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policy.

i 1

2

3

4

5

6



## I MMEDIATELY 

## D ANGEROUS TO 

## L IFE OR 

## H EALTH 

## (IDLH) V ALUE 

## P ROFILE 7

8

9

10



### FOR 11

12

13

14



## F URAN 15

16

17



## [CAS N O



## . 110-00-9] 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

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policy.

ii 

## 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 19External Review Draft Document

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iii 

## 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 ID LH value for furan (CAS # 110-00-9). The scientific 28

basis, toxicologic data and risk assessment approach u sed to derive the IDLH valu e are summarized to ensure 29

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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iv Centers for Disease Control and Prevention 1External Review Draft Document

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policy.

v 

## Table of Contents 1

FOREWORD

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

ABBREVIATIONS

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

GLOSSARY

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

ACKNOWLEDGMENTS

............................................................................................................................... .............. XI 5

1.0 INTRODUCTION

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

1.1 O VERVIEW OF THE IDLH V ALUE FOR F URAN

......................................................................................................................... 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

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

14

15

16

17

18External Review Draft Document

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vi 

## 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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vii 

## 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

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policy.

viii 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

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policy.

ix 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

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policy.

x 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

4External Review Draft Document

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policy.

xi 

## 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

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policy.

1 

## 1.0 Introduction 1



### 1.1 Overview of the IDLH Value for Furan 2

3

IDLH Value: 43 ppm (120 mg/m 3 ) 4

5

Basis for IDLH Value: The IDLH value for furan is based on a rat LOAEL of 1,014 ppm for a 1- hour exposure 6

reported by Terrill et al. [1989] for potential escape- impa iring effects, such as respiratory distress. The 30- 7

minute duration adjusted concentration for the LOAEL is 1, 278 ppm. Applying a composite uncertainty factor of 8

30 to account for extrapolation from a concentration that cau ses an escape- impairing effect in animals, animal to 9

human differences, and human variability, results in an IDLH value of 43 ppm

. 10

11



### 1.2 Purpose 12

13

This IDLH Value Profile presents (1) a brief summary of technical data associated with acute inhalation 14

exposures to furan and (2) the rationale behind the Immedi ately Dangerous to Life or Health (IDLH) value for 15

furan. IDLH values are developed based on the scientific rationale and l ogic outlined in the Current Intelligence 16

Bulletin (CIB) 66: Derivation of Immediately Dangerous to Life or Health (IDLH) Values [NIOSH 2013]. As 17

described in CIB 66, NIOSH performs in-d epth literature searches to ensure th at all relevant data from human and 18

animal studies with acute exposures to the substance are identified. Information included in CIB 66 on the 19

literature search includes pertinent da tabases, key terms, and guides for eval uating data quality and relevance for 20

the establishment of an IDLH value. The information th at is identified in the in -depth literature search is 21

evaluated with general considerations that include description of studies (i.e., species, study protocol, exposure 22

concentration and duration), health endpoint evaluated, and critical e ffect levels (e.g., NOAELs, LOAELs, LC 50 23

values). For furan, the in-depth literatu re search was conducted through February 2014. 24

25



### 1.3 General Substance Information 26

27

Chemical: Furan 28

CAS No: 110-00-9 29

Synonyms: 1,4-Epoxy-1,3-butadiene; Axole; Oxole; Divinylene oxide * 30

Chemical category: Oxygen heterocycles † 31External Review Draft Document

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policy.

