Acetonitrile

CAS® No. 75-05-8

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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Immediately Dangerous to Life or Health (IDLH) Value Profile

Acetonitrile

[CAS® No. 75-05-8]

H3C N

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Centers for Disease Control and Prevention

National Institute for Occupational Safety and Health
This document is in the public domain and may be freely copied or reprinted.

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Suggested Citation

NIOSH [2017]. Immediately dangerous to life or health (IDLH) value profile: acetonitrile. 

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 2017-203.

DHHS (NIOSH) Publication No. 2017-203

October 2017

Table 2 was revised for accuracy. This revision did not affect the current IDLH value.

ii IDLH Value Profile for Acetonitrile
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 non-routine 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 non-routine 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 acetonitrile (CAS®

No. 75-05-8). 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

IDLH Value Profile for Acetonitrile	 iii
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IDLH Value Profile for Acetonitrile	 v

 Contents

Foreword. . 

Abbreviations  .

Glossary. . 

Acknowledgments. .

1 Introduction  

1.1 Overview of the IDLH Value for Acetonitrile. 

1.2 Purpose. 

1.3 General Substance Information  

2 Animal Toxicity Data  

3 Human Data. 

4 Summary. 

5 References. 
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

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

CI confidence interval

CIB Current Intelligence Bulletin

ERPGsTM Emergency Response Planning Guidelines 

°F degrees Fahrenheit

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 

LCLO lowest concentration that caused death in humans or animals

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 

NR not recommended 

OSHA Occupational Safety and Health Administration

PEL permissible exposure limit 

ppm parts per million 

REL recommended exposure limit 

TLV® Threshold Limit Value 

TWA time-weighted average 

UEL upper explosive limit

WEELs® Workplace Environmental Exposure Levels

vi IDLH	Value	Profile	for	Acetonitrile
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. 

IDLH	Value	Profile	for	Acetonitrile	 vii
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 situation 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. 

viii IDLH	Value	Profile	for	Acetonitrile
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 (29 

CFR 1910.1000) or MSHA (30 CFR 57.5001) 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. 

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

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.

x		 IDLH	Value	Profile	for	Acetonitrile
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 J. Marcel, Ph.D., Environmental Health Consultant, United States Air Force, 

Wright-Patterson 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

IDLH	Value	Profile	for	Acetonitrile	 xi
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1 Introduction 

1.1 Overview of the IDLH 

Value for Acetonitrile

IDLH value: 137 ppm (230 mg/m3)

Basis for IDLH value: The mouse LC50 value 

of 2,693 ppm for a 60 minute exposure to acetonitrile [Willhite 1981] was selected as the 

basis for the IDLH value. Duration adjustment 

resulted in the calculation of a 30-minute 

equivalent LC50 value of 4,120 ppm. A composite uncertainty factor of 30 was applied to 

account for extrapolation from a concentration 

that is lethal to animals, animal to human differences, and human variability, resulting in an 

IDLH value for acetonitrile of 137 ppm. 

1.2 Purpose

This IDLH Value Profile presents (1) a brief 

summary of technical data associated with 

acute inhalation exposures to acetonitrile and 

(2) the rationale behind the immediately dangerous to life or health (IDLH) value for acetonitrile. 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 acetonitrile, 

the in-depth literature search was conducted 

through July 2017.

1.3 General Substance Information 

Chemical: Acetonitrile

CAS No: 75-05-8

Synonyms: Cyanomethane; ethanenitrile; nitrile of acetic acid; methyl cyanide; ethyl 

nitrile; methanecarbonitrile*

Chemical category: Nitriles†

Structural formula:

H3C N

References: *NAS [2014], †IFA [2017]

IDLH Value Profile for Acetonitrile	 1
Table 1 highlights selected physiochemical properties of acetonitrile relevant to IDLH conditions. Table 2 provides alternative exposure guidelines for acetonitrile. Table 3 summarizes the 

Acute Exposure Guidelines Level (AEGL) values for acetonitrile.

