Chloroacetonitrile

CAS® No. 107-14-2

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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Cl

N

Immediately Dangerous to Life or Health (IDLH) Value Profile

Chloroacetonitrile

[CAS® No. 107-14-2]

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Centers for Disease Control and Prevention

National Institute for Occupational Safety and Health
ii IDLH Value Profile for Chloroacetonitrile

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Suggested Citation

NIOSH [2017]. Immediately dangerous to life or health (IDLH) value profile: Chloroacetonitrile. 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 2017-201.

DHHS (NIOSH) Publication No. 2017-201

September 2017
IDLH Value Profile for Chloroacetonitrile	 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 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 chloroacetonitrile (CAS® No. 107-14-2). 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 Chloroacetonitrile	 v

 Contents

Foreword. . 

Abbreviations. .

Glossary. . 

Acknowledgments. .

1 Introduction  

1.1 Overview of the IDLH Value for Chloroacetonitrile. 

1.2 Purpose. 

1.3 General Substance Information  

2 Animal Toxicity Data  

3 Human Data. 

4 Summary. 

5 References. 
vi IDLH Value Profile for Chloroacetonitrile

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 on 1% of animals

LC50 median lethal concentration 

LCLO lowest concentration that caused death in humans or animals

LD50 median lethal dose

LEL lower explosive limit

LOAEL lowest observed adverse effect level 

mg/kg milligram(s) per kilogram of body weight

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
IDLH Value Profile for Chloroacetonitrile	 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 Chloroacetonitrile

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 Chloroacetonitrile	 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 Chloroacetonitrile

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 Chloroacetonitrile	 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 

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 Chloroacetonitrile	 1

References: *NAS [2014], †IFA [2017]

1 Introduction 

1.1 Overview of the 

IDLH Value for 

Chloroacetonitrile

IDLH value: 14 ppm (23 mg/m3)

Basis for IDLH value: No inhalation exposure data were located for chloroacetonitrile. 

Therefore, acetonitrile is used as a surrogate, 

as the effects and mode of action are similar; 

however, acetonitrile is less potent. 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. 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 an IDLH value for acetonitrile of 

137 ppm. Available data [Lewis 1996; NAS 

2014] indicate that chloroacetonitrile is 10 

times more toxic than acetonitrile. A modifying factor of 10 is applied to the IDLH value 

to account for the greater potency of chloroacetonitrile compared to the potency of the 

surrogate, acetonitrile, resulting in an IDLH 

value of 14 ppm. 

1.2 Purpose

This IDLH Value Profile presents (1) a brief 

summary of technical data associated with 

acute inhalation exposures to chloroacetonitrile and (2) the rationale behind the immediately dangerous to life or health (IDLH) 

value for chloroacetonitrile. 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 chloroacetonitrile, the in-depth 

literature search was conducted through 

July 2017.

1.3 General Substance Information 

Chemical: Chloroacetonitrile

CAS No: 107-14-2

Synonyms: 2-Chloroacetonitrile; 

alpha-Chloroacetonitrile; Monochloroacetonitrile; Monochloromethyl cyanide*

Chemical category: Nitriles; Organic 

chlorine compounds†

Structural formula:

Cl

N
2 IDLH Value Profile for Chloroacetonitrile

Table 1 highlights selected physiochemical properties of chloroacetonitrile relevant to IDLH 

conditions. Table 2 provides alternative exposure guidelines for chloroacetonitrile. Table 3 

summarizes the Acute Exposure Guidelines Level (AEGL) values for chloroacetonitrile.

Table 1: Physiochemical properties of chloroacetonitrile

Property Value

Molecular weight 75.50*

Chemical formula C2H2ClN*

Description Colorless liquid*

Odor Pungent

Odor threshold Not available

UEL Not available

LEL Not available

Vapor pressure 8 mmHg at 20°C* 

Flash point 54°C (129.2°F)†

Ignition temperature Not available

Solubility Soluble in water, hydrocarbons, and alcohols*

References: *NAS [2014]; †IFA [2017]

Table 2: Alternative exposure guidelines for chloroacetonitrile

Organization Value

NIOSH (1994) IDLH value* None

NIOSH REL† None

OSHA PEL‡ None

ACGIH TLV®§ None

AIHA ERPGsTM¶ None 

AIHA WEELs®¶ None

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

3

Table 3: AEGL values for chloroacetonitrile

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

AEGL-1 NR* NR NR NR NR Insufficient DataAEGL-2 8.0 ppm

25 mg/m3

8.0 ppm25 mg/m3

5.0 ppm15 mg/m3

2.1 ppm6.5 mg/m3

1.4 ppm4.3 mg/m3

Based on AEGL-2 values for 

acetonitrile [NAS 2014]

