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policy. 1

2

3

4

5

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## I MMEDIATELY 

## D ANGEROUS TO 

## L IFE OR 

## H EALTH 

## (IDLH) V ALUE 

## P ROFILE 7

8

9

10



### FOR 11

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14



## 1,3-B UTADIENE 15

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## [CAS N O



## . 106-99-0] 19

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25

Department of Health and Human Services 26

Centers for Disease Control and Prevention 27

National Institute for Occupa tional Safety and Health 28

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30External Review Draft Document

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

policy. 

## Disclaimer 1

2

Mention of any company or product does not constitute endorsement by the National Institute for Occupational 3

Safety and Health (NIOSH). In add ition, citations to Web sites extern al to NIOSH do not constitute NIOSH 4

endorsement of the sponsoring organizations or thei r programs or products. Furthermore, NIOSH is not 5

responsible for the content of these Web sites. 6

7



## Ordering Information 8

9

To receive this document or information about other o ccupational safety and health topics, contact NIOSH: 10

11

Telephone: 1-800-CDC-INFO (1-800-232-4636) 12

TTY: 1-888-232-6348 13

E-mail: cdcinfo@cdc.gov 14

Or visit the NIOSH Web site: www.cdc.gov/niosh 15

16

For a monthly update on news at NIOSH, subscribe to NIOSH eNews by visiting www.cdc.gov/niosh/eNews. 17

18

DHHS (NIOSH) Publication No. XXX 19

20

21External Review Draft Document

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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 pr iority chemicals is outlined in the Current Intelligence 22

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

provides 1) an update on the scientific basis and risk asse ssment methodology used to de rive IDLH values, 2) the 24

rationale and derivation process for ID LH values, and 3) a demonstration of the derivation of scientifically 25

credible IDLH values using available data resources. 26

27

The purpose of this technical report is to present the IDLH value for 1,3-butadiene (CAS # 106-99-0). 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

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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 1External Review Draft Document

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policy. 

## Table of Contents 1

FOREWORD

............................................................................................................................... ................................. III 2

ABBREVIATIONS

............................................................................................................................... ........................ VI 3

GLOSSARY

............................................................................................................................... .................................. VII 4

ACKNOWLEDGMENTS

............................................................................................................................... ............... X 5

1.0 INTRODUCTION

............................................................................................................................... ............... 1 6

1.1 O VERVIEW OF THE IDLH V ALUE FOR 1,3-B UTADIENE

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

1.2 P URPOSE

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

1.3 G ENERAL S UBSTANCE I NFORMATION

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

2.0 ANIMAL TOXICITY DATA

............................................................................................................................. 4 10

3.0 HUMAN DATA

............................................................................................................................... .................. 7 11

4.0 SUMMARY

............................................................................................................................... ......................... 7 12

5.0 REFERENCES

............................................................................................................................... .......................... 9 13

14

15

16

17

18External Review Draft Document

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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 50 median lethal concentration 12

LC Lo lowest concentration of a chemical that caused death in humans or animals 13

LEL lower explosive limit 14

LOAEL lowest observed adverse effect level 15

mg/m 3 milligram(s) per cubic meter 16

NAC National Advisory Committee 17

NAS National Academy of Sciences 18

NIOSH National Institute for O ccupational 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

RD 50 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 32External Review Draft Document

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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 levels used during rare events or single once-in-a8

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

threshold exposure limits are designed to protect the ge neral 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 duration (24 hours or less) of the human population 14

(including sensitive subgroups) that is likely 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 limitations 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

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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 sign 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 e xposure is likely to cause death or imme diate 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 concentr ation 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 concentration of a substa nce 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 the deaths resulting from acute toxicity studies. May 33

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

death. 35

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

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

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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 concen tration 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 ar e 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 deve loped by OSHA (29 CFR 1910.1000) or 11

