TOXICOLOGICAL PROFILE FOR 

ACROLEIN 

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES 

Public Health Service 

Agency for Toxic Substances and Disease Registry
 

August 2007 
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DISCLAIMER 

The use of company or product name(s) is for identification only and does not imply endorsement by the 

Agency for Toxic Substances and Disease Registry. 
ACROLEIN iii 

UPDATE STATEMENT 

A Toxicological Profile for Acrolein, Draft for Public Comment was released in September 2005. This 

edition supersedes any previously released draft or final profile. 

Toxicological profiles are revised and republished as necessary. For information regarding the update 

status of previously released profiles, contact ATSDR at: 

Agency for Toxic Substances and Disease Registry
 

Division of Toxicology and Environmental Medicine/Applied Toxicology Branch 

1600 Clifton Road NE 

Mailstop F-32 

Atlanta, Georgia 30333 
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ACROLEIN v 

FOREWORD 

This toxicological profile is prepared in accordance with guidelines developed by the Agency for Toxic 

Substances and Disease Registry (ATSDR) and the Environmental Protection Agency (EPA). The 

original guidelines were published in the Federal Register on April 17, 1987. Each profile will be revised 

and republished as necessary. 

The ATSDR toxicological profile succinctly characterizes the toxicologic and adverse health effects 

information for the hazardous substance described therein. Each peer-reviewed profile identifies and 

reviews the key literature that describes a hazardous substance’s toxicologic properties. Other pertinent 

literature is also presented, but is described in less detail than the key studies. The profile is not intended 

to be an exhaustive document; however, more comprehensive sources of specialty information are 

referenced. 

The focus of the profiles is on health and toxicologic information; therefore, each toxicological profile 

begins with a public health statement that describes, in nontechnical language, a substance’s relevant 

toxicological properties. Following the public health statement is information concerning levels of 

significant human exposure and, where known, significant health effects. The adequacy of information to 

determine a substance’s health effects is described in a health effects summary. Data needs that are of 

significance to protection of public health are identified by ATSDR and EPA. 

Each profile includes the following: 

(A) The examination, summary, and interpretation of available toxicologic information and 

epidemiologic evaluations on a hazardous substance to ascertain the levels of significant human 

exposure for the substance and the associated acute, subacute, and chronic health effects; 

(B) A determination of whether adequate information on the health effects of each substance 

is available or in the process of development to determine levels of exposure that present a 

significant risk to human health of acute, subacute, and chronic health effects; and 

(C) Where appropriate, identification of toxicologic testing needed to identify the types or 

levels of exposure that may present significant risk of adverse health effects in humans. 

The principal audiences for the toxicological profiles are health professionals at the Federal, State, and 

local levels; interested private sector organizations and groups; and members of the public. 

This profile reflects ATSDR’s assessment of all relevant toxicologic testing and information that has been 

peer-reviewed. Staff of the Centers for Disease Control and Prevention and other Federal scientists have 

also reviewed the profile. In addition, this profile has been peer-reviewed by a nongovernmental panel 

and was made available for public review. Final responsibility for the contents and views expressed in 

this toxicological profile resides with ATSDR. 

Julie Louise Gerberding, M.D., M.P.H. 

Administrator 

Agency for Toxic Substances and 

Disease Registry
 
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*Legislative Background 

The toxicological profiles are developed in response to the Superfund Amendments and Reauthorization 

Act (SARA) of 1986 (Public Law 99 499) which amended the Comprehensive Environmental Response, 

Compensation, and Liability Act of 1980 (CERCLA or Superfund). This public law directed ATSDR to 

prepare toxicological profiles for hazardous substances most commonly found at facilities on the 

CERCLA National Priorities List and that pose the most significant potential threat to human health, as 

determined by ATSDR and the EPA. The availability of the revised priority list of 275 hazardous 

substances was announced in the Federal Register on December 7, 2005 (70 FR 72840). For prior 

versions of the list of substances, see Federal Register notices dated April 17, 1987 (52 FR 12866); 

October 20, 1988 (53 FR 41280); October 26, 1989 (54 FR 43619); October 17,1990 (55 FR 42067); 

October 17, 1991 (56 FR 52166); October 28, 1992 (57 FR 48801); February 28, 1994 (59 FR 9486); 

April 29, 1996 (61 FR 18744); November 17, 1997 (62 FR 61332); October 21, 1999(64 FR 56792); 

October 25, 2001 (66 FR 54014) and November 7, 2003 (68 FR 63098). Section 104(i)(3) of CERCLA, 

as amended, directs the Administrator of ATSDR to prepare a toxicological profile for each substance on 

the list. 
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QUICK REFERENCE FOR HEALTH CARE PROVIDERS 

Toxicological Profiles are a unique compilation of toxicological information on a given hazardous 

substance. Each profile reflects a comprehensive and extensive evaluation, summary, and interpretation 

of available toxicologic and epidemiologic information on a substance. Health care providers treating 

patients potentially exposed to hazardous substances will find the following information helpful for fast 

answers to often-asked questions. 

Primary Chapters/Sections of Interest 

Chapter 1: Public Health Statement: The Public Health Statement can be a useful tool for educating 

patients about possible exposure to a hazardous substance. It explains a substance’s relevant 

toxicologic properties in a nontechnical, question-and-answer format, and it includes a review of 

the general health effects observed following exposure. 

Chapter 2: Relevance to Public Health: The Relevance to Public Health Section evaluates, interprets, 

and assesses the significance of toxicity data to human health. 

Chapter 3: Health Effects: Specific health effects of a given hazardous compound are reported by type 

of health effect (death, systemic, immunologic, reproductive), by route of exposure, and by length 

of exposure (acute, intermediate, and chronic). In addition, both human and animal studies are 

reported in this section. 

NOTE: Not all health effects reported in this section are necessarily observed in the clinical 

setting. Please refer to the Public Health Statement to identify general health effects observed 

following exposure. 

Pediatrics: Four new sections have been added to each Toxicological Profile to address child health 

issues: 

Section 1.6 How Can (Chemical X) Affect Children? 

Section 1.7 How Can Families Reduce the Risk of Exposure to (Chemical X)? 

Section 3.7 Children’s Susceptibility 

Section 6.6 Exposures of Children 

Other Sections of Interest: 

Section 3.8 Biomarkers of Exposure and Effect 

Section 3.11 Methods for Reducing Toxic Effects 

ATSDR Information Center 

Phone: 1-800-CDC-INFO (800-232-4636) or Fax: (770) 488-4178 

1-888-232-6348 (TTY)

 E-mail: cdcinfo@cdc.gov Internet: http://www.atsdr.cdc.gov 

The following additional material can be ordered through the ATSDR Information Center: 

Case Studies in Environmental Medicine: Taking an Exposure History—The importance of taking an 

exposure history and how to conduct one are described, and an example of a thorough exposure 

history is provided. Other case studies of interest include Reproductive and Developmental 

Hazards; Skin Lesions and Environmental Exposures; Cholinesterase-Inhibiting Pesticide 

Toxicity; and numerous chemical-specific case studies. 
ACROLEIN viii 

Managing Hazardous Materials Incidents is a three-volume set of recommendations for on-scene 

(prehospital) and hospital medical management of patients exposed during a hazardous materials 

incident. Volumes I and II are planning guides to assist first responders and hospital emergency 

department personnel in planning for incidents that involve hazardous materials. Volume III— 

Medical Management Guidelines for Acute Chemical Exposures—is a guide for health care 

professionals treating patients exposed to hazardous materials. 

Fact Sheets (ToxFAQs) provide answers to frequently asked questions about toxic substances. 

Other Agencies and Organizations 

The National Center for Environmental Health (NCEH) focuses on preventing or controlling disease, 

injury, and disability related to the interactions between people and their environment outside the 

workplace. Contact: NCEH, Mailstop F-29, 4770 Buford Highway, NE, Atlanta, 

GA 30341-3724 • Phone: 770-488-7000 • FAX: 770-488-7015. 

The National Institute for Occupational Safety and Health (NIOSH) conducts research on occupational 

diseases and injuries, responds to requests for assistance by investigating problems of health and 

safety in the workplace, recommends standards to the Occupational Safety and Health 

Administration (OSHA) and the Mine Safety and Health Administration (MSHA), and trains 

professionals in occupational safety and health. Contact: NIOSH, 200 Independence Avenue, 

SW, Washington, DC 20201 • Phone: 800-356-4674 or NIOSH Technical Information Branch, 

Robert A. Taft Laboratory, Mailstop C-19, 4676 Columbia Parkway, Cincinnati, OH 45226-1998 

• Phone: 800-35-NIOSH. 

The National Institute of Environmental Health Sciences (NIEHS) is the principal federal agency for 

biomedical research on the effects of chemical, physical, and biologic environmental agents on 

human health and well-being. Contact: NIEHS, PO Box 12233, 104 T.W. Alexander Drive, 

Research Triangle Park, NC 27709 • Phone: 919-541-3212. 

Referrals 

The Association of Occupational and Environmental Clinics (AOEC) has developed a network of clinics 

in the United States to provide expertise in occupational and environmental issues. Contact: 

AOEC, 1010 Vermont Avenue, NW, #513, Washington, DC 20005 • Phone: 202-347-4976 

• FAX: 202-347-4950 • e-mail: AOEC@AOEC.ORG • Web Page: http://www.aoec.org/. 

The American College of Occupational and Environmental Medicine (ACOEM) is an association of 

physicians and other health care providers specializing in the field of occupational and 

environmental medicine. Contact: ACOEM, 25 Northwest Point Boulevard, Suite 700, Elk 

Grove Village, IL 60007-1030 • Phone: 847-818-1800 • FAX: 847-818-9266. 
ACROLEIN ix 

CONTRIBUTORS 

CHEMICAL MANAGER(S)/AUTHOR(S): 

Nickolette Roney, MPH. 

Jessilynn Taylor, M.S. 

Annette Ashizawa, Ph.D. 

ATSDR, Division of Toxicology and Environmental Medicine, Atlanta, GA 

Michael H. Lumpkin, Ph.D. 

Daniel J. Plewak, B.S. 

Syracuse Research Corporation, North Syracuse, NY 

THE PROFILE HAS UNDERGONE THE FOLLOWING ATSDR INTERNAL REVIEWS: 

1. Health Effects Review. The Health Effects Review Committee examines the health effects 

chapter of each profile for consistency and accuracy in interpreting health effects and classifying 

end points. 

2.	 Minimal Risk Level Review. The Minimal Risk Level Workgroup considers issues relevant to 

substance-specific Minimal Risk Levels (MRLs), reviews the health effects database of each 

profile, and makes recommendations for derivation of MRLs. 

3. Data Needs Review. The Applied Toxicology Branch reviews data needs sections to assure 

consistency across profiles and adherence to instructions in the Guidance. 

4. Green Border Review. Green Border review assures the consistency with ATSDR policy. 
ACROLEIN x 

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PEER REVIEW 

A peer review panel was assembled for the acrolein public comment document of September 2005. The 

panel consisted of the following members: 

1.	 Ghulam Ahmad Shakeel Ansari, Ph.D., Department of Human Biological Chemistry and 

Genetics, Department of Pathology, University of Texas Medical Branch, Galveston, Texas; 

2. James Kehrer, Ph.D., Professor of Pharmacology, Center for Molecular and Cellular Toxicology, 

The University of Texas at Austin, Austin, Texas; and 

3. John Morris, Ph.D., Department of Pharmaceutical Sciences, University of Connecticut, School 

of Pharmacy, Storrs, Connecticut. 

These experts collectively have knowledge of acrolein's physical and chemical properties, toxicokinetics, 

key health end points, mechanisms of action, human and animal exposure, and quantification of risk to 

humans. All reviewers were selected in conformity with the conditions for peer review specified in 

Section 104(I)(13) of the Comprehensive Environmental Response, Compensation, and Liability Act, as 

amended. 

Scientists from the Agency for Toxic Substances and Disease Registry (ATSDR) have reviewed the peer 

reviewers' comments and determined which comments will be included in the profile. A listing of the 

peer reviewers' comments not incorporated in the profile, with a brief explanation of the rationale for their 

exclusion, exists as part of the administrative record for this compound. 

The citation of the peer review panel should not be understood to imply its approval of the profile's final 

content. The responsibility for the content of this profile lies with the ATSDR. 
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ACROLEIN xiii 

CONTENTS 

DISCLAIMER ..............................................................................................................................................ii 

UPDATE STATEMENT .............................................................................................................................iii 

FOREWORD ................................................................................................................................................v 

QUICK REFERENCE FOR HEALTH CARE PROVIDERS....................................................................vii 

CONTRIBUTORS.......................................................................................................................................ix 

PEER REVIEW ...........................................................................................................................................xi 

CONTENTS...............................................................................................................................................xiii 

LIST OF FIGURES ..................................................................................................................................xvii 

LIST OF TABLES.....................................................................................................................................xix 

1. PUBLIC HEALTH STATEMENT..........................................................................................................1 

1.1 WHAT IS ACROLEIN?.............................................................................................................1 

1.2 WHAT HAPPENS TO ACROLEIN WHEN IT ENTERS THE ENVIRONMENT?................2 

1.3 HOW MIGHT I BE EXPOSED TO ACROLEIN? ....................................................................2 

1.4 HOW CAN ACROLEIN ENTER AND LEAVE MY BODY? .................................................4 

1.5 HOW CAN ACROLEIN AFFECT MY HEALTH? .................................................................. 4 

1.6 HOW CAN ACROLEIN AFFECT CHILDREN? .....................................................................5 

1.7 HOW CAN FAMILIES REDUCE THE RISK OF EXPOSURE TO ACROLEIN? .................5 

1.8 IS THERE A MEDICAL TEST TO DETERMINE WHETHER I HAVE BEEN
 

EXPOSED TO ACROLEIN? .....................................................................................................6 

1.9 WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT MADE TO 

PROTECT HUMAN HEALTH?................................................................................................6 

1.10 WHERE CAN I GET MORE INFORMATION? ......................................................................7 

2. RELEVANCE TO PUBLIC HEALTH ...................................................................................................9 

2.1 BACKGROUND AND ENVIRONMENTAL EXPOSURES TO ACROLEIN IN 

THE UNITED STATES .............................................................................................................9 

2.2 SUMMARY OF HEALTH EFFECTS .....................................................................................10 

2.3 MINIMAL RISK LEVELS (MRLs).........................................................................................12 

3. HEALTH EFFECTS..............................................................................................................................19 

3.1 INTRODUCTION ....................................................................................................................19 

3.2 DISCUSSION OF HEALTH EFFECTS BY ROUTE OF EXPOSURE..................................19 

3.2.1 Inhalation Exposure ..........................................................................................................20 

3.2.1.1 Death ............................................................................................................................20 

3.2.1.2 Systemic Effects...........................................................................................................35 

3.2.1.3 Immunological and Lymphoreticular Effects...............................................................39 

3.2.1.4 Neurological Effects.....................................................................................................40 

3.2.1.5 Reproductive Effects....................................................................................................40 

3.2.1.6 Developmental Effects .................................................................................................41 

3.2.1.7 Cancer...........................................................................................................................41 

3.2.2 Oral Exposure ...................................................................................................................41 

3.2.2.1 Death ............................................................................................................................41 

3.2.2.2 Systemic Effects...........................................................................................................42 

3.2.2.3 Immunological and Lymphoreticular Effects...............................................................56 

3.2.2.4 Neurological Effects.....................................................................................................56 

3.2.2.5 Reproductive Effects....................................................................................................56 

3.2.2.6 Developmental Effects .................................................................................................56 

3.2.2.7 Cancer...........................................................................................................................57 
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3.2.3 Dermal Exposure ..............................................................................................................58 

3.2.3.1 Death ............................................................................................................................58 

3.2.3.2 Systemic Effects...........................................................................................................58 

3.2.3.3 Immunological and Lymphoreticular Effects...............................................................60 

3.2.3.4 Neurological Effects.....................................................................................................61 

3.2.3.5 Reproductive Effects....................................................................................................61 

3.2.3.6 Developmental Effects .................................................................................................61 

3.2.3.7 Cancer...........................................................................................................................61 

3.3 GENOTOXICITY ....................................................................................................................61 

3.4 TOXICOKINETICS .................................................................................................................64 

3.4.1 Absorption ........................................................................................................................64 

3.4.1.1 Inhalation Exposure......................................................................................................64 

3.4.1.2 Oral Exposure...............................................................................................................65 

3.4.1.3 Dermal Exposure ..........................................................................................................65 

3.4.2 Distribution .......................................................................................................................65 

3.4.2.1 Inhalation Exposure......................................................................................................65 

3.4.2.2 Oral Exposure...............................................................................................................66 

3.4.2.3 Dermal Exposure ..........................................................................................................66 

3.4.2.4 Other Routes of Exposure ............................................................................................66 

3.4.3 Metabolism .......................................................................................................................66 

3.4.3.1 Inhalation Exposure......................................................................................................67 

3.4.3.2 Oral Exposure...............................................................................................................67 

3.4.3.3 Dermal Exposure ..........................................................................................................69 

3.4.4 Elimination and Excretion ................................................................................................69 

3.4.4.1 Inhalation Exposure......................................................................................................69 

3.4.4.2 Oral Exposure...............................................................................................................69 

3.4.4.3 Dermal Exposure ..........................................................................................................72 

3.4.4.4 Other Routes of Exposure ............................................................................................72 

3.4.5 Physiologically Based Pharmacokinetic (PBPK)/Pharmacodynamic (PD) Models.........72 

3.5 MECHANISMS OF ACTION.................................................................................................. 73 

3.5.1 Pharmacokinetic Mechanisms .......................................................................................... 73 

3.5.2 Mechanisms of Toxicity ...................................................................................................75 

3.5.3 Animal-to-Human Extrapolations.....................................................................................76 

3.6 TOXICITIES MEDIATED THROUGH THE NEUROENDOCRINE AXIS .........................76 

3.7 CHILDREN’S SUSCEPTIBILITY ..........................................................................................77 

3.8 BIOMARKERS OF EXPOSURE AND EFFECT ...................................................................79 

3.8.1 Biomarkers Used to Identify or Quantify Exposure to Acrolein ......................................80 

3.8.2 Biomarkers Used to Characterize Effects Caused by Acrolein ........................................81 

3.9 INTERACTIONS WITH OTHER CHEMICALS....................................................................81 

3.10 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE .............................................. 82 

3.11 METHODS FOR REDUCING TOXIC EFFECTS.................................................................. 82 

3.11.1 Reducing Peak Absorption Following Exposure ..............................................................83 

3.11.2 Reducing Body Burden.....................................................................................................83 

3.11.3 Interfering with the Mechanism of Action for Toxic Effects ...........................................83 

3.12 ADEQUACY OF THE DATABASE.......................................................................................84 

3.12.1 Existing Information on Health Effects of Acrolein.........................................................84 

3.12.2 Identification of Data Needs .............................................................................................86 

3.12.3 Ongoing Studies................................................................................................................92 
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4. CHEMICAL AND PHYSICAL INFORMATION................................................................................95 

4.1 CHEMICAL IDENTITY..........................................................................................................95 

4.2 PHYSICAL AND CHEMICAL PROPERTIES.......................................................................95 

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL............................................................99 

5.1 PRODUCTION.........................................................................................................................99 

5.2 IMPORT/EXPORT...................................................................................................................99 

5.3 USE.........................................................................................................................................101 

5.4 DISPOSAL .............................................................................................................................101 

6. POTENTIAL FOR HUMAN EXPOSURE .........................................................................................103 

6.1 OVERVIEW...........................................................................................................................103 

6.2 RELEASES TO THE ENVIRONMENT ...............................................................................106 

6.2.1 Air...................................................................................................................................107 

6.2.2 Water...............................................................................................................................113 

6.2.3 Soil..................................................................................................................................114 

6.3 ENVIRONMENTAL FATE...................................................................................................115 

6.3.1 Transport and Partitioning ..............................................................................................115 

6.3.2 Transformation and Degradation ....................................................................................116 

6.3.2.1 Air...............................................................................................................................116 

6.3.2.2 Water ..........................................................................................................................116 

6.3.2.3 Sediment and Soil.......................................................................................................118 

6.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT ..............................119 

6.4.1 Air...................................................................................................................................119 

6.4.2 Water...............................................................................................................................120 

6.4.3 Sediment and Soil ...........................................................................................................122 

6.4.4 Other Environmental Media ...........................................................................................122 

6.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE ....................................123 

6.6 EXPOSURES OF CHILDREN ..............................................................................................126 

6.7 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES...........................................127 

6.8 ADEQUACY OF THE DATABASE.....................................................................................128 

6.8.1 Identification of Data Needs ...........................................................................................128 

6.8.2 Ongoing Studies..............................................................................................................132 

7. ANALYTICAL METHODS ...............................................................................................................133 

7.1 BIOLOGICAL MATERIALS ................................................................................................133 

7.2 ENVIRONMENTAL SAMPLES...........................................................................................135 

7.3 ADEQUACY OF THE DATABASE.....................................................................................139 

7.3.1 Identification of Data Needs ...........................................................................................139 

7.3.2 Ongoing Studies..............................................................................................................140 

8. REGULATIONS AND ADVISORIES ...............................................................................................141 

9. REFERENCES ....................................................................................................................................145 

10. GLOSSARY ......................................................................................................................................171 
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APPENDICES 

A. ATSDR MINIMAL RISK LEVELS AND WORKSHEETS .............................................................A-1 

B. USER'S GUIDE ..................................................................................................................................B-1 

C. ACRONYMS, ABBREVIATIONS, AND SYMBOLS......................................................................C-1 

D. INDEX ................................................................................................................................................D-1 
ACROLEIN xvii 

LIST OF FIGURES 

3-1. Levels of Significant Exposure to Acrolein – Inhalation ................................................................... 32 

3-2. Levels of Significant Exposure to Acrolein – Oral............................................................................. 50 

3-3. Proposed Metabolic Scheme for Acrolein In Vitro ............................................................................68 

3-4. Proposed Metabolic Scheme for Acrolein In Vivo .............................................................................70 

3-5. Proposed Pathway for the Metabolism of Acrolein in Rats................................................................71
 

3-6. Conceptual Representation of a Physiologically Based Pharmacokinetic (PBPK) Model for a 

Hypothetical Chemical Substance......................................................................................................74 

3-7. Existing Information on Health Effects of Acrolein...........................................................................85 

6-1. Frequency of NPL Sites with Acrolein Contamination....................................................................104
 
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ACROLEIN xix 

LIST OF TABLES 

3-1. Levels of Significant Exposure to Acrolein – Inhalation ................................................................... 21 

3-2. Levels of Significant Exposure to Acrolein – Oral............................................................................. 43 

3-3. Levels of Significant Exposure to Acrolein – Dermal........................................................................ 59 

3-4. Genotoxicity of Acrolein In Vitro.......................................................................................................62 

4-1. Chemical Identity of Acrolein ............................................................................................................96 

4-2. Physical and Chemical Properties of Acrolein ...................................................................................97 

5-1. Facilities that Produce, Process, or Use Acrolein.............................................................................100 

6-1. Releases to the Environment from Facilities that Produce, Process, or Use Acrolein .....................108 

6-2. Acrolein in Emissions from Combustion .........................................................................................109 

6-3. Estimated Acrolein Emissions from Onroad Mobile Sources in 1996 and 2007 .............................111 

6-4. Estimated Acrolein Emissions from Nonroad Mobile Sources in 1996 and 2007 ...........................112 

6-5. Acrolein Concentrations in Indoor Air.............................................................................................121 

7-1. Analytical Methods for Determining Acrolein in Biological Samples.............................................134 

7-2. Analytical Methods for Determining Acrolein in Environmental Samples......................................137 

8-1. Regulations and Guidelines Applicable to Acrolein.........................................................................142 
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ACROLEIN 1 

1. PUBLIC HEALTH STATEMENT 

This public health statement tells you about acrolein and the effects of exposure to it. 

The Environmental Protection Agency (EPA) identifies the most serious hazardous waste sites in 

the nation. These sites are then placed on the National Priorities List (NPL) and are targeted for 

long-term federal clean-up activities. Acrolein has been found in at least 32 of the 1,684 current 

or former NPL sites. Although the total number of NPL sites evaluated for this substance is not 

known, the possibility exists that the number of sites at which acrolein is found may increase in 

the future as more sites are evaluated. This information is important because these sites may be 

sources of exposure and exposure to this substance may harm you. 

When a substance is released either from a large area, such as an industrial plant, or from a 

container, such as a drum or bottle, it enters the environment. Such a release does not always 

lead to exposure. You can be exposed to a substance only when you come in contact with it. 

You may be exposed by breathing, eating, or drinking the substance, or by skin contact. 

If you are exposed to acrolein, many factors will determine whether you will be harmed. These 

factors include the dose (how much), the duration (how long), and how you come in contact with 

it. You must also consider any other chemicals you are exposed to and your age, sex, diet, 

family traits, lifestyle, and state of health. 

1.1 WHAT IS ACROLEIN? 

Acrolein is a clear or yellow liquid with a burnt, sweet, pungent odor. Most people begin to 

smell acrolein in air at concentrations of 0.25 parts acrolein per million parts of air (ppm). It 

ignites and burns easily in air. Acrolein changes into a vapor much faster than water does at 

normal temperatures. The change of acrolein from a liquid to a vapor becomes faster as 

temperature increases. Acrolein might be found in the air, water, or soil near hazardous waste 

sites if it was not properly stored. Although acrolein may be found in surface water and soil, it 

can quickly evaporate or can be rapidly inactivated by binding to materials in soil; as such, it is 

not likely to last a long time in the environment. 
ACROLEIN 2 

1. PUBLIC HEALTH STATEMENT 

Acrolein is primarily used to make other chemicals and may also be found in some livestock 

feed. Acrolein is itself a pesticide and is added to irrigation canals and the water supplies of 

some industrial plants to control underwater plant, algae, and slime growth. At much higher 

concentrations, it is used to make chemical weapons. 

Small amounts of acrolein can be formed and can enter the air when organic matter such as trees 

and other plants (including tobacco) are burned and also when fuels such as gasoline and oil are 

burned. Acrolein is also formed in building fires at concentrations that can be deadly for 

occupants. Please refer to Chapters 4, 5, and 6 for more information. 

1.2 WHAT HAPPENS TO ACROLEIN WHEN IT ENTERS THE ENVIRONMENT? 

Acrolein can enter the environment as a result of burning wood, tobacco, vehicle fuels; 

overheating of cooking oils; and accidental release from chemical plants or release from a 

hazardous waste site. Acrolein that enters the air as a vapor changes into other chemicals within 

days. When acrolein is introduced into water, it dissolves easily. Some of the acrolein in water 

changes into a vapor and enters the air. The acrolein left in the water is changed into other 

chemicals, which are rapidly broken down, or it may be removed by binding to substances in 

water. 

Acrolein that enters the soil can change into vapor and enter the air, be washed out with water, or 

may bind to soils in such a way as to make it non-toxic. Please refer to Chapter 6 for more 

information. 

1.3 HOW MIGHT I BE EXPOSED TO ACROLEIN? 

If you live near a hazardous waste site in which acrolein is not stored properly, you could be 

exposed to acrolein from breathing air or drinking water that contains acrolein. Because acrolein 

easily changes into a vapor, you are more likely to be exposed to it from breathing air than from 

drinking water. A child playing in this hazardous waste site could be exposed to acrolein by 

drinking surface water, eating soil, or having skin contact with soil that contains acrolein. 
ACROLEIN 3 

1. PUBLIC HEALTH STATEMENT 

However, unless a large amount of acrolein was released at the site, it is unlikely that children 

would be exposed to acrolein in soil given that the acrolein vaporizes from the surface of the soil 

or is changed by binding with soil. 

Acrolein is formed by the breakdown of many pollutants found in outdoor air. Burning tobacco 

and other plants forms acrolein. You breathe in acrolein when you smoke tobacco or when you 

are near someone who is smoking (secondhand smoke). You also breathe in acrolein when you 

are near automobiles, because burning gasoline forms acrolein which enters the air. However, 

the amount of acrolein in automobile exhaust tends to be very low. Your own body can produce 

very small amounts of acrolein when certain fatty molecules or amino acids are broken down. If 

you live near an oil or coal power plant, you breathe in small amounts of acrolein. You could 

breathe in acrolein if you work in an industry that uses acrolein to make other chemicals. 

Acrolein is formed when fats are overheated. Small amounts of acrolein may also be found in 

foods such as fried foods, cooking oils, and roasted coffee. Although we know acrolein is in 

certain foods, the amount that is in the foods that you eat is not known. 

The levels of acrolein are usually low in outside air, averaging around 0.20 parts acrolein in one 

billion parts air (0.2 ppb) in urban air and 0.12 ppb in rural air. However, in several large cities 

acrolein has been measured at levels of 5.6 ppb. The levels of acrolein within the air of a typical 

home range between less than 0.02 and 12 ppb but can be higher if you smoke tobacco in your 

home. 

Acrolein has not been found in drinking water, and it is not commonly found in surface waters 

such as lakes and streams. The background levels of acrolein in these waters or in soil are not 

known. 

Please refer to Chapter 6 for more information on how you might be exposed to acrolein. 
ACROLEIN 4 

1. PUBLIC HEALTH STATEMENT 

1.4 HOW CAN ACROLEIN ENTER AND LEAVE MY BODY? 

If you breathed in acrolein, most of it would enter your body’s tissues within seconds. If you 

swallowed acrolein or spilled it on your skin, some of it would rapidly enter your body’s tissues, 

but we do not know how much. Once in your body tissues, acrolein changes into other 

chemicals called metabolites. This probably occurs within minutes or hours. Some of these 

metabolites leave your body in your urine. It is not known how long this takes. For further 

information on how acrolein can enter and leave your body, see Chapter 3. 

1.5 HOW CAN ACROLEIN AFFECT MY HEALTH? 

Scientists use many tests to protect the public from harmful effects of toxic chemicals and to find 

ways for treating persons who have been harmed. 

One way to learn whether a chemical will harm people is to determine how the body absorbs, 

uses, and releases the chemical. For some chemicals, animal testing may be necessary. Animal 

testing may also help identify health effects such as cancer or birth defects. Without laboratory 

animals, scientists would lose a basic method for getting information needed to make wise 

decisions that protect public health. Scientists have the responsibility to treat research animals 

with care and compassion. Scientists must comply with strict animal care guidelines because 

laws today protect the welfare of research animals. 

How a chemical affects your health depends on the amount and length of time of exposure. As 

you are exposed to more acrolein, and for a longer period of time, the effects that you experience 

are likely to become worse. If you breathed in low levels of acrolein for a short time, your eyes 

might water and your nose and throat might become sore. These effects disappear within 

minutes after the exposure stops. However, if you were exposed to higher levels, your lungs 

might be affected more severely and for a longer time. Breathing in very high levels of acrolein 

might affect your lungs so severely that you might die. 

We do not know if eating food or drinking water containing acrolein affects your health. 

However, animals that swallowed acrolein had stomach irritation, vomiting, stomach ulcers, and 
ACROLEIN 5 

1. PUBLIC HEALTH STATEMENT 

bleeding. No one knows if breathing or eating acrolein or spilling it on your skin causes birth 

defects, affects your ability to have children, or causes cancer. The Department of Health and 

Human Services (DHHS) has not classified acrolein as to its carcinogenicity. The International 

Agency for Resarch on Cancer (IARC) has determined that acrolein is not classifiable as to 

carcinogenicity in humans. The EPA has stated that the potential carcinogenicity of acrolein 

cannot be determined based on an inadequate database. For further information on the health 

effects of acrolein in animals and humans, see Chapters 2 and 3. 

1.6 HOW CAN ACROLEIN AFFECT CHILDREN? 

This section discusses potential health effects in humans from exposures during the period from 

conception to maturity at 18 years of age. 

Acrolein is very irritating to the eyes, nose, throat, lungs, stomach, and skin. In general, children 

are not likely to be affected by acrolein more than adults. However, children who are sensitive 

to irritants in the air (such as children with asthma) may be more sensitive to lung irritation from 

acrolein. 

In animal studies, ingestion of very large amounts of acrolein during pregnancy caused reduced 

birth weights and skeletal deformities in newborns. However, the levels causing these effects 

were often fatal to the mother. These effects were not seen at levels that were also not toxic to 

the mother. 

More information on the effect of acrolein in children can be found in Section 3.7. 

1.7 HOW CAN FAMILIES REDUCE THE RISK OF EXPOSURE TO ACROLEIN? 

If your doctor finds that you have been exposed to substantial amounts of acrolein, ask whether 

your children might also have been exposed. Your doctor might need to ask your state health 

department to investigate. 
ACROLEIN 6 

1. PUBLIC HEALTH STATEMENT 

Children are expected to be exposed to acrolein in the same ways that adults are exposed. Like 

adults, children may be exposed to unknown levels from inhaling second-hand tobacco smoke. 

Children’s exposure from eating or touching contaminated soil is not likely to differ from that of 

adults, because acrolein evaporates quickly, does not move well in soil, and doesn’t last long in 

the environment. You can reduce your family’s exposure to acrolein by reducing their exposure 

to tobacco smoke, smoke from burning wood products or cooking oils and grease, and exhaust 

from diesel or gasoline vehicles. 

1.8 IS THERE A MEDICAL TEST TO DETERMINE WHETHER I HAVE BEEN 

EXPOSED TO ACROLEIN? 

Tests have been developed that can measure acrolein or its breakdown products in blood or 

urine. These tests require specialized laboratory equipment and cannot be performed in a 

physician’s office. These tests also cannot be used to determine whether or not you have been 

exposed to acrolein in the environment, because acrolein can be produced by the breakdown of 

other chemicals in the body. For more detailed information, see Chapters 3 and 7. 

1.9 WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT MADE TO 

PROTECT HUMAN HEALTH? 

The federal government develops regulations and recommendations to protect public health. 

Regulations can be enforced by law. The EPA, the Occupational Safety and Health 

Administration (OSHA), and the Food and Drug Administration (FDA) are some federal 

agencies that develop regulations for toxic substances. Recommendations provide valuable 

guidelines to protect public health, but cannot be enforced by law. The Agency for Toxic 

Substances and Disease Registry (ATSDR) and the National Institute for Occupational Safety 

and Health (NIOSH) are two federal organizations that develop recommendations for toxic 

substances. 

Regulations and recommendations can be expressed as “not-to-exceed” levels, that is, levels of a 

toxic substance in air, water, soil, or food that do not exceed a critical value that is usually based 

on levels that affect animals; they are then adjusted to levels that will help protect humans. 
ACROLEIN 7 

1. PUBLIC HEALTH STATEMENT 

Sometimes these not-to-exceed levels differ among federal organizations because they used 

different exposure times (an 8-hour workday or a 24-hour day), different animal studies, or other 

factors. 

Recommendations and regulations are also updated periodically as more information becomes 

available. For the most current information, check with the federal agency or organization that 

provides it. Some regulations and recommendations for acrolein include the following: 

The EPA: 

•	 has restricted the use of all pesticides containing acrolein and has also identified acrolein 

as a toxic waste; 

•	 requires that companies that make, transport, treat, store, or dispose of acrolein comply 

with the regulations of a federal hazardous waste management program; 

•	 has also proposed standards that limit the amount of acrolein put into publicly owned 

waste water treatment plants; and 

•	 requires that releases or spills of one pound or more be reported to the National Response 

Center. 

The FDA has determined that levels of acrolein used to prepare modified food starch must not be 

more than 0.6%. 

OSHA has set a limit of 0.1 ppm acrolein in workroom air to protect workers during an 8-hour 

shift over a 40-hour workweek. NIOSH recommends that the concentration in workroom air be 

limited to 0.1 ppm averaged over a 10-hour shift. 

1.10 WHERE CAN I GET MORE INFORMATION? 

If you have any more questions or concerns, please contact your community or state health or 

environmental quality department, or contact ATSDR at the address and phone number below. 
 

 

 

 

 

ACROLEIN 8 

1. PUBLIC HEALTH STATEMENT 

ATSDR can also tell you the location of occupational and environmental health clinics. These 

clinics specialize in recognizing, evaluating, and treating illnesses that result from exposure to 

hazardous substances. 

Toxicological profiles are also available on-line at www.atsdr.cdc.gov and on CD-ROM. You 

may request a copy of the ATSDR ToxProfilesTM CD-ROM by calling the toll-free information 

and technical assistance number at 1-800-CDCINFO (1-800-232-4636), by e-mail at 

cdcinfo@cdc.gov, or by writing to: 

Agency for Toxic Substances and Disease Registry 

 Division of Toxicology and Environmental Medicine 

1600 Clifton Road NE 

 Mailstop F-32 

 Atlanta, GA 30333 

 Fax: 1-770-488-4178 

Organizations for-profit may request copies of final Toxicological Profiles from the following: 

National Technical Information Service (NTIS) 

5285 Port Royal Road 

 Springfield, VA 22161 

 Phone: 1-800-553-6847 or 1-703-605-6000 

 Web site: http://www.ntis.gov/ 
 

 

 

ACROLEIN 9 

2. RELEVANCE TO PUBLIC HEALTH 

2.1 BACKGROUND AND ENVIRONMENTAL EXPOSURES TO ACROLEIN IN THE 

UNITED STATES 

Acrolein is a reactive aldehyde primarily used as an intermediate in chemical manufacturing and as a 

biocide. It is used in the synthesis of many organic chemicals, as a biocide in agricultural and industrial 

water supply systems, in the manufacture of methionine (an animal feed supplement), as a warning agent 

(due to its pungent odor) in methyl chloride refrigerant, and as a component of chemical weapons. 

Acrolein can be formed in burning tobacco, wood, plastics, gasoline and diesel fuel, paraffin wax, and in 

the heating of animal and vegetable fats and oils at high temperatures. It is also found naturally in the 

body in very small amounts. 

Because acrolein is formed naturally in the body as a product of lipid oxidation and the metabolism of 

α-hydroxyamino acids, the general population is endogenously exposed to small amounts of acrolein. 

However, the general population is not likely to receive high exposures of acrolein. Individuals likely to 

receive the highest exposures include smokers and those inhaling second-hand smoke, persons in close 

proximity to sources of wood and plastic smoke, including those in the forest products and firefighting 

communities, and populations living or working in areas of dense automotive traffic. The predominant 

route of environmental exposure would be inhalation of smoke or automotive exhaust. No significant 

acrolein exposure is expected from ingestion of drinking water or from dermal contact during bathing or 

showering. 

Acrolein is expected to volatilize rapidly from surface water and soil. Degradation in water, soil, and air 

occur quickly. Thus, environmental persistence is not expected. When applied to surface water as an 

herbicide, acrolein may persist for up to 6 days. It has been detected in 32 of 1,684 National Priority List 

(NPL) sites. It has not been found as a contaminant in drinking water. Acrolein has been detected in very 

low levels in rainwater in Los Angeles, California, a high-smog area. Average acrolein concentrations 

measured at various monitoring stations ranging from 0.5 to 3.186 ppbv (parts acrolein per billion parts of 

air by volume). The concentrations of acrolein in indoor air range from <0.02 to 12 ppb in residential 

homes. Acrolein concentrations are found to be typically higher in indoor air when comparing paired 

indoor/outdoor samples taken at a site. A burned cigarette has been measured to generate 0.06–0.22 mg 

of acrolein, which may result in a variable and significant inhaled concentration for the smoker or by 

stander by increasing the concentration of acrolein in the air of a typical room by 0.4–2 ppb. 
ACROLEIN 10 

2. RELEVANCE TO PUBLIC HEALTH 

With the exception of smoking, children and adults are expected to be exposed to acrolein by the same 

routes of exposure. Like adults, however, children may be exposed to unknown levels of acrolein from 

inhaling second-hand tobacco smoke. Since acrolein is volatile, ineffectively transported in soil, and 

nonpersistent in the environment, children’s dermal exposure from soil contact or ingestion is not likely 

to differ from adults. 

See Chapter 6 for detailed information regarding concentrations of acrolein found in environmental 

media. 

2.2 SUMMARY OF HEALTH EFFECTS 

Acrolein can exert toxic effects following inhalation, oral, and dermal exposures. It is a potent irritant to 

the mucous membranes. At high concentrations, it can also cause irritation to skin. As such, its toxicity 

is exerted at the point of contact with tissues. Signs and symptoms resulting from inhalation exposure to 

airborne acrolein may include irritation of the nose, throat and lungs, pulmonary edema, lung hemorrhage, 

and death. The nasal tissues appear to be the most sensitive target of inhalation exposure, with onset of 

noticeable irritation occurring in seconds (0.3 ppm). Higher airborne concentrations of acrolein (2– 

5 ppm) result in increasingly severe manifestations of irritation over the entire respiratory tract. Oral 

acrolein exposure may result in gastrointestinal discomfort, vomiting, and stomach ulceration and/or 

hemorrhage. The stomach epithelium appears to be the most sensitive target for oral exposure 

(0.75 mg/kg). Higher concentrations of ingested acrolein have primarily resulted in increasingly severe 

irritation effects in the stomach (2 mg/kg and higher). Dermal exposure to acrolein vapors or liquids may 

cause stinging of the eyes, lacrimation, and reddening, ulceration, or necrosis of the skin (10% acrolein 

solution). The eye appears to be the most sensitive target for dermal exposure (0.3 ppm in air). 

Histological changes in respiratory and gastrointestinal epithelium have been observed from both 

inhalation and oral exposures, respectively. Changes in body and organ weights, hematology, and serum 

biochemistry have been observed in animals. Developmental effects, such as skeletal malformations and 

reduced weight of offspring, occurred at exposure levels resulting in maternal mortality. Developmental 

effects were not observed independent of frank maternal toxicity. Some of these effects are believed to be 

secondary effects of gastrointestinal and/or respiratory tract irritation (i.e., loss of appetite and weight loss 

due to gastrointestinal irritation). Similar effects appear to result from similar exposure levels across 

durations of inhalation exposures. In vitro studies have shown acrolein to be weakly mutagenic, capable 

of interfering with DNA repair mechanisms. The evidence for the carcinogenicity of acrolein is weak, 

with a significant tumor incidence found in a single animal drinking water study. Pathology samples 
ACROLEIN 11 

2. RELEVANCE TO PUBLIC HEALTH 

from this study were re-evaluated by an independent pathology working group and tumor incidence was 

determined to be not significantly different than historical controls. A later well-designed cancer bioassay 

in rats orally-gavaged at lower doses failed to detect significant increases in cancer incidence. The 

Department of Health and Human Services (DHHS) has not classified acrolein as to its carcinogenicity. 

The International Agency for Research on Cancer (IARC) has determined that acrolein is not classifiable 

as to carcinogenicity in humans. The EPA has stated that the potential carcinogenicity of acrolein cannot 

be determined based on an inadequate database. 

The following sections discuss significant effects resulting from exposure to acrolein in greater detail: 

eye irritation, respiratory, and gastrointestinal. 

Eye Irritation. Acrolein vapor or liquid causes adverse ocular effects through simple point-of-contact 

irritation. At low airborne levels (0.3 ppm), ocular irritation is perceived as rapid-onset mild to moderate 

stinging of the eyes accompanied by increased blinking. Lacrimation occurs at higher levels (0.81 ppm), 

with an increase in severity of irritant sting. At low levels of vapor exposure, humans appear to adapt to 

ocular irritation, as volunteers exposed to a constant level of acrolein vapors for 60 minutes reported 

increasing irritation of the eyes up to 40 minutes, but reported no further increase in discomfort thereafter. 

Dogs and monkeys appear to be more sensitive than rodents to acrolein, as evidenced by lacrimation and 

blinking or closing of the eyes during intermediate-duration exposures to 3.7 ppm; however, no 

observable ocular changes were reported in guinea pigs and rats exposed for the same duration. It is not 

known at what exposure level acrolein liquid or vapor causes structural damage to the eye, as no 

histological evaluation of the eye following acrolein exposure has been conducted. 

Respiratory Effects. Acrolein may affect the entire respiratory tract, from the nasal epithelium to the 

alveolar spaces. The variety and severity of effects and depth of the respiratory tract to which effects 

extend increases as exposure level increases. Nasal irritation appears to be the most sensitive respiratory 

effect, based on reported irritation in humans and animals and cellular changes observed in animals. 

Rapid onset of nose and throat irritation and a reduction in breathing rate (believed to be a protective 

measure triggered by nose irritation) was reported by volunteers acutely exposed to low levels (0.3 ppm); 

mild nasal epithelial dysplasia, necrosis, and focal basal cell metaplasia have been reported in rats at 

similar concentrations (0.25 ppm). Respiratory irritation was observed in animals as evidenced by 

decreased respiratory rates in mice and rats exposed to 1–3 ppm. Higher acute inhalation exposure levels 

(2–5 ppm) have resulted in more severe effects in animals, including epithelial hyperplasia, inflammation, 

and moderate to severe histological alterations of the nasal, tracheal, and bronchial epithelium, bronchial 
ACROLEIN 12 

2. RELEVANCE TO PUBLIC HEALTH 

epithelial destruction, pulmonary edema, and lung hemorrhage have been seen in mice, rats, and guinea 

pigs. Four human case reports of massive acute acrolein inhalation exposures, either occupationally or 

from heated cooking fats, list similar effects, including high fever, dyspnea, coughing, foamy 

expectoration, cyanosis, pulmonary edema, and death (concentrations unknown). Fatal pulmonary edema 

may develop many hours after a high, acute exposure. Observed effects following intermediate- and 

chronic-duration exposures to acrolein (1–3 ppm) include histological alterations and inflammation across 

the entire respiratory tract of rats, monkeys, guinea pigs, dogs, rabbits, and hamsters. Respiratory effects 

seem to be similar in type of effect and severity across species and exposure duration. 

Gastrointestinal Effects. The irritation of gastrointestinal mucosa appears to be the primary effect 

of oral exposure to acrolein. Human data for oral exposures are not available. The clinical signs of 

gastrointestinal effects in animals are similar and dose-related across species and acute and intermediate 

exposures, although possible adaptation to irritating effects may occur during chronic exposures. Effects 

of increasing severity include vomiting, epithelial hyperplasia, ulceration, hemorrhage, and edema of the 

stomach mucosa. There are little data for low-level (<2 mg/kg/day) acute doses. Acute and intermediate 

exposure effects of high doses (4–25 mg/kg) in mice, rats, and rabbits include severe mucosal 

inflammation ulceration, focal hemorrhage, and edema. Effects from low, intermediate-duration doses of 

2.5 mg/kg/day in mice and female rats resulted in forestomach squamous epithelial hyperplasia. 