Table 1: Physiochemical properties of acetonitrile

Property Value

Molecular weight 41.05*

Chemical formula CH3CN*

Description Colorless liquid*

Odor Pungent

Odor threshold Not available

UEL Not available

LEL Not available

Vapor pressure 88.8 mmHg at 25°C (77°F)*

Flash point 5.6°C (42.1°F) open cup*

Ignition temperature Not available

Solubility Infinitely soluble in water; readily miscible with

ethanol, ether, acetone, chloroform, carbon 

tetrachloride, and ethylene chloride; immiscible with saturated hydrocarbons (petroleum

fractions)*

Reference: *NAS [2014]

Table 2: Alternative exposure guidelines for acetonitrile

Organization Value

NIOSH (1994) IDLH value* 500 ppm

NIOSH REL† 20 ppm (33 mg/m3), 8-hr TWA

OSHA PEL‡ 40 ppm (66 mg/m3), 8-hr TWA

ACGIH TLV®§ 20 ppm (33 mg/m3), 8-hr TWA

AIHA ERPGsTM¶ None 

AIHA WEELs®¶ None

References: *NIOSH [1994]; †NIOSH [2017]; ‡OSHA [2017]; §ACGIH [2016]; ¶AIHA [2014]

2 IDLH Value Profile for Acetonitrile
Table 3: AEGL values for acetonitrile

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

AEGL-1 13 ppm

22 mg/m3

13 ppm22 mg/m3

13 ppm22 mg/m3

13 ppm22 mg/m3

NR* Slight chest tightness and cooling sensation in lung 

[Pozzani et al. 1959]

AEGL-2 80 ppm

130 mg/m3

80 ppm130 mg/m3

50 ppm84 mg/m3

21 ppm35 mg/m3

14 ppm

24 mg/m3

One-third of AEGL-3 values

AEGL-3 240 ppm

74 mg/m3

240 ppm

400 mg/m3

150 ppm

250 mg/m3

64 ppm

110 mg/m3

42 ppm71 mg/m3

No-effect level for maternal and 

fetal lethality in rats [Saillenfait et al. 1993]

Reference: NAS [2014]*Not recommended. Absence of an AEGL-1 value does not imply that exposure below the AEGL-2 value is without adverse effects.

IDLH Value Profile for Acetonitrile	3
2 Animal Toxicity Data 

LC50 data and information on the nonlethal 

effects of acetonitrile are available in multiple 

species, with pulmonary effects increasing with 

progression to lethality as the exposure concentration increased [Monsanto 1986; Ponzzani et 

al. 1959; Willhite 1981]. A study performed in 

rats reported a LOAEL of 10,100 ppm and a 

LC50 value of 19,950 ppm for a 4-hour exposure, suggesting a potentially steep dose-response curve following inhalation of acetonitrile 

[Monsanto 1986]. Pozzani et al. [1959] investigated the effects of inhalation exposures to 

acetonitrile in multiple species, including rats, 

dogs, and guinea pigs. Male and female rats 

were exposed to concentrations ranging from 

1,000 to 32,000 ppm for either 1 or 2 hours. 

The 4-hour LC50 value for both sexes was calculated at 16,000 ppm [NAS 2014]. The 8-hour 

LC50 values for male and female rats were 7,551 

and 12,435 ppm, respectively [NAS 2014]. In

another experiment, dogs were treated for 4

hours at concentrations ranging from 2,000-

32,000 ppm. No LC50 value was calculated, but 

Pozzani et al. [1959] reported that all animals 

treated at 16,000 and 32,000 ppm died. Pozzani 

et al. [1959] exposed guinea pigs to acetonitrile 

at concentrations ranging from 4,000–16,000 

ppm for 4 hours. The 4-hour LC50 value was

calculated at 5,655 ppm [NAS 2014]. Pathological investigations revealed that exposed animals 

experienced prostration, convulsive seizures, 

and death with pathological examination revealing pulmonary effects including congestion and 

hemorrhaging. 