MSHA (30 CFR 57.5001) for allowable occupational air borne exposure concentra tions. 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 from which dose extrapolation is initiated. 15

This point can be the lower bound on dose for an estima ted 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 concentration of a substa nce in the air that is est imated 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 establishe d 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 occupational exposure to airborne 27

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

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

that nearly all workers may be rep eatedly exposed, day 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

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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 effects 2

related to occupational chemical expos ures expressed as a TWA or ceiling limit. 3

4

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8

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10

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## Acknowledgments 18

19

This document was developed by the Education and Info rmation Division (Paul Schulte, Ph.D., Director). G. 20

Scott Dotson, Ph.D., was the project officer and lead NIOS H author for this technical report. The basis for this 21

document was a report contracted by NIOSH and prepar ed by Andrew Maier, Ph.D., Ann Parker, and Lynn 22

Haber, Ph.D. (Toxicology Excellen ce for Risk Assessment [TERA]). 23

24



### Education and Information Division 25

Devin Baker, M.Ed. 26

Charles L. Geraci, Ph.D. 27

Thomas J. Lentz, Ph.D. 28

Richard Niemeier, Ph.D. 29

Chris Sofge, Ph.D. 30

31

NIOSH would like to acknowledge the contribution of th e following subject matter experts for their critical 32

technical review of this report. 33

34

Michael S. Bisesi, Ph.D., R.E.H.S., C.I.H., Senior Asso ciate Dean for Academic Affairs; Director, Center 35

for Public Health Practice; Interim Chair & Asso ciate Professor, Division of Environmental Health 36

Science, College of Public H ealth, Ohio State University 37

38

Mary A. Fox, Ph.D., Assistant Professor; Co-Direct or, Risk Sciences and Public Policy Institute; 39

Department of Health Policy and Management, Bl oomberg School of Public Health, Johns Hopkins 40

University 41External Review Draft Document

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1

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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 1,3-Butadiene 2

3

IDLH Value: 1,400 ppm (>10% LEL) 4

5

Basis for IDLH Value: Despite the availability of toxicity data capab le of being used to calculate health-based 6

estimates for 1,3-butadiene (see Tables 4 and 5), these est imates are all are greater than 10% of the lower 7

explosive limit (>10% LEL). NIOSH has adopted a thres hold of 10% LEL as a default basis for the IDLH values 8

based on explosivity concerns [NIOSH 2014]. Safety considerations related to the potential hazard of explosion 9

must be taken into account and the IDLH value is set at the 10% LEL for 1,3-butadiene of 1,400 ppm

. 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 1,3-butadiene and (2) the rationale behind the Immediately Dangerous to Life or Health (IDLH) 14

value for 1,3-butadiene. IDLH values are developed based on the scientific rationale and logic outlined in the 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 1,3-butadiene, the in-depth lite rature search was conducted through February 2014. 23

24



### 1.3 General Substance Information 25

26

Chemical: 1,3-Butadiene 27

CAS No: 106-99-0 28

Synonyms: Butadiene; Divinyl; Biethylene; Erythrene * 29

Chemical category: Unsaturated, aliphatic hydrocarbons; Organic gases † 30

31External Review Draft Document

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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

Structural formula: 4

5

6

7

Table 1 highlights selected physiochemical properties of 1,3-butadiene relevant to IDLH conditions. Table 2 8

provides alternative exposure guidelines for 1,3-butadie ne. Table 3 summarizes the Acute Exposure Guidelines 9

Level (AEGL) values for 1,3-butadiene. 10

11

Table 1: Physiochemical Properties of 1,3-Butadiene 12

13

Property Value

Molecular weight 54.09 *

Chemical formula C 4 H 6 Description Colorless gas

Odor Mild aromatic or gasoline-like

Odor Threshold 0.45 ppm *

UEL 16.3% †

LEL 1.4% †

Vapor pressure 2110 mmHg at 25°C (77°F) ‡

Flash point -76.11°C (-105°F) ‡

Ignition temperature 414.44°C (788°F) ‡

Solubility Slightly soluble in water †

Abbreviation: °C – Celsius; °F – Fahrenheit; mmHg – millimeter mercury; LEL – lower explosive limit; UEL – upper explosive limit 14