Conversely, chronic dosing levels of 2–4.5 mg/kg/day produced no significant gross or histopathological 

effects in rats, mice, or dogs. The reported differences in gastrointestinal sensitivity are not well 

understood; however, study differences in dose volumes may play a role. Dogs chronically given acrolein 

doses by capsule as low as 0.5 mg/kg/day vomited significantly through the first 4 weeks of exposure, but 

appeared to adapt as vomiting incidence was reduced thereafter. Data are not available to determine if an 

adaptive effect for chronic oral exposures would be observed at higher dose levels. 

2.3 MINIMAL RISK LEVELS (MRLs) 

Estimates of exposure levels posing minimal risk to humans (MRLs) have been made for acrolein. An 

MRL is defined as an estimate of daily human exposure to a substance that is likely to be without an 

appreciable risk of adverse effects (noncarcinogenic) over a specified duration of exposure. MRLs are 

derived when reliable and sufficient data exist to identify the target organ(s) of effect or the most sensitive 

health effect(s) for a specific duration within a given route of exposure. MRLs are based on 

noncancerous health effects only and do not consider carcinogenic effects. MRLs can be derived for 
ACROLEIN 13 

2. RELEVANCE TO PUBLIC HEALTH 

acute, intermediate, and chronic duration exposures for inhalation and oral routes. Appropriate 

methodology does not exist to develop MRLs for dermal exposure. 

Although methods have been established to derive these levels (Barnes and Dourson 1988; EPA 1990), 

uncertainties are associated with these techniques. Furthermore, ATSDR acknowledges additional 

uncertainties inherent in the application of the procedures to derive less than lifetime MRLs. As an 

example, acute inhalation MRLs may not be protective for health effects that are delayed in development 

or are acquired following repeated acute insults, such as hypersensitivity reactions, asthma, or chronic 

bronchitis. As these kinds of health effects data become available and methods to assess levels of 

significant human exposure improve, these MRLs will be revised. 

Inhalation MRLs 

•	 An MRL of 0.003 ppm has been derived for acute-duration inhalation exposure (14 days or less) 

to acrolein. 

Studies in both humans and animals have reported acute effects of airborne acrolein. Observed effects 

include nasal irritation, discomfort, and reduction in respiratory rate in humans (Weber-Tschopp et al. 

1977), reduction in respiratory rate in mice (Buckley et al. 1984; Kane and Alarie 1977) and rats (Cassee 

et al. 1996), histological changes in nasal epithelium of rats and mice (Cassee et al. 1996; Nielsen et al. 

1984; Steinhagen and Barrow 1984), and reduction in bactericidal activity (as reflected by macrophagic 

clearance of Klebsiella pneumoniae bacteria) in mice (Aranyi et al. 1986). More severe observed effects 

include high fever, dyspnea, coughing, foamy expectoration, cyanosis, tracheal and alveolar epithelial 

destruction, pulmonary edema, lung hemorrhage, and possible death in humans, mice, rats, guinea pigs, 

hamsters, and dogs (Buckley et al. 1984; Catilina et el. 1966; Champeix et al. 1966; Dahlgren et al. 1972; 

Hales et al. 1988; Kilburn and Mackenzie 1978; Murphy et al. 1964; Skog 1950). 

A reduction in bactericidal activity in rat lungs was observed at 0.1 ppm (Aranyi et al. 1986), the lowest 

lowest-observed-adverse-effect level (LOAEL) identified, and at 3 ppm (Astry and Jakab 1983). The 

biological significance of this finding is unclear. Irritation of the nasal epithelium of rats exposed to 

0.25 ppm resulted in mild disarrangement and necrosis of nasal epithelium (Cassee et al. 1996). Animals 

in the same study exposed to 0.67 ppm exhibited focal basal cell metaplasia, reduced epithelial 

glutathione reductase activity, cellular disarrangement, necrosis, and cell proliferation of the nasal 

respiratory epithelium. Mice and rats exhibited decreased respiratory rates following exposures of 1– 

3 ppm (Kane and Alarie 1977; Nielsen et al. 1984; Steinhagen and Barrow 1984). Severe irritation and 
ACROLEIN 14 

2. RELEVANCE TO PUBLIC HEALTH 

lung hemorrhage were observed in rats exposed to 130 ppm (Skog 1950). Death occurred in rats exposed 

to acrolein levels ranging from 130 to 327 ppm for 30 and 10 minutes, respectively (Catilina et al. 1966; 

Skog 1950). 

Nasal irritation in humans has been observed at levels similar to those seen in animals. Weber-Tschopp et 

al. (1977) exposed volunteers for 40 minutes to gradually increasing levels of acrolein vapors. At the end 

of 15 minutes, exposure levels were approximately 0.26 ppm. Volunteers scored irritancy as “a little” or 

“medium”, which was statistically different from controls. However, the changing concentrations of 

acrolein made it difficult to fix the duration or level of exposure that was actually responsible for the 

onset of significant irritation. In another test reported in Weber-Tschopp et al. (1977), volunteers exposed 

to 0.3 ppm acrolein for 60 minutes scored nose and throat irritation as “a little irritating” by 40 minutes 

into the exposure. A decrease in respiratory rate was also observed. This test, with a fixed exposure level 

and duration, was used as the basis for an acute duration inhalation MRL, providing a LOAEL of 

0.3 ppm. 

An acute duration inhalation MRL of 0.003 ppm was derived using the LOAEL of 0.3 ppm for nasal and 

throat irritation and decreased respiratory rate in humans. The LOAEL of 0.3 ppm was divided by an 

uncertainty factor of 100 (10 for using a LOAEL and 10 for human variability). 

While Aranyi et al. (1986) reported a LOAEL of 0.1 ppm for reduced bactericidal activity in rats, the 

toxicological significance of this finding is unclear. Cassee et al. (1996) reported a LOAEL of 0.25 ppm, 

which was very similar to the human LOAEL of 0.3 ppm. This being the case, the human-derived data 

were deemed preferable for the basis of the MRL, eliminating the introduction of uncertainty from interspecies extrapolation. 

•	 An MRL of 0.00004 ppm has been derived for intermediate-duration inhalation exposure (15– 

364 days) to acrolein. 

No data were available for intermediate-duration exposure of humans to acrolein. Exposures to airborne 

acrolein concentrations between 0.4 and 5.0 ppm for up to 180 days caused a continuum of histological 

alterations, inflammation, and severe tissue destruction across the entire respiratory tract of rats, rabbits, 

guinea pigs, and monkeys (Costa et al. 1986; Feron et al. 1978; Kutzman et al. 1984, 1985; Lyon et al. 

1970). Effects in the deeper respiratory tract became more severe at the 3–5 ppm exposure levels. 

Effects included tracheal epithelial metaplasia in hamsters (Feron et al. 1978), epithelial dysplasia in rats 

(Leach et al. 1987), squamous lung epithelial metaplasia in rats (Kutzman et al. 1985), tracheal metaplasia 
ACROLEIN 15 

2. RELEVANCE TO PUBLIC HEALTH 

and bronchial necrosis in rats (Feron et al. 1978; Kutzman et al. 1985), pulmonary edema in rats (Costa et 

al. 1986), and lung hemorrhage in monkeys (Lyon et al. 1970). 

The most sensitive effect for intermediate-duration inhalation appears to be nasal epithelial metaplasia 

and bronchial inflammation. These effects were observed in rats at 0.4 ppm (Feron et al. 1978; Kutzman 

et al. 1984). Lung inflammation was seen in monkeys and guinea pigs at 0.7 ppm (Lyon et al. 1970). At 

1–1.4 ppm, bronchiolar, lung, and liver inflammation were observed in guinea pigs, hamsters, and rats 

(Feron et al. 1978; Kutzman et al. 1985; Lyon et al. 1970). At 1.4–1.8 ppm, lung and tracheal hyperplasia 

was seen in rats and monkeys (Costa et al. 1986; Lyon et al. 1970). Lung hemorrhage and decreased 

weight gain occurred in monkeys at 3.7 ppm (Lyon et al. 1970). Increased brain weight, tracheal 

squamous metaplasia, bronchial necrosis, and lung edema were observed in rats at 4 ppm (Costa et al. 

1986; Kutzman et al. 1985). Monkeys and rats died at 3.7–4 ppm (Kutzman et al. 1985; Lyon et al. 

1970). 

The intermediate-duration inhalation MRL was based on the lowest identified LOAEL of 0.4 ppm for 

nasal metaplasia in rats (Feron et al. 1978). This study compared the effects of a 13-week exposure of 

rats, rabbits, and hamsters for 6 hours/day, 5 days/week to 0.4, 1.4, and 4.0 ppm acrolein. The rat 

appeared to be the most sensitive species in the study, exhibiting more severe histological changes across 

the respiratory tract than the other species. Though bronchiolar inflammation was also observed in rats at 

0.4 ppm (Feron et al. 1978), structural changes in the nasal epithelium appear to be a more sensitive 

effect, as such changes have been observed in lower, acute inhalation exposures of rats (Cassee et al. 

1996). Structural changes to lung cells have not been observed in rats below 1.4 ppm (Costa et al. 1986). 

For these reasons, the LOAEL of 0.4 ppm for nasal metaplasia in rats was chosen as the most sensitive 

end point for the derivation of an intermediate-duration inhalation MRL. 

The intermediate-duration inhalation MRL of 0.00004 ppm was derived by dividing the human equivalent 

LOAEL (LOAELHEC) of 0.012 ppm by 300 (10 for using a LOAEL, 3 for species extrapolation using 

dosimetric adjustment, and 10 for human variability). The duration-adjusted LOAEL (LOAELADJ) was 

calculated as follows: 

LOAELADJ = 0.4 ppm x 6 hours/24 hours x 5 days / 7 days = 0.071 ppm 
ACROLEIN 16 

2. RELEVANCE TO PUBLIC HEALTH 

Dosimetric adjustments for species differences for a category 1 gas in rats and humans (EPA 1994b) 

resulted in a regional gas dose ratio for the extrathoracic region (RGDRET) of 0.17. The LOAELADJ was 

multiplied by the RGDRET to derive the LOAELHEC of 0.012 ppm as follows: 

LOAELHEC = LOAELADJ x RGDR = 0.071 x 0.17 = 0.012 ppm 

No chronic-duration MRL for inhalation of acrolein was derived due to an inadequate database. An 

18-month study with rats (Le Bouffant et al. 1980) reported epithelial hyperplasia. However, the study 

involved a 1-hour exposure to a very high concentration (8 ppm) of acrolein in which acrolein-treated 

animals were compared histologically to animals exposed daily to cigarette smoke rather than controls. 

The study is unclear as to whether this effect was attributable to the animals' exposure to acrolein or 

cigarette smoke. 

Oral MRLs 

No human oral exposure data for any exposure duration were available. Oral exposure studies in rabbits 

(Parent et al. 1993) and rats (Sakata et al. 1989) exposed to 4 and 25 mg/kg/day, respectively, reported 

severe stomach ulceration and edema, and death. Pregnant rabbits given 2 mg/kg/day by gavage 

exhibited a transient decrease in body weight which rebounded completely in 3 days (Parent et al. 1993). 

The lowest acute LOAEL identified was capsule dosing of 0.5 mg/kg/day in dogs, which resulted in 

vomiting shortly after dosing for the first 4 weeks of a chronic study (Parent et al. 1992b). This effect 

was transient and may have been impacted by the capsule sub-route of administration. Further, statistical 

significance of the vomiting incidence was not determined. Since a higher no-observed-adverse-effect 

level (NOAEL) of 1.25 mg/kg/day was identified in a well-conducted intermediate-duration oral gavage 

study (NTP 2006), no acute-duration MRL for ingestion of acrolein was derived. 

•	 An MRL of 0.004 mg/kg/day has been derived for intermediate-duration oral exposure (15– 

364 days) to acrolein. 

No studies were located for intermediate-duration oral exposure to acrolein in humans. The limited 

number of animal studies identified for this exposure duration reported similar effects on the 

gastrointestinal and respiratory mucosa from oral and inhalation exposures, respectively. Forestomach 

squamous epithelial hyperplasia was seen in rats and mice given 2.5 mg/kg/day by gavage (NTP 2006). 

Forestomach and glandular stomach hyperplasia, ulcers, and glandular stomach hemorrhage were 

observed in rats given 3 mg/kg/day (Parent et al. 1992c). Stomach ulceration and hemorrhage was 
 

 

ACROLEIN 17 

2. RELEVANCE TO PUBLIC HEALTH 

observed in rats given 5.4–10 mg/kg/day (King 1984; NTP 2006). Labored breathing and increased 

mortality were seen in rats given 6 mg/kg/day (Parent et al. 1992c). Stomach hemorrhage was observed 

in rats and mice given 10 and 20 mg/kg/day, respectively, while stomach necrosis was observed in mice 

given 20 mg/kg/day (NTP 2006). 

The 14-week gavage toxicity study in rats and mice (NTP 2006) served as the basis for deriving an 

intermediate-duration oral MRL. In this study, rats were administered 0.75, 1.25, 2.5, 5, and 

10 mg/kg/day by gavage for 14 weeks, while mice were given 1.25, 2.5, 5, 10, and 20 mg/kg/day for the 

same duration. Glandular stomach lesions were observed in male and female mice gavaged with 

20 mg/kg/day. Glandular stomach lesions were observed in rats given 10 mg/kg/day. Forestomach 

squamous epithelial hyperplasia was observed in male and female rats gavaged with 5 and 2.5 mg/kg/day, 

respectively, and in male and female mice gavaged with 2.5 mg/kg/day. No significant effect was 

observed in male or female mice or female rats given 1.25 mg/kg/day or in male rats given 

2.5 mg/kg/day. Although humans do not have a forestomach, this study provides an example of 

gastrointestinal mucus membrane irritation. Similar irritative effects are expected in humans. This effect 

represented the highest identified NOAEL associated with the lowest LOAEL in a well-designed study 

and served as the basis for the intermediate oral MRL. 

The intermediate-duration oral MRL of 0.004 mg/kg/day was derived by dividing the 95% lower 

confidence limit on the benchmark dose for 10% extra risk (BMDL10) of 0.36 mg/kg/day for forestomach 

squamous epithelial hyperplasia in mice by a factor of 100 (10 for species extrapolation and 10 for human 

variability). 

No chronic-duration oral MRL was derived for acrolein due to an inadequate database. Chronic gavage 

studies in which rats were dosed with up to 2.5 mg/kg/day for 24 months (Parent et al. 1992a), mice were 

gavage dosed with up to 4.5 mg/kg/day for 18 months (Parent et al. 1991a), and dogs were gavage dosed 

with up to 2 mg/kg/day for 12 months (Parent et al. 1992b) all failed to produce significant gross or 

histopathological changes as have been observed in other studies of the same species at lower dose levels 

(NTP 2006). One possible explanation for discrepancies in effects observed by Parent et al. (1991a, 

1992a, 1992b) and NTP (2006) is the use of a thickening agent in the dosing vehicle of the NTP (2006) 

study, which may have increased the gastrointestinal residence time compared to doses in the Parent et al. 

(1991a, 1992a, 1992b) studies, which administered acrolein in a deionized water vehicle. Body weight 

decreases were significant in male mice and rats (Parent et al. 1991a, 1992c); however, the magnitude of 

body weight change could not be determined since variation between treatment groups was not reported. 
ACROLEIN 18 

2. RELEVANCE TO PUBLIC HEALTH 

The Parent et al. (1992b) rat study also reported significantly depressed serum creatinine phosphokinase 

levels. However, the significance of this finding is unknown. Decreased survival (increased mortality) 

was observed in rats and mice dosed with 0.5 and 4.5 mg/kg/day, respectively (Parent et al. 1991a, 

1992a), but no explanation for the mortality was given. 
ACROLEIN 19 

3. HEALTH EFFECTS 

3.1 INTRODUCTION 

The primary purpose of this chapter is to provide public health officials, physicians, toxicologists, and 

other interested individuals and groups with an overall perspective on the toxicology of acrolein. It 

contains descriptions and evaluations of toxicological studies and epidemiological investigations and 

provides conclusions, where possible, on the relevance of toxicity and toxicokinetic data to public health. 

A glossary and list of acronyms, abbreviations, and symbols can be found at the end of this profile. 

3.2 DISCUSSION OF HEALTH EFFECTS BY ROUTE OF EXPOSURE 

To help public health professionals and others address the needs of persons living or working near 

hazardous waste sites, the information in this section is organized first by route of exposure (inhalation, 

oral, and dermal) and then by health effect (death, systemic, immunological, neurological, reproductive, 

developmental, genotoxic, and carcinogenic effects). These data are discussed in terms of three exposure 

periods: acute (14 days or less), intermediate (15–364 days), and chronic (365 days or more). 

Levels of significant exposure for each route and duration are presented in tables and illustrated in 

figures. The points in the figures showing no-observed-adverse-effect levels (NOAELs) or lowestobserved-adverse-effect levels (LOAELs) reflect the actual doses (levels of exposure) used in the studies. 

LOAELs have been classified into "less serious" or "serious" effects. "Serious" effects are those that 

evoke failure in a biological system and can lead to morbidity or mortality (e.g., acute respiratory distress 

or death). "Less serious" effects are those that are not expected to cause significant dysfunction or death, 

or those whose significance to the organism is not entirely clear. ATSDR acknowledges that a 

considerable amount of judgment may be required in establishing whether an end point should be 

classified as a NOAEL, "less serious" LOAEL, or "serious" LOAEL, and that in some cases, there will be 

insufficient data to decide whether the effect is indicative of significant dysfunction. However, the 

Agency has established guidelines and policies that are used to classify these end points. ATSDR 

believes that there is sufficient merit in this approach to warrant an attempt at distinguishing between 

"less serious" and "serious" effects. The distinction between "less serious" effects and "serious" effects is 

considered to be important because it helps the users of the profiles to identify levels of exposure at which 

major health effects start to appear. LOAELs or NOAELs should also help in determining whether or not 
ACROLEIN 20 

3. HEALTH EFFECTS 

the effects vary with dose and/or duration, and place into perspective the possible significance of these 

effects to human health. 

The significance of the exposure levels shown in the Levels of Significant Exposure (LSE) tables and 

figures may differ depending on the user's perspective. Public health officials and others concerned with 

appropriate actions to take at hazardous waste sites may want information on levels of exposure 

associated with more subtle effects in humans or animals (LOAELs) or exposure levels below which no 

adverse effects (NOAELs) have been observed. Estimates of levels posing minimal risk to humans 

(Minimal Risk Levels or MRLs) may be of interest to health professionals and citizens alike. 

A User's Guide has been provided at the end of this profile (see Appendix B). This guide should aid in 

the interpretation of the tables and figures for Levels of Significant Exposure and the MRLs. 

3.2.1 Inhalation Exposure 

3.2.1.1 Death 

The only available information regarding lethal effects in humans after inhalation exposure to acrolein 

was provided by Gosselin et al. (1979), who described the cases of 2- and 4-year-old boys exposed for 

2 hours to acrolein-containing smoke from an overheated fryer. The 2-year-old boy died 24 hours later of 

asphyxia. The data from this case report must be considered qualitative only, since smoke components 

other than acrolein may have contributed to the injury. 

The data in experimental animals clearly indicate that respiratory toxicity is a primary cause of acrolein 

lethality following inhalation and show an inverse relationship between the exposure concentration and 

the time it takes for death to occur after acute-duration exposures. Exposure of rats to airborne 

concentrations of acrolein of 100–40,000 ppm for short periods of time (<l hour) caused death ranging 

from minutes to 11 days (Catilina et al. 1966; Crane et al. 1986; Skog 1950). Death was attributed to 

obstruction of trachea and bronchi, pulmonary edema, or hemorrhage. Single and repeated exposures to 

3–4 ppm acrolein caused death in rats and monkeys before the 10th day of exposure (Carpenter et al. 

1949; Kutzman 1981; Kutzman et al. 1984, 1985; Lyon et al. 1970). Respiratory congestion was 

observed in the monkeys. Animal data regarding cause of death are in good agreement with observations 

made in humans after accidental exposure (Gosselin et al. 1979). Reliable LOAELs for lethality in 

experimental animals following inhalation exposure to acrolein are presented in Table 3-1 and Figure 3-1. 
126

3.7

1

327327

15

130

43

0.3

Table 3-1 Levels of Significant Exposure to Acrolein - Inhalation 

a 

Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) 

ACUTE EXPOSURE Death 

1 Monkey 6 wk 

5 d/wk 8 hr/d 

System 

NOAEL 

(ppm) 

Less Serious 

(ppm) 

LOAEL 

Serious 

(ppm) 

3.7 (1/9 died) 

Reference Chemical Form 

Lyon et al. 1970 

2 Rat 

(Wistar) 

1 d 10 min/d 327 (LC50) 

327 M (LC50) 

Catilina et al. 1966 

3 Rat 

(NS) 

1 d 30 min/d 130 (28/48 died) Skog 1950 

Systemic 

4 Human 1 d 

1 hr/d Resp 

b

0.3 (decreased respiratory 

rate, nose and throat irritation) 

Weber-Tschopp et al. 1
171

1

2

160

0.671.40.25

Table 3-1 Levels of Significant Exposure to Acrolein - Inhalation (continued) 

a 

Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) System NOAEL (ppm) Less Serious (ppm) 

LOAEL 

Serious 

(ppm) 

Reference Chemical Form 

5 Rat 

(Wistar) 

1 x 4 hr Resp 1 M (lipid peroxidation of respiratory tissues as 

indicated by reduced levels of ascorbic acid, alpha-tocopherol, reduced glutathione, thiols, angiotensin -converting enzyme, lactase, lactase dehydrogenase, catalase and glutathione peroxidase activities. Increased levels of TBARS, conjugated dienes, superoxide dismutase activity) 

2 M (desquamized and 

mononuclear cells, hyperemia, and emphysema) 

Arumugam et al. 1999 

6 Rat 

(Wistar) 

6 hr/d 3 d Resp 0.67 F (nasal epithelial dysplasia, moderate 

necrosis, desquamation, basal cell hyperplasia) 

Cassee et al. 1996 

1.4 F (nasal epithelial cell 

proliferation, reduced glutathione activity) 

0.25 F (nasal epithelial 

dysplasia, slight necrosis, desquamation, basal cell hyperplasia) 
2

327283

181

9.1

182

2

10

44

11

1 2.1

12

3.9

Table 3-1 Levels of Significant Exposure to Acrolein - Inhalation (continued) 

a 

Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) System NOAEL (ppm) 

LOAEL 

Less Serious 

(ppm) 

Serious 

(ppm) 

Reference Chemical Form 

7 Rat 

(Wistar) 

1 d 10 min/d Resp 327 (epithelial desctruction) Catilina et al. 1966

283 M (mucosal secretions, 

ciliary destruction, moderate laryngeal edema, scattered punctuate hemorrhaging) 

8 Rat 

(Fischer- 344) 

1 x/d 40 min Resp 9.1 M (increased albumin in Morris 1996 nasal lavage fluid) 

9 Rat 

(Fischer- 344) 

1 x/d 50 min Resp 2 M (vasodilation of upper Morris et al. 1999 respiratory tract) 

10 Rat 5 d 

4 hr/d Hepatic 4 (decrease in relative liver Murphy et al. 1964 weight) 

Bd Wt 4 (decreased body weight) 

11 Rat 20-81 hr Hepatic 1 2.1 (increase in liver weight) Murphy et al. 1964

12 Rat 9 d 

4 hr/d Hepatic 3.9 (decrease in relative liver Murphy et al. 1964 weight) 
13

12

16

130

22

1.7

24

1.7

177

1.1

178

1.3

179

0.3

Table 3-1 Levels of Significant Exposure to Acrolein - Inhalation (continued) 

Exposure/ 

Duration/ 

Frequency 

(Route) System NOAEL (ppm) Less Serious (ppm) 

LOAEL 

Serious 

(ppm) 

Reference Chemical Form 

1 d 4 hr/d Resp 12 (severe respiratory tract irritation) Murphy et al. 1964 

1 d 30 min/d Resp 130 (lung hemorrhage) Skog 1950 

5 d 6 hr/d Resp 1.7 (RD50, olfactory exfoliation erosion, 

ulceration, necrosis and squamous metaplasia) 

Buckley et al. 1984 

4 d 3 hr/d Resp 1.7 (RD50) Kane and Alarie 1977 

1 x/d 50 min Resp 1.1 (increased airflow resistance) Morris et al. 2003 

1 x/d 10 min Resp 1.3 (decreased breathing rate and airway 

resistance; increased respiratory pause) 

Morris et al. 2003 

1 x/d 10 min Resp 0.3 (decreased breathing rate relative to 

non-diseased animals) 

Morris et al. 2003 

a 

Key to 

Figure 

13 14 15 16 17 18 19 

Species 

(Strain) 

Rat Rat Mouse Mouse Mouse (C57BL/6N) Mouse (C57BL/6N) Mouse (C57BL/6N) 
25

2.9

26

1.03

27

1.41

35

17

36

0.6

18

0.1

20

3

173

4

Table 3-1 Levels of Significant Exposure to Acrolein - Inhalation (continued) 

a 

Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) System NOAEL (ppm) Less Serious (ppm) 

LOAEL 

Serious 

(ppm) 

Reference Chemical Form 

20 Mouse 1 d 

30 min/d Resp 2.9 (RD50) Nielsen et al. 1984 

21 Mouse 

(SwissWebster) 

1 d 10 min/d Resp 1.03 (RD50) Steinhagen and Barrow 

22 Mouse 

(B6C3F1) 

1 d 10 min/d Resp 1.41 (RD50) Steinhagen and Barrow 

23 Gn Pig 1 d 

60 min/d Resp 17 (decreased respiratory rate) Davis et al. 1967 

24 Gn Pig 

Immuno/ Lymphoret 

25 Mouse 

1 d 2 hr/d 5 d 3 hr/d 

Resp 0.6 

0.1 (decreased resistance to 

respiratory tract infection) 

Murphy et al. 1963 Aranyi et al. 1986 

26 Mouse 1 d 

8 hr/d 3 (decreased resistance to respiratory tract infection) Astry and Jakab 1983 

INTERMEDIATE EXPOSURE Death 

27 Rat 

(Fischer- 344) 

6 hr/d 5 d/wk 62 d 

4 M (32/57 died) Kutzman 1981 
47

0.550.550.55

172

262

50

1.4

4

4

Table 3-1 Levels of Significant Exposure to Acrolein - Inhalation (continued) 

a 

Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) System NOAEL (ppm) Less Serious (ppm) 

LOAEL 

Serious 

(ppm) 

Reference Chemical Form 

Systemic 

28 Rat >60<180 d 

7 d/wk 24 hr/d 

Resp 0.55 M (increased relative lung 

weight) 

Bouley et al. 1975 

Hepatic 0.55 M (increased relative liver 

weight) 

Bd Wt 0.55 M (decreased body weight 

gain) 

29 Rat 

(Wistar) 

8 wk 10 min/d Resp 262 M (peribronchiolar hemorrhage; bronchial 

lumen obstruction) 

Catilina et al. 1966 

30 Rat 

(Fischer- 344) 

62 d 5 d/wk 6 hr/d 

Resp 1.4 (lung hyperplasia) 4 (lung edema and 

decreased function) 

Costa et al. 1986 

Bd Wt 4 (decreased body weight 

gain) 
52

0.4 4.9

1.4 4.94.94.91.4

4.9

175

1.44

Table 3-1 Levels of Significant Exposure to Acrolein - Inhalation (continued) 

a 

Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) System NOAEL (ppm) 

LOAEL 

Less Serious 

(ppm) 

Serious 

(ppm) 

Reference Chemical Form 

31 Rat 13 wk 

5 d/wk 6 hr/d 

Resp 

c

0.4 (nasal squamous 

epithelial metaplasia) 

4.9 (lung hemorrhage, 

necrotizing rhinitis) 

Feron et al. 1978 

Cardio Hemato Hepatic Renal 

1.4 

4.9 4.9 1.4 

4.9 (increase in heart weight) 4.9 (increase in kidney 

weight) 

32 Rat 

(Fischer- 344) 

6 hr/d 5 d/wk 62 d 

Resp 1.4 (bronchiolar epithelial 

hyperplasia, necrosis) 

Kutzman 1981 

Bd Wt 4 M (decreased body weight 

gains) 
81

1.4

4

1.441.444

54

33

55

0.7

3.73.7

3.7

Table 3-1 Levels of Significant Exposure to Acrolein - Inhalation (continued) 

LOAEL 

a 

Key to 

Figure 

33 34 35 

Species 

(Strain) 

Rat Rat Rat 

Exposure/ 

Duration/ 

Frequency 

(Route) 

62 d 5 d/wk 6 hr/d 3 wk 5 d/wk 6 hr/d 6 wk 5 d/wk 8 hr/d 

NOAEL Less Serious 

(ppm) (ppm) 

1.4 (bronchiolar 

inflammation) 

1.4 

4 (increase in heart weight) 

1.4 

4 (increase in kidney 

weight) 

4 (decrease in body weight 

gain) 

3 (epithelial dysplasia) 3 (decreased body weight 

gain) 

0.7 (peribronchial 

inflammation) 

3.7 3.7 

3.7 (decreased body weight 

gain) 

Serious 

(ppm) 

4 (bronchiolar necrosis) 

Reference Chemical Form 

Kutzman et al. 1985 Leach et al. 1987 Lyon et al. 1970 

System 

Resp Cardio Hepatic Renal Bd Wt Resp Bd Wt Resp Renal Dermal Bd Wt 
58

1.81.81.80.22 11.81.8

1

77

0.320.06

0.32

170

0.22 11.80.22 1

Table 3-1 Levels of Significant Exposure to Acrolein - Inhalation (continued) 

Exposure/ 

Duration/ 

a 

Key to Species Frequency 

Figure (Strain) (Route) 

36 Rat 90 d 

7 d/wk 24 hr/d 

37 Rat 61 d 

24 hr/d 

38 Gn Pig 90 d 

7 d/wk (Hartley) 24 hr/d 

System 

Resp Cardio Hemato Hepatic Renal Dermal Bd Wt Hemato Bd Wt Resp Hemato Hepatic 

LOAEL 

NOAEL 

(ppm) 

Less Serious 

(ppm) 

Serious 

(ppm) 

Reference Chemical Form 

1.8 Lyon et al. 1970 

1.8 

1.8 

0.22 

1.8 1.8 

1 1 

(focal necrosis) (decreased body weight 

gain) 

0.32 Sinkuvene 1970 

0.06 0.32 (decreased body weight 

gain) 

0.22 1 (pulmonary inflammation) Lyon et al. 1970 

1.8 

0.22 1 (liver inflammation) 
70

0.7

3.73.73.73.7

68

0.4

1.4 4.9

1.4 4.9

4.9

4.91.4

4.9

1.4

4.9

53

3

59

3

Table 3-1 Levels of Significant Exposure to Acrolein - Inhalation (continued) 

a 

Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) System NOAEL (ppm) Less Serious (ppm) 

LOAEL 

Serious 

(ppm) 

Reference Chemical Form 

39 Gn Pig 

(Hartley) 

6 wk 5 d/wk 8 hr/d 

Resp 0.7 (peribronchial 

inflammation) 

Lyon et al. 1970 

Hemato 3.7 Renal 3.7 Dermal 3.7 Bd Wt 3.7 

40 Hamster 13 wk 

5 d/wk 6 hr/d 

Resp 0.4 1.4 (nasal epithelial 

inflammation) 

4.9 (tracheal metaplasia, 

necrotizing rhinitis) 

Feron et al. 1978 

Cardio Hemato Hepatic Renal 

1.4 

4.9 1.4 

4.9 (increased heart weight) 4.9 (increases in PCV) 4.9 (increase in kidney 

weight) 

Bd Wt 1.4 4.9 (decreased body weight 

gain) 

Immuno/ Lymphoret 

41 Rat 3 wk 

5 d/wk 6 hr/d 

3 Leach et al. 1987 

42 Rat 3 wk 

5 d/wk 6 hr/d 

3 Sherwood et al. 1986 
89

1.8

74

4

67

4.9

176

4

Table 3-1 Levels of Significant Exposure to Acrolein - Inhalation (continued) 

a 

Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) System NOAEL (ppm) Less Serious (ppm) 

LOAEL 

Serious 

(ppm) 

Reference Chemical Form 

Neurological 

43 Monkey 90 d 

7 d/wk 24 hr/d 

1.8 Lyon et al. 1970 

44 Rat 62 d 

5 d/wk 6 hr/d 

4 (increase in brain weight) Kutzman et al. 1984 

45 Hamster 13 wk 

5 d/wk 6 hr/d 

4.9 Feron et al. 1978 

Reproductive 

46 Rat 

(Fischer- 344) 

6 hr/d 5 d/wk 62 d 

4 Kutzman 1981 

a The number corresponds to the entries in Figure 3-1. b Used to derive an acute inhalation MRL of 0.003 ppm; dose divided by an uncertainty factor of 100 (10 for human variability and 10 for use of a LOAEL). c Used to derive an intermediate inhalation MRL of 0.00004 ppm; dose adjusted for duration and inter-species dosimetry of a category 1 gas, and divided by an unc300 (3 for interspecies dosimetry, 10 for human variability and 10 for use of a LOAEL). Bd Wt = body weight; Cardio = cardiovascular; d = day(s); F = Female; Gn pig = guinea pig; Hemato = hematological; hr = hour(s); LC50 = lethal concentration, 50%lowest-observed-adverse-effect level; M = male; min = minute(s); NOAEL = no-observed-adverse-effect level; PCV = packed cell volume; ppm = parts per million; Rdecrease in respiratory rate; Resp = respiratory; TBARS = thiobarbituric acid reactive substances; wk = week(s); x = time(s) 
Death 

Respiratory Hepatic Body Weight Immuno/Lymphor 

1000 

Figure 3-1 Levels of Significant Exposure to Acrolein - Inhalation
	

Acute (≤14 days)
	

Systemic
	

ppm 

2r 2r 7r 7r 

3r 14r 

100 

23g 

13r 10 8r 

1k 10r 12r 10r

20m 26m

5r 9r 11r 15m 16m 

18m 22m 6r

1 17m 21m 5r 11r 

6r 24g 

4 19m 6r 

0.1 25m 

0.01 

0.001 

c-Cat 

d-Dog

r-Rat 

p-Pig

q-Cow

 -Humans 

k-Monkey

m-Mouse 

h-Rabbit 

a-Sheep 

f-Ferret 

j-Pigeon

e-Gerbil 

s-Hamster 

g-Guinea Pig 

n-Mink 

o-Other

 Cancer Effect Level-Animals

 LOAEL, More Serious-Animals

LOAEL, Less Serious-Animals

NOAEL - Animals

 Cancer Effect Level-Humans

 LOAEL, More Serious-Humans

LOAEL, Less Serious-Humans

NOAEL - Humans

 LD50/LC50

Minimal Risk Level

 for effects

 other than

 Cancer 
Death 

Respiratory Cardiovascular Hematological Hepatic Renal Dermal Body Weight 

Figure 3-1 Levels of Significant Exposure to Acrolein - Inhalation (Continued)
 

Intermediate (15-364 days)
	

Systemic 

ppm

1000 

29r 

100 

10 

40s 31r 40s 31r 40s 31r 40s 31r 40s 31r 40s 27r 30r 33r 33r 39g 39g 33r 35r 39g 35r 39g 30r

34r
	

36r
	 36r 38g 36r 36r 36r 40s 30r 32r 33r 40s 31r 33r 33r 40s 31r 40s 

1 38g 38g 36r 

39g 35r 28r 28r 28r 

40s 31r 37r 

38g 38g 36r 

0.1 

0.01 

0.001 

0.0001 

c-Cat 

d-Dog

r-Rat 

p-Pig

q-Cow

 -Humans 

k-Monkey

m-Mouse 

h-Rabbit 

a-Sheep 

f-Ferret 

j-Pigeon

e-Gerbil 

s-Hamster 

g-Guinea Pig 

n-Mink 

o-Other

 Cancer Effect Level-Animals

 LOAEL, More Serious-Animals

LOAEL, Less Serious-Animals

NOAEL - Animals

 Cancer Effect Level-Humans

 LOAEL, More Serious-Humans

LOAEL, Less Serious-Humans

NOAEL - Humans

 LD50/LC50

 for effects

 other than

 Cancer 

Minimal Risk Level 
Body Weight 

Immuno/Lymphor Neurological Reproductive 

Figure 3-1 Levels of Significant Exposure to Acrolein - Inhalation (Continued)

Intermediate (15-364 days) 

Systemic 

ppm

1000 

100 

10 

45s 32r 33r 35r 44r 46r

34r 41r 42r 

43k 

1 36r 

37r 

0.1 

37r 

0.01 

0.001 

0.0001 

c-Cat 

d-Dog

r-Rat 

p-Pig

q-Cow

 -Humans 

k-Monkey

m-Mouse 

h-Rabbit 

a-Sheep 

f-Ferret 

j-Pigeon

e-Gerbil 

s-Hamster 

g-Guinea Pig 

n-Mink 

o-Other

 Cancer Effect Level-Animals

 LOAEL, More Serious-Animals

LOAEL, Less Serious-Animals

NOAEL - Animals

 Cancer Effect Level-Humans

 LOAEL, More Serious-Humans

LOAEL, Less Serious-Humans

NOAEL - Humans

 LD50/LC50

 for effects

 other than

 Cancer 

Minimal Risk Level 
ACROLEIN 35 

3. HEALTH EFFECTS 

3.2.1.2 Systemic Effects 

No studies were located regarding gastrointestinal, musculoskeletal, renal, or dermal effects in humans or 

animals after inhalation exposure to acrolein. NOAEL values and all reliable LOAEL values for systemic 

effects in each species and duration category are recorded in Table 3-1 and plotted in Figure 3-1. 

Respiratory Effects. Champeix et al. (1966) reported a case of a 36-year-old male who was 

accidentally exposed to unknown concentrations of acrolein vapors in the workplace for <1 day (duration 

assumed). Observed symptoms included high fever, dyspnea, coughing, foamy expectoration, and 

cyanosis. Eighteen months after the exposure, the chronic pneumopathy and dyspnea persisted, although 

no information was reported regarding any pre-existing pulmonary conditions or possible lifestyle factors 

(i.e., smoking) that may have impacted the diagnosis. 

Volunteers exposed to increasing levels of acrolein vapors for 35 minutes reported statistically significant 

nose irritation at 0.26 ppm, throat irritation at 0.43 ppm, and a decrease in respiratory rate at 0.60 ppm 

(Weber-Tschopp et al. 1977). No statistically significant difference was observed between controls and 

subjects exposed to 0.17 ppm. In the same study, constant exposure to 0.3 ppm acrolein for 40 minutes 

resulted in reports of mild nose irritation shortly after onset of exposure, while throat irritation was 

reported after 10 minutes. Severity of irritation was subjectively scored as “not at all’ to “a little”. A 

20% decrease in respiratory rate was also observed. The significance of the decrease in respiratory rate is 

not clear, but in animals, particularly rodents, it is considered to represent a reflex response to protect the 

respiratory tract from toxicants (Alarie 1973). Based on the nose and throat irritation and a decrease in 

respiratory rate in humans exposed to acrolein, an acute-duration MRL of 0.003 ppm has been calculated 

from the LOAEL of 0.3 ppm (Weber-Tschopp et al. 1977). 

Acute exposure of mice, rats, and guinea pigs to concentrations of 0.3–17 ppm acrolein for several 

minutes induced vasodilation (Morris et al. 1999), as well as an increase in airflow resistance and a reflex 

decrease in respiratory rate by activation of the sensory nerve endings in the nasal mucosa (Alarie 1973; 

Buckley et al. 1984; Davis et al. 1967; Kane and Alarie 1977; Leikauf et al. 1989a; Morris et al. 1999, 

2003; Murphy et al. 1963; Nielsen et al. 1984; Steinhagen and Barrow 1984). Significantly decreased 

respiratory rates were observed in allergic airway-diseased mice compared to nondiseased mice exposed 

to 0.3 ppm acrolein for 10 minutes (Morris et al. 2003). Increased albumin levels were observed in nasal 

lavage fluid of rats exposed to 9.1 ppm for 40 minutes (Morris 1996). Olfactory exfoliation, erosion, 
ACROLEIN 36 

3. HEALTH EFFECTS 

ulceration, necrosis, and squamous metaplasia were observed in mice exposed to 1.7 ppm for 5 days 

(Buckley et al. 1984). Several indicators of oxidative stress were reported in rats exposed to 1 ppm for 

4 hours (Arumugan et al. 1999), including reduced lung levels of ascorbic acid, alpha-tocopherol, reduced 

glutathione, thiols, angiotensin-converting enzyme, lactase, lactase dehydrogenase, catalase and 

glutathione peroxidase activities and increased levels of TBARS, conjugated dienes, and superoxide 

dismutase activity. In the same study, desquamized and mononuclear cells, hyperemia, and emphysema 

were observed in lung tissues following a 2-ppm exposure for 4 hours. Emphysema was not reported in 

any other acute-duration study. Rats exposed to 0.25–0.67 ppm for 6 hours on 3 consecutive days 

exhibited focal basal cell metaplasia, reduced epithelial glutathione reductase activity, slight to moderate 

epithelial necrosis, and disarrangement and cell proliferation of the nasal respiratory epithelium in a dosedependent manner (Cassee et al. 1996). Biochemical alterations in the nasal mucosa were observed in 

rats exposed to 0.1–2.5 ppm, but the toxicological significance of this finding is unclear (Lam et al. 1985). 

Rat lungs exhibited significantly reduced glutathione, ascorbic acid, and α-tocopherol levels as well as 

glutathione peroxidase, catalase, and superoxide dismutase activity levels following 4-hour exposures to 

1 or 2 ppm acrolein (Arumugam et al. 1999). Exposure to concentrations of 1.7–6 ppm induced epithelial 

hyperplasia, inflammation, and moderate to severe histological alterations of the nasal, tracheal, and 

bronchial epithelium of mice, rats, guinea pigs, hamsters, and dogs (Buckley et al. 1984; Feron et al. 

1978; Kilburn and Mackenzie 1978; Murphy et al. 1964). Severe respiratory tract irritation was observed 

in rats exposed to 12 ppm for 4 hours (Murphy et al. 1964). Exposures as short as 5 minutes to >100 ppm 

acrolein resulted in bronchial epithelial destruction, pulmonary edema, and lung hemorrhage in rats, 

guinea pigs, and dogs (Catilina et al. 1966; Dahlgren et al. 1972; Hales et al. 1988; Skog 1950). 

Intermediate-duration exposures to acrolein concentrations between 0.4 and 5.0 ppm for up to 180 days 

caused increased relative lung weights, as well as histological alterations, inflammation across the entire 

respiratory tract, and edema of rats (Bouley et al. 1975; Costa et al. 1986; Feron et al. 1978; Kutzman 

1981; Kutzman et al. 1984, 1985; Leach et al. 1987; Lyon et al. 1970), monkeys, guinea pigs, and dogs 

(Lyon et al. 1970), and rabbits and hamsters (Feron et al. 1978). Decreased pulmonary function was 

observed in rats exposed to 4 ppm for up to 62 days (Kutzman 1981). Daily 10-minute exposures of 

262 ppm for 8 weeks resulted in peribronchial hemorrhage and bronchial lumen obstruction in rats 

(Catilina et al. 1966). Based on the nasal epithelial metaplasia in rats exposed to acrolein, an 

intermediate-duration MRL of 0.00004 ppm has been calculated from the LOAEL of 0.4 ppm (Feron et 

al. 1978). 
ACROLEIN 37 

3. HEALTH EFFECTS 

In the chronic exposure study in rats (Le Bouffant et al. 1980), occasional emphysematous areas were 

reported in the alveoli after 18 months of exposure to 8 ppm acrolein for 1 hour daily, though the study is 

unclear as to whether this effect was attributable to the animal’s exposure to acrolein, cigarette smoke, or 

a combination of the two. 

The overall evidence from acute, intermediate, and chronic duration studies in experimental animals 

indicates that the respiratory system is a target for acrolein. While the entire respiratory tract may be 

affected by acrolein inhalation, the nasal epithelium appears to be more sensitive at lower exposures 

(<1 ppm), which is consistent with human perception of nasal irritation. The deeper respiratory regions 

(bronchiolar and alveolar regions) appear to be sensitive to higher exposure levels, with severe effects 

being observed from exposures of 100 ppm or higher. The available data do not suggest species 

differences in the respiratory toxicity of acrolein. Humans and animals appear to show similar low 

concentration effects (i.e., mild irritation). It should be noted, however, that rodents are obligate nosebreathers, while humans are mouth-breathers. As a result, the lower respiratory tract of rodents may not 

present as likely a target organ as that of humans. 

Cardiovascular Effects. No studies were located regarding cardiovascular effects in humans 

following inhalation exposure to acrolein. 

Nonspecific inflammatory lesions in the heart were reported in rats, dogs, monkeys, and guinea pigs after 

a continuous 90-day exposure to 0.22 ppm acrolein (Lyon et al. 1970). Also, an increase in relative heart 

weight was observed in hamsters and rats exposed to 4–5 ppm of acrolein (Feron et al. 1978; Kutzman et 

al. 1985). In both of these studies, dose-dependent changes in histology and gross pathology were only 

seen in the respiratory tract. Thus, the nonspecific cardiovascular effects may be secondary effects of 

acrolein on respiratory tissues. 

Hematological Effects. No studies were located regarding hematological effects in humans 

following inhalation exposure to acrolein. 

No adverse hematological effects were observed in rats, guinea pigs, dogs, male hamsters, and monkeys 

exposed to 0.2–4.9 ppm of acrolein for an intermediate duration (Feron et al. 1978; Lyon et al. 1970). 

However, statistically significant increased numbers of erythrocytes, hemoglobin, and lymphocytes were 

observed in female hamsters exposed at 4.9 ppm (Feron et al. 1978). The study authors did not discuss 

the implications of these changes. The toxicological significance of these changes, if any, is unknown. 
ACROLEIN 38 

3. HEALTH EFFECTS 

Hepatic Effects. No studies were located regarding hepatic effects in humans following inhalation 

exposure to acrolein. 

