Nitrogen Dioxide

CAS® No. 10102-44-0

VALUE PROFILE

IDLH

IMMEDIATELY 

DANGEROUS to

LIFE or HEALTH

Centers for Disease Control

and Prevention

National Institute for Occupational 

Safety and Health
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O N O

Immediately Dangerous to Life or Health (IDLH) Value Profile

Nitrogen Dioxide

[CAS® No. 10102-44-0]

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Centers for Disease Control and Prevention

National Institute for Occupational Safety and Health
ii IDLH Value Profile for Nitrogen Dioxide

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Suggested Citation

NIOSH [2017]. Immediately dangerous to life or health (IDLH) value profile: Nitrogen dioxide. By Dotson GS, Maier A, Parker A, Haber L. Cincinnati, OH: U.S. Department of Health 

and Human Services, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication 2017-202.

DHHS (NIOSH) Publication No. 2017-202

September 2017
IDLH Value Profile for Nitrogen Dioxide	 iii

Foreword

Chemicals are a ubiquitous component of the modern workplace. Occupational exposures 

to chemicals have the potential to adversely affect the health and lives of workers. Acute 

or short-term exposures to high concentrations of some airborne chemicals have the ability 

to quickly overwhelm workers, resulting in a spectrum of undesirable health outcomes 

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

the eyes and respiratory tract or cognitive impairment), cause severe irreversible effects 

(e.g., damage to the respiratory tract or reproductive toxicity), and in extreme cases, cause 

death. Airborne concentrations of chemicals capable of causing such adverse health effects 

or of impeding escape from high-risk conditions may arise from a variety of nonroutine 

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

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

(e.g., during transportation incidents or other uncontrolled-release scenarios). 

The immediately dangerous to life or health (IDLH) air concentration values developed 

by the National Institute for Occupational Safety and Health (NIOSH) characterize these 

high-risk exposure concentrations and conditions [NIOSH 2013]. IDLH values are based 

on a 30-minute exposure duration and have traditionally served as a key component of the 

decision logic for the selection of respiratory protection devices [NIOSH 2004]. 

Occupational health professionals have employed these values beyond their initial purpose as a component of the NIOSH Respirator Selection Logic to assist in developing risk 

management plans for nonroutine work practices governing operations in high-risk environments (e.g., confined spaces) and the development of emergency preparedness plans. 

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

NIOSH Current Intelligence Bulletin (CIB) 66: Derivation of Immediately Dangerous to Life 

or Health Values [NIOSH 2013]. CIB 66 provides (1) an update on the scientific basis and 

risk assessment methodology used to derive IDLH values, (2) the rationale and derivation 

process for IDLH values, and (3) a demonstration of the derivation of scientifically credible 

IDLH values using available data resources.

The purpose of this technical report is to present the IDLH value for nitrogen dioxide (CAS® No. 10102-44-0). The scientific basis, toxicologic data, and risk assessment 

approach used to derive the IDLH value are summarized to ensure transparency and 

scientific credibility.

John Howard, M.D.

Director

National Institute for Occupational

 Safety and Health

Centers for Disease Control and Prevention
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IDLH Value Profile for Nitrogen Dioxide	 v

 Contents

Foreword. . 

Abbreviations. .

Glossary. . 

Acknowledgments. .

1 Introduction  

1.1 Overview of the IDLH Value for Nitrogen Dioxide. 

1.2 Purpose. 

1.3 General Substance Information  

2 Animal Toxicity Data  

3 Human Data. 

4 Summary. 

5 References. 
vi IDLH Value Profile for Nitrogen Dioxide

Abbreviations

ACGIH® American Conference of Governmental Industrial Hygienists 

AEGLs Acute Exposure Guideline Levels

AIHA® American Industrial Hygiene Association 

BMCL benchmark concentration lower confidence limit 

°C degrees Celsius

CA California

CAS® Chemical Abstracts Service, a division of the American Chemical Society

CIB Current Intelligence Bulletin

ERPGsTM Emergency Response Planning Guidelines 

IDLH immediately dangerous to life or health

IFA Institut für Arbeitsschutz der Deutschen Gesetzlichen Unfallversicherung

(Institute for Occupational Safety and Health of the German Social

Accident Insurance) 