* AIHA [1989] 15

† IFA [2013] 16

‡ HSDB [2013] 17

18

19

Table 2: Alternative Exposure Guidelines for 1,3-Butadiene 20

21

Organization Value

Revised (1994) IDLH value 2000 ppm [LEL]

NIOSH REL Not available

OSHA PEL [2014] 1 ppm TWA; 5 ppm STEL

ACGIH TLV [2014] 2 ppm, TWA

AIHA ERPG [2010] ERPG-1: 10 ppm; ERPG-2: 200 ppm; ERPG-3: 5,000 ppm

AIHA WEEL [2010] Not available

Abbreviation: ACGIH – American Conference of Governmental I ndustrial Hygienists; AIHA – Am erican Industrial Hygiene 22

Association; ERPG – Emergency Re sponse Preparedness Guidelines; IDLH – immediatel y dangerous to life or health; NIOSH – Nationa l 23

Institute for Occupational Safety and Hea lth; OSHA – Occupational Safety and Health Administration; PEL – permissible exposure limit; 24

REL – recommended exposure limit; SCP – Standards Completion Program; TWA – time-weighted average; WEEL – workplace 25

environmental exposure level 26 H 2 C CH 2External Review Draft DocumentMarch 20153This 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 1,3-Butadiene12Classification 10-min 30-min 1-hour4-hour 8-hour Endpoint [reference]AEGL-1 670 ppm1,500 mg/m3670 ppm1,500 mg/m3670 ppm1,500 mg/m3670 ppm1,500 mg/m3670 ppm1,500 mg/m3Difficulty in focusing inhumans [Carpenter et al. 1944]AEGL-2 6,700 ppm*15,000 mg/m36,700 ppm*15,000 mg/m35,300 ppm*12,000 mg/m33,400 ppm*7,500 mg/m32,700 ppm*6,000 mg/m3No effects in humans[Carpenter et al. 1944]AEGL-3 27,000 ppm†60,000 mg/m327,000 ppm†60,000 mg/m322,000 ppm†49,000 mg/m314,000 ppm‡31,000 mg/m36,800 ppm*15,000 mg/m3Lethality in rats[Shugaev 1969]Abbreviation: AEGL – acute exposure guideline levels; mg/m3– milligrams per cubic meter; min – minute; NR – not recommended due to insufficient data; ppm – parts per million3References: NAS [2008]4*Safety considerations against the hazard(s)of explosion(s) must be taken into account.5†Extreme safety considerations against the hazard(s) of explosion(s) must be taken into account.6‡Extreme safety considerations against the hazard(s) of explosion(s) must be taken into account.7External Review Draft Document

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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

Several lethality studies in animals were available. The lowest LC 50 value of 122,000 ppm was reported by 3

Shugaev [1969]. In this study, mice were exposed to varyi ng concentrations of 1,3-butadiene for 2 hours. Prior to 4

death, deep narcosis was seen. The authors also reported a LC 16 value of 91,000 ppm and a LC 84 value of 169,000 5

ppm. 6

7

In a carcinogenicity study, Bucher et al. [1993] exposed mice to 0, 1,000, 5,000, or 10,000 ppm of 1,3-butadiene 8

for a single 2-hour period and held the animals for 2 years prior to microscopic examination of tissues. Even at 9

the highest concentration, there was no mortality. No effects were reported. 10

11

Although metabolism is qualitatively similar across species, there are substantial quantita tive differences, with the 12

toxic epoxide metabolite formed at much higher levels in mice than in rats. The higher susceptibility of mice 13

compared to rats is attributed to this difference, toge ther with the higher ventilation rate in mice. Based on the 14

lower ventilation rate in humans and the limited in vitr o metabolism data, humans are considered to be more 15

similar to rats than mice. 16

17

1,3-butadiene is carcinogenic to rats and mice, with mi ce being more susceptible than rats [IARC 1999; EC 2002; 18