Effects reported in rats after a 4-hour exposure to 8 ppm of acrolein included increases in alkaline 

phosphatase and tyrosine transaminase activities; however, these changes could represent adaptive 

responses (Murphy 1965; Murphy et al. 1964). Liver necrosis (minute foci without a specific pattern) 

was reported in rats and guinea pigs after intermediate-duration exposure to 1 ppm acrolein, but this effect 

was not found at a higher concentration (Lyon et al. 1970). Relative liver weight increases were observed 

in rats exposed to 0.55 ppm for 60–180 days (Bouley et al. 1975) and 4 ppm for 62 days (Kutzman et al. 

1984). An increase in relative liver weight was observed in rats exposed to 2.1 ppm for up to 81 hours 

(Murphy et al. 1964), while a decrease in relative liver weight resulted from exposure to 3.9 ppm for 5 or 

9 days. No adverse liver effects were seen in hamsters, rabbits, monkeys, dogs, or guinea pigs exposed to 

≤4.9 ppm acrolein (Feron et al. 1978). 

Renal Effects. No studies were located regarding renal effects in humans following inhalation 

exposure to acrolein. 

Renal effects in guinea pigs, dogs, and monkeys were described as nonspecific (Lyon et al. 1970). An 

increase in amorphous material in the urinary sediment was observed in rats, hamsters, and rabbits after 

intermediate-duration exposure to 4.9 ppm acrolein (Feron et al. 1978). However, without further 

characterization of the sediment, the significance of this finding is unclear. Increases in kidney weights 

were seen in rats and hamsters exposed to 4–5 ppm for 9–13 weeks (Feron et al. 1978; Kutzman et al. 

1985). 

Endocrine Effects. No studies were located regarding endocrine effects in humans following 

inhalation exposure to acrolein. 

Increased adrenal weights (up to 20% relative to controls 100 hours after exposure) were reported in rats 

after acute exposures to 6.4 ppm for 4 hours (Murphy et al. 1964). However, the toxicological 

significance of this difference cannot be ascertained since variation or statistical significance between 

groups was not reported. 
ACROLEIN 39 

3. HEALTH EFFECTS 

Ocular Effects. Eye irritation appears to be the most sensitive effect of airborne acrolein. This effect, 

however, is point-of-contact limited and is independent of acrolein inhalation. Therefore, ocular effects 

are discussed in detail in Section 3.2.3, Dermal Exposure. 

Body Weight Effects. In intermediate-duration studies, depressed body weight gains were reported 

in rats, hamsters, monkeys, and rabbits exposed to 0.32–4.9 ppm acrolein (Bouley et al. 1975; Feron et al. 

1978; Kutzman 1981; Kutzman et al. 1984, 1985; Leach et al. 1987; Lyon et al. 1970; Sinkuvene 1970). 

Significant differences in food consumption of rats were measured during exposure. However, food 

consumption increased significantly following cessation of exposure (Bouley et al. 1975). Anorexia was 

observed in rats exposed to 12 ppm for 4 hours (Murphy et al. 1964). It is not known why food 

consumption rates decreased during exposure. It is possible that animals minimized their activity levels 

in order to minimize respiration rates and, thus, relieve the discomfort of inhaling acrolein. 

3.2.1.3 Immunological and Lymphoreticular Effects 

No studies were located regarding immunological effects in humans after inhalation exposure to acrolein. 

Short-term exposures to acrolein reduced bactericidal activity of the respiratory tract in experimental 

animals. Aranyi et al. (1986) observed a significantly lower removal by alveolar macrophages of 

Klebsiella pneumoniae bacteria from a 3-hour aerosol infection following a 5-day exposure to 0.1 ppm 

acrolein in mice. No difference was observed in rats for this same exposure/infection protocol (Sherwood 

et al. 1986). Similarly, 8-hour exposures to 3 and 6 ppm acrolein in mice showed a concentration-related 

reduction in clearance of Staphylococcus aureus from an 8-hour pulmonary infection; however, exposures 

to 8–10 ppm did not significantly add to the impairment of bactericidal activity (Astry and Jakab 1983). 

Rats exposed to 0.55 ppm for 10–26 days had significantly lower numbers of alveolar macrophages, but 

rats exposed for 60–180 days showed no significant difference in macrophage levels (Bouley et al. 1975). 

No statistically significant differences in mortality were observed in rats intravenously exposed to Listeria 

monocytogenes following a 3-week exposure to up to 3 ppm acrolein (Leach et al. 1987). These studies 

do not suggest that inhaled acrolein causes an immune system effect, but the reduction in removal of 

bacteria from the alveolar spaces may result from the destruction of functionality of alveolar macrophages 

present in the respiratory epithelium. The highest NOAEL values and all reliable LOAEL values for 

immunological effects in each species and duration category are recorded in Table 3-1 and plotted in 

Figure 3-1. 
ACROLEIN 40 

3. HEALTH EFFECTS 

3.2.1.4 Neurological Effects 

No studies were located regarding neurological effects in humans after inhalation exposure to acrolein. 

Springall et al. (1990) indicate that acrolein may induce release of peptides that could play a role in the 

physiological response to irritants. Concentrations of acrolein between 22 and 249 ppm for 10 minutes 

induced a dose-related decrease in substance P (a short-chain polypeptide that functions as a 

neurotransmitter or neuromodulator) and calcitonin gene-related peptide in nerve terminals innervating 

the trachea of rats (Springall et al. 1990). No change was seen in total nerve distribution and number or in 

vasoactive intestinal peptide. Likewise, substance P-mediated vasodilation of the rat upper respiratory 

tract was observed at 20 ppm, but not at 2–10 ppm, for 50 minutes (Morris et al. 1999). 

In intermediate duration studies (Feron et al. 1978; Kutzman et al. 1984, 1985; Lyon et al. 1970), the 

neurological effects identified consisted of increases in the brain/body weight ratio and nonspecific 

inflammatory responses in sections of the brain (it is not clear from the original papers whether sections 

refer to anatomical areas or to histological preparations). These effects were observed in rats, guinea 

pigs, dogs, and monkeys at comparable concentrations of acrolein. The highest NOAEL values and all 

reliable LOAEL values for neurological effects in each species and duration category are recorded in 

Table 3-1 and plotted in Figure 3-1. 

3.2.1.5 Reproductive Effects 

No studies were located regarding reproductive effects in humans after inhalation exposure to acrolein. 

Two studies were identified regarding the reproductive effects of inhaled acrolein. Bouley et al. (1975) 

exposed male and female rats to 0.55 ppm acrolein continuously for 26 days (3 days prior to mating and 

presumed gestational days 0 through 22) and reported that exposure did not affect the number of 

pregnancies or the number and weights of the fetuses. Although Bouley et al. (1975) examined the most 

relevant indices and an adequate number of animals were tested, the use of only one dose level limits the 

reproductive assessment derived from this study. Kutzman (1981) found no effect on the reproductive 

fitness of rats exposed to 0.4–4 ppm for 62 days. The NOAEL value for reproductive effects in rats after 

an intermediate-duration exposure is recorded in Table 3-1 and plotted in Figure 3-1. 
ACROLEIN 41 

3. HEALTH EFFECTS 

3.2.1.6 Developmental Effects 

No studies were located regarding developmental effects in humans or animals after inhalation exposure 

to acrolein. 

3.2.1.7 Cancer 

No studies were located regarding carcinogenic effects in humans after inhalation exposure to acrolein. 

Only two studies in animals were located that examined the carcinogenic potential of acrolein after 

inhalation exposure. Feron and Kruysse (1977) exposed hamsters to a single acrolein concentration of 

4.0 ppm for 7 hours/day, 5 days/week for 52 weeks and found no evidence of respiratory tract tumors or 

tumors in other tissues and organs. However, this study is considered to be of too short duration to 

determine carcinogenicity. The maximum tolerable dose (MTD) of acrolein appears to have been 

achieved in this study, as indicated by the significant decrease in body weights of treated animals. 

Le Bouffant et al. (1980) exposed rats to 8 ppm acrolein for 1 hour/day, 7 days/week for 18 months and 

reported no evidence of tumors in the respiratory tract or in other tissues and organs. An MTD does not 

appear to have been achieved in this study due to the short daily duration of exposure. 

3.2.2 Oral Exposure 

3.2.2.1 Death 

No studies were located regarding lethality in humans after oral exposure to acrolein. 

The oral LD50 for rats was reported as 46 mg/kg, with a range of 39–56 mg/kg (Smyth et al. 1951). 

However, a single oral dose of 10–25 mg/kg in rats was lethal to over 40% of the animals (Draminski et 

al. 1983; Sakata et al. 1989; Sprince et al. 1979). Loss of reflexes occurred after 3 hours, and increased 

lethargy gradually led to death. Most of the animals died 3–8 hours after dosing (Sprince et al. 1979). 

Furthermore, increased maternal mortality was observed in rats treated with 10 mg/kg/day and in rabbits 

treated with 2 mg/kg/day during gestational days 7–19 (King 1982; Parent et al. 1993), although the 

rabbit deaths appeared to be related to misdosing. No increase in deaths was observed in a twogeneration reproductive study, in which rats were treated by gavage with 7.2 mg/kg/day (King 1984). 
ACROLEIN 42 

3. HEALTH EFFECTS 

The overall survival rate was not affected in dogs exposed to 1.5 mg/kg/day by capsule dosing for the first 

4 weeks and 2 mg/kg/day for the remainder of the 12-month study (Parent et al. 1992b). Decreased 

survival was, however, reported in male and female mice gavaged with 20 mg/kg/day for 14 weeks (NTP 

2006), in male and female rats gavaged with 6 mg/kg/day for 93–149 days (Parent et al. 1992c), and in 

male mice gavaged with 4.5 mg/kg/day for 18 months (Parent et al. 1991a). Survival of male and female 

rats was significantly decreased following intermediate-duration gavage exposure of 10 mg/kg/day for 

14 weeks (NTP 2006). Use of thickening agents in the dosing solutions of the NTP (2006) study may 

have increased the residence time of acrolein and contributed to the observed mortality. Chronically 

gavaged male mice and female rats receiving 4.5 and 0.5 mg/kg/day, respectively, experienced increased 

mortality, although the cause of mortality from the chronic exposure was not determined (Parent et al. 

1991a, 1992a). Chronic exposure of rats to 36 mg/kg/day or less of acrolein via the drinking water did 

not affect mortality (Lijinsky and Reuber 1987). There is high uncertainty in the actual acrolein dosage 

received by the rats, as 36 mg/kg/day is higher than the range of lethal doses of 10–25 mg/kg reported 

above (Draminski et al. 1983; Sakata et al. 1989; Sprince et al. 1979). High instability of acrolein in 

water reported by the study authors (18% reduction after 6 days at 5 °C; 27% reduction after 3 days at 

22 °C) likely resulted in unknown doses, making it difficult to compare the dose-response from Lijinsky 

and Reuber (1987) to other studies. Reliable LOAELs for death in each species and duration category are 

listed in Table 3-2 and plotted in Figure 3-2. 

3.2.2.2 Systemic Effects 

No studies were located regarding respiratory, cardiovascular, gastrointestinal, hematological, 

musculoskeletal, hepatic, renal, endocrine, dermal, or ocular effects in humans after oral exposure to 

acrolein. However, studies were located regarding these end points in several species of animals. The 

highest NOAEL values and all reliable LOAEL values for systemic effects in each species and duration 

category are recorded in Table 3-2 and plotted in Figure 3-2. 

Respiratory Effects. Abnormal breathing was observed in rats gavaged with 10 mg/kg/day for 

14 weeks (NTP 2006) and 6 mg/kg/day for 93–149 days (Parent et al. 1992c). No histopathological 

changes were observed in the respiratory systems of rats after intermediate-duration exposure to 

7.2 mg/kg/day (King 1984). Similarly, no changes were observed during histopathological examination 

of respiratory tract tissues from rats (Parent et al. 1992a), mice (Parent et al. 1991a), or dogs (Parent et al. 

1992b) chronically exposed to 2.5, 4.5, or 2 mg/kg/day, respectively. 
132

10

185

25

112

11.2

135

3.6

6

184

25

168

0.75

2

134

10

Table 3-2 Levels of Significant Exposure to Acrolein - Oral 

Exposure/ LOAEL 

Duration/ 

a 

Key to 

Figure 

Species 

(Strain) 

Frequency 

(Route) 

ACUTE EXPOSURE Death 

1 Rat Gd 7-19 

1 x/d (GW) 

System 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

Serious 

(mg/kg/day) 

10 (14/40 died) 

2 Rat 

(Fischer- 344) 

1 x/d 25 M (5/12 died) 

3 Rat 

Systemic 

4 Rat 

once (G) Gd 7-19 1 x/d (GW) 

Bd Wt 3.6 6 (decreased body weight 

gain) 

11.2 (LD90) 

5 Rat 

(Fischer- 344) 

1 x/d Gastro 25 M (severe erosive 

hemorrhagic gastritis, multi-focal ulceration of forestomach and glandular stomach) 

6 Rabbit 

(New Zealand) 

1 x/d Gd 7-19 (GW) 

Bd Wt 0.75 F 2 F (transient depressed 

maternal body weight gain) 

Reproductive 

7 Rat Gd 7-19 

1 x/d (GW) 

10 

Reference Chemical Form 

King 1982 Sakata et al. 1989 Sprince et al. 1979 King 1982 Sakata et al. 1989 Parent et al. 1993 King 1982 
189

6

10

156

2

188

10

162

6

187

20

Table 3-2 Levels of Significant Exposure to Acrolein - Oral (continued) 

a 

Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) System NOAEL (mg/kg/day) Less Serious (mg/kg/day) 

LOAEL 

Serious 

(mg/kg/day) 

Reference Chemical Form 

Developmental 

8 Rat Gd 7-19 

1 x/d (GW) 

6 10 (decreased litter weight, King 1984

increased skeletal anomalies) 

9 Rabbit 

(New Zealand) 

1 x/d Gd 7-19 (GW) 

INTERMEDIATE EXPOSURE Death 

10 Rat 

(Fischer- 344) 

1 x/d 13 wk (GW) 

2 F Parent et al. 1993 

10 (17/20 died) NTP 2006

11 Rat 

(SpragueDawley) 

1 x/d 93-149 d (GW) 

6 (increased mortality) Parent et al. 1992c

12 Mouse 

(B6C3F1) 

1 x/d 13 wk (GW) 

20 (20/20 died) NTP 2006
131

7.27.24 5.47.27.27.27.27.25.4

7.2

164

10

1.25

2.5

10

5

Table 3-2 Levels of Significant Exposure to Acrolein - Oral (continued) 

Exposure/ 

Duration/ 

a 

Key to Species Frequency 

Figure (Strain) (Route) 

Systemic 

13 Rat 115 d 

1 x/d (GW) 

14 Rat 1 x/d 

13 wk (Fischer- 344) (GW) 

System 

Resp Cardio Gastro Hemato Musc/skel Hepatic Renal Dermal Bd Wt Resp Gastro Hepatic 

LOAEL 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

Serious 

(mg/kg/day) 

Reference Chemical Form 

7.2 King 1984 

7.2 

4 

7.2 7.2 7.2 7.2 7.2 

5.4 

5.4 (stomach ulcerations) 7.2 (decreased body weight 

in F0 generation) 

10 (abnormal breathing) NTP 2006 

1.25 F 2.5 F (forestomach squamous 

epithelial hyperplasia) 

10 (forestomach necrosis 

and hemorrhage in females; glandular stomach hemorrhage in both males and females) 

5 F (increased relative liver 

weight) 
163

6

3

6

66

165

1.25

2.5 1010

130

7.2

166

6

Table 3-2 Levels of Significant Exposure to Acrolein - Oral (continued) 

a 

Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) System NOAEL (mg/kg/day) Less Serious (mg/kg/day) 

LOAEL 

Serious 

(mg/kg/day) 

Reference Chemical Form 

15 Rat 

(SpragueDawley) 

1 x/d 93-149 d (GW) 

Resp 6 (rales, labored/irregular 

breathing, gasping, hyperpnia in F0 and F1 generations) 

Parent et al. 1992c 

Gastro 3 (forestomach and 

glandular stomach hyperplasia, ulcers) 

6 (glandular stomach 

hemorrhage) 

Renal Bd Wt 

6 M (reddish-brown urine) 6 M (decreased body weight 

gains in F0 and F1 generations) 

16 Mouse 

(B6C3F1) 

1 x/d 13 wk (GW) 

Gastro 

b

1.25 2.5 (forestomach squamous 

epithelial hyperplasia) 

10 M (stomach necrosis and 

hemorrhage) 

NTP 2006 

Hepatic 10 M (increased absolute and 

relative liver weight) 

Reproductive 

17 Rat 115 d 

1 x/d (GW) 

7.2 King 1984 

18 Rat 

(SpragueDawley) 

1 x/d 93-149 d (GW) 

6 Parent et al. 1992c 
161

6

158

0.5

139

4.5

159

2.52.52.52.52.52.52.52.5

Table 3-2 Levels of Significant Exposure to Acrolein - Oral (continued) 

a 

Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) System NOAEL (mg/kg/day) 

LOAEL 

Less Serious 

(mg/kg/day) 

Serious 

(mg/kg/day) 

Reference Chemical Form 

Developmental 

19 Rat 

(SpragueDawley) 

1 x/d 93-149 d (GW) 

6 (decreased pup body 

weight) 

Parent et al. 1992c 

CHRONIC EXPOSURE Death 

20 Rat 

(SpragueDawley) 

1 x/d 102 wk (GW) 

0.5 F (increased mortality) Parent et al. 1992a 

21 Mouse 

(CD-1) 

18 mo 7 d/wk 1 x/d (GW) 

Systemic 

22 Rat 

(SpragueDawley) 

1 x/d 102 wk (GW) 

Resp 2.5 

4.5 M (increased mortality) Parent et al. 1991a 

Parent et al. 1992a 

Gastro 2.5 Hemato 2.5 Musc/skel 2.5 Hepatic 2.5 Endocr 2.5 Ocular 2.5 Bd Wt 2.5 
141

4.54.54.54.54.54.54.54.54.54.50.5

4.5

Table 3-2 Levels of Significant Exposure to Acrolein - Oral (continued) 

Exposure/ LOAEL 

Duration/ 

a 

Key to Species Frequency NOAEL Less Serious Serious Reference 

Figure (Strain) (Route) System (mg/kg/day) (mg/kg/day) (mg/kg/day) Chemical Form 

23 Mouse 18 mo 

7 d/wk 1 x/d (GW) 

Resp 4.5 Parent et al. 1991a 

Cardio 4.5 Gastro 4.5 Hemato 4.5 Musc/skel 4.5 Hepatic 4.5 Renal 4.5 Endocr 4.5 Dermal 4.5 Ocular 4.5 Bd Wt 0.5 4.5 M (decreased body weight 

gain) 
155

20.1

0.5

2222222

157

2.5

140

4.5

Table 3-2 Levels of Significant Exposure to Acrolein - Oral (continued) 

a 

Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) System NOAEL (mg/kg/day) Less Serious (mg/kg/day) 

LOAEL 

Serious 

(mg/kg/day) 

Reference Chemical Form 

24 Dog 

(Beagle) 

365 d 1 x/d (C) 

Resp 2 Parent et al. 1992b 

Gastro 0.1 0.5 (vomiting after daily 

dosing, incidence decreased after week 4) 

Musc/skel 2 Hepatic 2 Renal 2 Endocr 2 Dermal 2 Ocular 2 

Cancer 

25 Rat 

(SpragueDawley) 

1 x/d 102 wk (GW) 

Bd Wt 2 

2.5 Parent et al. 1992a 

26 Mouse 18 mo 

7 d/wk 1 x/d (GW) 

4.5 Parent et al. 1991a 

a The number corresponds to the entries in Figure 3-2. b Used to derive an intermediate oral MRL of 0.004 mg/kg/day, based on a BMDL10 (benchmark dose lower confidence limit 10%) of 0.36 mg/kg/day; dose divided factor of 100 (10 for human variability and 10 for species extrapolation). Bd Wt = body weight; (C) = capsule; Cardio = cardiovascular; CEL = cancer effect level; d = day(s); F = Female; (G) = gavage; Gastro = gastrointestinal; Gd = gest= gavage in water; Hemato = hematological; LD90 = lethal dose, 90% kill; LOAEL = lowest-observed-adverse-effect level; M = male; MCHC = mean corpuscular heconcentration; MCV = mean corpuscular volume; mo = month(s); NOAEL = no-observed-adverse-effect level; Resp = respiratory; wk = week(s); x = time(s) 
Death 

Gastrointestinal Body Weight Reproductive Developmental 

Figure 3-2 Levels of Significant Exposure to Acrolein - Oral 

Acute (≤14 days) 

Systemic 

mg/kg/day 

100 

2r 5r 

3r 10 1r 7r 8r 

4r 8r 

4r 

6h 9h 

1 

6h 

0.1 

c-Cat 

d-Dog

r-Rat 

p-Pig

q-Cow

 -Humans 

k-Monkey

m-Mouse 

h-Rabbit 

a-Sheep 

f-Ferret 

j-Pigeon

e-Gerbil 

s-Hamster 

g-Guinea Pig 

n-Mink 

o-Other

 Cancer Effect Level-Animals

 LOAEL, More Serious-Animals

LOAEL, Less Serious-Animals

NOAEL - Animals

 Cancer Effect Level-Humans

 LOAEL, More Serious-Humans

LOAEL, Less Serious-Humans

NOAEL - Humans

 LD50/LC50

Minimal Risk Level

 for effects

 other than

 Cancer 
Death 

Respiratory Cardiovascular Gastrointestinal Hematological Musculoskeletal Hepatic Renal Dermal Body Weight Reproductive Developmental 

Figure 3-2 Levels of Significant Exposure to Acrolein - Oral (Continued)
 

Intermediate (15-364 days)

Systemic 

mg/kg/day 

100 

12m 

10 10r 14r 16m 14r 16m 

13r 13r 13r 13r 13r 13r 13r 13r 17r 11r 15r 15r 15r 15r 18r 19r 13r 13r 14r 

13r 

15r 16m 14r

16m 14r 

1 

0.1 

0.01 

0.001 

c-Cat 

d-Dog

r-Rat 

p-Pig

q-Cow

 -Humans 

k-Monkey

m-Mouse 

h-Rabbit 

a-Sheep 

f-Ferret 

j-Pigeon

e-Gerbil 

s-Hamster 

g-Guinea Pig 

n-Mink 

o-Other

 Cancer Effect Level-Animals

 LOAEL, More Serious-Animals

LOAEL, Less Serious-Animals

NOAEL - Animals

 Cancer Effect Level-Humans

 LOAEL, More Serious-Humans

LOAEL, Less Serious-Humans

NOAEL - Humans

 LD50/LC50

 for effects

 other than

 Cancer 

Minimal Risk Level 
Death 

Respiratory Cardiovascular Gastrointestinal Hematological Musculoskeletal Hepatic Renal Endocrine Dermal Ocular Body Weight 

Figure 3-2 Levels of Significant Exposure to Acrolein - Oral (Continued)

Chronic (≥365 days)
	

Systemic 

mg/kg/day 

10 

21m 23m 23m 23m 23m 23m 23m 23m 23m 23m 23m 23m 

22r 22r 22r 22r 22r 22r 22r 22r 

24d 24d 24d 24d 24d 24d 24d 24d 

1 

20r 24d 23m 

0.1 24d 

c-Cat 

d-Dog

r-Rat 

p-Pig

q-Cow

 -Humans 

k-Monkey

m-Mouse 

h-Rabbit 

a-Sheep 

f-Ferret 

j-Pigeon

e-Gerbil 

s-Hamster 

g-Guinea Pig 

n-Mink 

o-Other

 Cancer Effect Level-Animals

 LOAEL, More Serious-Animals

LOAEL, Less Serious-Animals

NOAEL - Animals

 Cancer Effect Level-Humans

 LOAEL, More Serious-Humans

LOAEL, Less Serious-Humans

NOAEL - Humans

 LD50/LC50

 for effects

 other than

 Cancer 

Minimal Risk Level 
 

ACROLEIN 53 

3. HEALTH EFFECTS 

Cardiovascular Effects. Histopathological examination of the cardiovascular system revealed no 

effects after intermediate-duration exposure to acrolein in rats (King 1984) or after chronic exposure in 

rats (Parent et al. 1992a), mice (Parent et al. 1991a), or dogs (Parent et al. 1992b). 

Gastrointestinal Effects. Gastrointestinal irritation is the primary effect of oral exposure to acrolein. 

Though the clinical signs are consistent and dose-related across acute and intermediate exposures, 

possible adaptation to irritating effects may have important implications for chronic exposures. Rats 

administered a single gavage dose of 25 mg/kg of acrolein in saline showed severe multifocal ulceration 

of the forestomach and glandular stomach 48 hours after dosing, though no controls were used for 

comparison. The areas of ulceration showed severe inflammation, focal hemorrhage, and edema (Sakata 

et al. 1989). Gastric mucosa ulcerations were also observed in rabbits given gavage doses of 4 mg/kg/day 

during gestational days 7–19 (Parent et al. 1993, dose range-finding study) and in rats given gavage doses 

of 5.4 mg/kg/day for 115 days (King 1984). Stomach hemorrhage was observed in male and female rats 

gavaged with 10 mg/kg/day and male and female mice gavaged with 20 mg/kg/day, while stomach 

necrosis was observed in female mice gavaged with 20 mg/kg/day for 14 weeks (NTP 2006). 

Forestomach squamous epithelial hyperplasia was observed in male and female rats gavaged with 5 and 

2.5 mg/kg/day, respectively, for 14 weeks (NTP 2006), while glandular stomach squamous epithelial 

hyperplasia was seen in male and female mice gavaged with 2.5 mg/kg/day for the same time period. The 

addition of a thickening agent in the dosing solution may have served to extend the residence time of 

acrolein in the stomach, resulting in the observed effects at these doses. Glandular stomach hyperplasia, 

ulcers, and hemorrhage were found in rats gavaged with 3 mg/kg/day for 93–149 days (Parent et al. 

1992c). No significant gastrointestinal effects of acrolein exposure, however, were reported in rats 

(Parent et al. 1992a), mice (Parent et al. 1991a), or dogs (Parent et al. 1992b) after chronic gavage dosing 

with up to 2.5, 4.5, or 2 mg/kg/day, respectively. While no unusual gross pathological lesions in the 

gastrointestinal tract were observed in dogs given up to 2 mg/kg/day for 12 months (Parent et al. 1992b), 

increased incidences of vomiting were observed shortly after dosing, suggesting gastrointestinal irritation. 

However, adaptation seemed to occur in the 2 mg/kg/day group as late as 51 weeks into the study, as 

vomiting frequency was sharply reduced compared to the first 4 weeks of the study. Based on the 

occurrence of forestomach squamous epithelial hyperplasia in rats given gavage doses of acrolein, an 

intermediate-duration MRL of 0.004 mg/kg/day has been calculated from the 95% lower confidence limit 

on the benchmark dose for 10% extra risk (BMDL10) of 0.36 mg/kg/day (NTP 2006). Although humans 

do not have a forestomach, this study provides an example of gastrointestinal mucus membrane irritation. 

Similar irritative effects are expected in humans. 
 

ACROLEIN 54 

3. HEALTH EFFECTS 

Hematological Effects. No significant hematological effects were observed in rats given gavage 

doses of up to 7.2 mg/kg/day acrolein for 115 days (King 1984), in mice given gavage doses of up to 

4.5 mg/kg/day acrolein for 18 months (Parent et al. 1991a), or in rats given gavage doses of up to 

2.5 mg/kg/day for 2 years (Parent et al. 1992a). In dogs, decreased prothrombin times were seen in 

females while decreased serum protein, albumin, and calcium levels were observed in both sexes given 

2 mg/kg/day for 12 months (Parent et al. 1992b). In the same study, mean corpuscular hemoglobin 

concentration (MCH) and mean corpuscular volume (MCV) were significantly increased in male dogs, 

but were depressed in females given gavage doses of 0.5 or 2 mg/kg/day. The authors could not provide 

an explanation for these hematological changes, but state that the changes were not thought to be 

toxicologically meaningful. 

Metabolic Effects. Statistically significant decreases in serum calcium were observed in dogs given 

2 mg/kg/day acrolein for 12 months (Parent et al. 1992b). Serum creatinine phosphokinase levels were 

depressed in rats given 0.05–2.5 mg/kg/day for 24 months (Parent et al. 1992a). However, the 

toxicological significance of these findings is not clear, since no treatment-related effects were observed 

in any organs or tissues upon gross pathological or histological examination. 

Musculoskeletal Effects. No histopathological changes were observed in musculoskeletal tissues of 

rats after intermediate-duration exposure (King 1984). Similarly negative results were obtained in rats 

(Parent et al. 1992a), mice (Parent et al. 1991a), and dogs (Parent et al. 1992b) chronically exposed to 

acrolein, although the specific muscular tissues observed were not reported. 

Hepatic Effects. Altered liver or kidney weights were reported in rats administered 1.5 mg/kg/day 

acrolein in drinking water for 30 days (Smyth et al. 1951), although no liver or kidney weight changes 

occurred following administration of 0.17 mg/kg/day. It is unclear if the altered organ weight occurred in 

the liver and/or kidneys, or if the organ weights increased or decreased. Increased relative liver weights 

occurred in female rats and male mice gavaged with 5 or 10 mg/kg/day, respectively, for 14 weeks (NTP 

2006). No liver effects were observed upon gross pathological or histological examinations in rats after 

intermediate-duration exposure to 7.2 mg/kg/day acrolein (King 1984). Similarly, no significant hepatic 

changes were found in rats (Parent et al. 1992a), mice (Parent et al. 1991a), or dogs (Parent et al. 1992b) 

after chronic exposure to 2.5, 4.5, or 2 mg/kg/day acrolein, respectively. Reduced serum protein and 

albumin levels were observed in dogs chronically given 2 mg/kg/day (Parent et al. 1992b). It is uncertain 

as to whether these effects are indicative of hepatic changes, as the authors of this study reported that 

there were no dose-related differences in liver pathology. 
 

ACROLEIN 55 

3. HEALTH EFFECTS 

Renal Effects. As mentioned previously, altered kidney or liver weights were reported by Smyth et 

al. (1951) in rats given 1.5 mg/kg/day acrolein in drinking water for 30 days, with no effect on liver or 

kidney weights resulting from administration of 0.17 mg/kg/day. It is unclear from the report whether 

there was an alteration in kidney weight or liver weight or both, or if the organ weights increased or 

decreased. Reddish-brown urine was observed in rats during intermediate-duration exposure to 

6 mg/kg/day (Parent et al. 1992c). No histopathological changes were reported in kidneys of rats after 

intermediate-duration exposure to 7.2 mg/kg/day (King 1984) or in rats (Parent et al. 1992a), mice (Parent 

et al. 1991a), and dogs (Parent et al. 1992b) after chronic exposure to 2.5, 4.5, or 2 mg/kg/day acrolein, 

respectively. Negative results were also obtained from the urinalysis of dogs exposed to 0.05– 

2 mg/kg/day for 12 months (Parent et al. 1992b). Reduced serum protein and albumin levels were 

observed in dogs chronically given 2 mg/kg/day (Parent et al. 1992b). It is uncertain as to whether these 

effects are indicative of renal changes, as the authors of this study reported that there were no dose-related 

differences in liver pathology. 

Dermal Effects. No studies were located regarding dermal effects in humans following oral exposure 

to acrolein. 

No dermal effects were observed in rats receiving an intermediate-duration exposure of 7.2 mg/kg/day 

(King 1984). 

Ocular Effects. No treatment-related ocular effects were reported in rats (Parent et al. 1992a), mice 

(Parent et al. 1991a), or dogs (Parent et al. 1992b) chronically exposed to acrolein. 

Body Weight Effects. Rats treated with 2 mg/kg/day (King 1984) and rabbits treated with 

6 mg/kg/day (Parent et al. 1993) during gestation days 7–10 exhibited reduced body weight gains, but the 

rabbits resumed body weights comparable to controls thereafter. Decreased body weight gains were 

reported in rats given intermediate-duration exposures of 6 and 7.2 mg/kg/day (King 1984; Parent et al. 

1992c) and in mice given 4.5 mg/kg/day for 18 months (Parent et al. 1991a). No significant body weight 

changes were observed in dogs given 2 mg/kg/day for 12 months (Parent et al. 1992b) or in rats given 

2.5 mg/kg/day for 2 years (Parent et al. 1992a). 
ACROLEIN 56 

3. HEALTH EFFECTS 

3.2.2.3 Immunological and Lymphoreticular Effects 

No studies were located regarding immunological effects in humans or animals after oral exposure to 

acrolein. 

3.2.2.4 Neurological Effects 

No studies were located regarding neurological effects in humans after oral exposure to acrolein. 

3.2.2.5 Reproductive Effects 

No studies were located regarding reproductive effects after oral exposure to acrolein. 

Exposure of rats to 10 mg/kg/day acrolein during pregnancy had no effect on the number of implantations 

or resorptions or on the ratio of live/dead fetuses per litter (King 1982). No evidence of acrolein 

reproductive toxicity was found in a two-generation study in which rats of each generation were exposed 

to 7.2 mg/kg/day for 100–120 days prior to mating and then for 15 days during mating (King 1984). 

Reproductive performance was not affected in two generations of male and female rats given 1, 3, or 

6 mg/kg/day acrolein for 96–149 days (Parent et al. 1992c). Offspring of rabbits given 0.1–2 mg/kg/day 

on gestation days 7–19 were not observed to have premature deliveries, spontaneous abortions, or 

statistically significant gross or soft tissue malformations or variations (Parent et al. 1993). However, in 

the preliminary dose-range study reported by Parent et al. (1993), a dose-related, but statistically untested, 

increase in embryonic resorptions was observed after exposure of dams to 1 mg/kg/day or more. No 

explanation for this discrepancy was given in the study, although the treatment groups in the rangefinding study had only 3–4 animals, while the groups in the full study had 20 animals. No fetuses were 

alive in the litters of dams that were administered 4 mg/kg/day acrolein. The highest NOAEL values and 

all reliable LOAEL values for reproductive effects in each species and duration category are recorded in 

Table 3-2 and plotted in Figure 3-2. 

3.2.2.6 Developmental Effects 

No studies were located regarding developmental effects in humans after oral exposure to acrolein. 

Developmental effects have been observed in animals after oral exposure. In a preliminary dose-range 

finding study, exposure of rabbits to ≥1 mg/kg/day resulted in dose-related increased incidences of fetal 
ACROLEIN 57 

3. HEALTH EFFECTS 

resorption (Parent et al. 1993); however, fetal mortality was not affected in the primary study, in which 

rabbits were exposed to ≤2 mg/kg/day during gestation. No explanation for the discrepancy was 

provided, though maternal body weight loss in the range-finding study may have confounded fetal effects. 

It should be noted that the range-finding study utilized only 3–4 animals/dose group, while the definitive 

study used 20 animals/group, suggesting that greater weight should be given to the data from the full 

study. Body weights of pups from rats given 6 mg/kg/day through gestation and lactation were 

significantly reduced during gestation. Otherwise, litter viability and size, gestation duration, and pup 

growth and morphology were unaffected by acrolein exposure of the dams (Parent et al. 1992c). 

Increased incidences of skeletal anomalies and delayed ossification and decreased mean fetal weight and 

total litter weights were observed in the offspring of rats exposed to 10 mg/kg/day (King 1982). This 

dosage, however, was toxic to the dams, resulting in maternal deaths. The highest NOAEL values and all 

reliable LOAEL values for developmental effects in each species and duration category are recorded in 

Table 3-2 and plotted in Figure 3-2. 

3.2.2.7 Cancer 

No studies were located regarding carcinogenic effects in humans after oral exposure to acrolein. 

Questionable evidence of the carcinogenicity of acrolein in animals is provided by a few long-term 

studies. Lijinsky and Reuber (1987) reported a cancer bioassay in which groups of male rats were given 

acrolein in the drinking water at concentrations that provided doses of 0, 6, 14, or 36 mg/kg/day, 

5 days/week for 104–124 weeks. One group of females was also given the highest dose on the same 

schedule as the males. The only indication of a carcinogenic effect of acrolein was the incidence of 

neoplasms of the adrenal cortex in high-dose female rats. The increased incidence of hyperplastic 

nodules of the adrenal cortex in 2 of 20 female rats was significant with respect to controls. Other studies 

failed to detect significant cancer incidence in animals. Gavage treatment of rats with 0.05–2 mg/kg/day 

failed to produce tumor incidences, including adrenal tumors, which were significantly different from 

controls (Parent et al. 1992a). Extensive histopathological examination did not reveal any carcinogenic 

effects in mice (Parent et al. 1991a), or dogs (Parent et al. 1992b) after oral exposure to 2.5, 4.5, or 

2 mg/kg/day acrolein, respectively, for 12–24 months. Because of the disparate results of the Lijinsky 

and Reuber (1987) and Parent et al. (1991a and 1992a) studies, an independent pathology working group 

(PWG) re-evaluated the Lijinsky and Reuber tumor data (cited in Parent et al. 1992a). The PWG 

concluded that the incidence of cortical tumors in treated females was within the limits of historical 

controls and were of no biological significance for adrenal cancer from acrolein exposure. 
ACROLEIN 58 

3. HEALTH EFFECTS 

The DHHS has not classified acrolein as to its carcinogenicity (NTP 2005). IARC has determined that 

acrolein is not classifiable as to carcinogenicity in humans (IARC 2004). The EPA has stated that the 

potential carcinogenicity of acrolein cannot be determined based on an inadequate database (IRIS 2007). 

3.2.3 Dermal Exposure 

3.2.3.1 Death 

No studies were located regarding lethality in humans after dermal exposure to acrolein. 

In rabbits administered several dilutions of acrolein percutaneously, the LD50 values ranged from 160 to 

1,000 mg/kg body weight, depending on the vehicle and concentration (Albin 1962). It is uncertain 

whether the observed mortality was due to dermal absorption of acrolein or inhalation of off-gassing 

vapors from the skin applications. Salaman and Roe (1956) painted the backs of mice with 5 ppm 

acrolein (in sesame oil) for 10 weeks for a total dose of 12.6 mg and reported that acrolein did not cause 

mortality. 

3.2.3.2 Systemic Effects 

No studies were located regarding respiratory, gastrointestinal, hematological, musculoskeletal, hepatic, 

renal, endocrine, or body weight effects in humans or animals after dermal exposure to acrolein. Reliable 

LOAELs for systemic effects in humans are presented in Table 3-3. 

Cardiovascular Effects. No studies were located regarding cardiovascular effects in humans after 

dermal exposure to acrolein. When applied topically to the eyes of rabbits, acrolein (dose not reported) 

increased the heart rate (Basu et al. 1971). However, this effect is most likely due to the painful 

stimulation of the eye. 

Dermal Effects. A 57-year-old man who accidentally spilled acrolein over his genital area 

experienced swelling of the penis and scrotum. After 15 days, the genital area was deeply ulcerated and 

gangrenous. No follow-up information was provided (Schöning 1966). Volunteers receiving topical 

applications of a 10% solution of acrolein in ethanol exhibited irritation, papillary edema, 

polymorphonuclear infiltrates, and epidermal necrosis 48 hours after exposure (Lacroix et al. 1976). 
Percent (%)

ppm ppm

ppm

Table 3-3 Levels of Significant Exposure to Acrolein - Dermal 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) 

ACUTE EXPOSURE 

Systemic 

Human 1 d 

System 

Dermal 

NOAEL Less Serious 

LOAEL 

Serious 

10 (severe skin irritation) 

Percent (%) 

Reference Chemical Form 

Lacroix et al. 1976 

Human 1 d 

5-10 min Ocular 0.81 

ppm 

(eye irritation from vapor 

exposure) 

1.22 

ppm 

(eye irritation from vapor exposure) 

Sim and Pattle 1957 

Human 1 d 

7.5 min/d Ocular 0.3 B 

ppm 

(eye irritation from vapor 

exposure) 

Weber-Tschopp et al. 1

B = both males and females; d = day; LOAEL = lowest-observed-adverse-effect level; min = minute(s); NOAEL = no-observed-adverse-effect level; ppm = parts pe
ACROLEIN 60 

3. HEALTH EFFECTS 

Accidental exposure to vapors of acrolein produced burns of the cheeks and eyelids in a male subject 

(Champeix et al. 1966). 

Ocular Effects. Volunteers reported statistically significant eye irritation in two of three different 

vapor-exposure scenarios (Weber-Tschopp et al. 1977). In 90-second fixed-concentration exposures, 

0.6 ppm resulted in a significant increase in the number of positive reports scoring irritation as “a little.” 

In an exposure to gradually increasing acrolein levels in which participants were queried every 5 minutes 

as to irritation, a significant number of positive reports of irritation, scored as “a little”, were generated at 

the end of the first interval when the concentration was measured to be 0.09 ppm. Lastly, eye irritation 

from a 60-minute, 0.3-ppm exposure was scored by participants as “a little” at 10 minutes and “medium” 

at 40 minutes with no further increase in severity. In another human study, lacrimation occurred within 

20 seconds in individuals exposed to 0.81 ppm, and within 5 seconds at 1.22 ppm (Sim and Pattle 1957). 

Human data summarized by Kane and Alarie (1977) show concentrations of acrolein between 0.5 and 

5 ppm caused lacrimation and various degrees of eye irritation in exposure periods of 10 minutes or less. 

The ocular effects observed in experimental animals are qualitatively similar to those described in 

humans. Vapor concentrations of acrolein higher than 1.0 ppm (1.8–3.7 ppm) caused eye irritation in 

dogs and monkeys as evidenced by lacrimation and closing of the eyes, but guinea pigs and rats appeared 

to be less sensitive, since 3.7 ppm had no noticeable effect (Lyon et al. 1970). No histological evaluation 

of the eye was conducted, but other reports indicate that ocular discharge was commonly seen (Murphy et 

al. 1964; Skog 1950). 

3.2.3.3 Immunological and Lymphoreticular Effects 

Rappaport and Hoffman (1941) reported the case of a male smoker who developed a severe skin reaction 

on the fingers of his right hand (which he used to hold the cigarette) and on his upper and lower lips. The 

patient was subjected to numerous allergy tests and found to be sensitive to acrolein, as well as other 

simple, short-chain aldehydes. It should be noted that this individual, a histology laboratory worker, was 

also likely to be exposed frequently to formaldehyde. It is difficult to determine whether the 

immunological response was a result of exposure to acrolein or other aldehydes. 

No studies were located regarding immunological effects in animals after dermal exposure to acrolein. 
ACROLEIN 61 

3. HEALTH EFFECTS 

No studies were located regarding the following effects in humans or animals after dermal exposure to 

acrolein: 

3.2.3.4 Neurological Effects 

3.2.3.5 Reproductive Effects 

3.2.3.6 Developmental Effects 

3.2.3.7 Cancer 

No studies were located regarding carcinogenic effects in humans after dermal exposure to acrolein. 

Salaman and Roe (1956) applied acrolein (in sesame oil) to the backs of mice once a day for 10 weeks. 

The total dose applied was 12.6 mg (5% solution). The authors reported no tumors at the site of 

application or at remote sites. These results should be interpreted with caution, since the duration of the 

study was too short to evaluate carcinogenic potential, and only 15 mice were used. 

3.3 GENOTOXICITY 

No studies were located regarding the genotoxic effects of acrolein in humans or animals by inhalation, 

oral, or dermal routes. Acrolein was not mutagenic in vivo as judged by the dominant lethal assay in the 

mouse (Epstein et al. 1972) or the sex-linked recessive lethal test in Drosophila (Zimmering et al. 1985). 

The in vitro genotoxicity of acrolein has been investigated in prokaryotic and eukaryotic organisms and in 

mammalian cell systems. The overall evidence, presented in Table 3-4, indicates that acrolein is weakly 

mutagenic without activating systems and non-mutagenic in the presence of activating systems in 

Salmonella typhimurium (Andersen et al. 1972; Bartsch et al. 1980; Basu and Marnett 1984; Bignami et 

al. 1977; Eder et al. 1982; Florin et al. 1980; Foiles et al. 1989; Khudoley et al. 1987; Lijinsky and 

Andrews 1980; Loquet et al. 1981; Lutz et al. 1982; Marnett et al. 1985; Parent et al. 1996b; 

Waegemaekers and Bensink 1984) and Escherichia coli (Bilimoria 1975; Ellenberger and Mohn 1977; 

Hemminki et al. 1980; Parent et al. 1996b; VanderVeen et al. 2001; Von der Hude et al. 1988). In the 

yeast, Saccharomyces cerevisiae, acrolein was not mutagenic without activating systems (Izard 1973). In 

mammalian cells, acrolein gave positive results without activating systems (Au et al. 1980; Moule et al. 