LC lethal concentration

LC01 lethal concentration estimated to cause death in 1% of animals

LC50 median lethal concentration 

LEL lower explosive limit

LOAEL lowest observed adverse effect level 

mg/m3 milligram(s) per cubic meter

min minutes

mmHg millimeter(s) of mercury

NAS National Academy of Sciences

NIOSH National Institute for Occupational Safety and Health

NLM National Library of Medicine

NOAEL no observed adverse effect level 

NOEL no observed effect level 

NR not recommended 

OSHA Occupational Safety and Health Administration

PEL permissible exposure limit 

ppm parts per million 

REL recommended exposure limit 

STEL short-term exposure limit 

TLV® Threshold Limit Value 

TWA time-weighted average 

UEL upper explosive limit

WEELs® Workplace Environmental Exposure Levels
IDLH Value Profile for Nitrogen Dioxide	 vii

Glossary

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

Acute Exposure Guideline Levels (AEGLs): Threshold exposure limits for the general public, 

applicable to emergency exposure periods ranging from 10 minutes to 8 hours. AEGL-1, 

AEGL-2, and AEGL-3 are developed for five exposure periods (10 and 30 minutes, 1 hour, 

4 hours, and 8 hours) and are distinguished by varying degrees of severity of toxic effects, 

ranging from transient, reversible effects to life-threatening effects [NAS 2001]. AEGLs are 

intended to be guideline levels used during rare events or single once-in-a-lifetime exposures 

to airborne concentrations of acutely toxic, high-priority chemicals [NAS 2001]. The threshold 

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

and other potentially sensitive groups that are generally not considered in the development of 

workplace exposure recommendations (additional information available at http://www.epa.

gov/oppt/aegl/). 

Acute reference concentration (Acute RfC): An estimate (with uncertainty spanning perhaps 

an order of magnitude) of a continuous inhalation exposure for an acute duration (24 hours 

or less) of the human population (including sensitive subgroups) that is likely to be without 

an appreciable risk of deleterious effects during a lifetime. It can be derived from a NOAEL, 

LOAEL, or benchmark concentration, with uncertainty factors (UFs) generally applied to 

reflect limitations of the data used. Generally used in U.S. EPA noncancer health assessments 

[U.S. EPA 2016]. 

Acute toxicity: Any poisonous effect produced within a short period of time following an 

exposure, usually 24 to 96 hours [U.S. EPA 2016]. 

Adverse effect: A substance-related biochemical change, functional impairment, or pathologic 

lesion that affects the performance of an organ or system or alters the ability to respond to 

additional environmental challenges. 

Benchmark dose/concentration (BMD/BMC): A dose or concentration that produces a predetermined change in response rate of an effect (called the benchmark response, or BMR) 

compared to background [U.S. EPA 2016] (additional information available at http://www.

epa.gov/ncea/bmds/). 

Benchmark response (BMR): A predetermined change in response rate of an effect. Common 

defaults for the BMR are 10% or 5%, reflecting study design, data variability, and sensitivity 

limits used. 

BMCL: A statistical lower confidence limit on the concentration at the BMC [U.S. EPA 2016]. 

Bolus exposure: A single, relatively large dose. 

Ceiling value (“C”): U.S. term in occupational exposure indicating the airborne concentration 

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

Chronic exposure: Repeated exposure for an extended period of time. Typically exposures are 

more than approximately 10% of life span for humans and >90 days to 2 years for laboratory 

species. 
viii IDLH Value Profile for Nitrogen Dioxide

Critical study: The study that contributes most significantly to the qualitative and quantitative 

assessment of risk [U.S. EPA 2016].

Dose: The amount of a substance available for interactions with metabolic processes or biologically significant receptors after crossing the outer boundary of an organism [U.S. EPA 2016]. 

ECt50: A combination of the effective concentration of a substance in the air and the exposure 

duration that is predicted to cause an effect in 50% (one half) of the experimental test subjects. 

Emergency Response Planning Guidelines (ERPGsTM): Maximum airborne concentrations 

below which nearly all individuals can be exposed without experiencing health effects for 

1-hour exposure. ERPGs are presented in a tiered fashion, with health effects ranging from 

mild or transient to serious, irreversible, or life threatening (depending on the tier). ERPGs are 

developed by the American Industrial Hygiene Association [AIHA 2006]. 

Endpoint: An observable or measurable biological event or sign of toxicity, ranging from biomarkers of initial response to gross manifestations of clinical toxicity. 