Willhite [1981] investigated the relative toxicity of the following aliphatic nitrile compounds: 

acetonitrile, propionitrile, and n-butyronitrile. 

Mice were exposed via the inhalation route to 

1 of 5 or 6 concentrations of the test compound 

for 60 minutes. All deaths occurred within 3 

days of the cessation of exposure. Animals 

that survived past 3 days were observed for 14 

days with gross pathology conducted following termination. Willhite [1981] stated that all 

animals experienced similar signs regardless of 

the aliphatic nitrile compound to which they 

were exposed. These signs included dyspnea, 

tachypnea, gasping, tremors, and convulsions. 

For acetonitrile, the concentration ranged from 

500–5000 ppm. Willhite [1981] reported a 

60-minute LC50 value of 2,693 ppm (95% CI 

1,955–4,272) for acetonitrile.

Saillenfait et al. [1993] investigated the effects 

of acetonitrile in pregnant Sprague-Dawley 

rats. Treatment groups (n=20) were exposed 

for 6 hours a day during gestation days 6-20 to 

the following nominal concentrations: 0, 900, 

1,200, 1,500, or 1,800 ppm. Eight of the twenty 

dams (40%) treated at 1,800 ppm died. Maternal body weight gain during the gestation days 

6–21 was significantly reduced in comparison 

to controls. In the 1,500 and 1,800 ppm treatment groups, maternal absolute weight gain 

was approximately 60% of controls. Incidence 

of pregnancy was not significantly affected. The 

authors reported an increase in the significant 

mean percentage of non-surviving implants per 

litter and mean percentage resorption site per 

litter in the 1,800 ppm treatment group. No significant effects on the mean number for implantation sites, fetal sex ratio, or fetal pup weights 

occurred in the 900 to 1,500 ppm treatment 

groups. No observed significant changes in the 

incidents of skeletal or soft tissue anomalies 

were observed in any treatment group. Saillenfait et al. [1993] concluded that exposures to 

1,800 ppm cause embryolethality.

Table 4 summarizes the lethal concentration 

(LC) data identified in animal studies and provides 30-minute equivalent derived values for 

acetonitrile. 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.

4		 IDLH	Value	Profile	for	Acetonitrile
Table 4: Lethal concentration data for acetonitrile

Reference Species

LC50

(ppm)

LCLO

(ppm)

Time 

(min)

Adjusted 

30-min 

concentration*

(ppm)

Composite 

uncertainty 

factor

30-min equivalent 

derived

value (ppm)†

Final

value‡ (ppm)

Pozzani et al. [1959] Guinea Pig 5,655 — 240 20,743 30§ 691.4 691Pozzani et al. [1959] Monkey 2,510 — 420 13,062 30§ 435.4 435Pozzani et al. [1959] Rats 7,551 — 480 42,715 30§ 1,424 1,424Pozzani et al. [1959] Rabbit 2,828 — 240 10,373 30§ 345.8 346

Willhite [1981] Mouse 2,693 — 60 4,120 30§ 137.3 137

*For exposures other than 30 minutes the ten Berge et al. [1986] relationship is used for duration adjustment (Cn × t = k); NAS [2014] provided an empirically estimated n of 1.6 for all

time-scaling. 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 concentration divided by the composite uncertainty factor.‡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.Table 5: Non-lethal concentration data for acetonitrile

Reference

Species

(reference)

Critical 

nonlethal effect

NOAEL 

(ppm)

Time 

(min)

Adjusted 

30-min 

concentration*

(ppm) 

Composite 

uncertainty 

factor 

30-min 

equivalent 

derived

value (ppm)†

Final

value‡ 

(ppm)

Saillenfait et al. [1993] Rats No-effect level for maternal 

and fetal lethality

1,500 360 7,089 30§ 236.3 236

*For exposures other than 30 minutes the ten Berge et al. [1986] relationship is used for duration adjustment (Cn × t = k); NAS [2014] provided an empirically estimated n of 1.6 for all

time-scaling. 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 concentration divided by the composite uncertainty factor.‡Values rounded to the appropriate significant figure.	§Composite uncertainty factor to account for interspecies differences, human variability, and extrapolation to an escape-impairing effect.