1971; Munsch et al. 1973, 1974). Acrolein inhibited the activity of DNA polymerase as well as DNA and 

RNA synthesis in rat liver cell nuclei (Crook et al. 1986a; Curren et al. 1988; Grafstrom et al. 1988; 

Krokan et al. 1985). The inconsistencies in the in vitro assay results may be due, in part, to the high 

cytotoxicity of acrolein to these systems. 
ACROLEIN 62 

3. HEALTH EFFECTS 

Table 3-4. Genotoxicity of Acrolein In Vitro 

Resultsa 

With Without 

End point Species (test system) activation activation Reference 

Prokaryotic organisms: 

 Gene mutation Salmonella typhimurium

 plate incorporation 

Liquid preincubation test: 

TA1535, 1537, 1538 

Liquid preincubation test: 

TA98 

Liquid preincubation test: 

TA100 

Liquid preincubation test 

Liquid preincubation method 

E. coli PQ37 (SOS chromotest) 

E. coli K-12/343/113 (plate 

incorporation) 

E. coli WP2uvrA (liquid 

preincubation)
 

E. coli WPuvrA (plate 

incorporation) 

DNA polymerase deficiency (plate 

incorporation) 

E. coli 

AB1157 derivatives 

Eukaryotic organisms: 

Fungi: 

 Gene mutation Saccharomyces cerevisiae (plate 

incorporation) 

 Chromosomal S. cerevisiae MB1072-2B (plate 

aberrations incorporation) 

– 

– 

– 

– 

– 

– 

– 

– 

No data 

No data 

– 

– 

+ 

No data 

No data 

– 

– 

– 

– 

No data 

No data 

– 

No data 

No data 

– 

– 

– 

– 

(+) 

+ 

+ 

– 

(+) 

– 

(+) 

+ 

+ 

+ 

(+) 

– 

No data 

(+) 

(+) 

+ 

No data 

– 

– 

Andersen et al. 1972 

Florin et al. 1980 

Loquet et al. 1981 

Bignami et al. 1977 

Lijinsky and Andrews 

1980 

Lutz et al. 1982 

Eder et al. 1982 

Basu and Marnett 1984 

Bartsch et al. 1980 

Khudoley et al. 1987 

Parent et al. 1996b 

Parent et al. 1996b 

Parent et al. 1996b 

Marnett et al. 1985 

Foiles et al. 1989 

Waegemaekers and 

Bensink 1984 

Von der Hude et al. 1988 

Ellenberger and Mohn 

1977 

Parent et al. 1996b 

Hemminki et al. 1980 

Bilimoria 1975 

VanderVeen et al. 2001 

Izard 1973 

Fleer and Brendel 1982 
ACROLEIN 

3. HEALTH EFFECTS 

63 

Table 3-4. Genotoxicity of Acrolein In Vitro 

End point Species (test system) 

Resultsa 

With Without 

activation activation Reference 

Mammalian cells: 

 DNA, RNA Rat liver cell nuclei No data + Moule et al. 1971 

synthesis 

DNA synthesis Human fibroblasts (xeroderma No data – Yang et al. 2002a 

pigmentusum and HeLa cells) 

DNA Rat liver No data + Munsch et al. 1973, 1974 

polymerase 

activity 

 Chromosome Chinese hamster ovary cells + + Au et al. 1980 

breakage 

 Sister chromatid Chinese hamster ovary cells + + Au et al. 1980 

exchange 

Gene mutation Chinese hamster ovary cells – – Parent et al. 1998a 

DNA damage Human myeloid cells K562 No data + Crook et al. 1986a 

DNA damage Human bronchial cells (culture) No data + Grafstrom et al. 1988 

DNA repair Human bronchial cells (culture) No data + Krokan et al. 1985 

DNA repair Human fibroblasts (culture) No data – Curren et al. 1988 

DNA repair Human fibroblasts (xeroderma No data + Curren et al. 1988 

pigmentation) 

Gene mutation Chinese hamster V79 cells No data + Smith et al. 1990a 

Gene mutation Human fibroblasts (with supF No data + Kawanishi et al. 1998 

plasmids) 

Gene mutation Human fibroblasts (xeroderma No data – Yang et al. 2002a 

pigmentusum and HeLa cells) 

+ = positive result; – = negative result; (+) = marginally positive result; DNA = deoxyribonucleic acid; 

RNA = ribonucleic acid 
ACROLEIN 64 

3. HEALTH EFFECTS 

Acrolein also induced chromosome breakage and sister-chromatid exchange in Chinese hamster ovary 

cells. DNA damage was seen in human myeloid cells and bronchial cells in culture. Acrolein was not 

mutagenic to normal human fibroblasts in culture, but fibroblasts with a deficient DNA repair system 

showed a positive mutagenic response (Curren et al. 1988). Acrolein was also a potent inhibitor of the 

DNA repair enzyme 06-methylguanine-DNA methyl transferase. DNA base substitutions and intra-strand 

cross-links were observed in human fibroblasts containing shuttle vector plasmids bearing the supF 

marker gene (Kawanishi et al. 1998). The mechanism by which acrolein induces genotoxicity in 

mammalian cells is not known, but it has been shown that acrolein can form adducts with DNA, such as 

1N2 -propanodeoxyguanine (Chung et al. 1984; Foiles et al. 1989), 1N6-propanodeoxyadenine (Smith et 

al. 1990a), 3-[N6-(2’-deoxyadenosinyl)]propanal and 9-(2’-reoxyribosyl-6-(3-formyl-1,2,5,6-tetrahydropyridyl)purine (Pawlowicz et al. 2006). Yang et al. (2002b) showed that acrolein adduction to DNA may 

be insignificant for the introduction of miscoding errors, as translesion DNA synthesis was high and 

miscoding incidence was <1% in human HeLa and xeroderma pigmentosum cells. The same inability of 

acrolein DNA adducts to cause miscoding was observed in E. coli as well (VanderVeen et al. 2001). 

Because of the limited number of in vivo tests, there is insufficient evidence to predict that acrolein poses 

a genotoxic threat to humans. 

3.4 TOXICOKINETICS 

3.4.1 Absorption 

3.4.1.1 Inhalation Exposure 

No studies were located regarding the rate and extent of absorption in humans after inhalation exposure to 

acrolein. The collection of such data would be problematic, as acrolein is highly reactive with any 

nucleophilic binding site it encounters during exposure by any route. 

Egle (1972) exposed anesthetized dogs to concentrations of acrolein between 172 and 262 ppm for a brief 

period of time (1–3 minutes) and observed that acrolein uptake by the total respiratory tract at ventilation 

rates of 6–20 respirations/minute averaged 80–85% of the inhaled dose. Retention was independent of 

the respiratory rate. The author estimated that only about 20% of the inhaled dose reached the lower 

respiratory tract. Morris (1996) and Morris et al. (2003) exposed mice to 1.1 ppm and rats to 0.9–9.1 ppm 

acrolein. In both species, most of the inhaled acrolein was absorbed entirely into the upper respiratory 

tract. Mice absorbed 92% of 1.1 ppm over 10 minutes. Absorption in the upper respiratory tract of rats 
ACROLEIN 65 

3. HEALTH EFFECTS 

was found to be dose- and breathing-rate related. At a breathing rate of 50 mL/minute, absorption ranged 

from >90% to approximately 70% for 0.9–9.1 ppm, while approximately 50–30% was absorbed when 

breathing 300 mL/minute of the same concentrations for 40 minutes. 

Exposure of the lower respiratory tract alone resulted in 65–70% concentration-independent retention, but 

decreased slightly with increases in tidal volume from 100 to 160 mL. Although the study by Egle (1972) 

does not provide information on the disposition of the retained acrolein or on whether the uptake rates 

represent steady-state values, it indicates that acrolein at relatively high concentrations is effectively 

removed from inhaled air by both the upper and lower respiratory tracts. 

3.4.1.2 Oral Exposure 

No studies were located regarding absorption of acrolein in humans after oral exposure. 

Parent et al. (1996a) administered gavage doses of 2.5 or 15 mg/kg [2,3-14C]acrolein to male and female 

Sprague-Dawley rats. Doses of 2.5 mg/kg were extensively absorbed, as 12–15% of the initial dose was 

found in the feces. In the high-dose group, 28–31% of the initial dose was found in the feces. 

3.4.1.3 Dermal Exposure 

No studies were located regarding absorption of acrolein in humans after dermal exposure. In cases of 

accidental dermal exposure (described in Section 3.2.3), effects were restricted to the exposed region of 

the body, presumably because of the high reactivity of acrolein. 

Limited information is available regarding dermal absorption of acrolein in animals. The percutaneous 

LD50 for rabbits ranged from 160 to 1,000 mg/kg, depending on the acrolein concentration and vehicle 

(water or mineral spirits) (Albin 1962). LD50values for acrolein administered in mineral spirits are lower 

than those in which water served as the vehicle, likely because of the greater skin permeability of mineral 

spirits. 

3.4.2 Distribution 

3.4.2.1 Inhalation Exposure 

No studies were located regarding distribution of acrolein in humans or animals after inhalation exposure. 
ACROLEIN 66 

3. HEALTH EFFECTS 

3.4.2.2 Oral Exposure 

No studies were located regarding distribution of acrolein in humans after oral exposure. 

In a study conducted by Draminski et al. (1983), the acrolein conjugated metabolite S-carboxyethylmercapturic acid was identified in the urine of rats after oral administration of a single dose of 10 mg/kg 

of acrolein, suggesting distribution of acrolein to the liver and kidney, where conjugation most likely 

occurred. Parent et al. (1996a) found similar levels of [2,3-14C]acrolein in the kidney, spleen, lungs, 

blood, liver, fat, adrenals, and ovaries of rats sacrificed 168 hours after dosing. 

3.4.2.3 Dermal Exposure 

No studies were located regarding distribution of acrolein in humans or animals after dermal exposure. 

3.4.2.4 Other Routes of Exposure 

Parent et al. (1996a) found [2,3-14C]acrolein in the kidney, spleen, lungs, blood, liver, fat, adrenals, and 

ovaries of rats administered 2.5 mg/kg [2,3-14C]acrolein intravenously. The [2,3-14C]acrolein were very 

similar across tissues; however, all tissue measurements were made at 168 hours after dose 

administration. 

3.4.3 Metabolism 

There is limited information available regarding the metabolism of acrolein in humans and animals after 

inhalation, oral, and dermal exposures. The relevant data are presented below. 

In non-biological cell-free systems, acrolein forms thiol ethers within seconds when reacted with 

glutathione or cysteine (Esterbauer et al. 1975, 1976). In cell systems in vitro, such as cultured human 

bronchial cells and isolated cell preparations from rat liver and kidneys, acrolein forms conjugates with 

glutathione, cysteine, N-acetylcysteine, and/or thioredoxin (Dawson et al. 1984; Dupbukt et al. 1987; 

Gurtoo et al. 1981b; Yang et al. 2004; Zitting and Heinonen 1980). The formation of these conjugates 

greatly diminished the cytotoxic effects of acrolein, indicating that conjugation may be an important 

detoxification mechanism. In addition to the evidence provided by the numerous in vitro studies, three 

reports from the literature (Alarcon 1976; Kaye 1973; Parent et al. 1998) demonstrated that acrolein also 
 

 

ACROLEIN 67 

3. HEALTH EFFECTS 

reacts with glutathione in vivo. In two of these studies, the acrolein metabolite 3-hydroxypropylmercapturic acid was identified in the urine of rats after a subcutaneous dose of acrolein (Alarcon 1976; 

Kaye 1973). It should be noted that other compounds also metabolize to 3-hydroxypropylmercapturic 

acid, including allylamine (Boor et al. 1987), allyl halides (Kaye and Young 1972), and allyl alcohol and 

ester (Kaye 1973). Findings from the third study (Parent et al. 1998) are discussed in Section 3.4.3.2. 

Based on experimental results, Patel et al. (1980b) proposed an in vitro metabolic scheme for acrolein in 

rat liver and lung preparations. In this scheme, free acrolein can interact with proteins and nucleic acids, 

and/or with thiol groups such as glutathione. Acrolein can also be transformed into acrylic acid by liver 

cytosol or microsomes, or it can be oxidized to glycidaldehyde by lung or liver microsomes. Acrylic acid 

may be incorporated into amino acids, fatty acids, and sterol. Glycidaldehyde can be metabolized to 

glyceraldehyde, which then can enter the glycolytic pathways. From the scheme proposed by Patel et al. 

(1980b), glycidaldehyde appears to be the only chemical that could represent a risk to human health, since 

it has shown carcinogenic properties in mice and rats when applied dermally (Shamberger et al. 1974; 

Van Duuren et al. 1967a, 1967b). The metabolic pathway proposed by Patel et al. (1980b) is shown in 

Figure 3-3. 

3.4.3.1 Inhalation Exposure 

No studies were located regarding metabolism of acrolein in humans after inhalation exposure. 

Lam et al. (1985) found a dose-related depletion of glutathione in the nasal respiratory mucosa of rats 

after exposure to 0.1–2.5 ppm of acrolein for 3 hours. This finding is consistent with a chemical reaction 

leading to the formation of a glutathione-acrolein adduct. 

3.4.3.2 Oral Exposure 

No studies were located regarding metabolism of acrolein in humans after oral exposure. 

Draminski et al. (1983) administered 10 mg/kg of acrolein as a single oral dose to rats and collected the 

urine during 3 days. Since the metabolite S-carboxyethylmercapturic acid was found in the urine, but 

S-hydroxypropylmercapturic acid (which should have been formed if acrolein had reacted with 

glutathione) was not, an alternative pathway was proposed. In this metabolic scheme, acrolein is first 

metabolized to acrylic acid with subsequent formation of the methyl ester, which is then conjugated with 

glutathione to form S-carboxyethylmercapturic acid methyl ester. Both metabolic schemes proposed by 
Figure 3-3. Proposed Metabolic Scheme for Acrolein In Vitro 

H ACRYLIC CH2=CH-COOH H C C CHO GLYCIDALDEHYDE 2 ACID O 

Epoxide hydrolase Amino acids Sterol 

Interaction with 

proteins and nucleic acids 

Interaction with 

thiols 

 Liver cytosol 

Acrolein 

CH2=CH-CHO 

NAD+ or 

NADP+ 

Lung or liver or microsomes microsomes 

NADPH 

Fatty acids H2C C 

H 

CHO GLYCERALDEHYDE 

OH OH 

GLYCOLYTIC PATHWAY 

Source: Patel et al. 1980 

ACROLEIN 68 

3. HEALTH EFFECTS 
ACROLEIN 69 

3. HEALTH EFFECTS 

Draminski et al. (1983) and Patel et al. (1980b) involve the hepatic formation of acrylic acid, but differ on 

the subsequent metabolism of that metabolite. The metabolic pathway postulated by Draminski et al. 

(1983) is shown in Figure 3-4. 

An in vivo study in rats identified six metabolites of [2,3-14C]acrolein in urine (Parent et al. 1998) arising 

from three proposed pathways. The main pathway involves Michael addition of glutathione to acrolein to 

generate S-3-oxypropylcysteine. Further oxidation or reduction results in two of the mercapturic acids 

found in urine, N-acetyl-S-2-carboxyethylcysteine and N-acetyl-S-2-hydropropylcysteine. The second 

pathway involves the epoxidation of acrolein to glycidaldehyde and subsequent attack by glutathione. 

Further oxidation produced urinary N-acetyl-S-2-hydroxyethylcysteine. Finally, urinary 3-hydroxypropionic acid, malonic acid, and oxalic acid were proposed to arise from non-enzymatic hydrolysis of 

acrolein and subsequent oxidation of the aldehyde. No metabolites were found in the feces. The 

metabolic scheme proposed by Parent et al. (1998) is shown in Figure 3-5. 

3.4.3.3 Dermal Exposure 

No studies were located regarding metabolism of acrolein in humans or animals after dermal exposure. 

3.4.4 Elimination and Excretion 

3.4.4.1 Inhalation Exposure 

No studies were located regarding excretion of acrolein or metabolites after inhalation exposure. 

3.4.4.2 Oral Exposure 

No studies were located regarding excretion of acrolein or metabolites in humans after oral exposure. 

In rats dosed with 2.5 mg/kg [2,3-14C]acrolein via gavage, Parent et al. (1996a) found 27–31% of the 

initial dose to be expired as CO2 while 52–63% was found in the urine and 12–15% was found in the 

feces. Rats dosed with 15 mg/kg [2,3-14C]acrolein exhibited similar expiration of the initial dose as CO2, 

but had a higher fraction of the initial dose going to feces (28–31%) and a lower fraction going to urine 

(37–41%). Six metabolites of [2,3-14C]acrolein were identified in the urinary fraction of the 2.5 mg/kg 

group: N-acetyl-S-2-carboxyethylcysteine; N-acetyl-S-2-hydropropylcysteine; N-acetyl-S-2-hydroxyethylcysteine; 3-hydroxypropionic acid; malonic acid; and oxalic acid (Parent et al. 1998). Draminski et 
3. HEALTH EFFECTS 

Figure 3-4. Proposed Metabolic Scheme for Acrolein In Vivo 

Acrolein 

CH2=CH-CHO 

Liver cytosol 

or microsomes 

CH2=CH-COOH ACRYLIC ACID 

Methylase 

O 

H2C C C METHYL ACRYLATE H 

OCH3 

GSH 

O 

O HN CH3

O 

C C C S C C C 

H2 H2 H2 CH H 3O OH 

S-CARBOXYETHYLMERCAPTURIC ACID METHYL ESTER 

Source: Draminski et al. 1983 

ACROLEIN 70 
3. HEALTH EFFECTS 

 

Figure 3-5. Proposed Pathway for the Metabolism of Acrolein in Rats* 

HOCH2CH2CO2H HO2CCH2CO2H HO2CCO2H + CO2 

3-Hydroxypropionic acid 

Metabolite 6 

Malonic acid 

Metabolite 2 

[O] Oxalic acid

 Metabolite 1 

[O]
 

O
 

O O O 

CH2 CHCH 

HOCH2CH2CH H2O CH2 CHCH Acrolein 

3-Hydroxypropionaldehyde Glycidaldehyde 

GSH 

GSH Polymers 

O O 

GSCH GSCH2CHOHCH 2CHCH 

S-3-Oxopropyl glutathione S-3-Hydroxy-3-oxopropyl glutathione 

gamma-Glutamyl gamma-Glutamyl 

transpeptidase transpeptidase 

O O

HO2CCHCH2SCH2CHOHCH 

reduction 

HO2CCHCH2SCH2CH2CH 

NH NH3 3
 

S-3-Oxopropylcysteine
 S-2-Hydroxy-3-oxopropylcysteine 

[O] [O] 

HO2CCHCH2SCH2CH2CO2H HO2CCHCH2SCH2CH2CH2OH HO2CCHCH2SCH2CHOHCO2H 

NH3 NH3 NH3 

S-2-Carboxyethylcysteine S-3-Hydroxypropylcysteine S-2-Carboxy-2-hydroxyethylcysteine 

ACROLEIN 71 

HO2CCHCH2SCH2CH2CO2H HO2CCHCH2SCH2CH2CH2OH HO2CCHCH2SCH2CHOHCO2H 

NHCCH3 NHCCH3 NHCCH3 

O O O 

N-Acetyl-S-2-carboxyethylcysteine 

Metabolite 4 

N-Acetyl-S-3-hydropropylcysteine 

Metabolite 5 

N-Acetyl-S-2-carboxy-2-hydroxyethylcysteine 

Metabolite 3 

*The structures in brackets represent postulated intermediates. 

Source: Parent et al. 1998 
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3. HEALTH EFFECTS 

al. (1983) reported the presence of the acrolein metabolite S-carboxyethylmercapturic acid in the urine of 

rats after administration of a single oral dose of 10 mg/kg of acrolein. The percentage of the dose 

recovered as the metabolite in the urine was not determined. 

3.4.4.3 Dermal Exposure 

No studies were located regarding excretion of acrolein or metabolites after dermal exposure. 

3.4.4.4 Other Routes of Exposure 

Rats administered 2.5 mg/kg [2,3-14C]acrolein intravenously expired 26–27% of the initial dose as CO2, 

which is lower, but not significantly different from animals orally exposed to the same dose (Parent et al. 

1996a). In this study, intravenously administered [2,3-14C]acrolein was predominantly eliminated in the 

urine (67–69%), with a small fraction found in the feces (1–2%). 

3.4.5 Physiologically Based Pharmacokinetic (PBPK)/Pharmacodynamic (PD) Models 

Physiologically based pharmacokinetic (PBPK) models use mathematical descriptions of the uptake and 

disposition of chemical substances to quantitatively describe the relationships among critical biological 

processes (Krishnan et al. 1994). PBPK models are also called biologically based tissue dosimetry 

models. PBPK models are increasingly used in risk assessments, primarily to predict the concentration of 

potentially toxic moieties of a chemical that will be delivered to any given target tissue following various 

combinations of route, dose level, and test species (Clewell and Andersen 1985). Physiologically based 

pharmacodynamic (PBPD) models use mathematical descriptions of the dose-response function to 

quantitatively describe the relationship between target tissue dose and toxic end points. 

PBPK/PD models refine our understanding of complex quantitative dose behaviors by helping to 

delineate and characterize the relationships between: (1) the external/exposure concentration and target 

tissue dose of the toxic moiety, and (2) the target tissue dose and observed responses (Andersen and 

Krishnan 1994; Andersen et al. 1987). These models are biologically and mechanistically based and can 

be used to extrapolate the pharmacokinetic behavior of chemical substances from high to low dose, from 

route to route, between species, and between subpopulations within a species. The biological basis of 

PBPK models results in more meaningful extrapolations than those generated with the more conventional 

use of uncertainty factors. 
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3. HEALTH EFFECTS 

The PBPK model for a chemical substance is developed in four interconnected steps: (1) model 

representation, (2) model parameterization, (3) model simulation, and (4) model validation (Krishnan and 

Andersen 1994). In the early 1990s, validated PBPK models were developed for a number of 

toxicologically important chemical substances, both volatile and nonvolatile (Krishnan and Andersen 

1994; Leung 1993). PBPK models for a particular substance require estimates of the chemical substancespecific physicochemical parameters, and species-specific physiological and biological parameters. The 

numerical estimates of these model parameters are incorporated within a set of differential and algebraic 

equations that describe the pharmacokinetic processes. Solving these differential and algebraic equations 

provides the predictions of tissue dose. Computers then provide process simulations based on these 

solutions. 

The structure and mathematical expressions used in PBPK models significantly simplify the true 

complexities of biological systems. If the uptake and disposition of the chemical substance(s) are 

adequately described, however, this simplification is desirable because data are often unavailable for 

many biological processes. A simplified scheme reduces the magnitude of cumulative uncertainty. The 

adequacy of the model is, therefore, of great importance, and model validation is essential to the use of 

PBPK models in risk assessment. 

PBPK models improve the pharmacokinetic extrapolations used in risk assessments that identify the 

maximal (i.e., the safe) levels for human exposure to chemical substances (Andersen and Krishnan 1994). 

PBPK models provide a scientifically sound means to predict the target tissue dose of chemicals in 

humans who are exposed to environmental levels (for example, levels that might occur at hazardous waste 

sites) based on the results of studies where doses were higher or were administered in different species. 

Figure 3-6 shows a conceptualized representation of a PBPK model. 

No PBPK models for acrolein were identified in the literature. 

3.5 MECHANISMS OF ACTION 

3.5.1 Pharmacokinetic Mechanisms 

No studies were located for animals or humans that describe observed mechanisms for acrolein absorption 

across the skin, lung, or gut, metabolism (either through passive adduct formation or enzymatically 

catalyzed transformation), or excretion. It is not known whether acrolein and its metabolites are 

transported across cell membranes via passive diffusion or active transport processes. Since acrolein is 
3. HEALTH EFFECTS 

Figure 3-6. Conceptual Representation of a Physiologically Based 

Pharmacokinetic (PBPK) Model for a Hypothetical 

Chemical Substance 

Inhaled chemical Exhaled chemical 

Ingestion 

Lungs 

Liver 

Fat 

Slowly 

perfused 

tissues 

Richly 

perfused 

tissues 

Kidney 

Skin 

V 

E 

N 

O 

U 

S 

B 

L 

O 

O 

D 

A 

R 

T 

E 

R 

I 

A 

L 

B 

L 

O 

O 

D 

Vmax Km 

GI 

Tract 

Feces 

Urine

 Chemicals in air 

ACROLEIN 74 

contacting skin 

Note: This is a conceptual representation of a physiologically based pharmacokinetic (PBPK) model for a 

hypothetical chemical substance. The chemical substance is shown to be absorbed via the skin, by inhalation, or by 

ingestion, metabolized in the liver, and excreted in the urine or by exhalation. 

Source: adapted from Krishnan et al. 1994 
ACROLEIN 75 

3. HEALTH EFFECTS 

known to react with any nucleophilic site, including protein thiol moieties, peptide-based active 

transporters may form adducts with acrolein, which may serve to diminish or inhibit the transporter’s 

functionality. 

3.5.2 Mechanisms of Toxicity 

As an ethenylic aldehyde, acrolein is a highly reactive compound. In biological systems, it binds 

extensively to lysine moieties and has the highest affinity for sulfhydryl groups found on many cellular 

molecules, including most proteins. As such, it binds rapidly and irreversibly to macromolecules to form 

thiol ethers (Beauchamp et al. 1985). In this fashion, acrolein may bind to structural and biological 

messenger compounds to produce direct cytotoxic effects or secondary effects from interrupted cell 

signaling pathways. Perturbation of inflammatory responses in bronchial epithelial cells was 

demonstrated by direct action of acrolein on IκB kinase, resulting in inhibition of NFκB activation and 

suppression of IL-8 production (Valacchi et al. 2005). Alarie (1973) hypothesized that rapid binding of 

acrolein to neural receptors in the corneal and nasal mucosa may result in rapid depolarization of the 

associated neurons to produce ocular and nasal irritation. Adams and Klaidman (1993) showed acrolein 

to bind rapidly to glutathione. Depletion of glutathione could be inhibitory to the enzyme glutathione 

peroxidase, resulting in a lower level of cellular protection against oxygen radical toxicity. Further, the 

adduction of glutathione resulted in generation of a GS-propionaldehyde, which was shown to produce 

oxygen and possibly hydroxy radicals via cytosolic aldehyde dehydrogenase. Glutathione depletion and 

inhibition of caspase-3 activation in human neutrophils was observed to inhibit neutrophil apoptosis, 

providing a possible mechanism for extended inflammatory responses (Finkelstein et al. 2005). 

Similarly, activation of caspase-7 and -9 and inhibition of caspase-3 accompanied apoptosis in Chinese 

hamster ovary cells (Tanel and Averill-Bates 2005). A dose-dependent increase in NO levels and 

decrease in thioredoxin reductase was correlated with apoptosis of acrolein-treated human umbilical vein 

endothelial cells (Misonou et al. 2006; Park et al. 2005). Arumugan et al. (1999) exposed rats to 1 and 

2 ppm acrolein for 4 hours and measured various markers for lipid peroxidation in lavage fluid from the 

lung. They were able to correlate changes in peroxidative status on the lungs with gross histological 

findings of desquamated alveolar endothelium, a metaplastic change in cell structure that has been 

observed over the entire respiratory tract of animals. They also found diminished glutathione levels in 

treated animals as well as an increase in superoxide dismutase and decreases in catalase and glutathione 

peroxidase, indicative of an imbalance in antioxidant defenses that favors oxidative stress. Further, 

increased levels of conjugated dienes and thiobarbituric acid reactive substances suggest the onset of lipid 

peroxidation. Reduction of glutathione and aconitase activity was correlated with increased ROS 
ACROLEIN 76 

3. HEALTH EFFECTS 

production and inhibited electron transport in brain and spinal cord mitochondria of guinea pigs (Luo and 

Shi 2004, 2005) and human PC12 cells (Luo et al. 2005). Beauchamp et al.’s analysis (1985) suggests 

that depletion of glutathione and other available cellular thiol sources may permit the movement of 

acrolein at high concentrations past the initial tissue point of contact. While data were not found that 

correlated gastrointestinal lesions with glutathione content and peroxidative status as was done in the lung 

(Arumugan et al. 1999), the appearance of endothelial metaplasia in multiple species of animals following 

oral exposures suggests that gastrointestinal and respiratory toxicity may occur by the same mechanism of 

action. 

Acrolein has been shown to be produced endogenously from hydroxyl-amino acids (Anderson et al. 1997) 

and as a product of lipid peroxidation (Uchida et al. 1998a, 1998b), which can form protein conjugates 

that may be significant factors in certain diseases. Acrolein conjugation with lysine residues of lowdensity lipoproteins has been suggested as a factor in the development of atherosclerosis (Uchida et al. 

1998b). Protein-acrolein binding products resulting from lipid peroxidation have been implicated in the 

formation of neurofibrillary tangles (Calingasan et al. 1999) and induction of protein tau 

hyperphosphorylation (Gomez-Ramos et al. 2003), both hallmarks of Alzheimer’s disease. 

3.5.3 Animal-to-Human Extrapolations 

The irritant properties of acrolein have been reported in both human and animal studies. In vivo studies in 

animals and in vitro studies in human and animal cell cultures have reported the common mechanisms of 

action of cellular thiol reactivity and glutathione depletion (Arumugan et al. 1999; Beauchamp et al. 

1985; Nardini et al. 2002). Acrolein exposure levels were very comparable for the appearance of cellular 

changes in nasal epithelium of animals (Cassee et al. 1996) and onset of nasal irritation in humans 

(Weber-Tschopp et al. 1977). Therefore, it is reasonable to extrapolate animal health effects to human 

health risk resulting from acrolein exposure. 

3.6 TOXICITIES MEDIATED THROUGH THE NEUROENDOCRINE AXIS 

Recently, attention has focused on the potential hazardous effects of certain chemicals on the endocrine 

system because of the ability of these chemicals to mimic or block endogenous hormones. Chemicals 

with this type of activity are most commonly referred to as endocrine disruptors. However, appropriate 

terminology to describe such effects remains controversial. The terminology endocrine disruptors, 

initially used by Thomas and Colborn (1992), was also used in 1996 when Congress mandated the EPA to 

develop a screening program for “...certain substances [which] may have an effect produced by a 
ACROLEIN 77 

3. HEALTH EFFECTS 

naturally occurring estrogen, or other such endocrine effect[s]...”. To meet this mandate, EPA convened a 

panel called the Endocrine Disruptors Screening and Testing Advisory Committee (EDSTAC), and in 

1998, the EDSTAC completed its deliberations and made recommendations to EPA concerning endocrine 

disruptors. In 1999, the National Academy of Sciences released a report that referred to these same types 

of chemicals as hormonally active agents. The terminology endocrine modulators has also been used to 

convey the fact that effects caused by such chemicals may not necessarily be adverse. Many scientists 

agree that chemicals with the ability to disrupt or modulate the endocrine system are a potential threat to 

the health of humans, aquatic animals, and wildlife. However, others think that endocrine-active 

chemicals do not pose a significant health risk, particularly in view of the fact that hormone mimics exist 

in the natural environment. Examples of natural hormone mimics are the isoflavinoid phytoestrogens 

(Adlercreutz 1995; Livingston 1978; Mayr et al. 1992). These chemicals are derived from plants and are 

similar in structure and action to endogenous estrogen. Although the public health significance and 

descriptive terminology of substances capable of affecting the endocrine system remains controversial, 

scientists agree that these chemicals may affect the synthesis, secretion, transport, binding, action, or 

elimination of natural hormones in the body responsible for maintaining homeostasis, reproduction, 

development, and/or behavior (EPA 1997). Stated differently, such compounds may cause toxicities that 

are mediated through the neuroendocrine axis. As a result, these chemicals may play a role in altering, 

for example, metabolic, sexual, immune, and neurobehavioral function. Such chemicals are also thought 

to be involved in inducing breast, testicular, and prostate cancers, as well as endometriosis (Berger 1994; 

Giwercman et al. 1993; Hoel et al. 1992). 

No studies were located regarding endocrine disruption in human or animals after exposure to acrolein. 

No in vitro studies were located regarding endocrine disruption of acrolein. Based on the mechanism of 

toxicity and data from animal studies (Parent et al. 1991a, 1992a, 1992b), acrolein is not expected to have 

endocrine-modulating activities. 

3.7 CHILDREN’S SUSCEPTIBILITY 

This section discusses potential health effects from exposures during the period from conception to 

maturity at 18 years of age in humans, when all biological systems will have fully developed. Potential 

effects on offspring resulting from exposures of parental germ cells are considered, as well as any indirect 

effects on the fetus and neonate resulting from maternal exposure during gestation and lactation. 

Relevant animal and in vitro models are also discussed. 
ACROLEIN 78 

3. HEALTH EFFECTS 

Children are not small adults. They differ from adults in their exposures and may differ in their 

susceptibility to hazardous chemicals. Children’s unique physiology and behavior can influence the 

extent of their exposure. Exposures of children are discussed in Section 6.6, Exposures of Children. 

Children sometimes differ from adults in their susceptibility to hazardous chemicals, but whether there is 

a difference depends on the chemical (Guzelian et al. 1992; NRC 1993). Children may be more or less 

susceptible than adults to health effects, and the relationship may change with developmental age 

(Guzelian et al. 1992; NRC 1993). Vulnerability often depends on developmental stage. There are 

critical periods of structural and functional development during both prenatal and postnatal life, and a 

particular structure or function will be most sensitive to disruption during its critical period(s). Damage 

may not be evident until a later stage of development. There are often differences in pharmacokinetics 

and metabolism between children and adults. For example, absorption may be different in neonates 

because of the immaturity of their gastrointestinal tract and their larger skin surface area in proportion to 

body weight (Morselli et al. 1980; NRC 1993); the gastrointestinal absorption of lead is greatest in infants 

and young children (Ziegler et al. 1978). Distribution of xenobiotics may be different; for example, 

infants have a larger proportion of their bodies as extracellular water, and their brains and livers are 

proportionately larger (Altman and Dittmer 1974; Fomon 1966; Fomon et al. 1982; Owen and Brozek 

1966; Widdowson and Dickerson 1964). The infant also has an immature blood-brain barrier (Adinolfi 

1985; Johanson 1980) and probably an immature blood-testis barrier (Setchell and Waites 1975). Many 

xenobiotic metabolizing enzymes have distinctive developmental patterns. At various stages of growth 

and development, levels of particular enzymes may be higher or lower than those of adults, and 

sometimes unique enzymes may exist at particular developmental stages (Komori et al. 1990; Leeder and 

Kearns 1997; NRC 1993; Vieira et al. 1996). Whether differences in xenobiotic metabolism make the 

child more or less susceptible also depends on whether the relevant enzymes are involved in activation of 

the parent compound to its toxic form or in detoxification. There may also be differences in excretion, 

particularly in newborns who all have a low glomerular filtration rate and have not developed efficient 

tubular secretion and resorption capacities (Altman and Dittmer 1974; NRC 1993; West et al. 1948). 

Children and adults may differ in their capacity to repair damage from chemical insults. Children also 

have a longer remaining lifetime in which to express damage from chemicals; this potential is particularly 

relevant to cancer. 

Certain characteristics of the developing human may increase exposure or susceptibility, whereas others 

may decrease susceptibility to the same chemical. For example, although infants breathe more air per 

kilogram of body weight than adults breathe, this difference might be somewhat counterbalanced by their 
ACROLEIN 79 

3. HEALTH EFFECTS 

alveoli being less developed, which results in a disproportionately smaller surface area for alveolar 

absorption (NRC 1993). 

Since point-of-contact irritation is the principal toxic action of acrolein, children are not likely to be more 

susceptible to acrolein’s effects at the tissue level. Despite uncertainties in age-related differences in lung 

architecture, surface area, and ventilation rates, simple dosimetry modeling of a category 1 gas, such as 

acrolein, does not suggest significant differences in early juvenile and adult internal inhalation exposure 

(Ginsberg et al. 2005). It is not known if there are age-related differences in the pharmacokinetics of 

acrolein. The amount of ingested acrolein available for gastrointestinal irritation would be the same for 

children and adults. While children may have a higher inhalation rate (per mass) than adults (NRC 1993), 

it is unknown whether they would continue to breathe more airborne acrolein than adults. While adults 

have been shown to reduce their respiration rate by as much as 20% in the presence of airborne acrolein 

(Weber-Tschopp et al. 1977), it is not known if children will react in the same or similar manner. Animal 

studies have shown offspring of acrolein-exposed mothers to have reduced body weights and skeletal 

deformities (King 1982; Parent et al. 1992c). However, these effects occurred at high oral doses that were 

fatal to the mothers. 

3.8 BIOMARKERS OF EXPOSURE AND EFFECT 

Biomarkers are broadly defined as indicators signaling events in biologic systems or samples. They have 

been classified as markers of exposure, markers of effect, and markers of susceptibility (NAS/NRC 

1989). 

Due to a nascent understanding of the use and interpretation of biomarkers, implementation of biomarkers 

as tools of exposure in the general population is very limited. A biomarker of exposure is a xenobiotic 

substance or its metabolite(s) or the product of an interaction between a xenobiotic agent and some target 

molecule(s) or cell(s) that is measured within a compartment of an organism (NAS/NRC 1989). The 

preferred biomarkers of exposure are generally the substance itself, substance-specific metabolites in 

readily obtainable body fluid(s), or excreta. However, several factors can confound the use and 

interpretation of biomarkers of exposure. The body burden of a substance may be the result of exposures 

from more than one source. The substance being measured may be a metabolite of another xenobiotic 

substance (e.g., high urinary levels of phenol can result from exposure to several different aromatic 

compounds). Depending on the properties of the substance (e.g., biologic half-life) and environmental 

conditions (e.g., duration and route of exposure), the substance and all of its metabolites may have left the 
ACROLEIN 80 

3. HEALTH EFFECTS 

body by the time samples can be taken. It may be difficult to identify individuals exposed to hazardous 

substances that are commonly found in body tissues and fluids (e.g., essential mineral nutrients such as 

copper, zinc, and selenium). Biomarkers of exposure to acrolein are discussed in Section 3.8.1. 

Biomarkers of effect are defined as any measurable biochemical, physiologic, or other alteration within an 

organism that, depending on magnitude, can be recognized as an established or potential health 

impairment or disease (NAS/NRC 1989). This definition encompasses biochemical or cellular signals of 

tissue dysfunction (e.g., increased liver enzyme activity or pathologic changes in female genital epithelial 

cells), as well as physiologic signs of dysfunction such as increased blood pressure or decreased lung 

capacity. Note that these markers are not often substance specific. They also may not be directly 

adverse, but can indicate potential health impairment (e.g., DNA adducts). Biomarkers of effects caused 

by acrolein are discussed in Section 3.8.2. 

A biomarker of susceptibility is an indicator of an inherent or acquired limitation of an organism's ability 

to respond to the challenge of exposure to a specific xenobiotic substance. It can be an intrinsic genetic or 

other characteristic or a preexisting disease that results in an increase in absorbed dose, a decrease in the 

biologically effective dose, or a target tissue response. If biomarkers of susceptibility exist, they are 

discussed in Section 3.10, Populations That Are Unusually Susceptible. 

3.8.1 Biomarkers Used to Identify or Quantify Exposure to Acrolein 

A product of the conjugation of acrolein with glutathione, 3-hydroxypropylmercapturic acid, has been 

identified in the urine of individuals receiving the drug cyclophosphamide (Alarcon 1976; Kaye and 

Young 1974). Since the same product was identified in the urine of rats administered acrolein 

subcutaneously (Alarcon 1976), it was thought that levels of 3-hydroxypropylmercapturic acid in the 

urine could be used to identify exposure to acrolein. However, Alarcon (1976) found no correlation 

between the dose of cyclophosphamide administered and the amount of 3-hydroxypropylmercapturic acid 

in the urine of patients. Parent et al. (1998b) found six urinary metabolites (predominantly mercapturic 

acids) following oral and intravenous dosing of radiolabled acrolein in rats, but did not correlate 

metabolite levels with dose. Methods developed to determine levels of acrolein in human tissues and 

fluids are described in Chapter 7. 
ACROLEIN 81 

3. HEALTH EFFECTS 

3.8.2 Biomarkers Used to Characterize Effects Caused by Acrolein 

No studies were located regarding levels of acrolein or its metabolites in human tissues and fluids 

associated with effects. No biochemical or histological changes specific for acrolein exposure were 

identified. Results from a toxicokinetic study suggested that acrolein can react with proteins and nucleic 

acids in the organism (Patel et al. 1980b). 

After transformation into acrylic acid, incorporation into amino acids, fatty acids, and sterols can be 

expected (Patel et al. 1980b). However, specific effects associated with these biochemical reactions are 

not known. 

3.9 INTERACTIONS WITH OTHER CHEMICALS 

Ansari et al. (1988a) showed that acrolein enhances the inhibitory effect that certain industrial chemicals, 

such as styrene and 1,2-dichloroethane, have on the αl-proteinase inhibitor of human plasma in vitro. A 

decrease in the activity of the αl-proteinase inhibitor may result in an increase in the activity of the lung 

enzyme neutrophil elastase, which can lead to the development of emphysema. Acrolein has also been 

shown to increase the pentobarbital- and hexobarbital-induced sleeping time in rats (Jaeger and Murphy 

1973a). The mechanism, according to the authors, could include changes in the absorption and 

distribution of the barbiturates. More recent information suggests that the mechanism may involve a 

covalent reaction between acrolein and cytochrome P-450 leading to inactivation of P-450 resulting in 

prolonged action of the barbiturates (Lame and Segall 1987). 

Acrolein forms adducts with thiols such as glutathione, cysteine, N-acetylcysteine, and others. Such 

reaction protects tissues and cells from the cytotoxic effects of acrolein or acrolein-releasing substances 

(Brock et al. 1981b; Chaviano et al. 1985; Dawson et al. 1984; Gurtoo et al. 1983; Ohno and Ormstad 

1985; Whitehouse and Beck 1975). 

Exposure of mice for 10 minutes to mixtures of sulfur dioxide and acrolein showed that either irritant can 

alter or block the effect of the other (Kane and Alarie 1979a). Furthermore, when the mice were exposed 

to mixtures, recovery was much slower than when exposed to the individual chemicals. The authors 

postulated that a bisulfite-acrolein adduct may be formed. When exposure ceased, this adduct would 

release acrolein, thus preventing immediate recovery. In addition, Kane and Alarie (1978) exposed mice 

to mixtures of acrolein and formaldehyde and showed that the respiratory response to mixtures was less 
 

 

ACROLEIN 82 

3. HEALTH EFFECTS 

pronounced than the response to either chemical alone. This is consistent with a mechanism in which 

both chemicals act on the same type of physiological receptor (free nerve endings). 

3.10 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE 

A susceptible population will exhibit a different or enhanced response to acrolein than will most persons 

exposed to the same level of acrolein in the environment. Reasons may include genetic makeup, age, 

health and nutritional status, and exposure to other toxic substances (e.g., cigarette smoke). These 

parameters result in reduced detoxification or excretion of acrolein, or compromised function of organs 

affected by acrolein. Populations who are at greater risk due to their unusually high exposure to acrolein 

are discussed in Section 6.7, Populations with Potentially High Exposures. 

In general, individuals whose respiratory function is compromised, such as those with emphysema, or 

individuals with allergic conditions such as asthma, will be at a higher risk of developing adverse 

respiratory responses when exposed to a strong respiratory irritant such as acrolein. This was 

demonstrated in animals in which allergic airway-diseased mice were more responsive than nondiseased 

mice to acute respiratory irritant effects of 0.3 ppm acrolein (Morris et al. 2003). 

3.11 METHODS FOR REDUCING TOXIC EFFECTS 

This section will describe clinical practice and research concerning methods for reducing toxic effects of 

exposure to acrolein. However, because some of the treatments discussed may be experimental and 

unproven, this section should not be used as a guide for treatment of exposures to acrolein. When specific 

exposures have occurred, poison control centers and medical toxicologists should be consulted for 

medical advice. The following texts provide specific information about treatment following exposures to 

acrolein: 

Bronstein AC, Currance PL. 1994. Emergency care for hazardous materials exposure. 2nd ed. 

St. Louis, MO: Mosby Lifeline. 

ITII. 1988. Toxic and hazardous industrial chemicals safety manual. Tokyo, Japan: The International 

Technical Information Institute. 

Goldfrank LR, Flomenbaum NE, Lewin NA, et al. 2002. Toxicologic emergencies. 7th ed. New York, 

NY:McGraw-Hill, Medical Publishing Division, 1470. 
ACROLEIN 83 

3. HEALTH EFFECTS 

3.11.1 Reducing Peak Absorption Following Exposure 

The mechanisms of absorption of acrolein following inhalation or oral exposures is not known. Since 

acrolein is a point-of-contact irritant, measures to dilute the concentration at the pulmonary, 

gastrointestinal, or dermal tissue surfaces may reduce absorption. Emergency treatment for acrolein 

inhalation exposure includes ventilation and oxygenation. Water may be ingested or used as a rinse to 

dilute oral or dermal exposures, respectively. Gastric lavage or nasogastric suction may be administered 

if life-threatening amounts of acrolein are ingested (HSDB 2007). 

3.11.2 Reducing Body Burden 

Acrolein is not believed to accumulate in the body. With the exception of gastric lavage and nasogastric 

suction (see Section 3.11.1), no studies or guidelines could be located with procedures for reducing the 

body burden of acrolein. 

3.11.3 Interfering with the Mechanism of Action for Toxic Effects 

Acrolein acts by contact reactivity (i.e., adduction) with nucleophilic sites on macromolecules of 

biological tissues, including binding to glutathione. There are no clinically-accepted procedures for 

therapeutically interfering with acrolein’s toxic mechanism of action. Several in vitro and in vivo studies 

suggest candidates for treatment of acrolein exposure at the cellular level. The anti-hypertensive drug 

hydrazinophthalazine is effective in trapping reactive acrolein-protein adducts formed following in vitro 

acrolein exposure of mouse hepatocytes (Burcham et al. 2004) and in vivo intraperitoneal allyl alcohol 

(which is metabolized to acrolein) exposure in mice (Kaminskas et al. 2004). Effective in vitro and 

in vivo concentrations of hydrazinophthalazine ranged from 2 to 50 μM and from 6 to 18 mg/kg, 

respectively. Pretreatment of rat A10 aortic smooth muscle cells with 1,2-dithiole-3-thione resulted in 

induction of cellular glutathione and glutathione-S-transferease (an enzyme that catalyzes the conjugation 

of reduced glutathione and reactive electrophiles, such as acrolein) and a marked decrease in acrolein 

cytotoxicity (Cao et al. 2003). Cells treated with 100 μM 1,2-dithiole-3-thione were 90–100% viable 

after 24 hours of exposure to as much as 40 μM acrolein. The antioxidants α-tocopherol and ascorbic 

acid served to significantly reduce acrolein-induced apoptosis (25 μM) in cultured human bronchial 

epithelial cells at levels of 5 and 50 μM, respectively (Nardini et al. 2002). While these studies report a 

variety of compounds and cellular concentrations capable of interfering with acrolein’s toxic mechanism 

of action, they do not provide data regarding an effective administered dose (by any route) or maximum 

delay in administration that would provide efficacy against acrolein toxicity in humans or animals. 
ACROLEIN 84 

3. HEALTH EFFECTS 

3.12 ADEQUACY OF THE DATABASE 

Section 104(I)(5) of CERCLA, as amended, directs the Administrator of ATSDR (in consultation with the 

Administrator of EPA and agencies and programs of the Public Health Service) to assess whether 

adequate information on the health effects of acrolein is available. Where adequate information is not 

available, ATSDR, in conjunction with the National Toxicology Program (NTP), is required to assure the 

initiation of a program of research designed to determine the health effects (and techniques for developing 

methods to determine such health effects) of acrolein. 