Exposure: Contact made between a chemical, physical, or biological agent and the outer boundary of an organism. Exposure is quantified as the amount of an agent available at the exchange 

boundaries of the organism (e.g., skin, lungs, gut). 

Extrapolation: An estimate of the response at a point outside the range of the experimental 

data, generally through the use of a mathematical model, although qualitative extrapolation 

may also be conducted. The model may then be used to extrapolate to response levels that 

cannot be directly observed. 

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

of harm under specific exposure conditions. 

Immediately dangerous to life or health (IDLH) condition: A condition that poses a threat of 

exposure to airborne contaminants when that exposure is likely to cause death or immediate 

or delayed permanent adverse health effects or prevent escape from such an environment 

[NIOSH 2004, 2013]. 

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

breathing apparatus providing maximum worker protection is permitted [NIOSH 2004, 2013]. 

IDLH values are based on a 30-minute exposure duration. 

LC01: The statistically determined concentration of a substance in the air that is estimated to 

cause death in 1% of the test animals. 

LC50: The statistically determined concentration of a substance in the air that is estimated to 

cause death in 50% (one half) of the test animals; median lethal concentration. 

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

for a small percentage of the test animals.

LD50: The statistically determined lethal dose of a substance that is estimated to cause death 

in 50% (one half) of the test animals; median lethal concentration. 

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

test animals. 
IDLH Value Profile for Nitrogen Dioxide	 ix

LEL: The minimum concentration of a gas or vapor in air, below which propagation of a flame 

does not occur in the presence of an ignition source. 

Lethality: Pertaining to or causing death; fatal; referring to the deaths resulting from acute 

toxicity studies. May also be used in lethality threshold to describe the point of sufficient 

substance concentration to begin to cause death. 

Lowest observed adverse effect level (LOAEL): The lowest tested dose or concentration of 

a substance that has been reported to cause harmful (adverse) health effects in people or 

animals. 

Mode of action: The sequence of significant events and processes that describes how a substance causes a toxic outcome. By contrast, the term mechanism of action implies a more 

detailed understanding on a molecular level. 

No observed adverse effect level (NOAEL): The highest tested dose or concentration of a substance that has been reported to cause no harmful (adverse) health effects in people or animals. 

Occupational exposure limit (OEL): Workplace exposure recommendations developed by governmental agencies and nongovernmental organizations. OELs are intended to represent the 

maximum airborne concentrations of a chemical substance below which workplace exposures 

should not cause adverse health effects. OELs may apply to ceiling limits, STELs, or TWA 

limits. 

Peak concentration: Highest concentration of a substance recorded during a certain period 

of observation. 

Permissible exposure limits (PELs): Occupational exposure limits developed by OSHA or 

MSHA for allowable occupational airborne exposure concentrations. PELs are legally enforceable and may be designated as ceiling limits, STELs, or TWA limits.

Point of departure (POD): The point on the dose–response curve from which dose extrapolation is initiated. This point can be the lower bound on dose for an estimated incidence or a 

change in response level from a concentration-response model (BMC), or it can be a NOAEL 

or LOAEL for an observed effect selected from a dose evaluated in a health effects or toxicology study. 

RD50: The statistically determined concentration of a substance in the air that is estimated to 

cause a 50% (one half) decrease in the respiratory rate. 

Recommended exposure limit (REL): Recommended maximum exposure limit to prevent 

adverse health effects, based on human and animal studies and established for occupational 

(up to 10-hour shift, 40-hour week) inhalation exposure by NIOSH. RELs may be designated 

as ceiling limits, STELs, or TWA limits. 

Short-term exposure limit (STEL): A worker’s 15-minute time-weighted average exposure 

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

Target organ: Organ in which the toxic injury manifests in terms of dysfunction or overt 

disease. 

Threshold Limit Values (TLVs®): Recommended guidelines for occupational exposure to airborne contaminants, published by the American Conference of Governmental Industrial 
x IDLH Value Profile for Nitrogen Dioxide

Hygienists (ACGIH®). TLVs refer to airborne concentrations of chemical substances and represent conditions under which it is believed that nearly all workers may be repeatedly exposed, 

day after day, over a working lifetime, without adverse effects. TLVs may be designated as 

ceiling limits, STELs, or 8-hr TWA limits. 

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

exposure concentration that shall not be exceeded during an 8-hour (or up to 10-hour) work 

shift of a 40-hour week. The average concentration is weighted to take into account the duration of different exposure concentrations. 