IDLH	Value	Profile	for	Acetonitrile	5
3 Human Data

Three male volunteers inhaled 40-160 ppm not report symptoms at this concentration. 

acetonitrile for 4 hours in an exposure cham- At the 160 ppm exposure, one of the preber [Pozzani et al. 1959]. One study par- viously unaffected subjects reported slight 

ticipant reported slight chest tightness and transitory flushing of face after 2 hours and 

cooling sensation in the lung following the slight bronchial tightness 5 hours later that 

40 ppm exposure, other participants did resolved overnight.

4 Summary

Limited human data on acetonitrile were 

identified. Pozzani et al. [1959] reported that 

effects of acetonitrile in human volunteers 

exposed for 4 hours to airborne concentrations 

ranging from 40–160 ppm. Although this data 

provided some insight into the effects of acetonitrile on humans, it is insufficient to serve as 

the basis of an IDLH value. 

Animal data from studies that investigated 

the effects of acute exposures to acetonitrile 

in rats, rabbits, guinea pigs, dogs, and monkeys 

[Monsanto 1986; Pozzani et al. 1959; Willhite 

1981] were evaluated. Among these species, 

mice appear to be the most sensitive species 

[Willhite 1981]. The mouse LC50 value of 2,693 

ppm for a 60 minute exposure to acetonitrile 

was selected as the basis for the IDLH value. 

Duration adjustment resulted in the calculation 

of a 30-minute equivalent LC50 value of 4,120 

ppm. An uncertainty factor of 30 was applied 

to account for extrapolation from a concentration that is lethal to animals, animal to human 

differences and human variability resulting in 

a potential IDLH value of 137 ppm. 

Saillenfait et al. [1993] provided an alternative 

point of departure for the IDLH value. This 

study investigated the reproductive effects of 

repeated exposures to acetonitrile on female 

rats. Inhalation exposures to 1,800 ppm for 6 

hours a day during gestation days 6–20 resulted 

in the death of 40% of exposed rats, decreased 

maternal body weight gain, mean percentage 

of non-surviving implants per litter, and mean 

percentage resorption site per litter. These 

effects were not reported at the next treatment 

level of 1,500 ppm. A potential IDLH value 

was calculated using 1,500 ppm as a NOAEL. 

Duration adjustment of this value from 6 hours 

resulted in a 30-minute equivalent NOAEL 

value of 7,089 ppm. An uncertainty factor of 

30 was applied to account for interspecies differences, human variability, and extrapolation 

to an escape-impairing effect resulting in a 

potential IDLH value of 236 ppm. 

Although basing the IDLH value for acetonitrile on Saillenfait et al. [1993] study is a viable 

option, NIOSH has selected the Willhite 

[1981] study as the basis of the IDLH value 

for acetonitrile. This study provided a point 

of departure (i.e., LC50 value of 2,693 ppm) 

based on single exposure to acetonitrile for 

60 minute, which aligns more closely with the 

exposure scenarios associated with an IDLH 

condition (i.e., acute, short-term exposures for 

30 minutes or less). In comparison, Saillenfait 

et al. [1993] relies on a repeat exposure study 

design (i.e., total of 14 exposures) and uses a 

6-hour exposure duration. Both of these factors 

introduce additional uncertainty into the analysis. The IDLH value of 138 ppm for acetonitrile 

based on the Willhite [1981] study resulted in 

the most health protective IDLH value.

6		 IDLH	Value	Profile	for	Acetonitrile
5 References

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IDLH	Value	Profile	for	Acetonitrile	 7
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8		 IDLH	Value	Profile	for	Acetonitrile
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