2 Structural formula: 1

2

3

4

5

6

Table 1 highlights selected physiochemical properties of furan relevant to IDLH conditions. Table 2 provides 7

alternative exposure guidelines for furan. Table 3 su mmarizes the Acute Exposure Guidelines Level (AEGL) 8

values for furan. 9

10

Table 1: Physiochemical Properties of Furan 11

Property Value

Molecular weight 68.07 ‡

Chemical formula C 4 H 4 O

Description Colorless liquid

Odor Strong ethereal; chloroform-like

Odor Threshold Not available

UEL 14.3% †

LEL 2.3% †

Vapor pressure 600 mmHg at 25°C (77°F) ‡

Flash point -35.56°C (-32°F) ‡

Ignition temperature 390°C (734°F) †

Solubility Sparingly soluble in water †

Abbreviation: °C – Celsius; °F – Fahrenheit; mmHg – millimeter mercury; LEL – lower explosive limit; UEL – upper explosive limit 12

* NLM [2014] 13

† IFA [2014] 14

‡ HSDB [2014] 15

16

Table 2: Alternative Exposure Guidelines for Furan 17

Organization Value

Original (SCP) IDLH value [NIOSH 2014] None

NIOSH REL [2014] Not available

OSHA PEL [2014] Not available

ACGIH TLV [2014] Not available

AIHA ERPG [2013] Not available

AIHA WEEL [2013] Worker exposure by a ll routes should be minimized to the

fullest extent possible.

Abbreviation: ACGIH – American Conference of Governmental I ndustrial Hygienists; AIHA – Am erican Industrial Hygiene 18

Association; ERPG – Emergency Re sponse Preparedness Guidelines; IDLH – immediatel y dangerous to life or health; NIOSH – Nationa l 19

Institute for Occupational Safety and Hea lth; OSHA – Occupational Safety and Health Administration; PEL – permissible exposure limit; 20

REL – recommended exposure limit; SCP – Standards Completion Program; WEEL – workplace envi ronmental exposure level 21 OExternal Review Draft DocumentMay 2015This 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.3Table 3: AEGL Values for Furan12Classification 10-min 30-min 1-hour4-hour 8-hour Endpoint [reference]AEGL-1 NR NR NR NR NR Not applicableAEGL-2 12.0 ppm33.0 mg/m38.5 ppm24.0 mg/m36.8 ppm19.0 mg/m31.7 ppm4.7 mg/m30.85 ppm2.4 mg/m31,014 ppm for 1 hour: threshold foradverse effects in rats; clinical signs:although the severity of respiratorydistress and increased secretoryresponse not reported, no decrease inbody weight occurred(Terrill et al. 1989)AEGL-3 35.0 ppm97.0 mg/m324.0 ppm67.0 mg/m319.0 ppm53.0 mg/m34.8 ppm13.0 mg/m32.4 ppm6.7 mg/m32,851 ppm for 1 hour: threshold forlethality in rats (Terrill et al. 1989)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 [2010]4External Review Draft Document

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policy.

4 

## 2.0 Animal Toxicity Data 1

Lethality studies were conducted in three different speci es. Koch and Cahan [1926] exposed a single rat and 2

rabbit via inhalation of furan from saturated cotton held ove r the nose. Both animals struggled; the rat died the 3

following day and the rabbit died shortly after collapsing from the exposure. There was no information available 4

on the exposure concentration because of the nonstandard exposure method. Egle and Gochberg [1979] reported 5

a 1-hour LC 50 of 42 ppm in mice exposed to furan vapor; no i ndividual concentrations were reported and hypoxia 6

contributed to the mortality observed. In addition to th e evaluation of lethality data, Terrill et al. [1989] also 7

evaluated non-lethal effects and repor ted a LOAEL of 1,014 ppm for a 1-hour exposure in rats, based on observed 8

respiratory distress. Symptoms of intoxication were seen at concentrations between the LOAEL and reported 9

lethal concentrations. These symptoms included increased respiratory rate, decreased blood pressure, 10

convulsions, complete anesthesia and death from asphyxia. In a 2-year NTP [1993] study, there was clear 11

evidence of carcinogenic activity in rats (based on liver neoplasms and leukemia) and in mice (based on liver and 12

adrenal gland tumors). However, no cancer pot ency values have been developed for furan. 13

14

Table 4 summarizes the LC data identified in animal st udies and provides 30-minute equivalent derived values for 15

furan. Table 5 provides non-lethal data reported in animal studies with 30-minute equivalent derived values. 16