Toxicity: The degree to which a substance is able to cause an adverse effect on an 

exposed organism.

Uncertainty factors (UFs): Mathematical adjustments applied to the POD when developing 

IDLH values. The UFs for IDLH value derivation are determined by considering the study and 

effect used for the POD, with further modification based on the overall database. 

Workplace Environmental Exposure Levels (WEELs®): Exposure levels developed by the 

American Industrial Hygiene Association (AIHA®) that provide guidance for protecting most 

workers from adverse health effects related to occupational chemical exposures, expressed as 

TWA or ceiling limits.
IDLH Value Profile for Nitrogen Dioxide	 xi

Acknowledgments

This document was developed by the Education and Information Division Paul Schulte, Ph.D., 

Director. G. Scott Dotson, Ph.D., was the project officer and lead NIOSH author. The basis 

for this document was a report contracted by NIOSH and prepared by Andrew Maier, Ph.D., 

Ann Parker, and Lynn Haber, Ph.D. (Toxicology Excellence for Risk Assessment [TERA]).

The following NIOSH staff are acknowledged for providing technical and editorial review of 

the report:

Education and Information Division 

Devin Baker, M.Ed. 

Charles L. Geraci, Ph.D. 

Thomas J. Lentz, Ph.D. 

Richard W. Niemeier, Ph.D. (retired)

R. Todd Niemeier, MS, CIH 

Pranav Rane, M.P.H.

Chris Whittaker, Ph.D. 

NIOSH acknowledges the following subject matter experts for their critical technical reviews: 

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

Director, Center for Public Health Practice; Interim Chair & Associate Professor, 

Division of Environmental Health Science, College of Public Health, Ohio State 

University, Columbus, OH

Ernest V. Falke, Ph.D., Senior Scientist, Risk Assessment Division (RAD), Office of 

Pollution Prevention and Toxics (OPPT), United States Environmental Protection Agency 

(USEPA), Washington, DC

Tala Henry, Ph.D., Director, RAD, OPPT, USEPA, Washington, DC 

Randall Keller, Ph.D., C.I.H., C.S.P., D.A.B.T., Professor; Occupational Safety and Health 

Department, Jesse D. Jones College of Science, Engineering, and Technology, Murray 

State University, Murray, KY 

Barry Marcel Ph.D., Environmental Health Consultant, United States Air Force, WrightPatterson Air Force Base, OH

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

Affairs and Research and Professor of Biology, Dyson College of Arts and Sciences, Pace 

University, New York, NY

George M. Woodall, Ph.D., Acting Coordinator, Science and Technology Policy Council 

Office of the Science Advisor, USEPA, Research Triangle Park, NC
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IDLH Value Profile for Nitrogen Dioxide	 1

References: *NLM [2017], †IFA [2017]

1 Introduction 

1.1 Overview of the IDLH 

Value for Nitrogen 

Dioxide

IDLH value: 13 ppm (24 mg/m3)

Basis for IDLH value: The IDLH value for 

nitrogen dioxide is based on a LOAEL of 30 

ppm for respiratory irritation and severe cough 

in volunteers following a 70 minute exposure 

[Henschler et al. 1960]. Duration adjustment 

resulted in the calculation of a 30-minute 

equivalent LOAEL of 38 ppm. A composite 

uncertainty factor of 3 was applied to account 

for human variability yielding an IDLH value 

13 ppm for nitrogen dioxide. 

1.2 Purpose

This IDLH Value Profile presents (1) a brief 

summary of technical data associated with 

acute inhalation exposures to nitrogen dioxide 

and (2) the rationale behind the immediately 

dangerous to life or health (IDLH) value for 

nitrogen dioxide. IDLH values are developed 

on the basis of scientific rationale and logic 

outlined in the NIOSH Current Intelligence 

Bulletin (CIB) 66: Derivation of Immediately 

Dangerous to Life or Health (IDLH) Values 

[NIOSH 2013]. As described in CIB 66, 

NIOSH performs in-depth literature searches 

to ensure that all relevant data from human 

and animal studies with acute exposures to 

the substance are identified. Information 

included in CIB 66 on the literature search 

includes pertinent databases, key terms, and 

guides for evaluating data quality and relevance for the establishment of an IDLH 

value. The information that is identified in the 

in-depth literature search is evaluated with 

general considerations that include description of studies (i.e., species, study protocol, 

exposure concentration and duration), health 

endpoint evaluated, and critical effect levels 

(e.g., NOAELs, LOAELs, and LC50 values). 