The following categories of possible data needs have been identified by a joint team of scientists from 

ATSDR, NTP, and EPA. They are defined as substance-specific informational needs that if met would 

reduce the uncertainties of human health assessment. This definition should not be interpreted to mean 

that all data needs discussed in this section must be filled. In the future, the identified data needs will be 

evaluated and prioritized, and a substance-specific research agenda will be proposed. 

3.12.1 Existing Information on Health Effects of Acrolein 

The existing data on health effects of inhalation, oral, and dermal exposure of humans and animals to 

acrolein are summarized in Figure 3-7. The purpose of this figure is to illustrate the existing information 

concerning the health effects of acrolein. Each dot in the figure indicates that one or more studies provide 

information associated with that particular effect. The dot does not necessarily imply anything about the 

quality of the study or studies, nor should missing information in this figure be interpreted as a “data 

need”. A data need, as defined in ATSDR’s Decision Guide for Identifying Substance-Specific Data 

Needs Related to Toxicological Profiles (Agency for Toxic Substances and Disease Registry 1989), is 

substance-specific information necessary to conduct comprehensive public health assessments. 

Generally, ATSDR defines a data gap more broadly as any substance-specific information missing from 

the scientific literature. 

As seen from Figure 3-7, very little information is available regarding the health effects of exposure of 

humans to acrolein. Experimental studies in humans have attempted to determine the thresholds for eye, 

nose, and throat irritation. Information on humans accidentally exposed to acrolein also indicates that 

acrolein irritates the skin, eyes, nose, and throat, and that severe respiratory effects can persist long after 

exposure occurs. 
3. HEALTH EFFECTS 

Figure 3-7. Existing Information on Health Effects of Acrolein 

Death

Acute 

Intermediate 

Chronic 

Immunologic/Lymphoretic 

Neurologic 

Reproductive 

Developmental 

Genotoxic 

Cancer 

Systemic 

Inhalation 

Oral 

Dermal 

Human 

Death

Acute 

Intermediate 

Chronic 

Immunologic/Lymphoretic 

Neurologic 

Reproductive 

Developmental 

Genotoxic 

Cancer 

Systemic 

Inhalation 

Oral 

Dermal 

Animal 

Existing Studies 

ACROLEIN 85 
ACROLEIN 86 

3. HEALTH EFFECTS 

Data are available for acute and intermediate inhalation exposures that resulted in death of animals. For 

the most part, these exposures also affected the respiratory tract and the immune response to bacterial 

agents. 

An intermediate inhalation exposure study of rats prior to mating and during pregnancy did not result in 

fetotoxic or teratogenic effects. Limited information is available regarding chronic inhalation exposure. 

Data are available for oral doses associated with death and increased mortality in acute, intermediate, and 

chronic exposure. The developmental and reproductive effects of oral exposure to acrolein have also 

been investigated. Chronic oral exposure of female rats may have resulted in neoplasms in the adrenal 

cortex, though the data are equivocal. 

Acrolein applied to the skin of animals results in skin irritation and death if applied in high concentration. 

Acrolein was not carcinogenic when applied to the skin of mice for 10 weeks. 

3.12.2 Identification of Data Needs 

Acute-Duration Exposure. Acute inhalation exposure to acrolein is irritating to the upper 

respiratory system in humans (Sim and Pattle 1957; Weber-Tschopp et al. 1977) and animals (Cassee et 

al. 1996). The respiratory tract is the primary target of acrolein toxicity via inhalation exposure. 

Desquamation of the respiratory epithelium followed by airway occlusion and asphyxiation was the main 

reason for acrolein-induced mortality in animals (Ballantyne et al. 1989; Catilina et al. 1966; Crane et al. 

1986; Skog 1950). An MRL for acute inhalation exposure was derived from human data (WeberTschopp et al. 1977) for respiratory effects. No data were located regarding acrolein toxicity in humans 

after oral exposure. Information regarding acute oral exposure of animals is limited to developmental 

toxicity studies (King 1982; Parent et al. 1993). The lowest LOAEL between the two studies, 

2 mg/kg/day in rabbits, resulted in significant decrement in weight gain followed by a rebound to control 

values. This transient effect on body weight was not observed in non-pregnant animals. It is not known 

if pregnancy contributed to the reversal of effect on body weight. Therefore, the acute oral data are not 

sufficient to derive an MRL. Acute-duration oral exposure studies in non-pregnant animals need to be 

performed using low doses about which clinical effects have been observed (i.e., vomiting in dogs from 

0.5 mg/kg [Parent et al. 1992b]). Histological examination of the gastrointestinal tissues may provide 

data regarding sensitive irritant effects, such as epithelial metaplasia, that may serve as a basis for an 

acute MRL. 
ACROLEIN 87 

3. HEALTH EFFECTS 

Skin contact with acrolein caused irritation, burns, and epidermal necrosis in humans (Champeix et al. 

1966; Lacroix et al. 1976; Schöning 1966). It is evident, therefore, that the necrotic effects of acrolein 

occur at the site of primary contact regardless of routes of exposure. Target organs for acrolein toxicity 

other than at the site of contact, however, were not identified and pharmacokinetic data are insufficient to 

identify target organs across routes of exposure. Further studies describing the tissue-specific 

pharmacokinetics of acrolein after exposure via all three routes would be useful. The information is 

important for populations living near hazardous waste sites that might be exposed to acrolein for brief 

periods of time. 

Intermediate-Duration Exposure. No studies were located regarding intermediate-duration 

exposure to acrolein in humans. Inhalation exposure studies in animals (Costa et al. 1986; Feron et al. 

1978; Kutzman et al. 1984; Lyon et al. 1970) suggest that the respiratory tract is the most sensitive target 

of toxicity for inhaled acrolein. The information was sufficient for derivation of an inhalation MRL 

(Feron et al. 1978). Oral exposure studies in animals (King 1984; NTP 2006; Parent et al. 1992b, 1992c) 

provide strong evidence that the stomach is the most sensitive target of toxicity. An intermediate-duration 

oral MRL was based on histological changes in the gastrointestinal tract of mice (NTP 2006). Studies are 

needed to assess the dermal effects of intermediate-duration exposures. While intermediate-duration data 

are available for ocular irritation in animals (Lyon et al. 1970), no data are available for the effects of 

acrolein exposure to skin. Studies examining effects on the skin of intermediate-duration exposures to 

acrolein would be of limited utility, as acrolein in the environment evaporates rapidly from water and 

binds significantly to nucleophilic sites in soil-born matter, likely resulting in low bioavailability. 

Chronic-Duration Exposure and Cancer. No studies were located regarding toxicity in humans 

following chronic exposure. Respiratory toxicity was observed in rats and hamsters after inhalation 

exposure (Feron and Kruysse 1977; Le Bouffant et al. 1980). However, the designs of these inhalation 

studies were not sufficient for MRL derivation. The studies used short daily exposures that are not 

indicative of chronic exposure, or had only one exposure level, which would not provide a NOAEL and 

corresponding LOAEL. Chronic-duration inhalation studies with multiple exposure levels and having 

extensive daily exposure periods are needed to derive a chronic-duration inhalation MRL. Chronic oral 

studies were performed in rats, mice, and dogs (Parent et al. 1991a, 1992a, 1992b). Extensive 

histopathological examination revealed no effects in any organs. Reduced survival of mice and rats (a 

frank effect level) was observed, although no cause of death could be determined. Chronic-duration oral 

studies identifying a NOAEL and/or less serious LOAEL are needed to derive a chronic-duration oral 
 

ACROLEIN 88 

3. HEALTH EFFECTS 

MRL. No studies were located regarding acrolein toxicity after chronic-duration dermal exposure in 

animals. Studies describing the effects of acrolein associated with chronic, low-level exposure of the skin 

would be useful. 

No studies were located regarding the carcinogenicity of acrolein in humans. No increase in tumor 

incidence was observed in two limited, chronic inhalation studies in animals. These studies either had a 

very short daily exposure of 1 hour (Le Bouffant et al. 1980) or were carried out for less-than-lifetime 

duration for the study animals (Feron and Kruysse 1977; Le Bouffant et al. 1980). Dermal application of 

acrolein to mice for ten weeks did not induce cancer (Salaman and Roe 1956). However, the length of the 

study is considered too short for proper evaluation of carcinogenicity. No carcinogenic effect was found 

in rats, mice, and dogs following extensive histopathological examinations after chronic oral exposure to 

acrolein (Parent et al. 1991a, 1992a, 1992b). An increased incidence of adrenocortical adenomas was 

reported in female rats after oral exposure to acrolein in another study (Lijinsky and Reuber 1987); 

however, these findings were dismissed by an independent pathology working group (Parent et al. 1992a). 

Although Parent et al. (1991a, 1992a, 1992b) provided carcinogenicity data in animals receiving lifetime 

gavage doses of acrolein, lifetime drinking water studies in animals are needed to further assess lack of 

carcinogenicity reported in the lifetime gavage studies. 

Genotoxicity. No studies were located regarding acrolein genotoxicity in humans. Dominant lethality 

of acrolein was not observed in mice (Epstein et al. 1972). However, in vitro data showed weak 

mutagenic potential of acrolein in bacterial and mammalian cells without metabolic activation 

(Table 3-4). Further studies in animals would be useful to determine the ability of acrolein to induce 

chromosomal aberrations after exposure. Cytogenetic analysis of peripheral lymphocytes of workers 

exposed to acrolein would provide an opportunity to assess its genotoxicity in humans. 

Reproductive Toxicity. No studies were located regarding reproductive effects of acrolein in 

humans. No changes in reproductive organs of rats after intermediate and chronic oral exposures or in 

mice or dogs after chronic exposures were found during histopathological examination (Parent et al. 

1991a, 1992a, 1992b). No reproductive effects were observed in rats after inhalation exposure to acrolein 

(Bouley et al. 1975). The results of a multi-generation oral exposure study in rats were also negative 

(King 1984). Although not reproduced in the main study, the statistically-untested results of a pilot doserange study indicated increased fetal resorptions in rabbits after oral exposure to acrolein (Parent et al. 

1993). Furthermore, dominant lethality was induced in mice exposed to acrolein by inhalation. These 

data indicated possible reproductive effects of acrolein exposure in animals, and further studies would be 
ACROLEIN 89 

3. HEALTH EFFECTS 

useful to support these results. No data were located regarding reproductive effects in animals after 

dermal exposure, and the pharmacokinetic data are insufficient to draw any conclusion. Further studies of 

reproductive toxicity following dermal exposure in animals would be useful for extrapolating the results 

to human exposure. 

Developmental Toxicity. No studies were located regarding developmental effects of acrolein in 

humans by any route of exposure. Increased incidences of skeletal anomalies and delayed ossification 

were observed in rats (King 1982) receiving oral exposures also resulting in frank toxicity to the dams. 

Developmental effects were not observed in rabbits exposed to oral dosing levels that did not result in 

maternal toxicity (Parent et al. 1993). These findings suggest that developmental effects of acrolein may 

be dependent on frank maternal toxicity. Results from parenteral administration in rats indicate that 

acrolein may cross the placenta (King 1982). This information is particularly relevant to individuals who 

are receiving the drug cyclophosphamide, of which acrolein is a metabolite. The developmental effects 

after inhalation or dermal exposure in animals were not studied. Pharmacokinetic data are insufficient to 

predict developmental effects after these routes of exposure. Further animal studies providing 

information on pre- and postnatal developmental toxicity of acrolein after oral, inhalation, and dermal 

exposure would be useful. The information is important for possible extrapolation of results to human 

exposure. 

Immunotoxicity. Information regarding immunological effects of acrolein in humans is limited to a 

single case study (Rappaport and Hoffman 1941). No information regarding immunological effects in 

animals after oral or dermal exposure to acrolein was located. Acute and subchronic inhalation studies 

indicate that acrolein may increase the risk of bacterial infections in the respiratory tract (Aranyi et al. 

1986; Bouley et al. 1975; Sherwood et al. 1986). Studies using a battery of immunotoxicity tests to 

correlate exposure intensity with specific end points of immune response would provide a more sensitive 

assessment of possible immunotoxic effects than histological examination of tissues and organs of the 

immune system. Since a possible case of an allergic response to acrolein derived from cigarette smoke 

was described in humans (Rappaport and Hoffman 1941), sensitization tests could help identify agents 

causing allergic responses in individuals exposed to tobacco smoke. 

Neurotoxicity. No information was located regarding neurological effects of acrolein in humans. 

Symptoms of central nervous system depression were observed in rodents after oral exposure to acrolein, 

but only after lethal concentrations (Sprince et al. 1979). No such effects were observed in animals after 

inhalation exposure; the animals died from asphyxia caused by epithelial desquamation and, 
 

ACROLEIN 90 

3. HEALTH EFFECTS 

consequently, respiratory obstruction (Ballantyne et al. 1989; Catilina et al. 1966; Crane et al. 1986; Skog 

1950). No behavioral changes were observed in animals exposed to acrolein by any route. Nonspecific 

histopathological effects on the brains of animals were found in subchronic inhalation studies (Feron et al. 

1978; Kutzman et al. 1984, 1985; Lyon et al. 1970). No histopathological changes in neurological tissues 

were observed after oral exposure (Parent et al. 1991a, 1992a, 1992b). No studies regarding neurotoxicity 

of acrolein after dermal exposure were located. However, the available data do not indicate that the 

central nervous system is the major target of acrolein toxicity. No data needs have been identified at this 

time. 

Epidemiological and Human Dosimetry Studies. The only information available concerning 

effects of acrolein in humans comes from two acute inhalation studies involving volunteers (Sim and 

Pattle 1957; Weber-Tschopp et al. 1977) and a limited number of cases of accidental inhalation (Bauer et 

al. 1977; Champeix et al. 1966; Gosselin et al. 1979) and dermal (Schöning 1966) exposures to unknown 

levels of acrolein (Champeix et al. 1966; Gosselin et al. 1979; Lacroix et al. 1976; Schöning 1966). In 

these cases, extremes in severity, either quickly reversible eye and respiratory irritation or severe burns of 

the eyes and respiratory tract mucosa (with some effects persisting for several months), were observed. 

No epidemiological studies are available. Epidemiology studies correlating the severity of end points 

such as respiratory and gastrointestinal epithelial metaplasia (obtained by histology of the pulmonary and 

gastric mucosa) with exposure intensity and duration are needed. Such studies would be useful for 

identifying effects of long term exposure to tolerable concentrations. This information would be useful 

for establishing the existence of a dose-response relationship for chronic human exposures and for 

monitoring individuals near hazardous waste sites for preventive purposes. 

Biomarkers of Exposure and Effect. 

Exposure. No reliable biomarkers of acrolein exposure have been identified. The finding of 3-hydroxypropylmercapturic acid in the urine after exposure to acrolein or cyclophosphamide seemed to be 

promising for use as an exposure identifier (Kaye and Young 1974). However, further studies found no 

correlation between the amount of 3-hydroxypropylmercapturic acid in the urine and the dose of parent 

compound administered (Alarcon 1976). Parent et al. (1996a) identified several mercapturic acid 

metabolites in urine following oral doses in rats. Further identification of acrolein metabolites in the 

urine and their correlation with levels of exposure would be useful. Iype (1987) presented preliminary 

results in an abstract regarding the development of an antibody-mediated assay to monitor subjects 

exposed to acrolein; however, these data are not available in a full, peer-reviewed publication. This assay 
ACROLEIN 91 

3. HEALTH EFFECTS 

exploits the possible formation of acrolein-adducted DNA in cells, or the formation of antibodies against 

such adducts in serum. Assays for acrolein-adducted DNA, thiols, and lysine could possibly be used to 

aid in etiology of respiratory diseases such as bronchitis, to which acrolein may be a contributor. Further 

studies regarding possible biochemical changes after acrolein exposure would be useful. 

Effect. As with biomarkers for exposure, no studies were located for animals or humans that correlated 

the concentration of acrolein or its metabolites with toxic effects in target tissues. No biochemical or 

histological changes specific to acrolein exposure have been identified in humans or animals. Although 

transformation, and subsequent incorporation into macromolecules, of acrolein to acrylic acid has been 

identified (Patel et al. 1980b), no specific health effects of these reactions are known. Studies designed to 

correlate the appearance of adduction products and metabolites with increasingly severe acrolein-induced 

lesions may be useful in identifying “fingerprints” of metabolites to serve as biomarkers of effect. 

Absorption, Distribution, Metabolism, and Excretion. There are no data available sufficient to 

derive the rates of acrolein absorption, distribution, metabolism, or excretion. Toxicokinetic data of 

acrolein are from the in vivo absorption study in dogs (Egle 1972) and rats (Morris 1996) and the oral 

exposure study in rats by Draminski et al. (1983) and Parent et al. (1996a), from which a possible 

metabolic pathways were proposed. However, dermal and inhalation exposures may very different 

absorption rates and lead to different metabolic pathways and patterns of distribution and excretion, 

which could account for differences in the degree of toxicity exhibited by different routes of exposure. 

The metabolism of acrolein in vitro seems to be well understood, including the reaction with glutathione 

(Patel et al. 1980b). This reaction represents an important mechanism for the protection of cells and 

tissues from the cytotoxic effects of acrolein. Determining the urinary excretion of acrolein conjugates in 

control volunteers and in individuals known to have been exposed to polluted environments could provide 

information concerning absorption and excretion of the xenobiotic. The use of human cell lines in culture 

might be considered a useful alternative to studying the metabolic fate of acrolein. 

Comparative Toxicokinetics. No studies were located regarding comparative toxicokinetics of 

acrolein in vivo. Differences in the toxicokinetics of a chemical among species may account for 

differences in toxic responses. Though similar inhalation effects have been observed in rats and humans 

(Cassee et al. 1996; Weber-Tschopp et al. 1977) at comparable exposure levels, the animal species that 

serves as the best model for extrapolating results to humans remains unknown. Although virtually no 

information is available regarding the toxicokinetics of acrolein in humans, analysis of the urine of 
ACROLEIN 92 

3. HEALTH EFFECTS 

individuals occupationally exposed to the chemical would provide valuable information on absorption and 

excretion rates, provided that exposure to acrolein could be reasonably estimated. 

Methods for Reducing Toxic Effects. Acrolein is known to react rapidly with nucleophilic groups 

in every type of tissue (Beauchamp et al. 1985). While systemic metabolism of acrolein to toxic 

metabolites has been proposed, animal studies (Morris 1996; Morris et al. 2003) and human case reports 

(Champeix et al. 1966; Gosselin et al. 1979) suggest that point-of-contact toxicity dominates the onset of 

adverse health effects. For this reason, simple dilution of acrolein at the point of tissue contact may 

provide the best protection against acrolein-induced injury and obviate the need for data concerning the 

reduction of toxic effects. Indeed, the standard treatments for inhalation, oral, and dermal acrolein 

exposures are provision of fresh air, ingestion of water, and copious rinsing with water, respectively 

(HSDB 2007). No data needs have been identified at this time. 

Children’s Susceptibility. Data needs relating to both prenatal and childhood exposures, and 

developmental effects expressed either prenatally or during childhood, are discussed in detail in the 

Developmental Toxicity subsection above. 

Although no data are available describing age-related differences in acrolein toxicity, acrolein is expected 

to affect children by the same mechanisms through which it affects adults. However, data are needed to 

determine if tissue-specific, age-related differences exist for glutathione levels, possibly resulting in an 

increased sensitivity to acrolein, particularly for respiratory effects. Children with asthma and reactive 

airway dysfunction may exhibit effects at levels different than adults with similar sensitivities. 

Child health data needs relating to exposure are discussed in Section 6.8.1, Identification of Data Needs: 

Exposures of Children. 

3.12.3 Ongoing Studies 

A. Bhatnagar, University of Louisville, Louisville, Kentucky, is identifying and defining the 

cardiovascular effects (an example of subtle, low-dose effects) of environmental aldehydes and pollutants 

that generate aldehydes (FEDRIP 2006). The project will integrate molecular and cellular aspects of 

aldehyde toxicity, delineate the contribution of individual pathways involved in the detoxification of the 

aldehydes, and elucidate how aldehydes affect atherosclerosis, platelet and endothelial activation, and 
ACROLEIN 93 

3. HEALTH EFFECTS 

myocardial function. Acrolein and trans-2-hexanal will be studied as model aldehydes most prevalent in 

the environment. 

D. Dorman and H. Clewell, Chemical Industry Institute of Toxicology, are exposing rats subchronically 

to inhaled acrolein to characterize the dose-response for nasal pathology and nasal cell proliferation and 

evaluate the uptake of inhaled acrolein into nasal tissues (FEDRIP 2006). The results of these studies will 

be used to develop a computational fluid dynamic model, coupled to a PBPK model, to predict regional 

dosimetry and perform benchmark dose modeling using internal dosimetric predictions of the models. 

D. Horohov and colleagues, Louisiana State University, are measuring immune responses of the 

respiratory tract in mice receiving intermediate-duration inhalation exposures to tobacco smoke or 

acrolein. Specifically, they will characterize the dose-response for allergic/asthmatic reactions, changes 

in pulmonary function, and changes in T-cell differentiation in the lung. 

S. Hecht, University of Minnesota Medical School, will study a number of biomarkers of harm in blood 

and urine from tobacco exposure, including the mercapturic acids of acrolein (FEDRIP 2006). The 

findings will be used to design further studies aimed at developing harm reduction methods for tobaccorelated cancer. 

A. Van Der Vliet, University of Vermont, will investigate the effect of aldehydes, including acrolein, on 

neutrophil regulation pathways, particularly with regard to apoptosis and neutrophil-mediated phagocytic 

clearance and granule component release (FEDRIP 2006). Cultures of human neutrophils and a mouse 

pulmonary inflammation model will be utilized to identify specific cellular targets and acrolein-mediated 

protein modifications to cellular effects. 

A. Bhatnagar, University of Louisville, Louisville, Kentucky, will expose low-density lipoprotein 

receptor-null mice to inhalation and dietary exposures of acrolein to determine the extent of 

atherogenecity and correlation with hypercholestremia (FEDRIP 2006). Acrolein-specific lipoprotein 

changes will be investigated and their atherogenic properties will be quantified. 

B. Freed, University of Colorado at Denver, will identify the molecular mechanisms involved with 

smoking-induced immune suppression by studying the effects of acrolein on NFκB and AP-1 induction 

and interaction with their respective target promoters (CRISP 2006). Human peripheral blood and lymph 

node lymphocyte will be used in these studies. 
ACROLEIN 94 

3. HEALTH EFFECTS 

S. D’Souza, University of Louisville, proposed that acrolein exposure may influence platelet and blood 

vessel endothelium interactions (CRISP 2006). Studies will be performed to evaluate processes involved 

with acrolein-induced platelet toxicity and the associated changes in platelet/endothelium interactions, 

including measurement of acrolein metabolite production. Specific changes in platelet activation and 

endothelium function will be investigated. 

G. Liekauf, University of Cincinnati, will study the ability of acrolein to induce mucus hypersecretion (a 

common feature of COPD) in the murine lung (CRISP 2006). Research will include development of a 

mouse model acrolein-induced COPD, elucidating the role of neutrophil or macrophage/monocyte 

induction on mucus hypersecretion, and determination of genetic bases of individual susceptibility. 

P. Russell, University of Louisville, will investigate the metabolism of acrolein and trans-2-hexanal in 

cardiovascular tissues of mice (CRISP 2006). The hypothesis that GST-mediated conjugation is the key 

metabolic pathway will be tested by identifying glutathione depletion, metabolite formation, and proteinacrolein adduct formation following oral or inhalation exposures to acrolein. The effects on acrolein 

metabolism from specific GST isoforms and hypercholestemia will be studied as well. 

S. Prabhu, University of Louisville, will study the mechanisms underlying acrolein-induced changes to 

cardiac function and cardiac ischemic injury. Acute effects will be observed, including changes to 

contractile function and excitation-contraction coupling in isolated cardiac myocytes. Changes of 

acrolein-induced ischemic injury will be studied by observing the severity of myocardial infarction and 

changes in cardioprotective signaling associated with delayed ischemic preconditioning. Experiments to 

assess chronic myocardial inflammation will measure changes in NFκB activity and cytokine expression. 
ACROLEIN 95 

4. CHEMICAL AND PHYSICAL INFORMATION 

4.1 CHEMICAL IDENTITY 

Data pertaining to the chemical identity of acrolein are listed in Table 4-1. 

4.2 PHYSICAL AND CHEMICAL PROPERTIES 

The physical and chemical properties of acrolein are presented in Table 4-2. 
ACROLEIN 96 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-1. Chemical Identity of Acrolein 

Characteristic Information Reference 

Synonyms Acraldehyde, acrylic aldehyde, HSDB 2007; RTECS 2007 

acrylaldehyde, allyl aldehyde, 

ethylene aldehyde, 2-propenal, 

propylene aldehyde 

Trade name Aqualin, Biocide, Crolean, RTECS 2007 

MAGNACIDE B®

, 

MAGNACIDE H®

, Slimicide 

Chemical formula C3H4O HSDB 2007 

Chemical structure O 

H2C 

Identification numbers: 

CAS registry 107-02-8 HSDB 2007 

 NIOSH RTECS AS1050000 RTECS 2007 

EPA hazardous waste P003 HSDB 2007 

 OHM/TADS 7216793 OHM/TADS 1988 

DOT/UN/NA/IMDG shipping UN 1092 HSDB 2007 

IMCO 3.1 HSDB 2007 

HSDB 177 HSDB 2007 

NCI Not available 

CAS = Chemical Abstracts Services; DOT/UN/NA/IMDG = Department of Transportation/United Nations/North 

America/Intergovernmental Maritime Dangerous Goods Code; EPA = Environmental Protection Agency; 

HSDB = Hazardous Substances Data Bank; NCI = National Cancer Institute; NIOSH = National Institute for 

Occupational Safety and Health; OHM/TADS = Oil and Hazardous Materials/Technical Assistance Data System; 

RTECS = Registry of Toxic Effects of Chemical Substances 
ACROLEIN 97 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-2. Physical and Chemical Properties of Acrolein 

Property Information Reference 

Molecular weight 56.06 O’Neil 2001 

Color Colorless or yellowish Lewis 1997 

Physical state Liquid Lewis 1997 

Melting point -87.7 °C Lide 2000 

Boiling point 52.6 °C Lide 2000 

Density at 20 °C 0.840 g/cm3

 Lide 2000 

Odor Disagreeable, choking odor, pungent Lewis 1997; O’Neil 2001 

Odor threshold: 

Water 0.11 ppm Amoore and Hautala 1983 

Air 0.16 ppm Amoore and Hautala 1983 

Solubility: 

Water at 25 °C 2.12x105

 mg/L Seidell 1941 

Organic solvents Miscible with lower alcohols, ketones, Tomlin 2003 

benzene, diethyl ether, and other 

common organic solvents 

Partition coefficients: 

 Log Kow -0.01 Hansch and Leo 1995 

Koc 24 (estimated)a

 Lyman 1982 

Vapor pressure at 25 °C 274 mmHg Daubert and Danner 1987 

Henry’s law constant at 1.22x10-4 atm-m3

/mol Gaffney et al. 1987 

25 °C 

Autoignition temperature 220 °C HSDB 2007 

Flashpoint -18 °C (open cup) HSDB 2007; O’Neil 2001 

-26 °C (closed cup) 

Flammability limits 2.8–31 volume % HSDB 2007 

Conversion factors 

Air 1 ppm (v/v)=2.328 mg/m3 Verschueren 2001 

1 mg/m3=0.43 ppm (v/v) 

a

Koc value was estimated using the measured log Kow (-0.01) and a linear regression equation described in Lyman 

(1982). 
ACROLEIN 98 

4. CHEMICAL AND PHYSICAL INFORMATION 

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ACROLEIN 99 

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

5.1 PRODUCTION 

Acrolein was first produced commercially in the 1930s through the vapor phase condensation of 

acetaldehyde and formaldehyde (Etzkorn et al. 2002). A second method was developed in the 1940s, 

which involved the vapor phase oxidation of propylene; however, this method was not used at first due to 

the poor performance of cuprous oxide catalysts. During the 1960s, propylene oxidation was greatly 

enhanced by the introduction of bismuth molybdate-based catalysts and has since become the primary 

method used for the commercial production of acrolein. Acrylic acid and carbon oxides are the major 

byproducts produced during this reaction. Minor byproducts are acetaldehyde, acetic acid, formaldehyde, 

and polyacrolein. 

Companies located in the United States that currently produce acrolein are: Baker Petrolite Corporation, 

Taft, California; Degussa Corporation, Theodore, Alabama; and Dow Chemical U.S.A., Taft, Louisiana 

(SRI 2006). Annual production capacities reported during the year 2000 were 110,000 metric tons/year 

(242 million pounds/year) for the Degussa Corporation and 72,000 metric tons/year (159 million 

pounds/year) for Dow Chemical (Etzkorn et al. 2002). Production capacity data were not provided for the 

Baker Petrolite Corporation. In 1978, domestic manufacturing plants produced approximately 

354 million pounds of acrolein (EPA 1983). The production volumes of acrolein reported by 

manufacturers in 1986, 1990, 1994, 1998, and 2002 were within the ranges of >10–50 million pounds, 

>50–100 million pounds, >50–100 million pounds, >100–500 million pounds, and >100–500 million 

pounds, respectively (IUR 2002). 

Table 5-1 summarizes information on companies that reported the production, import, or use of acrolein 

for the Toxics Release Inventory in 2004 (TRI04 2006). The TRI data should be used with caution since 

only certain types of facilities are required to report. This is not an exhaustive list. 

5.2 IMPORT/EXPORT 

Current information regarding the import or export of this compound could not be located. 
ACROLEIN 100 

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

Table 5-1. Facilities that Produce, Process, or Use Acrolein 

Minimum Maximum 

Number of amount on site amount on site 

Statea facilities in poundsb in poundsb Activities and usesc 

AL 5 0 999,999 1, 3, 5, 6, 13 

AR 2 0 9,999 1, 5, 12 

CA 4 0 999,999 1, 2, 4, 5, 9, 12 

GA 3 0 9,999 1, 5 

IA 2 0 9,999 1, 5, 13 

IL 2 0 999 1, 5 

IN 1 10,000 99,999 6 

KS 2 100 9,999 1, 13 

LA 14 0 10,000,000,000 1, 3, 4, 5, 6, 7, 8, 12, 13 

ME 1 0 99 1, 5 

MI 2 0 9,999 1, 5, 12 

MN 4 0 999,999 1, 5, 13, 14 

MS 1 0 99 1, 5 

NC 4 0 9,999 1, 5 

NE 2 100 9,999 1, 5, 13 

NY 1 1,000,000 9,999,999 12 

OH 1 1,000 9,999 1, 13 

OR 1 0 99 1, 5, 13 

TN 1 100,000 999,999 8, 9 

TX 44 0 9,999,999 1, 3, 4, 5, 6, 7, 9, 10, 12, 13 

VA 2 0 99,999 1, 5 

WI 3 0 9,999 1, 5, 13, 14 

WV 2 0 9,999 1, 5, 6 

a

Post office state abbreviations used 

b

Amounts on site reported by facilities in each state 

c

Activities/Uses: 

1. Produce 

2. Import 

3. Onsite use/processing 

4. Sale/Distribution 

5. Byproduct 

6. Impurity 

7. Reactant 

8. Formulation Component 

9. Article Component 

10. Repackaging 

11. Chemical Processing Aid 

12. Manufacturing Aid 

13. Ancillary/Other Uses 

14. Process Impurity 

Source: TRI04 2006 (Data are from 2004) 
ACROLEIN 101 

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

5.3 USE 

The largest single use for acrolein is as an unisolated intermediate in the manufacture of acrylic acid, most 

of which is converted to its lower alkyl esters (IARC 1995). Acrolein is also used as a herbicide and 

algicide in irrigation waters and drainage ditches; as a biocide in the control of algae, weeds, and 

mollusks in recirculating process water systems; as a slimicide in the paper industry; as a biocide in oil 

wells and liquid petrochemical fuels; in the cross-linking of protein collagen in leather tanning; as a tissue 

fixative in histological samples; in the manufacture of colloidal forms of metals; in the production of 

perfumes; as a warning agent in methyl chloride refrigerant; and as an intermediate in the manufacture of 

methionine and its hydroxyl analogue, glutaraldehyde, ally1 alcohol, pyridines, and tetrahydrobenzaldehyde (Arntz et al. 2002; Baker Petrolite 2005; Etzkorn et al. 2002; Hess et al. 1978; HSDB 2007; 

IARC 1995; Lewis 1997; O’Neil 2001; Windholz et al. 1983). Isolated, refined acrolein is used mainly as 

a biocide and as an intermediate in the production of methionine, which is a protein supplement used in 

animal feed (Arntz et al. 2002; IARC 1995). Acrolein has been used to make modified food starch, 

synthetic glycerine, acrolein polymers, polyurethane, and polyester resins (Arntz et al. 2002; HSDB 2007; 

Lewis 1997). It has also been used in military poison gas mixtures (IARC 1995). 

5.4 DISPOSAL 

Prior to implementing land disposal of waste residues (including waste sludge), environmental regulatory 

agencies should be consulted for guidance on acceptable disposal practices (HSDB 2007). Materials 

containing concentrated acrolein may be incinerated by: rotary kiln incineration, with a temperature 

range of 820–1,600 °C and a residence time of seconds; fluidized bed incineration, with a temperature 

range of 450–980 °C and a residence time of seconds; and liquid injection, with a temperature range of 

650–1,600 °C and a residence time of 0.1–2 seconds (HSDB 2007). Materials containing small amounts 

of acrolein may be disposed of by neutralization (if needed), followed by secondary biological treatment 

or by submerged combustion (to concentrate the waste) followed by incineration (Hess et al. 1978; OHMTADS 1988). On-site combustion is an option for disposal if the spill site is in a very remote, 

inaccessible area, and there is danger of subsequent discharge if other methods of disposal are attempted. 

Local, state, and federal Resource Conservation and Recovery Act (RCRA) approval must be obtained 

before burning on site (OHM-TADS 1988). 

Acrolein has been identified as a hazardous waste by the EPA, and the disposal of this compound is 

regulated under RCRA. Specific information regarding federal regulations concerning disposal of 
ACROLEIN 102 

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

hazardous wastes through land treatment, landfilling, incineration, thermal treatment, chemical/physical/ 

biological treatment, underground injection, and deep sea injection are provided in the Code of Federal 

Regulations (40 CFR 190–399). Release of acrolein in waste water is regulated under the Clean Water 

Act by the National Pollutant Discharge Elimination System (NPDES). 

Information regarding effluent guidelines and standards for acrolein may be found in 40 CFR 122, 

40 CFR 125, 40 CFR 268, 40 CFR 413, 40 CFR 423, and 40 CFR 433. 

Pursuant to RCRA Section 3004(g)(5), EPA has proposed to restrict the land disposal of acrolein (EPA 

1989b). Acrolein may be land disposed only if prior treatment standards have been met, or if disposal 

occurs in units that satisfy the statutory no migration standard (EPA 1989b). Proper guidelines and 

standards are outlined in the Federal Register (EPA 1989b). 
ACROLEIN 103 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.1 OVERVIEW 

Acrolein has been identified in at least 32 of the 1,684 hazardous waste sites that have been proposed for 

inclusion on the EPA National Priorities List (NPL) (HazDat 2006). However, the number of sites 

evaluated for acrolein is not known. The frequency of these sites can be seen in Figure 6-1. 

Acrolein may be released to the environment in emissions and effluents from its manufacturing and use 

facilities, in emissions from combustion processes (including cigarette smoking and combustion of 

petrochemical fuels), from direct application to water and waste water as a slimicide and aquatic 

herbicide, as a photooxidation product of various hydrocarbon pollutants found in air (including 

propylene and 1,3-butadiene), and from land disposal of some organic waste materials. Acrolein is a 

reactive compound and is unstable in the environment. 

In ambient air, the primary removal mechanism for acrolein is predicted to be reaction with photochemically generated hydroxyl radicals (half-life, 15–20 hours). Products of this reaction include carbon 

monoxide, formaldehyde, and glycolaldehyde. In the presence of nitrogen oxides, peroxynitrate and 

nitric acid are also formed. Small amounts of acrolein may also be removed from the atmosphere in 

precipitation. Insufficient data are available to predict the fate of acrolein in indoor air. In water, small 

amounts of acrolein may be removed by volatilization (half-life, 23 hours from a model river 1 m deep), 

aerobic biodegradation, or reversible hydration to β-hydroxypropionaldehyde, which subsequently 

biodegrades. Based on the reactivity of acrolein, it is expected that removal of acrolein from water 

through the binding of the chemical to dissolved and suspended organics will become increasingly 

important as the concentration of the organics in water increases. However, information on this removal 

process could not be located. 

Half-lives of <1–3 days for small amounts of acrolein in surface water have been observed. When highly 

concentrated amounts of acrolein are released or spilled into water, this compound may polymerize by 

oxidation or hydration processes. In soil, acrolein is expected to be subject to removal through 

volatilization, abiotic and biotic degradation processes, and possibly irreversible binding to soil 

components. This compound can be highly mobile in soil; however, this movement is expected to be 

attenuated by the removal processes given above. 
ACROLEIN 104 

6. POTENTIAL FOR HUMAN EXPOSURE 

Figure 6-1. Frequency of NPL Sites with Acrolein Contamination 

Frequency of 

NPL Sites 

1

2

3

Derived from HazDat 2006 4

5
ACROLEIN 105 

6. POTENTIAL FOR HUMAN EXPOSURE 

Data regarding the monitoring of acrolein are available for ambient and indoor air. Data from the EPA 

National Air Quality System show average acrolein concentrations in ambient air in the United States 

ranging between 0.5 and 3.186 ppbv (ppb based on volume) (EPA 2004a). For indoor air, acrolein 

concentrations range from <0.05 to 29 μg/m3

 (<0.02–12 ppb), with the higher concentrations in this range 

typically being obtained from indoor environments where the combustion of tobacco products occurs 

(CARB 1992; Highsmith and Zweidinger 1988; WHO 2002). 

No data indicated that acrolein is a contaminant of drinking water supplies. The EPA STORET data 

indicate that acrolein occurs at a low frequency in waste water streams, ambient surface water, and 

groundwater in the United States. Acrolein has been detected in surface water and groundwater samples 

collected offsite at 4 and 15 of the 32 hazardous waste sites, respectively, where acrolein has been 

detected in some environmental medium (HazDat 2006). The HazDat information includes data from 

both NPL and other Superfund sites. Concentrations of acrolein in landfill leachate ranged from 0.07 to 

2.1 ppm. In groundwater, the concentrations of acrolein ranged from 0.006 to 1.3 ppm (HazDat 2006). 

Acrolein is intentionally introduced into irrigation canal and other waterways to control underwater plants 

and other aquatic life. In 2001, 239,362 pounds (120 tons) of acrolein were used for this purpose in 

California (EPA 2003). Information on the quantities of acrolein that are released into waterways as a 

pesticide was not available for other U.S. states. 

Acrolein is a gaseous constituent of cigarette smoke and has been detected at levels equivalent to 3– 

220 μg per cigarette. Acrolein is formed when fats are heated to high temperatures. It has also been 

found in foods and food products such as raw cocoa beans, volatiles from cooked mackerel and white 

bread, and vegetable oils, wine, whiskey, and lager beer. Acrolein concentrations in food are typically 

under 40 μg/g, with most concentrations at 1 μg/g or less (WHO 2002). Acrolein can be produced 

endogenously as a product of lipid peroxidation (Uchida et al. 1998a, 1998b) and can form protein 

adducts that have been implicated in atherosclerosis and Alzheimer’s disease. 

Monitoring data indicate that the general population may be exposed to acrolein through inhalation of 

contaminated air and through ingestion of certain foods. Other than exposures to acrolein through the 

inhalation of tobacco smoke, another important source of acrolein exposure may be via the overheating of 

fats contained in all living matter. Because of the lack of recent, comprehensive monitoring data the 

average daily intake of acrolein through the consumption of food and drinking water, and the relative 

importance of each of these sources of exposure, cannot be adequately determined. Estimating the typical 

level of exposure to acrolein is complicated because acrolein is a common component of tobacco smoke, 
ACROLEIN 106 

6. POTENTIAL FOR HUMAN EXPOSURE 

and there is wide variation among individuals regarding the frequency and level of exposure to tobacco 

smoke. Even so, estimates of acrolein exposure in both the general population and for nonsmokers living 

with a resident smoker are available. A study from Canada (Environment Canada 2000) suggests that the 

general population is exposed to an average acrolein concentration of 1.3 μg/m3

 with a median value of 

0.6 μg/m3

. Based on this average acrolein exposure and an inhalation volume of 20 m3, it can be 

estimated that the average adult inhales 26 μg acrolein/day. Nazaroff and Singer (2004) estimated that 

the daily average inhalation intake of acrolein through environmental tobacco smoke (ETS) over the 

lifetime of a nonsmoker is 22–50 μg/day for males and 16–36 μg/day for females. These exposure levels 

for nonsmokers in a household with ETS are approximately 2.2–3.7 times higher than residents living 

within a household without ETS. 

There is potential for exposure to acrolein in many occupational settings as the result of its varied uses 

and its formation during the combustion and pyrolysis of materials such as wood, petrochemical fuels, 

and plastics. As a result, it would be difficult to list all the occupations in which work-related exposure to 

acrolein occurs. It appears that occupational exposure can occur via inhalation and dermal contact. 

6.2 RELEASES TO THE ENVIRONMENT 

The Toxics Release Inventory (TRI) data should be used with caution because only certain types of 

facilities are required to report (EPA 2005j). This is not an exhaustive list. Manufacturing and 

processing facilities are required to report information to the TRI only if they employ 10 or more full-time 

employees; if their facility is included in Standard Industrial Classification (SIC) Codes 10 (except 1011, 

1081, and 1094), 12 (except 1241), 20–39, 4911 (limited to facilities that combust coal and/or oil for the 

purpose of generating electricity for distribution in commerce), 4931 (limited to facilities that combust 

coal and/or oil for the purpose of generating electricity for distribution in commerce), 4939 (limited to 

facilities that combust coal and/or oil for the purpose of generating electricity for distribution in 

commerce), 4953 (limited to facilities regulated under RCRA Subtitle C, 42 U.S.C. section 6921 et seq.), 

5169, 5171, and 7389 (limited S.C. section 6921 et seq.), 5169, 5171, and 7389 (limited to facilities 

primarily engaged in solvents recovery services on a contract or fee basis); and if their facility produces, 

imports, or processes ≥25,000 pounds of any TRI chemical or otherwise uses >10,000 pounds of a TRI 

chemical in a calendar year (EPA 2005j). 
ACROLEIN 107 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.2.1 Air 

Estimated releases of 152,201 pounds (69 metric tons) of acrolein to the atmosphere from 49 domestic 

manufacturing and processing facilities in 2004, accounted for about 54% of the estimated total 

environmental releases from facilities required to report to the TRI (TRI04 2006). These releases are 

summarized in Table 6-1. 

Potential sources of atmospheric release of acrolein include: emissions from facilities involved in the 

manufacture or use of products containing acrolein; volatilization from treated waters and contaminated 

waste streams; formation as a photooxidation product of various hydrocarbon pollutants such as 

propylene, 1,3-butadiene, and other diolefins; emissions from combustion processes; and use in petroleum 

operations (Eisler 1994; Ghilarducci and Tjeerdema 1995; Graedel et al. 1978; Maldotti et al. 1980; WHO 

1991, 2002). 

Specific combustion sources include exhaust gas from engines powered by gasoline, diesel or other 

petrochemical fuels, power plants, burning vegetation (i.e., forest fires), combustion of cellulose materials 

such as wood, cotton, tobacco, and marijuana, and combustion of polyethylene plastics (EPA 1998a; 

1998b; Hodgkin et al. 1982; Jonsson et al. 1985; Lipari et al. 1984; WHO 1991, 2002). 

Acrolein is also a pyrolysis product of polyethylene, animal fats and vegetable oils, cellophane, plastics, 

and paraffin wax (Boettner and Ball 1980; EPA 1980; Potts et al. 1978; Tanne 1983; Wharton 1978). The 

concentrations of acrolein in emissions from various combustion and pyrolysis processes are listed in 

Table 6-2. 

Recent estimates of the atmospheric loading rate of acrolein from a number of sources in the United 

States are available. Based on a report on national air pollutant emission trends for 1990–1993, it is 

estimated that total emissions of acrolein in the United States from all sources was 62,660 tons/year (EPA 

1998a). The major sources of acrolein emissions were attributed to mobile (12,271 tons/year) and 

unspecified stationary (49,400 tons/year) combustion sources. The mobile source emission estimates for 

acrolein were subdivided into 5,541 tons/year for highway (e.g., automobiles, trucks, buses, and 

motorcycles) and 6,729 tons/year for off-highway (e.g., airplanes, boats, railway engines, lawnmowers, 

and off-road vehicles) combustion sources. 
ACROLEIN 108 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-1. Releases to the Environment from Facilities that Produce, Process, or 

Use Acroleina
 

Reported amounts released in pounds per yearb 

Total release 

Statec

 RFd Aire Waterf UIg Landh On-sitej

 Off-sitek On- and off-site 

AL 1 95 No data 0 13 95 13 108 

AR 1 0 No data 0 0 0 0 0 

CA 1 138 0 0 0 138 0 138 

GA 1 31,335 No data 0 0 31,335 0 31,335 

IA 3 2,472 No data 0 0 2,472 0 2,472 

IL 1 22,030 No data 0 0 22,030 0 22,030 

KS 4 6,609 No data 0 0 6,609 0 6,609 

LA 3 3,651 1 0 0 3,652 0 3,652 

MN 4 3,493 No data 0 0 3,493 0 3,493 

MS 1 25,000 No data 0 0 25,000 0 25,000 

NC 2 250 No data 0 0 250 0 250 

NE 4 2,476 No data 0 0 2,476 0 2,476 

OH 1 990 No data 480 0 1,470 0 1,470 

TX 17 26,639 0 131,784 1 158,423 1 158,424 

VA 2 14,036 0 0 0 14,036 0 14,036 

WI 2 12,966 No data 0 0 12,966 0 12,966 

WV 1 22 No data 0 0 22 0 22 

Total 49 152,201 1 132,264 14 284,466 14 284,480 

a

The TRI data should be used with caution since only certain types of facilities are required to report. This is not an 

exhaustive list. Data are rounded to nearest whole number.
 b

Data in TRI are maximum amounts released by each facility.
 c

Post office state abbreviations are used. 

d

Number of reporting facilities.
 e

The sum of fugitive and point source releases are included in releases to air by a given facility. f

Surface water discharges, waste water treatment-(metals only), and publicly owned treatment works (POTWs) (metal 

and metal compounds). 

g

Class I wells, Class II-V wells, and underground injection. 

h

Resource Conservation and Recovery Act (RCRA) subtitle C landfills; other on-site landfills, land treatment, surface 

impoundments, other land disposal, other landfills. i

Storage only, solidification/stabilization (metals only), other off-site management, transfers to waste broker for 

disposal, unknown 

j

The sum of all releases of the chemical to air, land, water, and underground injection wells. k

Total amount of chemical transferred off-site, including to POTWs. 