Information in these tables includes species of test an imals, toxicological metrics (i.e., LC, NOAEL, LOAEL), 17

adjusted 30-minute concentration, and th e justification for the composite uncer tainty factors applied to calculate 18

the derived values. 19External Review Draft DocumentMay 2015This 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.5Table 4: Lethal Concentration Data for Furan12Reference Species(sex)LC50(ppm)LCLo(ppm)Time(min)Adjusted30-minuteConcentration*(ppm)CompositeUncertaintyFactorDerivedValue(ppm)†Terrill et al. [1989] Rat(males)3,398 -- 60 4,281 100‡43Terrill et al. [1989] Rat(females)3,550 -- 60 4,473 100‡45Terrill et al. [1989] Rat(both sexes)3,464 -- 60 4,364 100‡443Abbreviation: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 were available,7therefore 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.11121314151617181920212223242526External Review Draft DocumentMay 2015This 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.6Table 5: Non-lethal Concentration Data for Furan12Reference Species(reference)NOAEL(ppm)LOAEL(ppm)Time(min)Adjusted30-minuteConcentration*(ppm)CompositeUncertaintyFactorDerivedValue(ppm)†Terrill et al. [1989]+Rat(both sexes)-- 1,014 60 1,278 30‡43Abbreviation: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 were available,5therefore 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+Identified study is the primary basis of the IDLH value for furan.8‡Composite uncertainty factor assigned to account for adjusting from a LOAEL to NOAEL, interspecies differences and human variability.9External Review Draft Document

May 2015

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.

7 

## 3.0 Human Data 1

No human studies for furan were found. 2



## 4.0 Summary 3

A single acute lethality study in the rat provides the only adequate toxicity data for development of an IDLH 4

value. The study reports a 1-hour LC 50 value of 3,464 ppm for both sexes combined [Terrill et al. 1989]. This 5

study also identified a LOAEL of 1,014 ppm for a 1-hour exposure for potential escape-impairing effects, such as 6

respiratory distress. This LOAEL is more appropriate as the basis of the IDLH value because it protects against 7

potential escape-impairing effects such as respiratory dist ress. The 30-minute duration adjusted concentration for 8

the LOAEL is 1,278 ppm. Applying a composite uncertain ty factor of 30 to account for extrapolation from a 9

concentration that causes an escape-impairing effect in an imals, animal to human differences, human variability 10

and potential cancer risks, results in an IDLH value of 43 ppm

. 11

12

It should be noted that the IDLH value for furan differs by more than an order of magnitude from the AEGL-2 30- 13

minute value, which is intended to represent an airborne concentration of a substance above which it is predicted 14

that the general population, including susceptible individua ls, could experience irrevers ible or other serious, long15

lasting adverse health effects or an impaired ability to escape [NAS 2001]. The AEGL-2 value for furan is based 16

on a threshold effect (i.e., respiratory distress and increased secretory response) in male and female rats exposed 17

at 1,014 ppm for 1 hour [Terrill et al. 1989, NAS 2010]. NIOSH based the IDLH value for furan on the same data 18

set and endpoint. The differences between the AEGL-2 valu e for 30-minute and the IDLH value can be attributed 19

to the use of a much larger uncertainty factor during the derivation of the AEGL values. A total uncertainty factor 20

and modifying factor of 150 were applied to account for limited data, interspecies variability and human 21

variability to derive the AEGL-2. In comparison, NIOSH a pplied a composite uncertainty factor of 30 to account 22

for adjusting from a LOAEL to NOAEL, inters pecies differences and human variability. 23

24External Review Draft Document

May 2015

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.