For nitrogen dioxide, the in-depth literature 

search was conducted through July 2017.

1.3 General Substance Information 

Chemical: Nitrogen dioxide

CAS No: 10102-44-0

Synonyms: Nitrogen oxide (NO2); Nitrogen peroxide*

Chemical category: Nitrogen oxides; Inorganic gases†

Structural formula:

O N O
2 IDLH Value Profile for Nitrogen Dioxide

Table 1 highlights selected physiochemical properties of nitrogen dioxide relevant to IDLH 

conditions. Table 2 provides alternative exposure guidelines for nitrogen dioxide. Table 3 summarizes the Acute Exposure Guidelines Level (AEGL) values for nitrogen dioxide.

Table 1: Physiochemical properties of nitrogen dioxide

Property Value

Molecular weight 46.01*

Chemical formula NO2

*

Description Reddish-brown gas above 21°C, pale yellow/

yellowish-brown liquid above 21°C†

Odor Pungent, acrid‡

Odor threshold 0.058 ppm‡

UEL Not applicable

LEL Not applicable

Vapor pressure 720 mmHg at 20°C; 800 mmHg at 25°C*

Flash point Not flammable

Ignition temperature Not flammable

Solubility Reacts with water†

Reactivity Decomposes in water forming nitric oxide and

nitric acid*

References: *NAS [2012]; †HSDB [2017]; ‡Murnane et al. [2013]

Table 2: Alternative exposure guidelines for nitrogen dioxide

Organization Value

NIOSH (1994) IDLH value* 20 ppm

NIOSH REL† 1 ppm - STEL

OSHA PEL‡ 5 ppm - Ceiling

CA OSHA PEL§ 1 ppm - STEL

ACGIH® TLV¶ 0.2 ppm TWA

AIHA® ERPGsTM** ERPG-1: 1 ppm; ERPG-2: 15 ppm; ERPG-3: 30 ppm

AIHA® WEELs®** Not available 

References: *NIOSH [1994]; †NIOSH [2017]; ‡OSHA [2017]; §CAL OSHA [2017]; ¶ACGIH [2016]; **AIHA [2014]
IDLH Value Profile for Nitrogen Dioxide	

3

Table 3: Interim AEGL values for nitrogen dioxide

Classification 10-min 30-min 1-hour 4-hour 8-hour Endpoint [reference]

AEGL-1 0.50 ppm

0.94 mg/m3

0.50 ppm0.94 mg/m3

0.50 ppm0.94 mg/m3

0.50 ppm0.94 mg/m3

0.50 ppm0.94 mg/m3

Slight burning of the eyes, slight

headache, chest tightness orlabored breathing with exercisein 7/13 asthmatics[Kerr et al. 1978, 1979]

AEGL-2 20 ppm

38 mg/m3

15 ppm28 mg/m3

12 ppm23 mg/m3

8.2 ppm15 mg/m3

6.7 ppm13 mg/m3

Burning sensation in nose and

chest, cough, dyspnea, sputumproduction in normal volunteers [Henschler et al. 1960]

AEGL-3 34 ppm

64 mg/m3

25 ppm47 mg/m3

20 ppm38 mg/m3

14 ppm26 mg/m3

11 ppm21 mg/m3

Marked irritation, histopathologic

changes in lungs, fibrosis andedema of cardiac tissue, necrosis in liver, no deaths in monkeys [Henry et al. 1969]

Reference: NAS [2012]
4 IDLH Value Profile for Nitrogen Dioxide

2 Animal Toxicity Data 

Nitrogen dioxide is an irritant to the mucous 

membranes and has been shown to cause 

coughing and dyspnea during exposure. 

Severe exposure pulmonary edema with 

symptoms of chest pain, cough, dyspnea, and 

cyanosis have been reported [NIOSH 1976; 

Douglas et al. 1989]. Lethality from nitrogen 

dioxide exposure is reported to be due to 

bronchospasm and pulmonary edema occurring with hypoxemia and respiratory acidosis, 

metabolic acidosis, decreased oxygenation of 

hemoglobin and low arterial blood pressure 

[Douglas et al. 1989]. Furthermore, after 

acute nitrogen dioxide intoxication and an 

apparent recovery, a late-onset bronchiolar 

injury in the form of bronchiolitis fibrosa 

obliterans is observed [NIOSH 1976; Hamilton 1983; Douglas et al. 1989]. 