RF = reporting facilities; UI = underground injection 

Source: TRI04 2006 (Data are from 2004) 
ACROLEIN 109 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-2. Acrolein in Emissions from Combustion 

Source Concentration References 

Auto exhaust gas 

Gasoline engine Not detected to 27.7 ppm IARC 1995; Lipari and Swarin 1982; 

(detection limit 0.01 ppm); Nishikawa et al. 1987a; Seizinger and 

0–7.79% of total aldehydes, Dimitriades 1972; Sigsby et al. 1987; 

excluding acetone Zweidinger et al. 1988 

Gasoline engine 0.16 mg/L gasoline Grosjean et al. 2001 

Diesel engine 2.26 mg/L diesel fuel 

Diesel engine 0.05–0.3 ppm IARC 1985, 1995; Seizinger and 

Dimitriades 1972 

Ethanol engine Not detected (detection limit Lipari and Swarin 1982 

0.01 ppm) 

Cigarette smoke 3–220 μg/cigarette Dong et al. 2000; Guerin et al. 1987; 

Hoffman et al. 1975; Horton and 

Guerin 1974; Lau et al. 1997; Magin 

1980; Manning et al. 1983 

Marijuana smoke 92–145 μg/cigarette Hoffman et al. 1975; Horton and 

Guerin 1975 

Smoke 

Wood 50 ppm Einhorn 1975

 Cotton 60 ppm 

 Kerosene <1 ppm 

Emissions from woodburning 21–132 mg/kg wood Lipari et al. 1984 

fireplaces 20–103 mg/kg wood EPA 1993 

Softwood 46.90 mg/kg wood McDonald et al. 2000 

Hardwood 91.23 mg/kg wood 

Hardwood, wood stove 45.54 mg/kg wood 

Emissions from power plants: 

Coal-fueled 0.002 pounds of aldehydes/ Natusch 1978 

1,000 pounds of fuel 

Gas-fueled 0.2 pounds of aldehydes/ 

1,000 pounds of fuel 

Oil-fueled 0.1 pounds of aldehydes/ 

1,000 pounds of fuel 

Pyrolysis of polyvinyl chloride 27–151 ng/cut Boettner and Ball 1980 

food-wrap film during hot wire 

cutting 

Emissions from the combustion of 2–23 Potts et al. 1978 

polyethylene foam 

Pyrolysis of polyethylene foam 76–180 ppm Potts et al. 1978 

15 cm above heated cooking oil 2.5–30 mg/m3

 EPA 1980b 

Emissions from burning candle 0.18 μg/kg Lau et al. 1997 
ACROLEIN 110 

6. POTENTIAL FOR HUMAN EXPOSURE 

Mobile source emissions of acrolein into air for the 48 contiguous states were estimated to be 

30,619 tons/year in 1996 (EPA 2001b). This estimate is based on data obtained from the 1996 National 

Toxics Inventory. The emissions were divided out into onroad (23,393 tons/year) and nonroad 

(7,226 tons/year) sources. Projected estimates of acrolein emissions in 2007 for onroad and nonroad 

sources were 11,203 and 5,019 tons/year, respectively. The projections assume a 30 ppm cap on sulfur in 

gasoline nationwide and implementation of Tier 2 mobile source exhaust emissions standards for light 

duty vehicles, but do not account for a phase-out of methyl tert-butyl ether (MTBE) in the reformulated 

gasoline program. Tables 6-3 and 6-4 provide specific release data based on the type of onroad and 

nonroad mobile sources, respectively. The major onroad acrolein emissions are generated from light duty 

gasoline vehicles and light duty gasoline trucks. The major generators of acrolein emissions from 

nonroad sources are nonroad diesel vehicles and airports. 

Production of acrolein in air is known to occur through photochemical reactions of volatile organic 

compounds (VOCs) that are released from a number of differing source types, including solvent and fuel 

vapors and automobile exhaust (Ghilarducci and Tjeerdema 1995; Liu et al. 1999a; 1999b). Harley and 

Case (1994) estimated a total daily production of 4,600 kg/day for acrolein from both source emissions 

and photochemical production in air over the Los Angeles area for August 1987. The estimate is derived 

from a photochemical air quality model that tracks the transport and chemical reactions of selected VOCs 

and uses emission rates of carbon monoxide, nitrogen oxides, and VOCs from 800 source types prepared 

by the California Air Resources Board and the South Coast Air Quality Management District. Based on 

the modeling, the contribution of direct emissions and photochemical production to the total acrolein 

emissions are roughly similar. The model also shows that the total daily production rate of 4,600 kg/day 

results in a predicted range of 1.1–2.1 ppb carbon for the concentration of acrolein in air over the 

Los Angeles region. 

Emissions of acrolein from coal-fired electric utility steam plants in the United States were estimated to 

be 27 tons/year in 1994 (EPA 1998b). This estimate was based on emission data obtained from 52 of 

684 utility plants that were considered to be generally representative of the industry. Acrolein emissions 

of 34 tons/year were estimated for the year 2010 and are based on projected increases in electrical power 

usage and changes in fuel choices. However, the projections used to derive the 2010 estimate do not 

account for factors such as industry restructuring, new particulate and ozone standards, or global climate 

change programs. 
ACROLEIN 111 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-3. Estimated Acrolein Emissions from Onroad Mobile Sources in 1996 

and 2007a 

Acrolein emissions (tons/year) 

Year LDGV LDGT HDGV MC LDDVb LDDT HDDV Total 

1996 10,682 8,822 1,756 281 164 84 1,604 23,393 

2007 3,044 5,444 687 363 0 16 1,649 11,203 

a

EPA 2001b 

b

LDDV usage is expected to be phased out by 2007. 

HDDV = heavy duty diesel vehicles; HDGV = heavy duty gasoline vehicles; LDDT = light duty diesel trucks; 

LDDV = light duty diesel vehicles; LDGT = light duty gasoline trucks, categories 1 and 2; LDGV = light duty gasoline
 

vehicles; MC=motorcycles 
ACROLEIN 112 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-4. Estimated Acrolein Emissions from Nonroad Mobile Sources 

in 1996 and 2007a 

Acrolein emissions (tons/year) 

2-Stroke 4-Stroke 

Year gasoline gasoline Nonroad diesel Marine diesel Railroad Airports Total 

1996 511 470 4,996 77 167 1,006 7,226 

2007 385 297 2,836 84 139 1,277 5,019 

a

EPA 2001b 
ACROLEIN 113 

6. POTENTIAL FOR HUMAN EXPOSURE 

Emissions of acrolein into air from paper and wood product manufacturing in Canada have been 

estimated for the year 1995. Acrolein emissions ranged from 3,208 to 25,664 kg/year (3.544– 

28.289 tons/year) for oriented strand board producers and from 3,747 to 18,735 kg/year (4.130– 

20.651 tons/year) for pulp and paper (kraft) mills (WHO 2002). 

The intentional release of acrolein into irrigation channels as an herbicide and molluscicide also results in 

the volatilization of acrolein into air (Eisler 1994; EPA 2003; Ghilarducci and Tjeerdema 1995). In the 

San Joaquin Valley of California, it was reported that 194,668 pounds (97.3 tons) of acrolein were 

emitted into the air from agricultural uses of the pesticide in 2001, which amounted to 1.4% of the total 

pesticide emissions from this region (CEPA 2002). 

EPA (1983) estimated the total loading rate of acrolein in 1978 for the United States to be 91,450 pounds 

(45.7 tons) from facilities involved in its production and use as a chemical intermediate. Loading rates of 

acrolein into the environment from various industrial sources were as follows: acrylic acid manufacturers, 

15,175 pounds (7.59 tons); refined acrolein and glycerin manufacturers, 55,660 pounds (27.8 tons); 

methionine manufacturers, 18,150 pounds (9.08 tons); and miscellaneous intermediate uses, 2,420 pounds 

(1.21 tons). These loading rates were based on a total production volume of 350 million pounds 

(175,000 tons) for acrolein with 87% of this volume consumed in the production of acrylic acid and its 

derivatives. 

6.2.2 Water 

Estimated releases of 1 pound (<0.01 metric tons) of acrolein to surface water from 49 domestic 

manufacturing and processing facilities in 2004, accounted for <0.1% of the estimated total 

environmental releases from facilities required to report to the TRI (TRI04 2006). These releases are 

summarized in Table 6-1. 

Acrolein may be released to water in effluents from its manufacturing plants and use facilities (see 

Section 5.3 for specific information regarding uses) and from its direct application to water as a broadrange biocide in irrigation canals, cooling towers, water treatment basins, and process water circuits 

(Eisler 1994; EPA 2003; Ghilarducci and Tjeerdema 1995; IARC 1985; Lue-Hing et al. 1981; Nordone et 

al. 1996a, 1996b; WHO 1991; WSSA 1983). 
ACROLEIN 114 

6. POTENTIAL FOR HUMAN EXPOSURE 

The amount of acrolein released from industrial operations to publicly owned treatment works (POTW) in 

the U.S. waters in 1986 was estimated to be 1,645,600 pounds/year (823 tons/year) (EPA 1991). 

However, it is reported that a large portion of the acrolein that is received by POTWs is removed before 

discharge in effluent streams, with 5% released to surface waters, 0–5% to air, and 10% to sludge (EPA 

1991). 

Data on the release of acrolein into water as a consequence of its use as a pesticide are available only for 

the state of California. It is reported that usage of acrolein in California declined from 328,238 pounds 

(164 tons) in 1999 to 290,180 pounds (145 tons) and 233,928 pounds (117 tons) in 2000 and 2001, 

respectively (EPA 2003). The predominant use of acrolein is as an aquatic herbicide with releases into 

rights-of-way (i.e., irrigation canals) and other water areas amounting to 326,767 pounds (163 tons), 

297,320 pounds (149 tons), and 239,362 pounds (120 tons) in 1999, 2000, and 2001, respectively. The 

decrease in acrolein usage is due to changes in the permitting process required prior to acrolein treatment 

of irrigation canals instituted in 2001. Once irrigation districts in California work through the new 

permitting process, it is expected that future usage of acrolein will be comparable to acrolein usage 

reported for 1999–2000. 

6.2.3 Soil 

Estimated releases of 14 pounds (<0.01 metric tons) of acrolein to soils from 49 domestic manufacturing 

and processing facilities in 2004, accounted for <0.1% of the estimated total environmental releases from 

facilities required to report to the TRI (TRI04 2006). An additional 132,264 million pounds (~60 metric 

tons), constituting about 46% of the total environmental emissions, were released via underground 

injection (TRI04 2006). These releases are summarized in Table 6-1. 

The occurrence of acrolein in soil at one hazardous waste site in the United States and leachate from 

several municipal landfills provides evidence that this compound has been released to soil as the result of 

land disposal of some organic wastes. No data were located regarding the amount of acrolein released to 

soil. 
ACROLEIN 115 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.3 ENVIRONMENTAL FATE 

6.3.1 Transport and Partitioning 

Acrolein is relatively unstable in the atmosphere; therefore, transport within the atmosphere is expected to 

be limited. The relatively high vapor pressure of acrolein (274 mm Hg at 25 °C [Daubert and Danner 

1987]) suggests that this compound will not partition from the vapor phase to particulates in the 

atmosphere. Occurrence of acrolein in rainwater (Grosjean and Wright 1983; Nishikawa et al. 1987b) 

indicates that this compound may be removed from the atmosphere by washout. 

Volatilization is expected to be a significant removal process for any acrolein released to surface waters 

(Nordone et al. 1996a, 1996b). Based on a measured Henry's law constant of 1.22x10-4 atm-m3

/mol at 

25 °C (Gaffney et al. 1987), the volatilization half-life from a model river 1 m deep, flowing 1 m/set with 

a wind speed of 3 m/second was estimated to be 23 hours using the method of Thomas (1982). Veith et 

al. (1980) measured a bioconcentration factor (BCF) of 344 for acrolein in bluegill sunfish; however, this 

may be an overestimate, since total 14C was measured in the fish, which may have resulted in the 

measurement of acrolein metabolites. A BCF of 0.6 was estimated for acrolein using a linear regression 

equation based on a log octanol/water partition coefficient (Kow) of -0.01 (Bysshe 1982; Hansch and Leo 

1995). These BCFs, as well as the relatively high water solubility of this compound, suggest that acrolein 

does not bioconcentrate significantly in aquatic organisms. Acrolein did not accumulate in leaf lettuce 

after both single and multiple applications in irrigation water at a concentration of 75 ppm (Nordone et al. 

1997). Acrolein residues in the lettuce fell to 0% within 53 days following the initial application. 

Using a linear regression equation based on log Kow data (Lyman 1982), an adsorption coefficient (Koc) 

of 24 was estimated, which suggests that adsorption of acrolein to suspended solids and sediments in 

water would not be significant. This does not take into account the reactivity of acrolein which could lead 

to the removal of acrolein from water through chemical binding of the compound to dissolved or 

suspended organics in water and sediments. The relatively low estimated Koc value suggests that acrolein 

will be highly mobile in soil and that this compound has the potential to leach significantly (Swann et al. 

1983). 

The relatively high vapor pressure of acrolein and its volatility from water suggest that this compound 

will evaporate rapidly from soil surfaces and that volatilization is probably a major removal process from 

soil. The relatively low Koc value for acrolein indicates high mobility in soil and suggests that this 
ACROLEIN 116 

6. POTENTIAL FOR HUMAN EXPOSURE 

compound has the potential to leach significantly (Swann et al. 1983). Degradation processes and 

volatilization, however, are expected to significantly retard movement of acrolein through soil. 

6.3.2 Transformation and Degradation 

6.3.2.1 Air 

The dominant removal process for acrolein in ambient air is predicted to be reaction with 

photochemically generated hydroxyl radicals in the troposphere. The atmospheric half-life for acrolein is 

estimated to be 15–20 hours, based on experimentally determined hydroxyl radical reaction rate constants 

ranging between 1.90x10-11 and 2.53x10-11 cm3

/molecules-sec at 25–26 °C and an average ambient 

hydroxyl radical concentration of 5.0x105

 molecules/cm3 (Atkinson 1985). Acrolein reacts with hydroxyl 

radicals as both an olefin and an aldehyde (Grosjean 1990). Products of this reaction include carbon 

monoxide, formaldehyde, glyoxal, and glycolaldehyde. In the presence of nitrogen oxides, products 

include peroxynitrate, nitric acid, glycidaldehyde, malonaldehyde, and 3-hydroxypropanaldehyde (Edney 

et al. 1986; Grosjean 1990; Liu et al. 1999b). 

Direct photolysis in the ambient atmosphere occurs but is expected to be of minor importance. Gardner et 

al. (1987) reported that the quantum yields for irradiation of acrolein at low air pressures were 0.0066 at 

313 nm and 0.0044 at 334 nm. The authors used a computer analysis of their photodissociation data to 

estimate the half-life of acrolein to be 10 days in the lower troposphere and <5 days in the upper 

troposphere. 

Experimental data indicate that reaction of acrolein with ozone (k=2.8x10-19cm3

/molecules-sec at 25 °C; 

half-life, 59 days) or nitrate radicals (k=5.9±2.8x10-16 cm3

/molecules-sec at 25 °C; half-life, 16 days) in 

the troposphere would be too slow to be environmentally significant (Atkinson 1985; Atkinson et al. 

1987). The fate of acrolein in indoor air is expected to be different from its fate in outdoor air because of 

differences in the concentrations of oxidants in indoor air compared to outdoor air and the possibility of 

other mechanisms of removal. 

6.3.2.2 Water 

Low concentrations of acrolein may degrade in natural water by either aerobic biodegradation or 

reversible hydration to β-hydroxypropionaldehyde, which subsequently undergoes aerobic biodegradation 

(Bowmer and Higgins 1976; EPA 1979; Ghilarducci and Tjeerdema 1995; Tabak et al. 1981). Acrolein at 
ACROLEIN 117 

6. POTENTIAL FOR HUMAN EXPOSURE 

a concentration of 5–10 mg/L was completely degraded in 7–10 days in a static culture flask screening 

procedure (Tabak et al. 1981). Acrolein applied to surface waters at application rates suggested for 

herbicidal use can persist up to 6 days (WSSA 1983). Bowmer and Higgins (1976) measured acrolein 

removal in both laboratory water and in field experiments using irrigation channels. Their studies 

suggested that the degradation of the hydration product of acrolein, 3-hydroxypropanal, occurs after the 

concentration of acrolein falls below 2–3 ppm. The degradation of 3-hydroxypropanal was also preceded 

by a 100-hour lag period, suggesting that biodegradation was occurring through the action of acclimated 

cultures. 

In buffered laboratory water, acrolein reached its equilibrium apparently with β-hydroxypropionaldehyde 

in approximately 300 hours (92% β-hydroxypropionaldehyde, 8% acrolein); in irrigation channels, 

acrolein removal was complete. Half-lives were reportedly <1–3 days in surface water, but values were 

for the combined effect of degradation and volatilization (Bowmer and Higgins 1976; Bowmer et al. 

1974). Kissel et al. (1978) measured acrolein removal in buffered laboratory water and natural river 

water using both chemical analysis methods and bioassays. Complete hydrolysis (which according to the 

authors includes hydration to 3-hydroxypropanal) occurred within 150, 120–180, and 5–40 hours in 

buffered solutions at 22 °C and pH 5, 7, and 9, respectively. Based on fish kill bioassays in natural river 

water at pH 8.1, >93% degradation of acrolein occurred within 6 days. The half-lives of acrolein in 

aerobic test systems that were treated at an application rate of 15 mg/L were 9.5 hours in water and 

7.6 hours in sediment (Smith et al. 1995). The half-lives of acrolein in anaerobic test systems treated at 

the same rate were 10.3 hours in water and approximately 10 days in sediment. Degradation products 

included 3-hydroxypropanal, acrylic acid, and allyl alcohol, which indicate that both hydrolysis and 

biodegradation contributed to the degradation of acrolein during this study. 

Jacobson and Smith (1990) studied the dissipation of acrolein, applied at the highest recommended rate 

according to the label, to achieve a 15 ppm concentration for a 2-hour duration in an irrigation canal and a 

lateral of the canal, which was infested with aquatic plants. The dissipation half-lives for acrolein in the 

irrigation and lateral canals were 275 and 64 minutes, respectively. No acrolein residues were detected 

(detection limit, 0.01 ppm). No residues of 3-hydroxypropanal were detected (detection limit, 2.0 ppm) in 

any of the water samples from either canal. These data suggest that acrolein will not persist for moderate 

or long periods of time in aerobic aquatic environments and that hydration of acrolein may not be an 

important degradation pathway for acrolein (Jacobson and Smith 1990). The decay rate constants for 

acrolein applied to irrigation canals have been reported to be similar (0.14–0.21) regardless of the 

difference in time-concentration regimens (100 μg/L for 48 hours to 15,000 μg/L for several hours) 
ACROLEIN 118 

6. POTENTIAL FOR HUMAN EXPOSURE 

(Eisler 1994). The half life of acrolein, applied at a flow rate of 3,964 L/second to achieve 15 ppm for 

1 hour, was 10.2 hours in a weedy canal and 7.3 hours in a nonweedy canal (Nordone et al. 1996b; 

Rathbun 1998). The concentration of acrolein was 25 μg/L in samples from the Columbia River collected 

65 km from where it was applied at a concentration of 125 μg/L (Eisler 1994). Nordone et al. (1996a) 

studied the dissipation of acrolein applied to agriculture canals with flow rates of 142, 283, and 

453 L/second to achieve target concentrations of 7.5, 11.6, and 10.4 ppm, respectively. These authors 

concluded that typical application of acrolein as an aquatic herbicide in agricultural canals does not result 

in the introduction of acrolein into natural receiving waters 2.7 km downstream. 

The ultraviolet (UV) spectrum of acrolein in hexane shows moderate absorption of UV light in the 

environmentally significant range (wavelengths >290), suggesting that acrolein might undergo photolysis 

in natural waters; however, hydration of acrolein destroys the chromophores that absorb UV light (EPA 

1979), and the equilibrium appears to be far on the side of the hydration product. Thus, the potential for 

direct photolysis of acrolein in natural waters is probably slight. Oxidation of small amounts of acrolein 

in natural waters would not be environmentally significant; however, highly concentrated acrolein 

solutions (i.e., spills) may be polymerized by oxidation or hydration processes (EPA 1979). Insufficient 

data are available regarding anaerobic biodegradation to establish the significance of this process as a 

removal mechanism or to determine the rate at which such a process would proceed. This information 

would be particularly useful in determining the fate of acrolein under conditions frequently encountered 

in groundwater and in landfills. 

Based on the reactivity and nucleophilicity of acrolein, it is expected that acrolein has the potential to 

react with dissolved and suspended organics in water. This removal process would become increasingly 

important for determining the fate of acrolein in water as the concentration of organics in water increased. 

However, no studies have been conducted to describe this possible route for removal of acrolein from 

water. 

6.3.2.3 Sediment and Soil 

Experimental data specifically pertaining to the degradation or transformation of acrolein in soil were not 

located. Results of studies in aquatic systems suggest that acrolein, at low concentrations, may be subject 

to aerobic biodegradation in soil or transformation via hydration followed by aerobic biodegradation of 

the hydrated product (see Section 6.3.2.2). 
ACROLEIN 119 

6. POTENTIAL FOR HUMAN EXPOSURE 

Since acrolein is a very reactive compound, abiotic processes, such as oxidation or conjugation with 

organic matter in soils, may be the most important degradation processes. However, no information could 

be located for these possible acrolein reaction pathways in soil. 

6.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT 

Reliable evaluation of the potential for human exposure to acrolein depends in part on the reliability of 

supporting analytical data from environmental samples and biological specimens. Concentrations of 

acrolein in unpolluted atmospheres and in pristine surface waters are often so low as to be near the limits 

of current analytical methods. In reviewing data on acrolein levels monitored or estimated in the 

environment, it should also be noted that the amount of chemical identified analytically is not necessarily 

equivalent to the amount that is bioavailable. The analytical methods available for monitoring acrolein in 

a variety of environmental media are detailed in Chapter 7. 

6.4.1 Air 

The atmospheric concentrations of acrolein have been measured in several locations, and the most 

comprehensive monitoring studies are discussed below. Data for 2004 obtained from EPA’s Air Quality 

System (AQS) database show average concentrations of acrolein at various monitoring stations ranging 

from 0.3 to 2.048 ppb carbon (0.5–3.186 ppbv), with maximum values ranging from 0.3 to 3.6 ppb carbon 

(0.5–5.6 ppbv) (EPA 2004a). Data obtained for 1996 show similar average concentrations for acrolein, 

ranging from 0.05 to 3.2 ppb carbon (0.08–5.6 ppbv) with maximum values ranging from 0.5 to 

11.46 ppb carbon (0.8–17.82 ppbv). Lower average concentrations of 0.05–0.64 ppb carbon (0.08– 

1.00 ppbv) for acrolein (maximum values ranging from 0.05 to 9.9 ppb carbon [0.08–15 ppbv]) were 

found for 2000. The National Air Toxics Monitoring Program (EPA) reported peak concentrations for 

acrolein of <1 ppbv at 12 monitoring sites, with one site reporting a peak concentration between 1 and 

5 ppbv (Mohamed et al. 2002). These data were obtained in 1996 at 13 monitoring sites in New Jersey, 

Louisiana, Texas, and Vermont. 

In the National Air Quality and Emissions Trend Report for 1998, the concentrations of acrolein in 

ambient air averaged 0.20 and 0.12 μg/m3

 (0.086 and 0.052 ppb) for urban and rural locations, 

respectively, based on emission and monitoring data obtained in 1996 (EPA 1998c). In the report 

submitted for 1999, it was noted that during the period of 1994–1999, the concentrations of acrolein are 

either showing no trend or are trending upwards in concentration in six urban areas (EPA 1999). 
ACROLEIN 120 

6. POTENTIAL FOR HUMAN EXPOSURE 

Information on trends in acrolein concentrations in rural areas was available for only one rural location, 

showing a downward trend within the same time period. 

A concentration of acrolein in ambient air in California has been estimated to average 0.36 μg/m3 

(0.16 ppb) and is based on emissions and census tract data obtained in 1999 (Morello-Frosch et al. 2000). 

Estimated concentrations of acrolein in ambient air for the San Francisco Area in 1990–1991 ranged from 

0.012 to 0.28 μg/m3

 (0.005–0.12 ppb) (Rosenbaum et al. 1999). Ambient air concentrations of acrolein at 

the Oakland-San Francisco Bay Bridge Toll Plaza obtained in April 2001 showed differing concentrations 

between morning and evening measurements. Acrolein concentrations ranged from 0.096 to 0.140 μg/m3 

(0.041–0.060 ppb) during the morning commute, which were lower than the concentrations of 0.031– 

0.047 and 0.058–0.079 μg/m3

 (0.013–0.020 and 0.025–0.034 ppb) during two evening monitoring periods 

taken on consecutive days (Destaillats et al. 2002). Altshuller and McPherson (1963) and Renzetti and 

Bryan (1961) determined that acrolein levels in air samples collected in Los Angeles, California, during 

1960–1961 averaged between 5 and 8 ppb. Air samples collected in the Los Angeles Basin over a 

12-week period during 1968 contained levels ranging between none detected to 18 ppb, although most 

values ranged between 0.9 and 9 ppb (IARC 1985). 

Acrolein has been detected in indoor air and its concentrations are summarized in Table 6-5. The 

concentrations of acrolein range from <0.05 to 29 μg/m3

 (<0.02–12 ppb) in residential homes (CARB 

1992; Highsmith and Zweidinger 1988; WHO 2002). Acrolein concentrations are found to be typically 

higher in indoor air when comparing paired indoor/outdoor samples taken at a site (CARB 1991; WHO 

1991, 2002) 

Acrolein has been detected in air samples collected at 6 of the 32 hazardous waste sites where acrolein 

has been detected in some environmental medium (HazDat 2006). The HazDat information includes data 

from both NPL and other Superfund sites. Concentrations of acrolein in outdoor air ranged from 0.01– 

9 to 0.013–106 ppbv in onsite and offsite sampling, respectively (HazDat 2006). 

6.4.2 Water 

Data from the EPA STORET Data Base indicate that acrolein has a low frequency of occurrence in waste 

water streams, ambient surface water, and groundwater in the United States (EPA 2007; Staples et al. 

1985). Acrolein has not been found as a contaminant of drinking water (EPA 1980; Krill and Sonzogni 

1986; Otson 1987; WHO 2002). Grosjean and Wright (1983) detected acrolein, in combination with 
ACROLEIN 121 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-5. Acrolein Concentrations in Indoor Air 

Type of builiding Concentration Location References 

Residential 0.36–1.95 ppbva 

(0.85–4.62 μg/m3

)

b 

Raleigh, North Carolina Highsmith and Zweidinger 

1988 

Residential NQ–29 μg/m3c 

7.1 μg/m3 (average) 

Woodland, California CARB 1992 

Residential 0.4–8.1 μg/m3 Windsor, Ontario WHO 2002 

Residential <0.05–5.4 μg/m3 Hamilton, Ontario 

Residential 16–23 μg/m3 Toronto, Ontario 

Restaurants 8–18 ppb 

(19–43 μg/m3

)

b 

Zürich, Switzerland Weber et al. 1979 

Student lounge 

 Non-smoking 0.8–1.6 μg/m3 Bounds Green, United Williams et al. 1996 

Kingdom 

 Smoking 6.4 μg/m3 

Tavern 21–24 μg/m3 Research Triangle Park, Löfroth et al. 1989 

North Carolina 

a

ppbv = parts per billion by volume 

b

Converted measurement in ppbv to μg/m3, assuming an ambient temperature of 20 °C and an atmospheric 

pressure of 1,013 mbars. 

c

NQ = not quantifiable below detection limit of 2.0 μg/m3 
ACROLEIN 122 

6. POTENTIAL FOR HUMAN EXPOSURE 

acetone, at a concentration of 0.05 μg/mL (50 ppb) in rain water collected in Los Angeles, California; 

however, these compounds were not detected in rain water samples collected in four less densely 

populated sites in California. 

More recently, acrolein has been detected in surface water and groundwater samples collected at 4 and 

15 of the 32 hazardous waste sites, respectively, where acrolein has been detected in some environmental 

medium (HazDat 2006). The HazDat information includes data from both NPL and other Superfund 

sites. Concentrations of acrolein in landfill leachate ranged from 0.07 to 2.1 ppm (HazDat 2006). In 

groundwater, the concentrations of acrolein ranged from 0.006 to 1.3 ppm (HazDat 2006). 

6.4.3 Sediment and Soil 

Acrolein was identified in sediment/ soil/water samples collected from Love Canal in Niagara Falls, New 

York (Hauser and Bromberg 1982); however, no quantitative data were available. 

More recently, acrolein has been detected in soil and sediment samples collected at 1 and 2 of the 

32 hazardous waste sites, respectively, where acrolein has been detected in some environmental medium 

(HazDat 2006). The HazDat information includes data from both NPL and other Superfund sites. One 

soil sample site was found to have an acrolein concentration of 100 ppm (HazDat 2006). 

6.4.4 Other Environmental Media 

Acrolein can be produced in endogenously as a product of lipid peroxidation (Uchida et al. 1998a, 1998b) 

and can form protein adducts that have been implicated in atherosclerosis (Uchida et al. 1998b) and 

Alzheimer’s disease (Calingasan et al. 1999). Acrolein has been identified in foods and food components 

such as raw cocoa beans, chocolate liquor, souring salted pork, fried potatoes and onions, raw and cooked 

turkey, and volatiles from cooked mackerel, white bread, raw chicken breast, ripe Arctic bramble berries, 

heated animal fats and vegetable oils, and roasted coffee (Cantoni et al. 1969; EPA 1980, 1985; Feron et 

al. 1991; IARC 1985; Umano and Shibamoto 1987). Feron et al. (1991) reported concentrations of 

acrolein of <0.01–0.05 ppm in various fruits and up to 0.59 ppm in cabbage, carrots, potatoes, and 

tomatoes. The concentration in food is <40 μg/g and, in most instances, is <1 μg/g (WHO 2002). The 

acrolein concentrations in heated fats and oils and in the headspace above these materials increase with 

increasing cooking temperature (Casella and Contursi 2004; Ghilarducci and Tjeerdema 1995; WHO 

2002). For example, peanut oil heated for 2 hours at 110, 145, and 200 °C resulted in the production of 

acrolein at concentrations of 0.2, 2.7, and 24 μM, respectively (Casella and Contursi 2004). In 
ACROLEIN 123 

6. POTENTIAL FOR HUMAN EXPOSURE 

comparison to other oils, peanut oil was found to have the lowest production of acrolein after 2 hours of 

heating at 145 °C, with higher concentrations found in sunflower (2.9 μM), corn oil (4.3 μM), and olive 

oil (9.3 μM) when heated under the same conditions. Sufficient data are not available to establish the 

level of acrolein typically encountered in these foods. Trace levels of acrolein have been found in wine, 

whiskey, and lager beer (IARC 1985). Further information regarding the occurrence of acrolein in food 

and related products is provided by EPA (1980). 

Acrolein is a gaseous constituent of tobacco and marijuana smoke, occurring in both mainstream and 

sidestream smoke (Ayer and Yeager 1982; Hoffman et al. 1968; Holzer et al. 1976; Rylander 1974; 

Weber-Tschopp et al. 1977). The level of acrolein in sidestream smoke has been found to be notably 

higher (12 times higher) than in mainstream smoke (Triebig and Zober 1984). The amount of acrolein 

emitted in tobacco smoke varies depending upon the kind of cigarette, smoking conditions, puff volume, 

puff rate, nature, and type of tobacco, as well as a number of other extraneous factors (Holzer et al. 1976). 

Smoke from various cigarettes has been found to contain 3–220 μg acrolein per cigarette (Dodson 1994; 

Hoffman et al. 1968; Horton and Guerin 1974; Magin 1980; Manning et al. 1983). Smoke from a 

marijuana cigarette was also found to contain 92–145 μg/cigarette (Hoffman et al. 1968; Horton and 

Guerin 1974). Studies performed to determine the concentration of acrolein in smoke-filled rooms 

(Rylander 1974; Triebig and Zober 1984; Weber-Tschopp et al. 1977) indicate that the concentration of 

acrolein in indoor air is highly dependent upon such factors as the number of cigarettes smoked, rate at 

which the cigarettes are smoked, size of the room, number of people in the room, and type of ventilation. 

Acrolein levels measured in various settings where people were smoking are: cafe, 30–100 ppb; train, 

10–120 ppb; car with three smokers (windows open), 30 ppb (average); car with three smokers (windows 

closed), 300 ppb (average); restaurant, 3–13 ppb; tavern, 5–18 ppb; and cafeteria, l–10 ppb (Triebig and 

Zober 1984). 

6.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE 

The general population may be exposed to acrolein through inhalation of contaminated air, inhalation of 

cigarette smoke, and through ingestion of certain foods. Widespread exposure occurs due to the 

formation of acrolein during the overheating of fats. Acrolein has been detected in the vapor of rapeseed 

oil, which is used frequently in Chinese wok cooking (Pellizzari et al. 1995). Primary factors influencing 

the level of exposure to acrolein via inhalation are: location (urban versus rural), duration and frequency 

of exposure to tobacco smoke, concentration of tobacco smoke, duration and frequency of exposure to 

high concentrations of vehicle exhaust (e.g., in parking garages, in heavy traffic), occupational exposure, 
ACROLEIN 124 

6. POTENTIAL FOR HUMAN EXPOSURE 

and downwind distance of residence or work site relative to stationary point sources. Primary factors 

influencing the level of exposure to acrolein via ingestion are diet and volume of intake, which is 

typically related to age and sex. 

Because of the lack of recent comprehensive monitoring data for acrolein in water and food, the average 

daily intake of acrolein and the relative importance of each source of exposure cannot be determined. 

However, probabilistic estimates of 24-hour time-weighted concentrations of acrolein in air have been 

used to assess human exposures to acrolein in the Canadian population (Environment Canada 2000; 

WHO 2002). Mean and median estimates of acrolein concentration of 1.3 and 0.6 μg/m3

 (0.56 and 

0.26 ppb), respectively, were derived, with a 95% percentile value of 5.0 μg/m3

 (2.1 ppb). The estimate 

uses measured data on acrolein concentrations obtained between 1989 and 1996 for outdoor air in rural, 

suburban, and urban sites and indoor air measurements taken in 40 homes between 1991 and 1993. The 

exposure estimate assumes both a mean time of 3 hours spent outdoors and that the general population is 

exposed to concentrations of acrolein similar to those in indoor air of their homes. Based on the mean 

estimate for acrolein concentration and an inhalation volume of 20 m3

 of air per day, it is estimated that 

an average adult will inhale 26 μg acrolein/day. 

ETS is a major source of acrolein exposure for many individuals in the general population. Nazaroff and 

Singer (2004) estimate that in 2000, between 31 and 53 million nonsmokers in the United States were 

exposed to acrolein concentrations in indoor air ranging from 1.6 to 3.6 μg/m3

 in households where ETS 

is generated by one or more individuals residing in the same household. Between 15 and 25 million of 

the affected number of nonsmokers are adults. Based on the lifetime average for the volume of inspired 

air of 14 m3

/day for males and 10 m3/day for females, it is estimated that the inhalation intake of acrolein 

through inspiration of ETS over a lifetime is 22–50 μg/day for males and 16–36 μg/day for females. 

Assuming that the exposure data obtained from the Canadian study (Environment Canada 2000) 

discussed above are representative of exposures of residents in the United States to acrolein in households 

without ETS, then it is estimated that the inhalation intake of acrolein for nonsmokers exposed to ETS in 

the residence is 2.2–3.8 times greater for both males and females than in households without ETS. This 

comparison is based on inhalation intakes of acrolein for males and females in non-ETS households of 

18 and 13 μg/day, respectively, that are based on an estimated mean acrolein concentration in air of 

1.6 μg/L taken from the Canadian study (Environment Canada 2000) and on the average daily inhalation 

volumes of air for males and females given by Nazaroff and Singer (2004). 
ACROLEIN 125 

6. POTENTIAL FOR HUMAN EXPOSURE 

Everybody is exposed to small amounts of endogenous acrolein. This endogenous acrolein is formed as a 

consequence of the peroxidation of lipid membranes and metabolism of α-hydroxy amino acids and 

polyamines (Alarcon 1970; Uchida et al. 1998a; WHO 2002). Acrolein has also been shown to be formed 

by phagocytes in response to infection or inflammation and as a result of the progression of Alzheimer’s 

disease and atherosclerosis (Anderson et al. 1997; Calingasan et al. 1999; Gόmez-Ramos et al. 2003; 

Uchida et al. 1998b). Due to the reactivity of acrolein with biomolecules, especially thiol-containing 

proteins and glutathione, the formation of acrolein in vivo has been measured as the byproducts of the 

reaction of acrolein with these biomolecules. These biomarkers of in vivo acrolein formation include 

acrolein-protein adducts and the urine metabolites, S-(3-hydroxypropyl)mercapturic acid and 

S-(2-carboxyethyl)mercapturic acid (Calingasan et al. 1999; Li et al. 2004; WHO 2002). However, 

studies to correlate the concentrations of these biomarkers with in vivo acrolein production in humans 

have yet to be conducted. 

According to a National Occupational Exposure Survey (NOES) by NIOSH between 1981 and 1983, an 

estimated 1,298 workers (including 5 females) in 37 facilities in the United States are occupationally 

exposed to acrolein (NIOSH 1988). This is a tentative estimate and is subject to change as further 

information regarding trade name compounds becomes available. There is potential for exposure to 

acrolein in many occupational settings as the result of its varied uses and its formation during the 

combustion and pyrolysis of materials such as wood, petrochemical fuels, and plastics. As a result, it 

would be difficult to list all the occupations in which work-related exposure to acrolein occurs. Some of 

these occupations include those involved in the production of acrylates, methionine, perfumes, plastics, 

refrigerants, rubber, or textile resins (Ghilarducci and Tjeerdema 1995). 

Acrolein has been detected in workplace air at a number of locations (Ahrenholz and Egilman 1983; Apol 

1982; IARC 1985; Tharr and Singal 1986; Treitman et al. 1980; Woskie et al. 1988). Acrolein 

concentrations of 0.057–0.085 ppm were detected during system testing conducted as part of a submarine 

overhaul in Portsmouth Naval Shipyard in Portsmouth, New Hampshire (Tharr and Singal 1986). 

Ahrenholz and Egilman (1983) reported >0.0044–0.18 ppm acrolein in the wire line department of 

Rubbermaid Inc. in Wooster, Ohio, and Apol (1982) reported >0.06 ppm in molding areas of Gerlinger 

Casting Corp. in Salem, Oregon. 

The concentrations of acrolein were 0.01 mg/m3

 (0.004 ppm) in the air of a food factory, 0.59, 0.31, 0.15, 

0.16, and 0.06 mg/m3

 (0.25, 0.13, 0.064, 0.069, and 0.026 ppm) in the air of five restaurant kitchens, and 

0.02 mg/m3

 (0.009 ppm) in the air of two bakeries (Vainiotalo and Matveinen 1993). Henriks-Eckerman 
ACROLEIN 126 

6. POTENTIAL FOR HUMAN EXPOSURE 

et al. (1990) reported acrolein was emitted from coated steel plates heated to 350 °C. This indicates that 

workers involved in welding or heating painted metal may be exposed to acrolein 

Firefighters are at risk to exposure to acrolein when battling house fires and wild fires (Ghilarducci and 

Tjeerdema 1995; Gochfeld 1995; Lees 1995; Materna et al. 1992). The concentrations of acrolein 

measured in a NIOSH house fire study ranged from not detected to 3.2 ppm, with half of the exposures 

exceeding the 0.3 ppm short-term exposure limit. During a study of over 224 structural fires, firefighters 

were exposed to acrolein at levels as high as 6.9 mg/m3

 (2.3 ppm) (Ghilarducci and Tjeerdema 1995). 

The concentration of acrolein in a single sample collected during a wildfire was reported to be 0.23 ppm 

(Lees 1995; Materna et al. 1992). 

6.6 EXPOSURES OF CHILDREN 

This section focuses on exposures from conception to maturity at 18 years in humans. Differences from 

adults in susceptibility to hazardous substances are discussed in Section 3.7, Children’s Susceptibility. 

Children are not small adults. A child’s exposure may differ from an adult’s exposure in many ways. 

Children drink more fluids, eat more food, breathe more air per kilogram of body weight, and have a 

larger skin surface in proportion to their body volume. A child’s diet often differs from that of adults. 

The developing human’s source of nutrition changes with age: from placental nourishment to breast milk 

or formula to the diet of older children who eat more of certain types of foods than adults. A child’s 

behavior and lifestyle also influence exposure. Children crawl on the floor, put things in their mouths, 

sometimes eat inappropriate things (such as dirt or paint chips), and spend more time outdoors. Children 

also are closer to the ground, and they do not use the judgment of adults to avoid hazards (NRC 1993). 

For children living in a residence where one or more individuals smokes some form of tobacco product, 

long-term exposure to environmental tobacco smoke (ETS) and the compounds therein are expected, 

which can cause a number of health effects (WHO 1999). Consequently, because of the acrolein content 

in ETS it is expected that the largest source of acrolein exposure for children living with a smoker is 

through inhalation of ETS. Information on exposures of acrolein through ETS that are specific for 

children living in the United States could not be identified. However, based on data obtained from 

Nazaroff and Singer (2004), it is estimated that individuals who do not smoke over their lifetimes but 

reside with one or more individuals who do smoke, will intake between 22 and 50 μg acrolein/day for 

males and between 16 and 36 μg acrolein/day for females through the inhalation of acrolein in ETS over 
ACROLEIN 127 

6. POTENTIAL FOR HUMAN EXPOSURE 

their lifetimes. This amounts to 2.2–3.7 times greater exposure to acrolein for these children than for 

children who are not exposed to ETS over their lifetimes (see Section 6.5). For children without 

exposures to ETS, their main exposures to acrolein are expected to be similar to those noted for the 

general population in Section 6.5 in air. Estimates of the concentration in the total diet of children in the 

United States were not located in the available literature. Therefore, no estimate of daily acrolein intake 

from food can be made. Because of the lack of recent comprehensive monitoring data for acrolein in 

water, the average daily intake of acrolein and the relative importance of this source of exposure cannot 

be determined. 

6.7 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES 

Those segments of the general population with potentially high exposure to acrolein from exogenic 

sources include people who come in frequent or prolonged contact with tobacco or marijuana smoke, 

people who are occupationally exposed, and people who live or work near dense traffic areas, in smoggy 

areas (e.g., Los Angeles), or downwind from stationary point sources. Acrolein uptake from cigarette 

smoke for individuals working in bars and taverns can range from 15 to 1,830 μg/day, based on an 8-hour 

shift, a respiration volume of 20 m3

 air per day, and a concentration range of acrolein in air of 2.3– 

275 μg/m3

 (IARC 1995). Individuals who work or reside near irrigation canals and other bodies of water 

that are undergoing treatment with acrolein to eliminate unwanted plants or aquatic life are at risk for 

exposure to acrolein. Individuals living near some land-fills and other waste sites may be exposed to 

acrolein in ambient air or drinking water. For example, acrolein has been measured at concentrations of 

1.3, 4.24, and 43 ppb in groundwater obtained from private wells offsite from two NPL landfills (HazDat 

2006). 

Patients receiving oxazaphosphorine drugs, such as cyclophosphamide and ifosfamide, for their cancer 

treatment are at risk for exposure to acrolein, a metabolite of these drugs (Furlanut and Franceschi 2003; 

Kaijser et al. 1993). For example, patients receiving cyclophosphamide at a dose of 60 mg/kg body 

weight/day by 1-hour infusion for 2 consecutive days had peak blood acrolein concentrations ranging 

between 6.2 and 10.2 μM (Ren et al. 1999). The urinary clearance of acrolein from blood during therapy 

results in concentrations of acrolein in urine ranging from 0.3 to 406.8 nM, depending on urine volume 

(Takamoto et al. 2004). This range of urinary acrolein concentrations is sufficient to result in acroleininduced urotoxicities that must be reduced through increasing urine volume during treatment with 

diuretics or receiving uroprotective drugs during treatment (Kaijser et al. 1993). 
ACROLEIN 128 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.8 ADEQUACY OF THE DATABASE 

Section 104(i)(5) of CERCLA, as amended, directs the Administrator of ATSDR (in consultation with the 

Administrator of EPA and agencies and programs of the Public Health Service) to assess whether 

adequate information on the health effects of acrolein is available. Where adequate information is not 

available, ATSDR, in conjunction with NTP, is required to assure the initiation of a program of research 

designed to determine the health effects (and techniques for developing methods to determine such health 

effects) of acrolein. 

The following categories of possible data needs have been identified by a joint team of scientists from 

ATSDR, NTP, and EPA. They are defined as substance-specific informational needs that if met would 

reduce the uncertainties of human health assessment. This definition should not be interpreted to mean 

that all data needs discussed in this section must be filled. In the future, the identified data needs will be 

evaluated and prioritized, and a substance-specific research agenda will be proposed. 

6.8.1 Identification of Data Needs 

Physical and Chemical Properties. Physical and chemical property data are essential for 

estimating the partitioning of a chemical in the environment. Physical and chemical property data are 

available for acrolein and are sufficient for estimating the environmental fate of acrolein (Amoore and 

Hautala 1983; Daubert and Danner 1987; Gaffney et al. 1987; Hansch and Leo 1995; HSDB 2007; Lewis 

1997; Lide 2000; O’Neil 2001; Seidell 1941; Tomlin 2003; Verschueren 2001). 

