 14

relative to human carcinogenicity are inadequate and no cau sal association exists. NAS [2014] stated that it is 15

very unlikely that a single acute once-in-a-lifetime e xposure to acrylonitrile could cause cancer in humans. 16



## 4.0 Summary 17

18

The IDLH value for acrylonitrile is based on a leth ality study by Appel et al. [1981] reported a BMCL 05 of 1,784 19

ppm in rats exposed for 30 minutes. Application of a composite uncertainty factor of 30 to account for 20

extrapolation from a lethal concentration threshold in animals, animal to human differences and human 21

variability, yielded an IDLH value for acrylonitrile of 60 ppm . This value is believed to be protective of escape22

impairing, irreversible adverse health effects and deat hs associated with exposures to acrylonitrile for 30 minutes 23

or less. 24

25

It should be noted that the IDLH value for acrylonitrile differs by more than an order of magnitude from the 26

AEGL-2 30-minute value, which is intended to represent an airborne concentration of a substance above which it 27

is predicted that the general population, including suscep tible individuals, could experi ence irreversible or other 28

serious, long-lasting adverse health effects or an impa ired ability to escape [NAS 2001]. The AEGL-2 value for 29

acrylonitrile is based upon transient effects in rats e xposed to 305 ppm for 2 hours [Dudley and Heal 1942; NAS 30

2014]. NIOSH based the IDLH value for acrylonitrile on the 30-minute BMCL 05 value of 1748 ppm from Appel 31

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9 et al. [1981]. The use of this value as the basis of the IDLH value prevented the need for time duration 1

adjustment and allowed for the use of a lower uncertainty factor. Additionally, the IDLH value aligns closely 2

with the AEGL-3 30 minute value for acrylonitrile, which is intended to represent an airborne concentration of a 3

substance above which it is predicte d that the general population, including susceptible individuals, could 4

experience life-threatening health effects or death [NAS 2001]. 5

6

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10 

## 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) [1989] . Odor thresholds for chemicals with established 6

occupational health standards. Fairfax, VA: American Industrial Hygiene Association. 7

8

AIHA [2006]. AIHA Emergency Response Planning (ERP) Committee procedures and responsibilities. Fairfax, 9

VA: American Industrial Hygiene Association. [https://www.aiha.org/get10

involved/AIHAGuidelineFoundation/EmergencyResponseP lanningGuidelines/Documents/ERP-SOPs2006.pdf]. 11

Date accessed: March 17, 2014. 12

13

AIHA [2010a]. AIHA Emergency Response Planning (ERP) Committee procedures and responsibilities. Fairfax, 14

VA: American Industrial Hygiene Association. 15

16

AIHA [2010b]. Emergency response planning guidelines (E RPG) and workplace environmental exposure levels 17

(WEEL) handbook. Fairfax, VA: American Industrial Hygiene Association Press. 18

19

Appel KE, Peter H, Bolt M, Bolt HM [1981]. Interaction of acrylonitrile with hepatic microsomes of rats and 20

men. Toxicol Lett 7 :335–340. 21

22

Benz FW, Nerland DE [2005]. Effect of cytochrome P450 inhibitors and anticonvulsants on the acute toxicity of 23

acrylonitrile. Arch Toxicol 79 :610–614. 24

25

Cipollone R, Ascenzi P, Tomao P, Imperi F, Visca P. Enzymatic detoxification of cyanide: Clues from 26

Pseudomonas aeruginosa Rhodanese. J Mol Micro Biotech 15 : 199-211. 27

28

Drawbaugh RB, Marrs TC [1987]. Interspecies differences in rhodanese (thiosulfate sulfurtransferase, EC 2.8.1.1) 29

activity in liver, kidney and plasma. Comp Biochem Physiol 86B :307–310. 30

31

Dudley HC, Neal PA [1942]. Toxicology of acrylonitrile (vinyl cyanide). I. Study of the acute toxicity. J Ind Hyg 32

Toxicol 24 (2):27–36. 33

34

Ghanayem BI, Farooqui MYH, Elshabrawy O, Mumt az MM, Ahmed AE [1991]. Assessment of the acute 35

acrylonitrile-induced neurotoxicity in rats. Neurotoxicol Teratol 13 :499–502. 36

37

Haskell Laboratory [1942]. Toxicity of vinyl cyanide. Medical Research Project No. M-97. Wilmington, DE: 38

Haskell Laboratory of Industrial Toxicology. 39

40

Haskell Laboratory [1968]. Acute inhalation toxicity in rats with acrylonitrile (inhibited): methacrylonitrile 41

(inhibited) and acetonitrile, October 21, 1968. Submitted to EPA by DuPont, Wilmington, DE, with cover letter 42

dated October 15, 1992. EPA Document No . 88-920009947. Microfiche No. OTS0571605. 43

44

HSDB (Hazardous Substances Data Bank) [ 2014]. Acrylonitrile (CAS No. 107-13-1). 45

[http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen? HSDB]. Date accessed: March 17, 2014. 46

47

IFA (Institut für Arbeitsschutz der Deutschen Gesetzli chen Unfallversicherung) [2014]. GESTIS: database on 48

hazardous substances. 49

### External Review Draft

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This information is distributed solely fo r the purpose of pre-dissemination peer review under applicable information quality

guidelines. It has not been formally disseminated by the Nation al Institute for Occupational Safety and Health. It does not

represent and should not be construed to re present any agency determination or policy.