USEPA 2002]. EC [2002] and USEPA [ 2002] concluded that 1,3-butadiene is carcinogenic to humans, while 19

IARC [1999] concluded that there is limited evidence fo r the carcinogenicity of 1,3-butadiene. No increase in 20

tumor incidence was observed in the study by Bucher et al. [1993], in which mice were exposed to concentrations 21

up to 10,000 ppm for a single 2-hour period and held for 2 years prior to microscopic examination of tissues. 22

Based on this acute study, no additional factor was a dded to account for 1,3-butadiene carcinogenicity, even 23

though extrapolation from the chronic data indicates a risk greater than 1 x 10 -3 for a 30-minute exposure at the 24

level of the IDLH value. 25

26

Table 4 summarizes the LC data identified in animal st udies and provides 30-minute equivalent derived values for 27

1,3-butadiene. Table 5 provides non-lethal data reporte d in animal studies with 30-minute equivalent derived 28

values. Information in these tables includes species of test animals, toxicological metrics (i.e., LC, BMCL, 29

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

applied to calculate the derived values. 31External Review Draft DocumentMarch 20155This 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 1,3-Butadiene12Reference Species(reference)LC50(ppm)OtherLethality(ppm)Time(min)Adjusted30-minConcentration*(ppm)CompositeUncertaintyFactorDerivedValue(ppm)†Shugaev [1969] Mouse 122,000 -- 120 193,663 30±6,455Shugaev [1969] Mouse--91,000‡120 144,454 10^14,445Shugaev [1969] Rat 128,000 -- 240 256,000 30±8,533Von Oettingen [1940] Rat 130,000 -- 240 260,000 30±8,667AIHA [2010] Rat -- 200,000§30 200,000 30±6,667Shugaev [1969] Rat -- 79,000‡240 158,000 10^15,800Shugaev [1969] Rat -- 207,000**240 414,000 10^41,4003Abbreviation:LC – lethal concentration; LC50– median lethal concentration; LCLo– lowest concentration of a chemical that caused death in humans or animals; min – minute; ppm – parts4per million56*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 were7available, therefore the default values were used, n = 3 for exposures greater than 30 minutes and n = 1 for exposures less than 30 minutes.8†The derived value is the result of the adjusted 30-minute concentration divided by the composite uncertainty factor.9±Composite uncertainty factor to account for adjustment of LC50values to LC01values, use of lethal concentration threshold in animals, interspecies differences and10human variability.11‡Reported as LC1612^Composite uncertainty factor to account foruse of lethal concentration threshold inanimals, interspecies differences and human variability.13§Deaths in 2/5 rats14**Reported as LC84151617External 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 5: Non-lethal Concentration Data for 1,3-Butadiene12Reference Species(reference)NOAEL(ppm)LOAEL(ppm)Time(min)Adjusted30-minConcentration*(ppm)CompositeUncertaintyFactorDerivedValue(ppm)†Bucher et al. [1993] Mouse 10,000 -- 120 15,874 3±5,291Carpenter et al. [1944] Human -- 4,000 360 9,160 3‡3,053Carpenter et al. [1944] Human -- 2,000 420 4,820 3‡1,607Carpenter et al. [1944] Human -- 8,000 480 20,159 3‡6,720Abbreviation:NOAEL – no observed adverse effect level;min – minute; LOAEL – lowest observed adverse effect level; ppm– parts per million34*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 to account forinterspecies differences and human variability.8‡Composite uncertainty factor to account for adjustment froma severe effect threshold in humans and human variability.9External Review Draft Document