Production, Import/Export, Use, Release, and Disposal. According to the Emergency 

Planning and Community Right-to-Know Act of 1986, 42 U.S.C. Section 11023, industries are required 

to submit substance release and off-site transfer information to the EPA. The TRI, which contains this 

information for 2004, became available in May of 2006. This database is updated yearly and should 

provide a list of industrial production facilities and emissions. 

Data regarding the production methods for acrolein, production facilities, use, and disposal are adequate 

(Etzkorn et al. 2002; SRI 2004). Data regarding current gross estimates of production volumes and 

capacities are available (Arntz et al. 2002; EPA 1989b; Etzkorn et al. 2002; Hess et al. 1978; HSDB 2007; 

IARC 1995; IUR 2002; Lewis 1997; OHM-TADS 1988; O’Neil 2001; TRI04 2006; Windholz et al. 

1983). Production data may be difficult to obtain, since many companies desire to maintain their 

confidentiality. Information regarding import/export of acrolein could not be located. Data regarding 
ACROLEIN 129 

6. POTENTIAL FOR HUMAN EXPOSURE 

release of acrolein into air are available for mobile and stationary sources (CEPA 2002; EPA 1983, 

1998a, 1998b, 2001b; WHO 2002). Harley and Case (1994) estimated the relative contributions of source 

emissions and photochemical production of acrolein to the amount of acrolein in the air over Los 

Angeles. However, estimates could not be located on the contribution of photochemical production of 

acrolein to acrolein concentrations in the ambient air in other regions of the United States, nor were data 

available on the expected seasonal variations in photochemical production of acrolein. Limited data are 

available on the release of acrolein to publicly owned treatment works and the release of acrolein as a 

pesticide to irrigation waters in California (EPA 1991, 2003), but no data could be located on release of 

acrolein to soil. Use, release, and disposal information is useful for determining where environmental 

exposure to acrolein may be high. Determining the percentage of acrolein used as a captive intermediate 

(i.e., consumed in closed processes in which the compound is not isolated) rather than as an isolated, 

refined product is important in estimating the amount of release to the environment from stationary, 

noncombustion-related sources. An estimate of the amount of acrolein released from stationary sources 

would be useful in establishing the relative importance of each source of acrolein. Even with the 

availability of information on the production, use, and disposal of acrolein, the amounts released would be 

difficult to estimate, since major factors contributing to its occurrence in the environment are its 

formation as a product of the photochemical degradation of other atmospheric pollutants and its release in 

emissions from a wide variety of combustion processes. 

Environmental Fate. The environmental fate of acrolein in air is well studied (Atkinson 1985; 

Atkinson et al. 1987; Gardner et al. 1987; Grosjean 1990). Given that acrolein occurs in the atmosphere 

from both natural and anthropogenic sources (Eisler 1994; EPA 1998a, 1998b; Ghilarducci and 

Tjeerdema 1995; Graedel et al. 1978; Hodgkin et al. 1982; Jonsson et al. 1985; Lipari et al. 1984; Liu et 

al. 1999a, 1999b; Maldotti et al. 1980; WHO 1991, 2002), it would be helpful to have estimates of the 

relative contributions of these sources to acrolein concentrations in air, especially the contribution of the 

photochemical production of acrolein. Data on the dissipation and degradation of acrolein in water are 

available (Bowmer and Higgins 1976; Bowmer et al. 1974; EPA 1979; Ghilarducci and Tjeerdema 1995; 

Jacobson and Smith 1990; Kissel et al. 1978; Nordone et al. 1996a, 1996b; Rathbun 1998; Smith et al. 

1995; Tabak et al. 1981). No data were located on the removal of acrolein from water through reactions 

with dissolved and suspended organic matter in water. Studies on this route of removal of acrolein from 

water would be useful for determining the lifetime of acrolein in waters with high organic content. 

Measured soil-water partition coefficient data are not available. This information would be helpful for 

describing the absorption and mobility of acrolein in soil. Experimental data pertaining to the persistence 

of acrolein in soil and groundwater are lacking. Studies on volatilization from soil surfaces, anaerobic 
ACROLEIN 130 

6. POTENTIAL FOR HUMAN EXPOSURE 

biodegradation in soil and simulated groundwater, and aerobic biodegradation in simulated groundwater 

would be useful in establishing the likelihood of exposure near hazardous waste disposal sites resulting 

from volatilization from soil surfaces or from groundwater contamination. 

Bioavailability from Environmental Media. No studies were located regarding the bioavailability 

of acrolein from environmental media. Since acrolein has been detected in ambient air and in food and 

beverages (ppb levels), it is important to determine if acrolein can be absorbed by humans from 

environmental samples. However, the chemical structure of acrolein makes it a highly reactive molecule, 

which presumably is why its effects are, for the most part, restricted to the area of exposure (i.e., 

respiratory system for inhalation exposure or localized skin damage for dermal exposure). The limited 

information available regarding absorption parameters of acrolein in experimental animals indicates that 

acrolein is easily retained in the respiratory airways (Egle 1972; Morris 1996; Morris et al. 2003) and is, 

therefore, likely to act as an irritant of the eyes and respiratory tract with negligible absorption into the 

body. Virtually no information is available regarding absorption by the gastrointestinal tract or skin; 

additional studies would be useful in establishing whether acrolein is absorbed through these sites or is 

retained. 

Food Chain Bioaccumulation. Measured and estimated BCF values for acrolein indicate that this 

compound would not bioaccumulate significantly in fish (Bysshe 1982; Hansch and Leo 1995; Veith et 

al. 1980). No information was available on the bioaccumulation of acrolein in organisms at other trophic 

levels in aquatic environments. Monitoring for the accumulation of acrolein in organisms from several 

trophic levels would be useful in estimating the levels of acrolein to which humans are exposed through 

dietary intake. 

Exposure Levels in Environmental Media. Reliable monitoring data for the levels of acrolein in 

contaminated media at hazardous waste sites are needed so that the information obtained on levels of 

acrolein in the environment can be used in combination with the known body burden of acrolein to assess 

the potential risk of adverse health effects in populations living in the vicinity of hazardous waste sites. 

Data are available regarding the detection of acrolein in the environment, most notably in ambient air 

(Altshuller and McPherson 1963; CARB 1991; Destaillats et al. 2002; EPA 1998c, 1999, 2004a; 

Highsmith and Zweidinger 1988; IARC 1995; Mohamed et al. 2002; Morello-Frosch et al. 2000; Renzetti 

and Bryan 1961; Rosenbaum et al. 1999; WHO 1991, 2002), and also in water (Grosjean and Wright 

1983; Krill and Sonzogni 1986; Otson 1987; WHO 2002), soil, and sediment (Hauser and Bromberg 
ACROLEIN 131 

6. POTENTIAL FOR HUMAN EXPOSURE 

1982). Some data are available on acrolein concentrations in air, water, landfill leachate, soil, and 

sediment samples taken either onsite or offsite from NPL or Superfund sites (HazDat 2006; Sabel and 

Clark 1984). Additional information on exposure to acrolein in air in urban areas, rural areas, near 

hazardous waste disposal sites, as well as in water (specifically, drinking water supplied from 

groundwater down gradient from hazardous waste disposal sites and contaminated surface waters) and 

soil at waste disposal sites would be useful. Monitoring air and water over a 1-year period would provide 

some indication of seasonal variations. 

Exposure Levels in Humans. Data for residential exposure to acrolein are limited to a probabilistic 

study that provided a 24-hour time-weighted estimate of acrolein concentrations in air and inhalation 

intake for Canadian residents (Environment Canada 2000) and to a study on exposure of nonsmokers in 

the United States to acrolein in ETS (Nazaroff and Singer 2004). The development of a program for 

monitoring environmental media would provide information for better estimations of acrolein exposure 

levels in humans. Data are not available for intake of acrolein through the diet. Market basket surveys or 

total diet studies similar to those conducted by the FDA are needed to provide data on typical levels of 

exposure via dietary intake given the presence of acrolein in a number of foods (Cantoni et al. 1969; EPA 

1980, 1985; Feron et al. 1991; IARC 1985; Umano and Shibamoto 1987; WHO 2002). Monitoring 

studies of acrolein concentrations in air are available for a few occupations such as shipyard workers, 

welders, plastic manufacturers, food service employees, and firefighters (Ahrenholz and Egilman 1983; 

Apol 1982; Ghilarducci and Tjeerdema 1995; Gochfeld 1995; Henriks-Eckerman et al. 1990; IARC 1985; 

Lees 1995; Materna et al. 1992; Tharr and Singal 1986; Treitman et al. 1980; Vainiotalo and Matveinen 

1993; Woskie et al. 1988). Given the high likelihood of occupational exposures to acrolein as a 

consequence of its emission from combustion sources and the variability in the frequency and amount of 

exposures to the compound in various occupational settings, additional monitoring data are needed to 

provide reliable estimates of average daily intake of acrolein in workers. 

This information is necessary for assessing the need to conduct health studies on these populations. 

Exposures of Children. Data on the exposure of children to acrolein are very limited (Nazaroff and 

Singer 2004; WHO 2002). For children living in a residence where one or more individuals smokes some 

form of tobacco product, long-term exposure to acrolein and other compounds in ETS are expected 

(Nazaroff and Singer 2004; WHO 1999). Lifetime exposures to acrolein in ETS have been estimated for 

individuals residing with one or more smokers (Nazaroff and Singer 2004); however, there are no data 

that specifically address the inhalation intake of acrolein from ETS in individuals below the age of 18. 
ACROLEIN 132 

6. POTENTIAL FOR HUMAN EXPOSURE 

Information on acrolein concentrations in indoor air is limited for residences in the United States (CARB 

1992; Highsmith and Zweidinger 1988; WHO 2002). More data are needed to adequately assess the 

exposures of children to acrolein generated from indoor combustion sources, especially tobacco products. 

Determination of the average daily intake of acrolein would be complicated by the variability in the 

frequency and amount of exposure to cigarette smoke and other acrolein sources. Therefore, exposure 

studies should be structured to assess the temporal variations in acrolein concentrations over a typical day 

and should also account for seasonal changes in air exchange within a residence (i.e., winter versus 

summer). For children who are not exposed to ETS in the home environment, it is expected that the 

largest exposure to acrolein will be through inhalation of ambient air, especially in urban areas, and 

through the diet. Therefore, studies that are tailored to assessing exposure of children to acrolein in 

ambient air would be useful given the tendency for children to spend more time outdoors than many 

adults. Also, market basket surveys or total diet studies similar to those conducted by the FDA would be 

useful for providing data on typical levels of exposure via dietary intake for children. 

Child health data needs relating to susceptibility are discussed in Section 3.12.2, Identification of Data 

Needs: Children’s Susceptibility. 

Exposure Registries. No exposure registries for acrolein were located. This substance is not 

currently one of the compounds for which a sub-registry has been established in the National Exposure 

Registry. The substance will be considered in the future when chemical selection is made for subregistries to be established. The information that is amassed in the National Exposure Registry facilitates 

the epidemiological research needed to assess adverse health outcomes that may be related to exposure to 

this substance. 

6.8.2 Ongoing Studies 

The EPA is developing the methods, data, and models of exposure that will provide the scientific basis for 

EPA to move to a risk-based program that will enhance the National-Scale Air Toxics Assessment 

(NATA) program. No other pertinent ongoing studies were identified. 
ACROLEIN 133 

7. ANALYTICAL METHODS 

The purpose of this chapter is to describe the analytical methods that are available for detecting, 

measuring, and/or monitoring acrolein, its metabolites, and other biomarkers of exposure and effect to 

acrolein. The intent is not to provide an exhaustive list of analytical methods. Rather, the intention is to 

identify well-established methods that are used as the standard methods of analysis. Many of the 

analytical methods used for environmental samples are the methods approved by federal agencies and 

organizations such as EPA and the National Institute for Occupational Safety and Health (NIOSH). Other 

methods presented in this chapter are those that are approved by groups such as the Association of 

Official Analytical Chemists (AOAC) and the American Public Health Association (APHA). 

Additionally, analytical methods are included that modify previously used methods to obtain lower 

detection limits and/or to improve accuracy and precision. 

7.1 BIOLOGICAL MATERIALS 

Data regarding the analytical methods used in the determination of acrolein in biological samples are 

limited. Boor and Ansari (1986) developed a method capable of detecting nanogram (ng) quantities of 

acrolein in biological samples. In this method, a derivatizing agent, 2,4-dinitrophenylhydrazine (DNP), is 

incubated with liver or kidney homogenate for a short period of time. The acrolein-DNP adduct is then 

extracted from the sample with chloroform. Analysis for acrolein is accomplished by elution on a reverse 

phase column using high performance liquid chromatography (HPLC), and detection of the adduct by 

ultraviolet (UV) absorbency. Interferences due to the coincidental elution of DNP adducts of ketones or 

aldehydes other than acrolein are not ruled out by this method of analysis. 

In earlier attempts to quantify acrolein in biological media, Kissel et al. (1978) urged caution when using 

derivatization methods for the measurement of acrolein levels in biological media based upon data for 

analysis for acrolein in aqueous solutions (Kissel et al. 1978). Methods that utilized derivatives (DNP 

and 7-hydroxyquinoline) combined with colorimetric or fluorimetric detection were not specific for 

acrolein and consistently did not correlate with those obtained from bioassays. However, more recent 

studies have made better utilization of gas chromatography (GC) and HPLC techniques to improve the 

resolution of acrolein and acrolein derivatives from other interfering species (Al-Rawithi et al. 1993; Paci 

et al. 2000; Sakuragawa et al. 1999). These assays, in addition to other assays for quantifying acrolein in 

biological media, are summarized in Table 7-1. 
ACROLEIN 134 

7. ANALYTICAL METHODS 

Table 7-1. Analytical Methods for Determining Acrolein in Biological Samples 

Sample 

matrix Preparation method 

Analytical 

method 

Sample 

detection limit 

Percent 

Recovery Reference 

Urine Urine is heated to 80 °C, head- GC-MS 1–5 nM 7–87.9% Sakura et al. 

space vapors sampled, and 

injected directly into GC 

(0.056– 

0.28 μg/L) 

(100 nM) 1998 

Urine Urine is reacted with derivatizing 

reagent (m-aminophenol/ 

hydroxylamine/ferrous sulfate) 

and heated to 100 °C for 

HPLC-FDb

 <1 μg/L 99–104.1% Al-Rawithi et 

al. 1993 

15 minutes. 

Urine Urine is centrifuged, lypohilized, 

and reconstituted in water. The 

acrolein metabolite, 3-hydroxylpropyl-L-cysteine, is directly 

quantified. 

HPLC-UV 1.25 μg/mL 

(1.25 mg/L) 

No data Sanduja et 

al. 1988 

Urine The acrolein metabolite, Amino acid No data No data Alarcon 

3-hydroxypropylmercapturic acid, 

in urine is hydrolyzed to 

3-hydroxylpropyl-L-cysteine in 

2N HCl 

analyzer 1976 

Plasma Plasma is reacted with 

Luminarin 3a

 in 0.1 M sulfuric 

acid, extracted with methylene 

chloride, dried, reconstituted in 

HPLC-FDb

 5.6 ng/mL 

(5.6 μg/L) 

78–82% Paci et al. 

2000 

acetonitrile 

Tissue Homogenized tissued mixed with 

2,4-DNP stock solution, extract 

acrolein-DNP derivative with 

chloroform 

HPLC-UVb

 <0.2 ng (in 

extract reconstituted in 

0.5 mL 

4.6–43.8% 

(8 mg 

acrolein) 

Boor and 

Ansari 1986 

methanol) 

a

Derivatizing agent 

b

Derivative analyzed 

2,4-DNP = 2,4-dinitrophenylhydrazine; FD = fluorescence detection; GC = gas chromatography; HPLC = high 

performance liquid chromatography; MS = mass spectrometry; UV = ultraviolet 
ACROLEIN 135 

7. ANALYTICAL METHODS 

A method for the direct detection of acrolein in urine was developed by Sakura et al. (1998). In this 

method, a small volume of urine (0.5 mL) is heated to 80 °C, driving the dissolved acrolein into the 

headspace above the liquid. The headspace vapors are analyzed using GC-mass spectrometry (MS), 

which provides a detection sensitivity of between 1 and 5 nM (0.056 and 0.28 μg/L) acrolein in urine. 

The variability is due to differences in the ability to drive acrolein from various urine samples during the 

heating phase of the method. 

Biomarkers of acrolein exposure have been studied based either on acrolein metabolites in urine or the 

formation of protein-acrolein adducts. Alarcon (1976) developed a method for quantifying 3-hydroxypropylmercapturic acid (MCA), a known metabolite of acrolein, in urine. This method involves 

acidification of the urine to convert MCA to S-(3-hydroxypropyl)-L-cysteine. The amount of 

S-(3-hydroxypropyl)-L-cysteine can then be quantitated using an automated amino acid analyzer. 

Sanduja et al. (1989) directly measured S-(3-hydroxypropyl)-L-cysteine in urine at a sensitivity of 

1.25 μg/mL using HPLC with UV detection (210 nm). Li et al. (2004) developed an enzyme-linked 

immunosorbent assay (ELISA) for detecting acrolein-protein adducts (APA) in albumin obtained from 

blood. The APA levels in plasma were found to increase by 32 and 58% in rates exposed to one or seven 

doses of 9.2 mg/kg/day acrolein, respectively. However, more work is necessary to correlate APA levels 

in plasma and acrolein exposures. Decreased activity of the enzyme, glucose-6-phosphate dehydrogenase 

(G6PD), has been found to occur when the purified form of the enzyme is exposed to 0.2–1.0 mM 

acrolein (Trieff et al. 1993). Studies have yet to be conducted to determine whether dose-dependent 

changes in G6DH activity are obtained in vivo as a function of exposures to acrolein. 

7.2 ENVIRONMENTAL SAMPLES 

The detection and quantification of acrolein in air is accomplished mainly through the formation of 

acrolein derivatives (Nishikawa and Sakai 1995). In the NIOSH method 2501 (NIOSH 1994), a known 

volume of air is pumped through a tube containing a support coated with the derivatizing agent 

2-(hydroxymethyl)piperidine. The derivative is eluted from the tube with toluene, and analyzed by GC 

using a nitrogen specific detector (NSD). Variations of this procedure have also been reported. Rietz 

(1985) used DNP as a derivatizing agent on the adsorbent tube, and made a final analysis using HPLC 

coupled to a UV detector. Similarly, EPA method 8315A uses HPLC with UV detection to quantify the 

DNP derivative of acrolein that is obtained from the reaction of acrolein in air with 2,4-DNP coated on a 

silica matrix as air is pumped through a collection tube described in EPA method 100 (EPA 1996). The 
ACROLEIN 136 

7. ANALYTICAL METHODS 

DNP derivative is extracted with acetonitrile and analyzed using a C18 column and a detection wavelength 

of 360 nm. 

Another method for quantifying acrolein in air involves the trapping of acrolein by bubbling air through 

an aliquot of ethanol, adding methoxylamine hydrochloride to form a derivative, and then brominating the 

resulting adduct to allow increased detector sensitivity. Quantitation is achieved by GC using an electron 

capture detector (ECD) (Nishikawa et al. 1986). A summary of these techniques, along with methods for 

other environmental samples, are presented in Table 7-2. Interferences due to coincidental elution of 

derivatives of the compounds can be a potential problem of these techniques depending on the resolving 

power of the chromatographic technique. 

Derivatization methods for the measurement of acrolein levels in environmental media should be used 

with caution based upon data for analysis for acrolein in aqueous solutions (Kissel et al. 1978). In a 

comparison of chemical analytical methods to bioassays, results obtained using methods utilizing 

derivatives (DNP and 7-hydroxyquinoline) combined with colorimetric or fluorimetric detection were not 

specific for acrolein and consistently did not correlate with those obtained from bioassays. Certain direct 

methods of detection (nuclear magnetic resonance [NMR]), fluorescence, and differential pulse 

polarography) gave the best correlation to the bioassay results (see Table 7-2). 

The analysis of acrolein in wastewater can be performed using EPA method 603 (EPA 2001c). In closely 

related techniques, an aliquot of water is subjected to a purge and trap protocol, and the sample is 

thermally desorbed onto a GC for analysis and quantitation. Coincidental elution of compounds with 

acrolein may lead to interferences in this method. 

Ogawa and Fritz (1985) developed a method for the identification of acrolein in water. A known volume 

of water is passed over a column of zeolite that traps the acrolein. The column is then eluted with 

acetonitrile, and derivatization using DNP follows. By following this procedure, a sample that can be 

analyzed by HPLC is obtained. Similar approaches were used by Koostra and Herbold (1995) and 

Sakuragawa et al. (1999), but in their methods, DNP was coated on to a C18 matrix within a solid phase 

extraction (SPE) cartridge. The use of mass spectrometric techniques by Sakuragawa et al. (1999) to 

quantify acrolein-DNP derivatives provided for better detection sensitivities than the UV detection 

method used by Koostra and Herbold. Other derivatizing agents that have been used successfully for the 
ACROLEIN 137 

7. ANALYTICAL METHODS 

Table 7-2. Analytical Methods for Determining Acrolein in 

Environmental Samples 

Sample 

matrix Preparation method 

Analytical 

method 

Sample 

detection limit 

Percent 

recovery Reference 

Aira Collection on tube with 

2-(hydroxylmethyl)piperidineb 

coated on XAD-2 resin, desorbed 

by toluene extraction 

GC-NSDc 

(NIOSH 

2501) 

2 μg No data NIOSH 1994 

Air Collection on tube containing 

silica gel coated with 2,4-dinitrophenylhydrazine, tube 

backflushed with acetonitrile 

HPLC-UV 

(EPA 100/ 

8315A) 

0.03 ppb (500 L 

sample volume) 

No data EPA 1996 

Water Direct analysis using detector 

wavelength of 195 nm 

HPLC-UV 

(EPA 8316) 

30 μg/L No data EPA 1994a 

Waste 

waterd 

Purge at 85 °C and trap onto 

methyl silicone/2,6-diphenylene 

oxide adsorbent, thermal 

desorption 

GC-FID 

(EPA 603) 

0.7 μg/L 104% 

(5 μg/L, 

RW); 80% 

(5 μg/L, 

POTWe

); 2% 

(5 μg/L, IWf

); 

EPA 2001c 

Waste 

water 

Addition of isotopically-labeled 

standards, purge at 20–25 °C and 

trap onto methyl silicone/2,6-diphenylene oxide adsorbent, 

thermal desorption 

GC-MS 

(EPA 1624) 

50 μg/L No data EPA 2001a 

Air Trap in ethanol solution, add 

methoxylaminehydrochlorideb 

, 

brominate 

GC-ECDc

 <4 ppb 81–96% Nishikawa et 

al. 1986 

Trap on XAD-2 resin coated with 

2-(hydroxymethyl)piperidineb 

, 

desorb with toluene 

GC-NSDc

 NS NS Kennedy et 

al. 1984 

Trap on XAD-2 resin coated with 

2,4-DNPb

, elute adduct with 

HPLC-UVc

 0.01 mg/m3 No data Rietz 1985 

acetonitrile 

Sampled air passed through 

ozone scrubber then through SPE 

cartridge where analytes are 

trapped on a C18 matrix coated 

with 2,4-DNP, elute adduct with 

HPLC-UVc 50–150 ng/m3 >90% Koostra and 

Herbold 

1995 

acetontrile and dilute with water 

Trap on C18 SPE coated with 

2,4-DNP, extract with acetronitrile 

LC-MS 0.44 ppb 100% Sakuragawa 

et al. 1999 
ACROLEIN 138 

7. ANALYTICAL METHODS 

Table 7-2. Analytical Methods for Determining Acrolein in 

Environmental Samples 

Sample 

matrix Preparation method 

Analytical 

method 

Sample 

detection limit 

Percent 

recovery Reference 

Water Trap on Zeolite ZSM-5 column, 

elute with acetonitrile, derivatize 

HPLC-UVc

 <10 μg 98% Ogawa and 

Fritz 1985 

with 2,4-DNP 

Nondirect measurement of 

aldehyde signal compared to 

signal for a calibrated sealed 

external TMS standard 

NMR 5,000 ppm NS Kissel et al. 

1978 

Dilution of sample with deionized 

water 

Fluorescence 

spectrometer 

>20 ppm NS Kissel et al. 

1978 

Dilution of sample with deionized 

water, addition of phospate buffer 

and EDTA 

Differential 

pulse polarography 

>30 ppb NS Kissel et al. 

1978 

Personal 

Air 

Trap on carbon coated with 

hydroquinone, desorb with 

1,2-dichloroethane 

GC 0.02 ppb >75% Hurley and 

Ketcham 

1978 

Rain Add to collected sample methoxylaminehydrochlorideb

, brominate 

GC-ECDc 0.4 ng/mL 90–101% Nishikawa et 

al. 1987b 

Fats and Fat or oil is emulsified in distilled HPLC-ED 0.15 μM 49–116% Casella and 

natural 

oils 

water or 10 mM HClO4, aqueous 

phase separated, then filtered and 

injected into column 

Contursi 

2004 

a

NIOSH method 2501 is the preferred method for quantitative analysis; method 2539 can be used to screen samples 

for acrolein. 

b

Derivatizing agent 

c

Derivative analyzed 

d

EPA method 603 is the preferred method for quantitative analysis; method 624 can be used to screen samples for 

acrolein. 

e

POTW = prechlorination secondary effluent from a municipal sewage treatment plant 

f

IW = industrial waste water containing an unidentified acrolein reactant 

2,4-DNP = 2,4-dinitrophenylhydrazine; ECD = electron capture detector; ED = electrochemical detector; 

EDTA = ethylenediaminetetraacetic acid; FID = flame ionization detector; GC = gas chromatography; HPLC = high 

performance liquid chromatography; LC = liquid chromatography; MS = mass spectrometry; NMR = nuclear 

magnetic resonance; NS = not specified; NSD = nitrogen specific detector; POTW = publicly owned treatment works; 

RW = reagent water; SPE = solid phase extraction; TMS = tetramethylsilane; UV = ultraviolet 
ACROLEIN 139 

7. ANALYTICAL METHODS 

monitoring of acrolein in the environment include dimedon, phenylhydrazone, 4-hexylresorcinol, and 

3-methyl-2-benzothiazolone (Altshuller and McPherson 1963; Peltonen et al. 1984). 

Direct detection of acrolein in water is obtained using EPA method 8316 (EPA 1994a). The water sample 

is injected on to a C18 HPLC column and then quantified by UV at a wavelength of 195 nm. 

7.3 ADEQUACY OF THE DATABASE 

Section 104(i)(5) of CERCLA, as amended, directs the Administrator of ATSDR (in consultation with the 

Administrator of EPA and agencies and programs of the Public Health Service) to assess whether 

adequate information on the health effects of acrolein is available. Where adequate information is not 

available, ATSDR, in conjunction with NTP, is required to assure the initiation of a program of research 

designed to determine the health effects (and techniques for developing methods to determine such health 

effects) of acrolein. 

The following categories of possible data needs have been identified by a joint team of scientists from 

ATSDR, NTP, and EPA. They are defined as substance-specific informational needs that if met would 

reduce the uncertainties of human health assessment. This definition should not be interpreted to mean 

that all data needs discussed in this section must be filled. In the future, the identified data needs will be 

evaluated and prioritized, and a substance-specific research agenda will be proposed. 

7.3.1 Identification of Data Needs 

Methods for Determining Biomarkers of Exposure and Effect. 

Exposure. Methods have been identified that measure the concentrations of acrolein in blood, tissues, 

and urine (Al-Rawithi et al. 1993; Boor and Ansari 1986; Paci et al. 2000; Sakura et al. 1998). The 

methods used for the analysis of acrolein, however, can be susceptible to interferences. 

Several studies have been identified that explore the use of specific biomarkers that can be associated 

quantitatively with exposure of acrolein. There are methods that can detect 3-hydroxypropylmercapturic 

acid, which is a metabolite of acrolein, in urine (Alarcon 1976; Sanduja et al. 1989). Changes in the 

activity of the enzyme, glucose-6-phosphate dehydrogenase, and levels in acrolein adducts of albumin in 

blood as a function of exposure to acrolein have been studied (Li et al. 2004; Trieff et al. 1993), but 

further work is necessary to correlate exposures of acrolein with changes in the biomarkers in vivo. 
ACROLEIN 140 

7. ANALYTICAL METHODS 

Effect. There are no biomarkers that have been associated quantitatively with an acrolein-induced effect 

in humans. Identification and use of such biomarkers would be useful for establishing a more reliable 

assessment of the relationship between acrolein intake and acrolein-induced effects in humans than would 

be provided from monitoring data of acrolein concentrations in air, drinking water, or food. 

Methods for Determining Parent Compounds and Degradation Products in Environmental 

Media. Suitable methods are available for the determination of acrolein in air, which mainly involve 

the formation of acrolein derivatives (Altshuller and McPherson 1963; Nishikawa and Sakai 1995; 

Peltonen et al. 1984) that are quantified using GC (Kennedy et al. 1984; NIOSH 1994; Nishikawa et al. 

1986) or HPLC techniques (EPA 1996; Koostra and Herbold 1995; Rietz 1985). Suitable methods are 

also available for analyzing acrolein in water that either directly quantify acrolein in water (EPA 1994a; 

Kissel et al. 1978) or use an extraction step followed by either analysis of acrolein (EPA 1992) or acrolein 

derivatives (EPA 2001c; Ogawa and Fritz 1985). Nevertheless, new methodologies for the determination 

of acrolein have been reported. An LC-MS based method (Sakuragawa et al. 1999) can offer increased 

sensitivity and greater ease of performance than is currently available for the direct analysis of acrolein in 

water (Rietz 1985). Standardized methods for analyzing acrolein in soil were not located. However, 

given the extent to which acrolein is expected to volatilize from soil based on its high vapor pressure 

(274 mm Hg at 25 °C) and the irreversible binding of acrolein in soil, the lifetime of acrolein in soil may 

be too short for concern from the standpoint of being a source of human exposure to acrolein. Therefore, 

development of analytical methods for measuring acrolein in soil is not expected to provide data that 

would be useful in assessing human exposures to acrolein. 

7.3.2 Ongoing Studies 

The EPA is conducting a study on human exposure to air toxics, which includes optimizing the PAKS 

method for measuring airborne acrolein. At the University of California at Davis, Dr. M.J. Charles is 

developing an air sampling method that uses a Cofer scrubber for measuring acrolein in ambient air. Also 

at the University of California at Davis, Dr. Shibamoto is measuring the concentrations of acrolein in a 

variety of cooked foods and in beverages. Dr. Iype at the Biological Research Facility in Ijamsville, 

Maryland, is developing an antibody-mediated detection system for assessing human exposure to acrolein 

that is based on the quantification of acrolein-DNA adducts in white blood cells. No other ongoing 

studies concerning the determination of acrolein in environmental media or biological materials were 

identified. 
ACROLEIN 141 

8. REGULATIONS AND ADVISORIES 

The international and national regulations and guidelines regarding acrolein in air, water, and other media 

are summarized in Table 8-1. 

ATSDR derived an acute-duration inhalation MRL of 0.003 ppm using a LOAEL of 0.3 ppm for nasal 

and throat irritation and decreased respiratory rate in volunteers exposed for 60 minutes (Weber-Tschopp 

et al. 1977). The LOAEL of 0.3 ppm was divided by an uncertainty factor of 100 (10 for using a LOAEL 

and 10 for human variability). 

ATSDR derived an intermediate duration inhalation MRL of 0.00004 ppm using a LOAEL of 0.4 ppm for 

nasal epithelial metaplasia in rats in a 13-week study (Feron et al. 1978). The MRL was calculated by 

dividing the human equivalent LOAEL (0.012 ppm) by an uncertainty factor of 300 (10 for using a 

LOAEL, 3 for extrapolation from animals to humans using dosimetric adjustments, and 10 for human 

variability). 

ATSDR derived an intermediate-duration oral MRL of 0.004 mg/kg/day based on a BMDL10 of 

0.36 mg/kg/day for forestomach squamous epithelial hyperplasia in mice in a 14-week gavage study 

(NTP 2006) and an uncertainty factor of 100 (10 for species extrapolation and 10 for human variability). 

EPA (IRIS 2007) has derived an inhalation reference concentration (RfC) for acrolein of 2x10-5 mg/m3 

based on a LOAEL of 0.9 mg/m3

 (0.4 ppm) for nasal lesions in male and female rats exposed to acrolein 

6 hours/day, 5 days/week for 13 weeks (Feron et al. 1978) and an uncertainty factor of 1,000 (3 for use of 

a minimal LOAEL, 3 for interspecies extrapolation using dosimetric adjustments, 10 for extrapolation 

from subchronic to chronic duration, and 10 to account for human variability and sensitive 

subpopulations). 

EPA (IRIS 2007) has derived an oral reference dose (RfD) for acrolein of 5x10-4 mg/kg/day based on a 

NOAEL of 0.05 mg/kg/day for decreased survival in male and female rats treated by oral gavage for 

2 years (Parent et al. 1992a) and an uncertainty factor of 100 (10 for interspecies extrapolation and 10 for 

intraspecies variability). 
ACROLEIN 142 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Acrolein 

Agency Description Information Reference 

INTERNATIONAL 

Guidelines: 

IARC Carcinogenicity classification Group 3a

 IARC 2004 

WHO Air quality guidelines No data WHO 2000 

Drinking water quality guidelines No data WHO 2004 

NATIONAL 

Regulations and Guidelines: 

a. Air 

ACGIH 

NAS/NRC 

TLV (ceiling limit)b 

AEGL-1c 

0.10 ppm ACGIH 2004 

EPA 2005a 

10, 30, 60 minutes, 4 and 8 hours 

AEGL-2c 

0.03 ppm 

10 minutes 0.44 ppm 

30 minutes 0.18 ppm 

60 minutes, 4 and 8 hours 

AEGL-3c 0.10 ppm 

10 minutes 6.2 ppm 

30 minutes 2.5 ppm 

60 minutes 1.4 ppm 

4 hours 0.48 ppm 

8 hours 0.27 ppm 

EPA Hazardous air pollutant Yes EPA 2004b 

42 USC 7412 

Regulated toxic substances and threshold 5,000 pounds EPA 2005d 

quantities for accidental release prevention 

Toxic end points for accidental release 1.1x10-3 mg/L 

40 CFR 68.130 

EPA 2005i 

prevention 40 CFR 68, 

Appendix A 

NIOSH REL (10-hour TWA) 0.1 ppm NIOSH 2005

 STEL 0.3 ppm 

IDLH 2.0 ppm 

OSHA PEL (8-hour TWA) for general industry 0.1 ppm OSHA 2005a 

29 CFR 1910.1000 

PEL (8-hour TWA) for construction industry 0.1 ppm OSHA 2005b 

29 CFR 1926.55 

PEL (8-hour TWA) for shipyard industry 0.1 ppm OSHA 2005d 

29 CFR 1910.1000 

Highly hazardous chemical and threshold 150 poundsd

 OSHA 2005c 

quantity 29 CFR 1910.119 

b. Water 

EPA Designated as hazardous substances in Yes EPA 2005b 

accordance with Section 311 of the Clean 40 CFR 116.4 

Water Act 

Reportable quantities of hazardous 1 pound EPA 2005e 

substances designated pursuant to 40 CFR 117.3 

Section 311 of the Clean Water Act 

Water quality criteria for human health EPA 2002 

consumption of: 

Water + organism 190 μg/L 

Organism only 290 μg/L 

c. Food No data 
ACROLEIN 143 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Acrolein 

Agency Description Information Reference 

NATIONAL (cont.) 

d. Other 

 ACGIH Carcinogenicity classification A4e

 ACGIH 2004

 EPA Carcinogenicity classification Cannot be 

determinedf 

IRIS 2005 

RfC 

RfD 

Pesticide classified for restricted use 

2x10-5 mg/m3 

5x10-4 mg/kg/day 

Yesg

 EPA 2005c 

40 CFR 152.175 

Superfund, emergency planning, and 

community right-to-know 

Designated CERCLA hazardous 

substanceh 

EPA 2005f 

40 CFR 302.4 

 Reportable quantity 1 pound 

 RCRA waste number P003 

Effective date of toxic chemical release 01/01/87 EPA 2005h 

reporting 40 CFR 372.65 

Extremely hazardous substances EPA 2005g 

 Reportable quantity 1 pound 40 CFR 355, 

Threshold planning quantities 500 pounds Appendix A 

NTP Carcinogenicity classification No data NTP 2005 

a

Group 3: not classifiable as to carcinogenicity to humans. 

b

Skin notation: refers to the potential significant contribution to the overall exposure by the cutaneous route, including 

mucous membranes and the eyes, either by contact with vapors or, of probable greater significance, by direct skin 

contact with the substance. 

c

AEGL-1 is the airborne concentration of a substance above which it is predicted that the general population, 

including susceptible individuals, could experience notable discomfort, irritation, or certain asymptomatic nonsensory
 

effects. AEGL-2 is the airborne concentration of a substance above which it is predicted that the general population, 

including susceptible individuals, could experience irreversible or other serious, long-lasting adverse health effects or 

an impaired ability to escape. AEGL-3 is the airborne concentration of a substance above which it is predicted that 

the general population, including susceptible individuals, could experience life-threatening health effects or death. d

Highly hazardous chemical: presents a potential for a catastrophic event at or above the threshold quantity. e

A4: not classifiable as a human carcinogen.
 f

Potential carcinogenicity cannot be determined because the existing "data are inadequate for an assessment of 

human carcinogenic potential for either the oral or inhalation route of exposure”. 

g

Pesticide classified for restricted use because of the inhalation hazard to humans and the residue effects on avian 

species and aquatic organisms. 

h

Designated CERCLA hazardous substance pursuant to Section 311(b)(2) and 307(a) of the Clean Water Act, 

Section 112 of the Clean Air Act, and Section 3001 of RCRA. 

ACGIH = American Conference of Governmental Industrial Hygienists; AEGL = acute exposure guideline level; 

CERCLA = Comprehensive Environmental Response, Compensation, and Liability Act; CFR = Code of Federal
 

Regulations; EPA = Environmental Protection Agency; IARC = International Agency for Research on Cancer; 

IDLH = immediately dangerous to life or health; IRIS = Integrated Risk Information System; NAS/NRC = National 

Academy of Sciences/National Research Council; NIOSH = National Institute for Occupational Safety and Health; 

NTP = National Toxicology Program; OSHA = Occupational Safety and Health Administration; PEL = permissible 

exposure limit; RCRA = Resource Conservation and Recovery Act; REL = recommended exposure limit; 

RfC = inhalation reference concentration; RfD = oral reference dose; STEL = short-term exposure limit; 

TLV = threshold limit values; TWA = time-weighted average; USC = United States Code; WHO = World Health
 

Organization
 
ACROLEIN 144 

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_______________________ 

ACROLEIN 145 

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ACROLEIN 171 

10. GLOSSARY 

Absorption—The taking up of liquids by solids, or of gases by solids or liquids. 

Acute Exposure—Exposure to a chemical for a duration of 14 days or less, as specified in the 

Toxicological Profiles. 

Adsorption—The adhesion in an extremely thin layer of molecules (as of gases, solutes, or liquids) to the 

surfaces of solid bodies or liquids with which they are in contact. 

Adsorption Coefficient (Koc)—The ratio of the amount of a chemical adsorbed per unit weight of 

organic carbon in the soil or sediment to the concentration of the chemical in solution at equilibrium. 

Adsorption Ratio (Kd)—The amount of a chemical adsorbed by sediment or soil (i.e., the solid phase) 

divided by the amount of chemical in the solution phase, which is in equilibrium with the solid phase, at a 

fixed solid/solution ratio. It is generally expressed in micrograms of chemical sorbed per gram of soil or 

sediment. 

Benchmark Dose (BMD)—Usually defined as the lower confidence limit on the dose that produces a 

specified magnitude of changes in a specified adverse response. For example, a BMD10 would be the 

dose at the 95% lower confidence limit on a 10% response, and the benchmark response (BMR) would be 

10%. The BMD is determined by modeling the dose response curve in the region of the dose response 

relationship where biologically observable data are feasible. 

Benchmark Dose Model—A statistical dose-response model applied to either experimental toxicological 

or epidemiological data to calculate a BMD. 

Bioconcentration Factor (BCF)—The quotient of the concentration of a chemical in aquatic organisms 

at a specific time or during a discrete time period of exposure divided by the concentration in the 

surrounding water at the same time or during the same period. 

Biomarkers—Broadly defined as indicators signaling events in biologic systems or samples. They have 

been classified as markers of exposure, markers of effect, and markers of susceptibility. 

Cancer Effect Level (CEL)—The lowest dose of chemical in a study, or group of studies, that produces 

significant increases in the incidence of cancer (or tumors) between the exposed population and its 

appropriate control. 

Carcinogen—A chemical capable of inducing cancer. 

Case-Control Study—A type of epidemiological study that examines the relationship between a 

particular outcome (disease or condition) and a variety of potential causative agents (such as toxic 

chemicals). In a case-controlled study, a group of people with a specified and well-defined outcome is 

identified and compared to a similar group of people without outcome. 

Case Report—Describes a single individual with a particular disease or exposure. These may suggest 

some potential topics for scientific research, but are not actual research studies. 

Case Series—Describes the experience of a small number of individuals with the same disease or 

exposure. These may suggest potential topics for scientific research, but are not actual research studies. 
ACROLEIN 172 

10. GLOSSARY 

Ceiling Value—A concentration of a substance that should not be exceeded, even instantaneously. 

Chronic Exposure—Exposure to a chemical for 365 days or more, as specified in the Toxicological 

Profiles. 

Cohort Study—A type of epidemiological study of a specific group or groups of people who have had a 

common insult (e.g., exposure to an agent suspected of causing disease or a common disease) and are 

followed forward from exposure to outcome. At least one exposed group is compared to one unexposed 

group. 

Cross-sectional Study—A type of epidemiological study of a group or groups of people that examines 

the relationship between exposure and outcome to a chemical or to chemicals at one point in time. 

Data Needs—Substance-specific informational needs that if met would reduce the uncertainties of human 

health assessment. 

Developmental Toxicity—The occurrence of adverse effects on the developing organism that may result 

from exposure to a chemical prior to conception (either parent), during prenatal development, or 

postnatally to the time of sexual maturation. Adverse developmental effects may be detected at any point 

in the life span of the organism. 

Dose-Response Relationship—The quantitative relationship between the amount of exposure to a 

toxicant and the incidence of the adverse effects. 

Embryotoxicity and Fetotoxicity—Any toxic effect on the conceptus as a result of prenatal exposure to 

a chemical; the distinguishing feature between the two terms is the stage of development during which the 

insult occurs. The terms, as used here, include malformations and variations, altered growth, and in utero 

death. 

Environmental Protection Agency (EPA) Health Advisory—An estimate of acceptable drinking water 

levels for a chemical substance based on health effects information. A health advisory is not a legally 

enforceable federal standard, but serves as technical guidance to assist federal, state, and local officials. 

Epidemiology—Refers to the investigation of factors that determine the frequency and distribution of 

disease or other health-related conditions within a defined human population during a specified period. 

Genotoxicity—A specific adverse effect on the genome of living cells that, upon the duplication of 

affected cells, can be expressed as a mutagenic, clastogenic, or carcinogenic event because of specific 

alteration of the molecular structure of the genome. 

Half-life—A measure of rate for the time required to eliminate one half of a quantity of a chemical from 

the body or environmental media. 

Immediately Dangerous to Life or Health (IDLH)—The maximum environmental concentration of a 

contaminant from which one could escape within 30 minutes without any escape-impairing symptoms or 

irreversible health effects. 

Immunologic Toxicity—The occurrence of adverse effects on the immune system that may result from 

exposure to environmental agents such as chemicals. 

Immunological Effects—Functional changes in the immune response. 
ACROLEIN 173 

10. GLOSSARY 

Incidence—The ratio of individuals in a population who develop a specified condition to the total 

number of individuals in that population who could have developed that condition in a specified time 

period. 

Intermediate Exposure—Exposure to a chemical for a duration of 15–364 days, as specified in the 

Toxicological Profiles. 

In Vitro—Isolated from the living organism and artificially maintained, as in a test tube. 

In Vivo—Occurring within the living organism. 

Lethal Concentration(LO) (LCLO)—The lowest concentration of a chemical in air that has been reported 

to have caused death in humans or animals. 

Lethal Concentration(50) (LC50)—A calculated concentration of a chemical in air to which exposure for 

a specific length of time is expected to cause death in 50% of a defined experimental animal population. 

Lethal Dose(L0) (LDL0)—The lowest dose of a chemical introduced by a route other than inhalation that 

has been reported to have caused death in humans or animals. 

Lethal Dose(50) (LD50)—The dose of a chemical that has been calculated to cause death in 50% of a 

defined experimental animal population. 

Lethal Time(50) (LT50)—A calculated period of time within which a specific concentration of a chemical 

is expected to cause death in 50% of a defined experimental animal population. 

Lowest-Observed-Adverse-Effect Level (LOAEL)—The lowest exposure level of chemical in a study, 

or group of studies, that produces statistically or biologically significant increases in frequency or severity 

of adverse effects between the exposed population and its appropriate control. 

Lymphoreticular Effects—Represent morphological effects involving lymphatic tissues such as the 

lymph nodes, spleen, and thymus. 

Malformations—Permanent structural changes that may adversely affect survival, development, or 

function. 

Minimal Risk Level (MRL)—An estimate of daily human exposure to a hazardous substance that is 

likely to be without an appreciable risk of adverse noncancer health effects over a specified route and 

duration of exposure. 

Modifying Factor (MF)—A value (greater than zero) that is applied to the derivation of a Minimal Risk 

Level (MRL) to reflect additional concerns about the database that are not covered by the uncertainty 

factors. The default value for a MF is 1. 

Morbidity—State of being diseased; morbidity rate is the incidence or prevalence of disease in a specific 

population. 

Mortality—Death; mortality rate is a measure of the number of deaths in a population during a specified 

interval of time. 
ACROLEIN 174 

10. GLOSSARY 

Mutagen—A substance that causes mutations. A mutation is a change in the DNA sequence of a cell’s 

DNA. Mutations can lead to birth defects, miscarriages, or cancer. 

Necropsy—The gross examination of the organs and tissues of a dead body to determine the cause of 

death or pathological conditions. 