8 

## 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) [2006]. AIHA Emergency Response Planning (ERP) 6

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

https://www.aiha.org/get8

involved/AIHAGuidelineFoundation/EmergencyResponseP lanningGuidelines/Documents/ERP-SOPs2006.pdf. 9

10

AIHA (American Industrial Hygiene Association) [2013] . Emergency response planning guidelines (ERPG) and 11

workplace environmental exposure levels (WEEL) handbo ok. Fairfax, VA: American Industrial Hygiene 12

Association Press, https://www.aiha.org/get13

involved/AIHAGuidelineFoundation/EmergencyRespon sePlanningGuidelines/Pages/default.aspx. 14

15

Egle JL, Gochberg BJ [1979]. Respiratory retention and acute toxicity of furan. Am Ind Hyg Assoc J 40 :310–314. 16

17

HSDB (Hazardous Substances Data Bank) [2014]. HSDB . National Library of Medicine, Bethesda, MA, 18

http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?HSDB. 19

20

IFA (Institut für Arbeitsschutz der Deutschen Gesetzli chen Unfallversicherung) [2014]. GESTIS: Database on 21

hazardous substances, 22

http://gestis23

en.itrust.de/nxt/gateway.dll/gestis_en/000000.xml?f=t emplates$fn=default.htm $vid=gestiseng:sdbeng$3.0. 24

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Koch EM, Cahan MH [1926]. Physiologic action of furane. J Pharmacol Exp Ther 26 :281–285. 26

27

NAS (National Academy of Sciences) [2001]. Standing operating procedures for developing acute exposure 28

guideline levels for hazardous chemicals. National A cademy of Science, Committee on Toxicology, Board of 29

Environmental Studies and Toxicology, National Research Council. Washington, DC: National Academy Press, 30

http://www.nap.edu/. 31

32

NAS [2010]. Acute Exposure Guideline Levels (AEGLs) for selected airborne chemicals. Vol. 9. - Chapter 3: 33

Furan. National Academy of Science, Committee on Toxicology and Committee on Acute Exposure Guideline 34

Levels, Board on Environmental Studies and Toxicology, National Research Council. Washington, DC: National 35

Academy Press, http://www.epa.gov/oppt/aegl/pubs/fur an_final_volume9_2010.pdf. Data accessed: August 1, 36

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/05-100.pdf. 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 H ealth and Human Services, Centers for Disease Control 45

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

100, http://www.cdc.gov/niosh/docs/2014-100/. 47External Review Draft Document

May 2015

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.

9 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/. 4

5

NLM (National Library of Medicine) [2014]. ChemIDplus lite. National Li brary of Medicine, Bethesda, Md, 6

http://chem.sis.nlm.nih.gov/chemidplus/ProxyServlet? objectHandle=DBMaint&actionH andle=default&nextPage 7

=jsp/chemidlite/ResultScreen. jsp&TXTSUPERLISTID=0000110009. 8

9

NTP (National Toxicology Program) [1993]. Toxicology and carcinogenesis studies of furan (CAS No. 110-00-9) 10

in F344/N rats and B6C3F1 mice (gavage studies). Resear ch Triangle Park, NC: U.S. Department of Health and 11

Human Services, National Toxicology Program, NIH Publication No. 93-2857, NTP TR 402. 12

13

OSHA (Occupational Safety and Health Administration) [2014]. Occupational Safety and Health Standards. 29 14

CFR 1910. Subpart Z -- Toxic and Hazardous Substances. OSHA; Washington, DC, 15

http://www.osha.gov/pls/oshaweb/owadisp.s how_document?p_table=s tandards&p_id=9992. 16

17

ten Berge WF, Zwart A, Appelman LM [1986]. Concentra tion-time mortality response relationship of irritant and 18

systematically acting vapors and gases. J Haz Mat 13 :301–309. 19

20

Terrill JB, Van Horn WE, Robinson D, Thomas DL [1989]. Acute inhalation toxicity of furan, 2 methylfuran, 21

furfuryl alcohol, and furfural in the rat. Am Ind Hyg Assoc J 50 :A359–A361. 22

23

USEPA (United States Environmental Protection Agency) [ 2014]. Integrated Risk Information System (IRIS): 24

glossary. Washington, DC: U.S. Environmental Prot ection Agency, National Center for Environmental 25

Assessment, http://www.epa.gov/iris/ index.html. 26