March 2015

7

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 information was located on concentrations lethal to humans. Information regarding human exposure to 1,3- 3

butadiene is available from several clinical and ep idemiological studies. Larionov et al. [1934] exposed 4

volunteers to 10,000 ppm of 1,3-butadiene for 5 minutes. Blood pressure and respiration were monitored, but 5

only nose and throat irritation were reported. Exposure to 10,000 ppm for 5 minutes resulted in slight irritation 6

and dryness of the nose and mouth with some increase in pulse rate but no effect on blood pressure or respiration 7

[Shugaev 1968]. 8

9

Carpenter et al. [1944] exposed two males to 2,000 ppm 1,3-butadiene for 7 hours, 4,000 ppm for 6 hours, or 10

8,000 ppm for 8 hours, with a 1-hour lunch break in the middle of the exposure period; exposure concentrations 11

were monitored regularly. Effects reported included slight smarting of the eyes and difficulty in focusing. There 12

was no effect on a tapping test or steadiness test. 13



## 4.0 Summary 14

15

Despite the availability of toxicity data capable of bei ng used to calculate health-b ased estimates for 1,3-butadiene 16

(see Tables 4 and 5), these estimates are all greater than 10% of the lower explosive limit (>10% LEL). NIOSH 17

has adopted a threshold of 10% LEL as a default basis for the IDLH values based on explosivity concerns 18

[NIOSH 2014]. Safety considerations related to the pote ntial hazard of explosion must be taken into account and 19

the IDLH value is set at the 10% LEL for 1,3-butadiene of 1,400 ppm

. 20

21

If the explosive hazards of 1,3-butadiene are controlled or toxicity issues are the prim ary concern, a health-based 22

IDLH value could be derived from numerous datasets. Based on effects seen in humans, a NOAEL for escape23

impairing effects was identified at 8,000 ppm for a 6- hour exposure [Carpenter et al. 1944]. The exposure 24

concentration adjusted for a 30-minute exposure is 20,159 ppm. A composite uncertainty factor of 3 was applied 25

to account for extrapolation from a severe effect thres hold in humans, taking into account uncertainties with 26

regard to the quality of the study. This results in an IDLH value of 6,720 ppm. This value is supported by 27

lethality studies. Shugaev [1969] reported a rat 4-hour LC 50 value of 128,000 ppm, while Bucher et al. [1993] 28

reported a mouse 2-hour LC 50 value of 122,000 ppm. Extrapolating to a 30-minute duration and applying a 29

composite uncertainty factor of 30 to account for extra polation from a concentration that is lethal to animals, 30External 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. animal to human differences and human variability results in potential IDLH values of 8,533 ppm and 6,455 ppm, 1

respectively. Based on the overall data, and taking into acc ount that the rat is a better model for humans than the 2

mouse, this would result in a health-based IDLH value of 6,720 ppm. 3External 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. 

## 5.0 References 1

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

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

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Association Press. 11

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occupational health standards. Fairfax, VA: Am erican Industrial Hygiene Association, p. 13. 14

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Bucher JR, Melnick RL, Hildebrandt PK [1993]. Lack of carcinogenicity in mice exposed once to high 16

concentrations of 1,3-butadiene. J Nat Cancer Inst 85 :1866–1867. 17

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Carpenter CP, Shaffer CB, Weil CS, Smyth HF Jr [1944 ]. Studies on the inhalation of 1,3-butadiene; with a 19

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human. J Ind Hyg Toxicol 26 (3):69–78. 21

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[http://www.epa.gov/oppt/aegl/pubs/butadiene_interim_d ec_2008.pdf]. Date acce ssed: March 17, 2014. 44

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dangerous to life or health concentrations (IDLHs) - me thyl isocyanate. Cincinnati, OH: U.S. Department of 47External Review Draft Document

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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. Health and Human Services, Centers for Disease Contro l and Prevention, National Institute for Occupational 1

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