Five- to 60-minute LC50 values for nitrogen 

dioxide in the rat ranged from 416 to 115 

ppm, respectively in one study [Carson et al. 

1962] and from 833 to 168 ppm in another 

study [Gray et al. 1954]. Hine et al. [1970] 

studied the effects of varying concentrations 

(50–200 ppm) and durations (5 min to 24 

hours) of nitrogen dioxide exposure in several 

species (rat, mouse, guinea pig, rabbit and 

dog). During this study lethality in one guinea 

pig (n=6) was reported following the lowest 

exposure of 50 ppm for one hour (which was 

the shortest duration for this concentration). 

The highest exposure of 200 ppm for 5 minutes caused lethality in 6/12 rats, 4/6 mice 

and 2/2 guinea pigs. In squirrel monkeys 

exposed to 10–50 ppm nitrogen dioxide for 

2 hours [Henry et al. 1969], exposure to 35 

or 50 ppm resulted in a markedly increased 

respiratory rate and decreased tidal volume.

Table 4 summarizes the lethal concentration 

(LC) data identified in animal studies and 

provides 30-minute equivalent derived values 

for nitrogen dioxide. Table 5 provides non-lethal data reported in animal studies with 

30-minute equivalent derived values. Information in these tables includes species of test 

animals, toxicological metrics (i.e., BMCL, 

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

the derived values.
IDLH Value Profile for Nitrogen Dioxide	

5

Table 4: Lethal concentration data for nitrogen dioxide

Reference Species

LC50

(ppm)

Time 

(min)

Adjusted 

30-min 

concentration*

(ppm)

Composite 

uncertainty 

factor

30-min equivalent 

derived

value (ppm)†

Final

value‡ (ppm)

Carson et al. [1962] Rabbit 315 15 258 30§ 8.6 9.0Carson et al. [1962] Rat 162 30 162 30§ 5.4 5.0Gray et al. [1954] Rat 174 30 174 30§ 5.8 6.0

*For exposures other than 30 minutes the ten Berge et al. [1986] relationship is used for duration adjustment (Cn × t = k); ten Berge et al. [1986] empirically estimated n = 3.5. The n = 3.5

was used during all duration adjustments for nitrogen dioxide. Additional information on the calculation of duration-adjusted concentrations can be found in NIOSH [2013].

†The derived value is the result of the adjusted 30-minute LC value divided by the composite uncertainty factor. The composite uncertainty factor used varies for each study on the basis of

the nature and severity of the endpoint observed.

‡Values rounded to the appropriate significant figure.§Composite uncertainty factor to account for adjustment of LC50 values to LC01 values, use of lethal concentration threshold in animals, interspecies differences and human variability
6 IDLH Value Profile for Nitrogen Dioxide

Table 5: Non-lethal concentration data for nitrogen dioxide

Reference Species

Critical adverse

health effects

LOAEL 

(ppm)

Time 

(min)

Adjusted 

30-min 

concentration*

(ppm) 

Composite 

uncertainty 

factor 

Derived

value (ppm)†

Final

value‡ 

(ppm)

Morley and Silk [1970] Human Cyanosis, dyspnea and

pulmonary edema

30 40 33 3§ 10.9 11

Henschler et al. [1960] Human Burning sensation in upper respiratory tract and 

severe cough followed bydyspnea 

30 70 38 3§ 12.7 13

Norwood et al. [1966] Human Shortness of breath, chest

discomfort, and pulmonaryedema

90 40 98 3§ 32.6 33

Henry et al. [1969] Monkey

Increased respiratory rate 

and decreased tidal volume

35 120 52 10¶ 5.2 5.0

*For exposures other than 30 minutes the ten Berge et al. [1986] relationship is used for duration adjustment (Cn × t = k); ten Berge et al. [1986] empirically estimated n = 3.5. The n = 3.5

was used during all duration adjustments for nitrogen dioxide. Additional information on the calculation of duration-adjusted concentrations can be found in NIOSH [2013].

†The derived value is the result of the adjusted 30-min value divided by the composite uncertainty factor. The composite uncertainty factor used varies for each study on the basis of the

nature and severity of the endpoint observed.