AEGL-3 24 ppm

74 mg/m3

24 ppm74 mg/m3

15 ppm46 mg/m3

6.4 ppm20 mg/m3

4.2 ppm13mg/m3

Based on AEGL-3 values for

acetonitrile

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.
4 IDLH Value Profile for Chloroacetonitrile

2 Animal Toxicity Data 

Aliphatic nitriles, such as acetonitrile and 

chloroacetonitrile, are readily absorbed from 

the lung [NAS 2014]. The systemic toxicity 

of these compounds is due to the metabolism 

of the parent compound to cyanide by extrahepatic cytochrome P450 [NAS 2014]. Clinical signs of toxicity are reported to include: 

weakness, headache, dizziness, confusion, 

nausea, vomiting, convulsions, dilated pupils, 

weak pulse, tachypnea, dyspnea, and cyanosis [NAS 2014]. Acute inhalation exposure 

data for chloroacetonitrile was not located. 

Gage [1970] investigated the subacute effects 

of repeated exposures to chloroacetonitrile. 

Animals were exposed to 20, 80, or 300 ppm 

chloroacetonitrile for 6 hours/day for 20, 6, 

or 3 days, respectively. Gage [1970] reported 

that subacute exposures to 20 ppm resulted 

in no toxic signs, but autopsy revealed slight 

kidney congestion. In comparison, 80 ppm 

was associated with slight respiratory difficulty, lethargy, and low weight gain. The 

results of the autopsy provided evidence of 

congestion of lung, kidney, liver and spleen. 

The highest treatment level (300 ppm) 

resulted in respiratory difficulty, lachrymation, incoordination, low body temperature, 

and weight loss. Autopsy revealed unspecified 

organ congestion.

In the absence of acute inhalation data for 

chloroacetonitrile and the similar mode of 

action and effects for aliphatic nitriles, acetonitrile is used as a surrogate. Mouse intraperitoneal (i.p.) lethality studies reported an LD50

value of 100 mg/kg and 521 mg/kg [Lewis 

1996] for chloroacetonitrile and acetonitrile, 

respectively. These LD50 data suggest that, on 

a molar basis, chloroacetonitrile is approximately 10 times more toxic than acetonitrile 

[Lewis 1996; NAS 2014].

LC50 data and information on nonlethal 

effects of acetonitrile are available in multiple species, with pulmonary effects increasing 

with progression to lethality as the exposure 

concentration increased [Monsanto 1986; Pozzani 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 to 1 of 5 or 6 (unspecified) concentrations of the test compound for 60 minutes. 

Following cessation of exposure, all animals 

which died occurred within 3 days. 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 had been exposed. These 

signs included dyspnea, tachypnea, gasping, 
IDLH Value Profile for Chloroacetonitrile	 5

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, which is used as a surrogate 

for chloroacetonitrile. 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.
6 IDLH Value Profile for Chloroacetonitrile

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 Chloroacetonitrile	 7

3 Human Data

No information was located regarding human 

inhalation exposure to chloroacetonitrile. 

However for the surrogate, acetonitrile, three 

male volunteers inhaled 40-160 ppm acetonitrile for 4 hours in an exposure chamber 

[Pozzani et al. 1959]. One study participant 

reported slight chest tightness and cooling 

sensation in the lung following the 40 ppm 

exposure, other participants did not report 

symptoms at this concentration. At the 160 

ppm exposure, one of the previously unaffected subjects reported slight transitory flushing of face after 2 hours and slight bronchial 

tightness 5 hours later that resolved overnight.

4 Summary

No acute inhalation exposure data were 

located for chloroacetonitrile. Therefore, acetonitrile is used as a surrogate, as the effects 

and mode of action are similar for aliphatic 

nitriles [NAS 2014]. Available LD50 data suggest that, on a molar basis, chloroacetonitrile 

is approximately 10 times more potent than 

acetonitrile. For this reason, a modifying 

factor of 10 is added to account for potency 

differences between acetonitrile and chloroacetonitrile [Lewis 1996; NAS 2014]. Nonlethal effects of acetonitrile were identified in a 

study using rats, rabbits, guinea pigs, dogs and 

monkeys [Pozzani et al. 1959], however it is 

unclear whether using these effects are sufficiently health protective since mice appear 

to be more sensitive to acetonitrile exposure. 

Saillenfait et al. [1993] investigated the reproductive effects of repeated exposures to acetonitrile on female rats. 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. This results in a potential IDLH 

value of 137 ppm. Available data [Lewis 1996; 

NAS 2014] indicate that chloroacetonitrile is 

10 times more toxic than acetonitrile. A modifying factor of 10 is applied to the IDLH value 

to account for the greater potency of chloroacetonitrile compared to the potency of the 

surrogate, acetonitrile, resulting in an IDLH 

value of 14 ppm.
8 IDLH Value Profile for Chloroacetonitrile

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