11 [http://gestis-en.itrust.de/nxt/gateway.dll?f=templates&f n=default.htm&vid=gestiseng: sdbeng]. Date accessed: 1

March 17, 2014. 2

3

Jakubowski M, Linhart I, Pielas G, Kopecky J [1987]. 2- Cyanoethylmercapturic acid (CEMA) in the urine as a 4

possible indicator of exposure to acrylonitrile. Brit J Ind Med 44 :834–840. 5

6

Kedderis GL, Batra R, Turner MJ Jr. [1995]. Conjugation of acrylonitrile and 2-cyanoethylene oxide with hepatic 7

glutathione. Toxicol Appl Pharmacol 135 :9–17. 8

9

NAS (National Academy of Science) [2001]. Standing operating procedures for developing Acute Exposure 10

Guidelines Levels for hazardous chemicals. NAS, National Research Council (NRC), Committee on Toxicology, 11

Subcommittee on Acute Exposure Gu ideline Levels. National Academy Press: Washington, DC. IBSN: 0-309- 12

07553-X. [http://www.epa.gov/oppt/aegl/pubs/sop. pdf]. Date accessed : March 17, 2014. 13

14

NAS (National Academies of Science) [2014]. Acute Expos ure Guideline Levels (AEGLs) for selected airborne 15

chemicals - Volume: 17. Acrylonitrile (CAS Reg. No . 107-13-1). NAS, National Research Council, Committee 16

on Toxicology, Subcommittee on Acute Exposure Guidelin e Levels National Academy Press: Washington, DC. 17

[http://www.epa.gov/oppt/aegl/pubs/acrylonitrile_final_v17_% 20jun2014.pdf]. Data acce ssed: August 1, 2014. 18

19

Nerland EE, Benz FW, Babiuk C [1989]. Effects of cy steine isomers and derivatives on acute acrylonitrile 20

toxicity. Drug Metab Rev 20 :233–246. 21

22

NIOSH (National Institute for Occupational Safety and Health) [1994]. Documentation for immediately 23

dangerous to life or health concentra tions (IDLHs) - acrylonitrile. Cincinnati, OH: U.S. Department of Health and 24

Human Services, Centers for Disease Control and Preven tion, National Institute for Occupational Safety and 25

Health. [http://www.cdc.gov/niosh/idlh/107131. html]. Date accessed: March 17, 2014. 26

27

NIOSH [2004]. NIOSH respirator selection logic. Cinc innati, OH: U.S. Department of Health and Human 28

Services, Centers for Disease Control and Prevention, National Institute for Occupa tional Safety and Health, 29

DHHS (NIOSH) Publication No. 2005-100. [http://www. cdc.gov/niosh/docs/2005-100/pdfs/2005-100.pdf]. Date 30

accessed: March 17, 2014. 31

32

NIOSH [2013]. NIOSH Current Intelligence Bulletin 66: Deri vation of Immediately Dangero us to Life or Health 33

(IDLH) values. Cincinnati, OH: U.S. Department of Hea lth and Human Services, Centers for Disease Control and 34

Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 2014-100. 35

[http://www.cdc.gov/niosh/docs/2014-100/pdfs/2014- 100.pdf]. Date accessed : March 17, 2014. 36

37

NIOSH [2014]. NIOSH pocket guide to chemical hazards . Cincinnati, OH: U.S. Department of Health and 38

Human Services, Centers for Disease Control and Preven tion, National Institute for Occupational Safety and 39

Health, DHHS (NIOSH) Publication No. 2005-149. [http://www.cdc.gov/niosh/npg/]. Date accessed: March 17, 40

2014. 41

42

NLM (National Library of Medicine) [2014]. ChemIDplus lite: acrylonitrile. 43

[http://chem.sis.nlm.nih.gov/chemidplus/ProxyServlet? objectHandle=DBMaint&actionH andle=default&nextPage 44

=jsp/chemidlite/ResultScreen.jsp&TXTSUPERLI STID=0000107131]. Date acc essed: March 17, 2014. 45

46

OSHA [2014]. Chemical sampling information: acrylonitrile. 47

[https://www.osha.gov/dts/chemicalsampling/data/CH _217300.html]. Date accessed: March 17, 2014. 48

49

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12 Roberts AE, Kedderis GL, Turner MJ, Rickert DE, Swe nberg JA [1991]. Species comparison of acrylonitrile 1

expoxidation by microsomes from mice, rats and humans: Re lationship to epoxide concentrations in mouse and 2

rat blood. Carcinogenesis 12 :401–404. 3

4

Saillenfait, AM, Bonnet P, Guenier JP, De Ceaurriz J [ 1993]. Relative developmen tal toxicities of inhaled 5

aliphatic mononitriles in rats. Fundam Appl Toxicol 20 (3):365-375. 6

7

Sakurai, H, Onodera M, Utsunomiya T, Minakuchi H, Iwai H, Mutsumura H [1978]. Health effects of 8

acrylonitrile in acrylic fibre factories. Br J Ind Med 35 (3): 219-225. 9

10

Schwanecke R [1966]. Safety hazards in the handling of acr ylonitrile and methacrylonitrile (in German). Zentralbl 11

Arbeitsmed Arbeitsschutz 16 (1):1–3. 12

13

ten Berge WF, Zwart A, Appelman LM [1986]. Concentra tion-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

19

Vernon PA, Dulak LH, Deskin R [1990]. Acute toxicologic evaluation of acrylonitrile. J Amer Coll Toxicol Part 20

B 1 :114–115. 21

22

WIL Research Laboratories [2005]. Acute inhalation toxici ty study of acrylonitrile in albino rats. Ashland, OH: 23

WIL Research Laboratories, WIL-542001. 24

25

Wilson RH, Hough GV, McCormick WE [1948]. Medical pr oblems encountered in the manufacture of American26

made rubber. Ind Med 17 :199–207. 27