‡Values rounded to the appropriate significant figure.§Composite uncertainty factor assigned to account for human variability.¶Composite uncertainty factor assigned to account for interspecies differences and human variability.
IDLH Value Profile for Nitrogen Dioxide	 7

3 Human Data

Numerous human studies are available 

that describe effects of nitrogen dioxide in 

humans. Overall, the pattern of respiratory 

tract effects includes initial signs of respiratory tract irritation, with latent tracheobronchial and pulmonary involvement. Douglas 

et al. [1989] reported that death from the 

inhalation of nitrogen dioxide is caused by 

bronchospasm and pulmonary edema. NAS 

[2012] stated that a characteristic of nitrogen dioxide intoxication after the acute phase 

is a period of apparent recovery. A second 

phase of symptoms may occur after several 

hours or several days with the development 

of fever with progressively more severe dyspnea, cyanosis, and cough. An estimation of 

the concentration causing death in humans is 

approximately ≥150 ppm, but no duration of 

exposure was given.

Henschler et al. [1960] investigated the 

adverse effects of acute inhalation exposures 

to nitrogen dioxide. Using a controlled exposure design, healthy male volunteers were 

exposed to various concentrations of nitrogen 

dioxide and durations. The authors reported 

that a 2-hour exposure to 20 ppm did not 

cause irritation, but exposures at 30 ppm for 

2 hours cause definite discomfort. Effects 

observed after 30 to 40 minutes of exposure 

were limited to minimal signs of irritation 

in the nose and throat. After 70 minutes of 

exposure, volunteers reported a burning sensation with increasingly severe cough. With 

continued exposure, coughing decreased, 

but the burning sensation moved to deeper 

portions of the lung, accompanied by sputum 

secretion and dyspnea. The authors reported 

that the condition was described as bothersome and barely tolerable by the subjects. In 

addition, a sensation of pressure and increased 

sputum secretion continued for several hours 

after cessation of exposure. This study design 

cannot provide information on the degree to 

which latent respiratory tract effects would 

have occurred following exposure for only 

30 minutes in the subjects. In another study, 

Morley and Silk [1970] described occupational exposures to nitrous fumes, which 

may include nitrogen dioxide, dinitrogen trioxide, dinitrogen tetroxide, and dinitrogen 

pentoxide, in eleven welders. Health effects 

associated with exposures to the nitrous 

fumes included a variety of symptoms such 

as cough, headache, tightness/pain in chest, 

and nausea. Two of seven workers were hospitalized with cyanosis, dyspnea and pulmonary edema following exposure to 30 ppm of 

nitrogen dioxide for 40 minutes [Morley and 

Silk 1970]. Another welder developed shortness of breath, chest discomfort, and pulmonary edema while using an acetylene torch for 

metal-cutting in a poorly ventilated enclosed 

space for 30 minutes. The authors noted that 

seven other workers were exposed during this 

incident, but were unaffected. This indicates 

the potential for human variability in response 

to nitrogen dioxide. Simulation of the accident 

produced a nitrogen dioxide concentration of 

90 ppm [Norwood et al. 1966]. The reports of 

effects in welders as the basis for IDLH value 

derivation are limited since the effects of the 

complex mix of materials released during 

welding need to be considered. Table 5 provides non-lethal data reported in human studies with 30-minute equivalent derived values.
8 IDLH Value Profile for Nitrogen Dioxide

4 Summary

Nitrogen dioxide is an irritant to the mucous 

membranes and has been shown to cause 

coughing and dyspnea during exposure. 

Severe exposure pulmonary edema with 

symptoms of chest pain, cough, dyspnea, and 

cyanosis have been reported [NIOSH 1976; 

Douglas et al. 1989]. Human data indicate 

that acute inhalation exposures may induce 

potential escape-impairing effects of dyspnea, 

cyanosis, and pulmonary edema [Henschler 

et al. 1960; Norwood et al. 1969; Morley and 

Silk 1970]. Exposure to nitrogen dioxide at 

30 ppm for 70 minutes resulted in a severe 

cough and an increased burning sensation of 

the upper respiratory tract that progressed 

with continued exposures to include the 

lower section of the airways and in the chest 

[Henschler et al. 1960]. These effects can be 

considered a LOAEL and serve as the basis of 

the IDLH value for nitrogen dioxide. Duration adjustment (see Table 5) resulted in the 

calculation of a 30-minute equivalent concentration of 38 ppm. Application of a composite 

uncertainty factor of 3 to account for human 

variability yielding an IDLH value 13 ppm for 

nitrogen dioxide.

5 References

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