Neurotoxicity—The occurrence of adverse effects on the nervous system following exposure to a 

chemical. 

No-Observed-Adverse-Effect Level (NOAEL)—The dose of a chemical at which there were no 

statistically or biologically significant increases in frequency or severity of adverse effects seen between 

the exposed population and its appropriate control. Effects may be produced at this dose, but they are not 

considered to be adverse. 

Octanol-Water Partition Coefficient (Kow)—The equilibrium ratio of the concentrations of a chemical 

in n-octanol and water, in dilute solution. 

Odds Ratio (OR)—A means of measuring the association between an exposure (such as toxic substances 

and a disease or condition) that represents the best estimate of relative risk (risk as a ratio of the incidence 

among subjects exposed to a particular risk factor divided by the incidence among subjects who were not 

exposed to the risk factor). An OR of greater than 1 is considered to indicate greater risk of disease in the 

exposed group compared to the unexposed group. 

Organophosphate or Organophosphorus Compound—A phosphorus-containing organic compound 

and especially a pesticide that acts by inhibiting cholinesterase. 

Permissible Exposure Limit (PEL)—An Occupational Safety and Health Administration (OSHA) 

allowable exposure level in workplace air averaged over an 8-hour shift of a 40-hour workweek. 

Pesticide—General classification of chemicals specifically developed and produced for use in the control 

of agricultural and public health pests. 

Pharmacokinetics—The dynamic behavior of a material in the body, used to predict the fate 

(disposition) of an exogenous substance in an organism. Utilizing computational techniques, it provides 

the means of studying the absorption, distribution, metabolism, and excretion of chemicals by the body. 

Pharmacokinetic Model—A set of equations that can be used to describe the time course of a parent 

chemical or metabolite in an animal system. There are two types of pharmacokinetic models: data-based 

and physiologically-based. A data-based model divides the animal system into a series of compartments, 

which, in general, do not represent real, identifiable anatomic regions of the body, whereas the 

physiologically-based model compartments represent real anatomic regions of the body. 

Physiologically Based Pharmacodynamic (PBPD) Model—A type of physiologically based doseresponse model that quantitatively describes the relationship between target tissue dose and toxic end 

points. These models advance the importance of physiologically based models in that they clearly 

describe the biological effect (response) produced by the system following exposure to an exogenous 

substance. 
ACROLEIN 175 

10. GLOSSARY 

Physiologically Based Pharmacokinetic (PBPK) Model—Comprised of a series of compartments 

representing organs or tissue groups with realistic weights and blood flows. These models require a 

variety of physiological information: tissue volumes, blood flow rates to tissues, cardiac output, alveolar 

ventilation rates, and possibly membrane permeabilities. The models also utilize biochemical 

information, such as air/blood partition coefficients, and metabolic parameters. PBPK models are also 

called biologically based tissue dosimetry models. 

Prevalence—The number of cases of a disease or condition in a population at one point in time. 

Prospective Study—A type of cohort study in which the pertinent observations are made on events 

occurring after the start of the study. A group is followed over time. 

q1*—The upper-bound estimate of the low-dose slope of the dose-response curve as determined by the 

multistage procedure. The q1* can be used to calculate an estimate of carcinogenic potency, the 

incremental excess cancer risk per unit of exposure (usually μg/L for water, mg/kg/day for food, and 

μg/m3

 for air). 

Recommended Exposure Limit (REL)—A National Institute for Occupational Safety and Health 

(NIOSH) time-weighted average (TWA) concentration for up to a 10-hour workday during a 40-hour 

workweek. 

Reference Concentration (RfC)—An estimate (with uncertainty spanning perhaps an order of 

magnitude) of a continuous inhalation exposure to the human population (including sensitive subgroups) 

that is likely to be without an appreciable risk of deleterious noncancer health effects during a lifetime. 

The inhalation reference concentration is for continuous inhalation exposures and is appropriately 

expressed in units of mg/m3 or ppm. 

Reference Dose (RfD)—An estimate (with uncertainty spanning perhaps an order of magnitude) of the 

daily exposure of the human population to a potential hazard that is likely to be without risk of deleterious 

effects during a lifetime. The RfD is operationally derived from the no-observed-adverse-effect level 

(NOAEL, from animal and human studies) by a consistent application of uncertainty factors that reflect 

various types of data used to estimate RfDs and an additional modifying factor, which is based on a 

professional judgment of the entire database on the chemical. The RfDs are not applicable to 

nonthreshold effects such as cancer. 

Reportable Quantity (RQ)—The quantity of a hazardous substance that is considered reportable under 

the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA). Reportable 

quantities are (1) 1 pound or greater or (2) for selected substances, an amount established by regulation 

either under CERCLA or under Section 311 of the Clean Water Act. Quantities are measured over a 

24-hour period. 

Reproductive Toxicity—The occurrence of adverse effects on the reproductive system that may result 

from exposure to a chemical. The toxicity may be directed to the reproductive organs and/or the related 

endocrine system. The manifestation of such toxicity may be noted as alterations in sexual behavior, 

fertility, pregnancy outcomes, or modifications in other functions that are dependent on the integrity of 

this system. 

Retrospective Study—A type of cohort study based on a group of persons known to have been exposed 

at some time in the past. Data are collected from routinely recorded events, up to the time the study is 

undertaken. Retrospective studies are limited to causal factors that can be ascertained from existing 

records and/or examining survivors of the cohort. 
ACROLEIN 176 

10. GLOSSARY 

Risk—The possibility or chance that some adverse effect will result from a given exposure to a chemical. 

Risk Factor—An aspect of personal behavior or lifestyle, an environmental exposure, or an inborn or 

inherited characteristic that is associated with an increased occurrence of disease or other health-related 

event or condition. 

Risk Ratio—The ratio of the risk among persons with specific risk factors compared to the risk among 

persons without risk factors. A risk ratio greater than 1 indicates greater risk of disease in the exposed 

group compared to the unexposed group. 

Short-Term Exposure Limit (STEL)—The American Conference of Governmental Industrial 

Hygienists (ACGIH) maximum concentration to which workers can be exposed for up to 15 minutes 

continually. No more than four excursions are allowed per day, and there must be at least 60 minutes 

between exposure periods. The daily Threshold Limit Value-Time Weighted Average (TLV-TWA) may 

not be exceeded. 

Standardized Mortality Ratio (SMR)—A ratio of the observed number of deaths and the expected 

number of deaths in a specific standard population. 

Target Organ Toxicity—This term covers a broad range of adverse effects on target organs or 

physiological systems (e.g., renal, cardiovascular) extending from those arising through a single limited 

exposure to those assumed over a lifetime of exposure to a chemical. 

Teratogen—A chemical that causes structural defects that affect the development of an organism. 

Threshold Limit Value (TLV)—An American Conference of Governmental Industrial Hygienists 

(ACGIH) concentration of a substance to which most workers can be exposed without adverse effect. 

The TLV may be expressed as a Time Weighted Average (TWA), as a Short-Term Exposure Limit 

(STEL), or as a ceiling limit (CL). 

Time-Weighted Average (TWA)—An allowable exposure concentration averaged over a normal 8-hour 

workday or 40-hour workweek. 

Toxic Dose(50) (TD50)—A calculated dose of a chemical, introduced by a route other than inhalation, 

which is expected to cause a specific toxic effect in 50% of a defined experimental animal population. 

Toxicokinetic—The absorption, distribution, and elimination of toxic compounds in the living organism. 

Uncertainty Factor (UF)—A factor used in operationally deriving the Minimal Risk Level (MRL) or 

Reference Dose (RfD) or Reference Concentration (RfC) from experimental data. UFs are intended to 

account for (1) the variation in sensitivity among the members of the human population, (2) the 

uncertainty in extrapolating animal data to the case of human, (3) the uncertainty in extrapolating from 

data obtained in a study that is of less than lifetime exposure, and (4) the uncertainty in using lowestobserved-adverse-effect level (LOAEL) data rather than no-observed-adverse-effect level (NOAEL) data. 

A default for each individual UF is 10; if complete certainty in data exists, a value of 1 can be used; 

however, a reduced UF of 3 may be used on a case-by-case basis, 3 being the approximate logarithmic 

average of 10 and 1. 

Xenobiotic—Any chemical that is foreign to the biological system. 
ACROLEIN A-1 

APPENDIX A. ATSDR MINIMAL RISK LEVELS AND WORKSHEETS 

The Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) [42 U.S.C. 

9601 et seq.], as amended by the Superfund Amendments and Reauthorization Act (SARA) [Pub. L. 99– 

499], requires that the Agency for Toxic Substances and Disease Registry (ATSDR) develop jointly with 

the U.S. Environmental Protection Agency (EPA), in order of priority, a list of hazardous substances most 

commonly found at facilities on the CERCLA National Priorities List (NPL); prepare toxicological 

profiles for each substance included on the priority list of hazardous substances; and assure the initiation 

of a research program to fill identified data needs associated with the substances. 

The toxicological profiles include an examination, summary, and interpretation of available toxicological 

information and epidemiologic evaluations of a hazardous substance. During the development of 

toxicological profiles, Minimal Risk Levels (MRLs) are derived when reliable and sufficient data exist to 

identify the target organ(s) of effect or the most sensitive health effect(s) for a specific duration for a 

given route of exposure. An MRL is an estimate of the daily human exposure to a hazardous substance 

that is likely to be without appreciable risk of adverse noncancer health effects over a specified duration 

of exposure. MRLs are based on noncancer health effects only and are not based on a consideration of 

cancer effects. These substance-specific estimates, which are intended to serve as screening levels, are 

used by ATSDR health assessors to identify contaminants and potential health effects that may be of 

concern at hazardous waste sites. It is important to note that MRLs are not intended to define clean-up or 

action levels. 

MRLs are derived for hazardous substances using the no-observed-adverse-effect level/uncertainty factor 

approach. They are below levels that might cause adverse health effects in the people most sensitive to 

such chemical-induced effects. MRLs are derived for acute (1–14 days), intermediate (15–364 days), and 

chronic (365 days and longer) durations and for the oral and inhalation routes of exposure. Currently, 

MRLs for the dermal route of exposure are not derived because ATSDR has not yet identified a method 

suitable for this route of exposure. MRLs are generally based on the most sensitive chemical-induced end 

point considered to be of relevance to humans. Serious health effects (such as irreparable damage to the 

liver or kidneys, or birth defects) are not used as a basis for establishing MRLs. Exposure to a level 

above the MRL does not mean that adverse health effects will occur. 

MRLs are intended only to serve as a screening tool to help public health professionals decide where to 

look more closely. They may also be viewed as a mechanism to identify those hazardous waste sites that 

are not expected to cause adverse health effects. Most MRLs contain a degree of uncertainty because of 
ACROLEIN A-2 

APPENDIX A 

the lack of precise toxicological information on the people who might be most sensitive (e.g., infants, 

elderly, nutritionally or immunologically compromised) to the effects of hazardous substances. ATSDR 

uses a conservative (i.e., protective) approach to address this uncertainty consistent with the public health 

principle of prevention. Although human data are preferred, MRLs often must be based on animal studies 

because relevant human studies are lacking. In the absence of evidence to the contrary, ATSDR assumes 

that humans are more sensitive to the effects of hazardous substance than animals and that certain persons 

may be particularly sensitive. Thus, the resulting MRL may be as much as 100-fold below levels that 

have been shown to be nontoxic in laboratory animals. 

Proposed MRLs undergo a rigorous review process: Health Effects/MRL Workgroup reviews within the 

Division of Toxicology and Environmental Medicine, expert panel peer reviews, and agency-wide MRL 

Workgroup reviews, with participation from other federal agencies and comments from the public. They 

are subject to change as new information becomes available concomitant with updating the toxicological 

profiles. Thus, MRLs in the most recent toxicological profiles supersede previously published levels. 

For additional information regarding MRLs, please contact the Division of Toxicology and 

Environmental Medicine, Agency for Toxic Substances and Disease Registry, 1600 Clifton Road NE, 

Mailstop F-32, Atlanta, Georgia 30333. 
ACROLEIN A-3 

APPENDIX A 

MINIMAL RISK LEVEL (MRL) WORKSHEET 

Chemical Name: Acrolein 

CAS Number: 107-02-8 

Date: July 2007 

Profile Status: Post Public, Final 

Route: [X] Inhalation [ ] Oral 

Duration: [X] Acute [ ] Intermediate [ ] Chronic 

Graph Key: 4 

Species: Human 

Minimal Risk Level: 0.003 [ ] mg/kg/day [X] ppm 

Reference: Weber-Tschopp A, Fischer T, Gierer R, et al. 1977. [Experimental irritating effects of 

acrolein on man.] Int Arch Occup Environ Health 40:117-130. (German) 

Experimental design: Forty-six volunteers (21 men, 25 women) were placed into an exposure chamber in 

groups of 3 and exposed to 0.3 ppm acrolein for 60 minutes. At 5-minute intervals during exposure, 

participants used a questionnaire to score the level of eye, nose, and throat irritation as 1 (not at all), 2 (a 

little), 3 (medium), and 4 (strong). In each exposure group, blink rate was observed in two of the 

three participants, while breathing rate was measured in the third participant. There was no control group 

or statistical analysis. 

In another experiment reported in Weber-Tschopp et al. (1977), volunteers were exposed to a gradually 

increasing concentration of acrolein for 40 minutes. As acrolein levels rose from 0 to 0.6 ppm over a 

35-minute period, participants subjectively scored irritancy at 5-minute intervals as described previously. 

At the end of 35 minutes, volunteers were exposed for 5 additional minutes at 0.6 ppm. The LOAEL for 

nose irritation of 0.26 ppm had an average score between 1 and 2 and was statistically significant relative 

to controls. A NOAEL of 0.17 ppm was identified, which was not statistically different from controls. 

However, the changing concentrations of acrolein make it difficult to fix the duration or level of exposure 

that was actually responsible for the onset of noticeable irritation. 

Effects noted in study and corresponding doses: Intensity of nose irritation reached a maximum mean 

score of 2 (a little) at approximately 40 minutes into the exposure, with no change through the remaining 

20 minutes. Intensity of throat irritation reached a maximum mean score of between 1 (not at all) and 2 (a 

little) at approximately 40 minutes into the exposure, with no increase in intensity scores for the 

remaining 20 minutes. Intensity of nose and throat irritation was scored significantly higher than preexposure values beginning at 10 minutes. A 20% decrease in respiratory rate was also observed, 

compared to pre-exposure values. Controls from the dynamic concentration experiment reported mean 

scores that were very close to 1 (not at all) for the entire 40-minute test. 

Dose and end point used for MRL derivation: LOAEL of 0.3 ppm; decrease in respiratory rate, nose and 

throat irritation. 

[ ] NOAEL [X] LOAEL 
ACROLEIN A-4 

APPENDIX A 

Uncertainty Factors used in MRL derivation: 

[X] 10 for use of a LOAEL 

[ ] 10 for extrapolation from animals to humans 

[X] 10 for human variability 

Was a conversion used from ppm in food or water to a mg/body weight dose? No. 

If an inhalation study in animals, list the conversion factors used in determining human equivalent dose: 

Not applicable. 

Other additional studies or pertinent information which lend support to this MRL: Cassee et al. (1996) 

exposed 5–6 rats to acrolein vapor levels of 0.25, 0.67, and 1.4 ppm, 6 hours/day for 3 consecutive days. 

The most sensitive response was mild necrosis, dysplasia, and desquamation of nasal epithelium in rats 

exposed to 0.25 ppm. Statistically significant cellular proliferation was also observed at 0.25 ppm. 

Aranyi et al. (1986) reported reduced bactericidal activity of the respiratory tract in mice following acute 

acrolein inhalation exposures. Significantly lower alveolar macrophagic clearance of a 3-hour Klebsiella. 

pneumoniae infection was observed following a 5-day exposure to 0.1 ppm acrolein in mice. This 

exposure represents the lowest LOAEL identified for inhalation exposure to acrolein. Treated mice 

removed 77% of bacteria from their lungs, while controls removed 84%. Though statistically significant, 

it is not clear what, if any, significance for pathogenicity this difference has on secondary bacterial 

infections following acrolein exposures. No difference was observed in rats for this same exposure/ 

infection protocol (Sherwood et al. 1986). The Cassee et al. (1996) study provides a clinically objective 

measure of nasal irritation in rats; however, the derived LOAEL (0.25 ppm) was very similar to the 

human LOAEL (0.3 ppm) from Weber-Tschopp et al. (1977). This being the case, the human-derived 

data are preferable for the basis for the MRL, eliminating the introduction of uncertainty from interspecies extrapolation. 

Agency Contacts (Chemical Managers): Nickolette Roney, Jessilynn Taylor, and Annette Ashizawa 
ACROLEIN A-5 

APPENDIX A 

MINIMAL RISK LEVEL (MRL) WORKSHEET 

Chemical Name: Acrolein 

CAS Number: 107-02-8 

Date: July 2007 

Profile Status: Post Public, Final 

Route: [X] Inhalation [ ] Oral 

Duration: [ ] Acute [X] Intermediate [ ] Chronic 

Graph Key: 31 

Species: Rat 

Minimal Risk Level: 0.00004 [ ] mg/kg/day [X] ppm 

Reference: Feron VJ, Kruysse A, Til HP, et al. 1978. Repeated exposure to acrolein vapour: Subacute 

studies in hamsters, rats and rabbits. Toxicology 9:47-58. 

Experimental design: Groups of 12 rats, 20 hamsters, and 4 rabbits were exposed to 0, 0.4, 1.4, and 

4.9 ppm acrolein, 6 hours/day, 5 days/week for 13 weeks. General clinical observations were made daily. 

Body weights and food consumption was recorded weekly. Hematological and serum chemistry 

measurements were taken at week 12. After euthanasia of animals, organs were removed, weighed, and 

fixed for histological analysis. 

Effects noted in study and corresponding doses: Nasal metaplasia occurred in rats at 0.4 ppm. At 

1.4 ppm, rats exhibited squamous epithelia metaplasia, rabbits exhibited decreases in body weight gains, 

and hamsters exhibited nasal inflammation. At 4.9 ppm, all species exhibited necrotizing rhinitis. Rats 

exhibited increased heart and kidney weight, tracheal and bronchiolar metaplasia, and lung edema and 

hemorrhage, and death. Hamsters exhibited increased kidney and heart weight. 

Dose and end point used for MRL derivation: LOAEL of 0.4 ppm; nasal epithelial metaplasia in rats. In 

Feron et al. (1978), the authors did not report incidence data for inhalation effects. Therefore, benchmark 

dose analysis could not be performed. 

[ ] NOAEL [X] LOAEL 

Uncertainty Factors used in MRL derivation: 

[X] 10 for use of a LOAEL 

[X] 3 for extrapolation from animals to humans using dosimetric adjustments 

[X] 10 for human variability 

Was a conversion used from ppm in food or water to a mg/body weight dose? No. 

If an inhalation study in animals, list the conversion factors used in determining human equivalent dose: 

Duration adjusted LOAEL (LOAELADJ) = 0.4 ppm x 6/24 hours x 5/7 days = 0.071 ppm 
ACROLEIN A-6 

APPENDIX A 

Regional gas dose ratio for the extrathoracic region (RGDRER) for a category 1 gas = 

⎡ V&

E ⎤
 ⎢

⎣

⎡

⎥

⎦

⎤

⎥

⎦

R 

H 

= 0.17

SAET 

V&

E 

SAET 

RGDR =
 ET 

⎢

⎣
 

Where: 

Ve is the minute volume and SAET is the surface area of the extrathoracic (ET) region of the 

respiratory tract. 

Minute volume (Ve) 

Human: 13.8 L/minute (EPA 1994b) 

Rat: 0.16 L/minute; calculated using the following EPA (1994b), reference erroneously uses 

common logarithm in calculations) equation: 

 ln(Ve) = b0 + b1ln(BW) 

For rats, b0 equals -0.578 and b1 equals 0.821 and a body weight of 0.217 kg (EPA 1988b). 

EPA (1994b) rat and human respiratory surface area reference values: 

Extrathoracic 15.0 cm2

 (rat) 200 cm2 (human) 

LOAELHEC = LOAELADJ x RGDR = 0.071 ppm x 0.17 = 0.012 ppm 

Other additional studies or pertinent information which lend support to this MRL: In Feron et al. (1978), 

the rat appeared to be the most sensitive species, exhibiting more severe histological changes across the 

respiratory tract than the other species. In other studies, exposures to acrolein concentrations between 

0.4 and 5.0 ppm for up to 180 days caused a continuum of histological alterations, inflammation, and 

severe tissue destruction across the entire respiratory tract of rats, rabbits, guinea pigs, and monkeys. 

Several similar effects were observed throughout the respiratory tract and across species in the 1–2-ppm 

exposure level, including nasal epithelial inflammation in hamsters (Feron et al. 1978), tracheal 

hyperplasia in monkeys (Lyon et al. 1970), bronchiolar inflammation in rats (Kutzman et al. 1985), and 

lung hyperplasia and inflammation in rats (Costa et al. 1986; Lyon et al. 1970). Effects in the deeper 

respiratory tract became more severe at the 3–5-ppm exposure levels. Effects included tracheal epithelial 

metaplasia in hamsters (Feron et al. 1978), epithelial dysplasia in rats (Leach et al. 1987), squamous lung 

epithelial metaplasia in rats (Kutzman et al. 1985), tracheal metaplasia and bronchial necrosis in rats 

(Feron et al. 1978; Kutzman et al. 1985), pulmonary edema in rats (Costa et al. 1986), and lung 

hemorrhage in monkeys (Lyon et al. 1970). The Feron et al. (1978) study was chosen as the critical study 

since it provided the lowest LOAEL of 0.4 ppm for nasal epithelial metaplasia, the most sensitive effect. 

Agency Contacts (Chemical Managers): Nickolette Roney, Jessilynn Taylor, and Annette Ashizawa 
ACROLEIN A-7 

APPENDIX A 

MINIMAL RISK LEVEL (MRL) WORKSHEET 

Chemical Name: Acrolein 

CAS Number: 107-02-8 

Date: July 2007 

Profile Status: Post Public, Final 

Route: [ ] Inhalation [X] Oral 

Duration: [ ] Acute [X] Intermediate [ ] Chronic 

Graph Key: 16 

Species: Mouse 

Minimal Risk Level: 0.004 [X] mg/kg/day [ ] ppm 

Reference: NTP. 2006. NTP technical report on the comparative toxicity studies of allyl acetate, allyl 

alcohol, and acrolein administered by gavage to F344/N rats and B6C3F1 mice (Tox report #48). 

National Toxicology Program. 

Experimental design: Groups of 10 rats/sex/dose were administered 0.75, 1.25, 2.5, 5, and 10 mg/kg/day 

by gavage for 14 weeks, while groups of 10 mice/sex/dose were given 1.25, 2.5, 5, 10, and 20 mg/kg for 

the same duration. Dose volumes were 5 mL/kg for rats and 10 mL/kg for mice. 

Effects noted in study and corresponding doses: Common high-dose effects were observed for both 

species, including hemorrhage and necrosis, and forestomach and glandular stomach lesions. Rats 

receiving 10 mg/kg/day exhibited abnormal breathing, nasal discharge, and death. The lowest LOAEL 

observed was 2.5 mg/kg/day for forestomach squamous epithelial hyperplasia in male mice and female 

rats and mice, with an associated NOAEL of 1.25 mg/kg/day. In male rats, the lowest LOAEL observed 

was 5 mg/kg/day with an associated NOAEL of 2.5 mg/kg/day. Mice exhibited no clinical signs of 

toxicity. Glandular stomach lesions appeared in rats and mice given 10 and 20 mg/kg/day, respectively. 

Liver weights were significantly increased in female rats and male mice given 5 and 10 mg/kg/day, 

respectively. 

Squamous epithelial hyperplasia of the forestomach was the most sensitive end point observed in both 

rats and mice. However, the lowest LOAEL for this end point in rats was identified only in females, 

whereas the same LOAEL for this end point was identified in both sexes of mice. Combining the male 

and female mouse incidence data provided increased statistical sensitivity for data analysis. The 

incidences of this end point in mice (NTP 2006) are shown in Table A-1. 
ACROLEIN A-8 

APPENDIX A 

Table A-1. Incidences of Forestomach Squamous Epithelial Hyperplasia in Male 

and Female Mice Given Daily Doses of Acrolein by Oral Gavage for 14 Weeks 

Sex Control 

Daily gavage doses (mg/kg/day) 

1.25 2.5 5 10 20 

Mice 

Male 

Female 

Rats 

0/10 

0/10 

2/10 

0/10 

6/10a 

4/10b

 7/10a

 7/10a

 10/10a

 8/10a

 0/10 

2/10 

Female 1/10 3/10 5/10a

 8/10a 10/10a –c 

a

Significantly different from controls (p≤0.01) by Fisher exact test. b

Significantly different from controls (p≤0.05) by Fisher exact test. c

– = Not available 

Source: NTP 2006 

All dichotomous models in the Benchmark Dose Software (BMDS version 1.3.2) were fit to the 

combined incidence data for squamous epithelial hyperplasia in the forestomach of male and female mice 

and female rats. The highest dose (20 mg/kg/day) was dropped from the analysis of lesion incidences in 

mice in order to achieve an adequate fit of the models to the data. Exclusion of the 20 mg/kg/day group 

from the BMD analysis is appropriate, since all of the animals exhibited frank glandular stomach toxicity 

and died during the first week of exposure. The lower 95% confidence limit (BMDL10) of a 10% extra 

risk (BMD10) for forestomach squamous epithelial hyperplasia was selected as the benchmark response 

for the point of departure. For female rats, the Quantal Quadratic model provided the best fit as assessed 

by a chi-square goodness-of-fit test and the Akaike’s Information Criteria (AIC), giving a BMDL10 of 

0.88 mg/kg/day (Table A-2, Figure A-1). For mice, the Quantal Linear model provided the best fit 

(Table A-3), providing a BMDL10 of 0.36 mg/kg/day (Table A-3, Figure A-2). Forestomach hyperplasia 

in mice was chosen as the critical effect instead of the same effect in female rats because both sexes of 

mice exhibited significantly higher incidences of this lesion, compared to controls, and because the 

BMDL10 for mice was lower than that of female rats, thus being more health protective. The BMDL10 

value of 0.36 mg/kg/day, derived from the Quantal Linear model, was selected as the point of departure 

for calculating an intermediate-duration oral MRL. 
ACROLEIN A-9 

APPENDIX A 

Table A-2. BMD Modeling of the Incidence of Squamous Epithelial Hyperplasia of
 

the Forestomach in Female F-344/N Rats Exposed to Acrolein 

via Gavage for 14 Weeks: Goodness-of-fit Criteria 

for Applied Models 

Model AIC pa BMD10 BMDL10 

Gamma 42.7965 0.7397 0.8675 0.3596 

Logistic 45.6249 0.3914 1.1363 0.7697 

Log-Logistic 43.1105 0.6959 0.9318 0.4954 

Multistage 43.1919 0.7116 0.7244 0.3043 

Probit 45.2424 0.4178 1.0874 0.7478 

Log-probit 42.6336 0.7483 0.9531 0.5409 

Quantal-linear 43.6493 0.6863 0.3652 0.2551 

Quantal-quadratic 42.0101 0.5245 1.0881 0.8778 

Weibull 42.941 0.7375 0.7963 0.3440 

a

Values <0.1 fail to meet conventional goodness-of-fit criteria. 

AIC = Akaike’s Information Criteria; BMD = benchmark dose; BMDL = lower confidence limit (95%) on the 

benchmark dose; NA = not applicable; p = p value from the Chi-squared test; 

Source: NTP 2006 
ACROLEIN A-10 

APPENDIX A 

Figure A-1. Benchmark Dose Model Results for the Incidences of Squamous 

Epithelial Hyperplasia in the Forestomach of Female F344/N Rats Given 

Daily Gavage Doses of Acrolein for 14 Weeks 

Quantal Quadratic Model with 0.95 Confidence Level 

1 

0.8 

0.6 

0.4 

0.2 

0 

dose 

13:35 05/24 2007 

Source: NTP 2006 

BMDL BMD 

Quantal Quadratic 

BMD Lower Bound 

0 2 4 6 8 10 

Fraction Affected 
ACROLEIN A-11 

APPENDIX A 

Table A-3. BMD Modeling of the Incidence of Squamous Epithelial Hyperplasia 

of the Forestomach in Male and Female B6C3F1 Mice Exposed to Acrolein via 

Gavage for 14 Weeks: Goodness-of-fit Criteria for Applied Models 

Model AIC pa BMD10 BMDL10 

Gamma 84.4571 0.5301 0.7791 0.3813 

Logistic 92.7143 0.0224 NA NA 

Log-Logistic 83.4164 0.7490 0.9800 0.5061 

Multistage 85.1092 0.4483 0.5470 0.3680 

Probit 93.2507 0.0193 NA NA 

Log-probit 83.3748 0.7575 1.0151 0.6617 

Quantal-linear 83.3634 0.6011 0.4736 0.3635 

Quantal-quadratic 93.4813 0.0017 NA NA 

Weibull 84.6961 0.4978 0.6851 0.3761 

a

Values <0.1 fail to meet conventional goodness-of-fit criteria. 

AIC = Akaike’s Information Criteria; BMD = benchmark dose; BMDL = lower confidence limit (95%) on the 

benchmark dose; NA = not applicable; p = p value from the Chi-squared test 

Source: NTP 2006 
ACROLEIN A-12 

APPENDIX A 

Figure A-2. Benchmark Dose Model Results for the Combined Incidences of 

Squamous Epithelial Hyperplasia in the Forestomach of Male and Female 

B6C3F1 Mice Given Daily Gavage Doses of Acrolein for 14 Weeks
 

Quantal Linear Model with 0.95 Confidence Level 

Fraction Affected 

Quantal Linear 

1 

BMD Lower Bound 

0.8 

0.6 

0.4 

0.2 

0 

BMDL BMD 

0 2 4 6 8 10 

dose 

11:42 01/24 2007 

Source: NTP 2006 

Dose and end point used for MRL derivation: BMDL10 of 0.36 mg/kg/day; forestomach squamous 

epithelial hyperplasia in mice. 

[ ] NOAEL [ ] LOAEL [X] BMDL10 

Uncertainty Factors used in MRL derivation: 

[ ] 10 for use of a LOAEL 

[X] 10 for extrapolation from animals to humans 

[X] 10 for human variability 

Was a conversion used from ppm in food or water to a mg/body weight dose? No. 

If an inhalation study in animals, list the conversion factors used in determining human equivalent dose: 

Not applicable. 
ACROLEIN A-13 

APPENDIX A 

Other additional studies or pertinent information which lend support to this MRL: Gastric ulceration was 

observed in rats given an acute gavage doses of 25 mg/kg (Sakata et al. 1989) and in rabbits given 

4 mg/kg/day for 12 days (Parent et al. 1993). Gastric ulceration was also seen in rats given intermediateduration doses of 5.4 mg/kg/day for 115 days (King 1984). Vomiting was also observed in a chronic 

gavage study in which dogs were given 0.1 mg/kg/day (Parent et al. 1992b). Epithelial hyperplasia is a 

sensitive end point for nasal effects of acrolein inhalation as seen in rats receiving 1.4 ppm for 62 days 

(Costa et al. 1986) and in dogs exposed to 3.7 ppm for 6 weeks (Lyon et al. 1970). Forestomach 

squamous epithelial hyperplasia represented the lowest identified LOAEL in a well-designed study. 

Agency Contacts (Chemical Managers): Nickolette Roney, Jessilynn Taylor, and Annette Ashizawa 
ACROLEIN A-14 

APPENDIX A 

This page is intentionally blank. 
ACROLEIN	 B-1 

APPENDIX B. USER'S GUIDE 

Chapter 1 

Public Health Statement 

This chapter of the profile is a health effects summary written in non-technical language. Its intended 

audience is the general public, especially people living in the vicinity of a hazardous waste site or 

chemical release. If the Public Health Statement were removed from the rest of the document, it would 

still communicate to the lay public essential information about the chemical. 

The major headings in the Public Health Statement are useful to find specific topics of concern. The 

topics are written in a question and answer format. The answer to each question includes a sentence that 

will direct the reader to chapters in the profile that will provide more information on the given topic. 

Chapter 2 

Relevance to Public Health 

This chapter provides a health effects summary based on evaluations of existing toxicologic, 

epidemiologic, and toxicokinetic information. This summary is designed to present interpretive, weightof-evidence discussions for human health end points by addressing the following questions: 

1.	 What effects are known to occur in humans? 

2. What effects observed in animals are likely to be of concern to humans? 

3. What exposure conditions are likely to be of concern to humans, especially around hazardous 

waste sites? 

The chapter covers end points in the same order that they appear within the Discussion of Health Effects 

by Route of Exposure section, by route (inhalation, oral, and dermal) and within route by effect. Human 

data are presented first, then animal data. Both are organized by duration (acute, intermediate, chronic). 

In vitro data and data from parenteral routes (intramuscular, intravenous, subcutaneous, etc.) are also 

considered in this chapter. 

The carcinogenic potential of the profiled substance is qualitatively evaluated, when appropriate, using 

existing toxicokinetic, genotoxic, and carcinogenic data. ATSDR does not currently assess cancer 

potency or perform cancer risk assessments. Minimal Risk Levels (MRLs) for noncancer end points (if 

derived) and the end points from which they were derived are indicated and discussed. 

Limitations to existing scientific literature that prevent a satisfactory evaluation of the relevance to public 

health are identified in the Chapter 3 Data Needs section. 

Interpretation of Minimal Risk Levels 

Where sufficient toxicologic information is available, ATSDR has derived MRLs for inhalation and oral 

routes of entry at each duration of exposure (acute, intermediate, and chronic). These MRLs are not 

meant to support regulatory action, but to acquaint health professionals with exposure levels at which 

adverse health effects are not expected to occur in humans. 
ACROLEIN B-2 

APPENDIX B 

MRLs should help physicians and public health officials determine the safety of a community living near 

a chemical emission, given the concentration of a contaminant in air or the estimated daily dose in water. 

MRLs are based largely on toxicological studies in animals and on reports of human occupational 

exposure. 

MRL users should be familiar with the toxicologic information on which the number is based. Chapter 2, 

"Relevance to Public Health," contains basic information known about the substance. Other sections such 

as Chapter 3 Section 3.9, "Interactions with Other Substances,” and Section 3.10, "Populations that are 

Unusually Susceptible" provide important supplemental information. 

MRL users should also understand the MRL derivation methodology. MRLs are derived using a 

modified version of the risk assessment methodology that the Environmental Protection Agency (EPA) 

provides (Barnes and Dourson 1988) to determine reference doses (RfDs) for lifetime exposure. 

To derive an MRL, ATSDR generally selects the most sensitive end point which, in its best judgement, 

represents the most sensitive human health effect for a given exposure route and duration. ATSDR 

cannot make this judgement or derive an MRL unless information (quantitative or qualitative) is available 

for all potential systemic, neurological, and developmental effects. If this information and reliable 

quantitative data on the chosen end point are available, ATSDR derives an MRL using the most sensitive 

species (when information from multiple species is available) with the highest no-observed-adverse-effect 

level (NOAEL) that does not exceed any adverse effect levels. When a NOAEL is not available, a 

lowest-observed-adverse-effect level (LOAEL) can be used to derive an MRL, and an uncertainty factor 

(UF) of 10 must be employed. Additional uncertainty factors of 10 must be used both for human 

variability to protect sensitive subpopulations (people who are most susceptible to the health effects 

caused by the substance) and for interspecies variability (extrapolation from animals to humans). In 

deriving an MRL, these individual uncertainty factors are multiplied together. The product is then 

divided into the inhalation concentration or oral dosage selected from the study. Uncertainty factors used 

in developing a substance-specific MRL are provided in the footnotes of the levels of significant exposure 

(LSE) tables. 

Chapter 3 

Health Effects 

Tables and Figures for Levels of Significant Exposure (LSE) 

Tables and figures are used to summarize health effects and illustrate graphically levels of exposure 

associated with those effects. These levels cover health effects observed at increasing dose 

concentrations and durations, differences in response by species, MRLs to humans for noncancer end 

points, and EPA's estimated range associated with an upper- bound individual lifetime cancer risk of 1 in 

10,000 to 1 in 10,000,000. Use the LSE tables and figures for a quick review of the health effects and to 

locate data for a specific exposure scenario. The LSE tables and figures should always be used in 

conjunction with the text. All entries in these tables and figures represent studies that provide reliable, 

quantitative estimates of NOAELs, LOAELs, or Cancer Effect Levels (CELs). 

The legends presented below demonstrate the application of these tables and figures. Representative 

examples of LSE Table 3-1 and Figure 3-1 are shown. The numbers in the left column of the legends 

correspond to the numbers in the example table and figure. 
ACROLEIN	 B-3 

APPENDIX B 

LEGEND 

See Sample LSE Table 3-1 (page B-6) 

(1) Route of Exposure. One of the first considerations when reviewing the toxicity of a substance 

using these tables and figures should be the relevant and appropriate route of exposure. Typically 

when sufficient data exist, three LSE tables and two LSE figures are presented in the document. 

The three LSE tables present data on the three principal routes of exposure, i.e., inhalation, oral, 

and dermal (LSE Tables 3-1, 3-2, and 3-3, respectively). LSE figures are limited to the inhalation 

(LSE Figure 3-1) and oral (LSE Figure 3-2) routes. Not all substances will have data on each 

route of exposure and will not, therefore, have all five of the tables and figures. 

(2) Exposure Period. Three exposure periods—acute (less than 15 days), intermediate (15– 

364 days), and chronic (365 days or more)—are presented within each relevant route of exposure. 

In this example, an inhalation study of intermediate exposure duration is reported. For quick 

reference to health effects occurring from a known length of exposure, locate the applicable 

exposure period within the LSE table and figure. 

(3) Health Effect. The major categories of health effects included in LSE tables and figures are 

death, systemic, immunological, neurological, developmental, reproductive, and cancer. 

NOAELs and LOAELs can be reported in the tables and figures for all effects but cancer. 

Systemic effects are further defined in the "System" column of the LSE table (see key number 

18). 

(4) Key to Figure. Each key number in the LSE table links study information to one or more data 

points using the same key number in the corresponding LSE figure. In this example, the study 

represented by key number 18 has been used to derive a NOAEL and a Less Serious LOAEL 

(also see the two "18r" data points in sample Figure 3-1). 

(5) Species. The test species, whether animal or human, are identified in this column. Chapter 2, 

"Relevance to Public Health," covers the relevance of animal data to human toxicity and 

Section 3.4, "Toxicokinetics," contains any available information on comparative toxicokinetics. 

Although NOAELs and LOAELs are species specific, the levels are extrapolated to equivalent 

human doses to derive an MRL. 

(6) Exposure Frequency/Duration. The duration of the study and the weekly and daily exposure 

regimens are provided in this column. This permits comparison of NOAELs and LOAELs from 

different studies. In this case (key number 18), rats were exposed to “Chemical x” via inhalation 

for 6 hours/day, 5 days/week, for 13 weeks. For a more complete review of the dosing regimen, 

refer to the appropriate sections of the text or the original reference paper (i.e., Nitschke et al. 

1981). 

(7) System. This column further defines the systemic effects. These systems include respiratory, 

cardiovascular, gastrointestinal, hematological, musculoskeletal, hepatic, renal, and 

dermal/ocular. "Other" refers to any systemic effect (e.g., a decrease in body weight) not covered 

in these systems. In the example of key number 18, one systemic effect (respiratory) was 

investigated. 

(8) NOAEL. A NOAEL is the highest exposure level at which no harmful effects were seen in the 

organ system studied. Key number 18 reports a NOAEL of 3 ppm for the respiratory system, 

which was used to derive an intermediate exposure, inhalation MRL of 0.005 ppm (see 

footnote "b"). 
ACROLEIN	 B-4 

APPENDIX B 

(9) LOAEL. A LOAEL is the lowest dose used in the study that caused a harmful health effect. 

LOAELs have been classified into "Less Serious" and "Serious" effects. These distinctions help 

readers identify the levels of exposure at which adverse health effects first appear and the 

gradation of effects with increasing dose. A brief description of the specific end point used to 

quantify the adverse effect accompanies the LOAEL. The respiratory effect reported in key 

number 18 (hyperplasia) is a Less Serious LOAEL of 10 ppm. MRLs are not derived from 

Serious LOAELs. 

(10) Reference. The complete reference citation is given in Chapter 9 of the profile. 

(11) CEL. A CEL is the lowest exposure level associated with the onset of carcinogenesis in 

experimental or epidemiologic studies. CELs are always considered serious effects. The LSE 

tables and figures do not contain NOAELs for cancer, but the text may report doses not causing 

measurable cancer increases. 

(12) Footnotes. Explanations of abbreviations or reference notes for data in the LSE tables are found 

in the footnotes. Footnote "b" indicates that the NOAEL of 3 ppm in key number 18 was used to 

derive an MRL of 0.005 ppm. 

LEGEND 

See Sample Figure 3-1 (page B-7) 

LSE figures graphically illustrate the data presented in the corresponding LSE tables. Figures help the 

reader quickly compare health effects according to exposure concentrations for particular exposure 

periods. 

(13) Exposure Period. The same exposure periods appear as in the LSE table. In this example, health 

effects observed within the acute and intermediate exposure periods are illustrated. 

(14) Health Effect. These are the categories of health effects for which reliable quantitative data 

exists. The same health effects appear in the LSE table. 

(15)	 Levels of Exposure. Concentrations or doses for each health effect in the LSE tables are 

graphically displayed in the LSE figures. Exposure concentration or dose is measured on the log 

scale "y" axis. Inhalation exposure is reported in mg/m3

 or ppm and oral exposure is reported in 

mg/kg/day. 

(16) NOAEL. In this example, the open circle designated 18r identifies a NOAEL critical end point in 

the rat upon which an intermediate inhalation exposure MRL is based. The key number 18 

corresponds to the entry in the LSE table. The dashed descending arrow indicates the 

extrapolation from the exposure level of 3 ppm (see entry 18 in the table) to the MRL of 

0.005 ppm (see footnote "b" in the LSE table). 

(17) CEL. Key number 38m is one of three studies for which CELs were derived. The diamond 

symbol refers to a CEL for the test species-mouse. The number 38 corresponds to the entry in the 

LSE table. 
ACROLEIN	 B-5 

APPENDIX B 

(18)	 Estimated Upper-Bound Human Cancer Risk Levels. This is the range associated with the upperbound for lifetime cancer risk of 1 in 10,000 to 1 in 10,000,000. These risk levels are derived 

from the EPA's Human Health Assessment Group's upper-bound estimates of the slope of the 

cancer dose response curve at low dose levels (q1*). 

(19)	 Key to LSE Figure. The Key explains the abbreviations and symbols used in the figure. 
SAMPLE 

1 → Table 3-1. Levels of Significant Exposure to [Chemical x] – Inhalation 

LOAEL (effect) Exposure 

Key to frequency/ NOAEL Less serious Serious (ppm)

figurea Species duration System (ppm) (ppm) Reference 

2 → INTERMEDIATE EXPOSURE 

5 6 7 8 9 

3 → Systemic ↓ ↓ ↓ ↓ ↓

3b 18 Rat 13 wk Resp 10 (hyperplasia) 

4 → 5 d/wk

6 hr/d 

CHRONIC EXPOSURE Cancer 11

↓

38 Rat 18 mo 20 

5 d/wk7 hr/d 

39 Rat 89–104 wk 10 

5 d/wk6 hr/d 

40 Mouse 79–103 wk 10 

5 d/wk6 hr/d 

(CEL, multiple organs) (CEL, lung tumors, nasal tumors)(CEL, lung tumors, hemangiosarcomas) 

10

↓

Nitschke et al. 1981 Wong et al. 1982 NTP 1982 NTP 1982 

12 → a The number corresponds to entries in Figure 3-1. b Used to derive an intermediate inhalation Minimal Risk Level (MRL) of 5x10-3 ppm; dose adjusted for intermittent exposure and divided 

by an uncertainty factor of 100 (10 for extrapolation from animal to humans, 10 for human variability). 

ACROLEIN B-6 

APPENDIX B 
ACROLEIN B-7 

APPENDIX B 
ACROLEIN B-8 

APPENDIX B 

This page is intentionally blank. 
ACROLEIN C-1 

APPENDIX C. ACRONYMS, ABBREVIATIONS, AND SYMBOLS 

ACGIH American Conference of Governmental Industrial Hygienists 

ACOEM American College of Occupational and Environmental Medicine 

ADI acceptable daily intake 

ADME absorption, distribution, metabolism, and excretion 

AED atomic emission detection 

AFID alkali flame ionization detector 

AFOSH Air Force Office of Safety and Health 

ALT alanine aminotransferase 

AML acute myeloid leukemia 

AOAC Association of Official Analytical Chemists 

AOEC Association of Occupational and Environmental Clinics 

AP alkaline phosphatase 

APHA American Public Health Association 

AST aspartate aminotransferase 

atm atmosphere 

ATSDR Agency for Toxic Substances and Disease Registry 

AWQC Ambient Water Quality Criteria 

BAT best available technology 

BCF bioconcentration factor 

BEI Biological Exposure Index 

BMD benchmark dose 

BMR benchmark response 

BSC Board of Scientific Counselors 

C centigrade 

CAA Clean Air Act 

CAG Cancer Assessment Group of the U.S. Environmental Protection Agency 

CAS Chemical Abstract Services 

CDC Centers for Disease Control and Prevention 

CEL cancer effect level 

CELDS Computer-Environmental Legislative Data System 

CERCLA Comprehensive Environmental Response, Compensation, and Liability Act 

CFR Code of Federal Regulations 

Ci curie 

CI confidence interval 

CL ceiling limit value 

CLP Contract Laboratory Program 

cm centimeter 

CML chronic myeloid leukemia 

CPSC Consumer Products Safety Commission 

CWA Clean Water Act 

DHEW Department of Health, Education, and Welfare 

DHHS Department of Health and Human Services 

DNA deoxyribonucleic acid 

DOD Department of Defense 

DOE Department of Energy 

DOL Department of Labor 

DOT Department of Transportation 

DOT/UN/ Department of Transportation/United Nations/ 

NA/IMCO North America/Intergovernmental Maritime Dangerous Goods Code 
ACROLEIN C-2 

APPENDIX C 

DWEL drinking water exposure level 

ECD electron capture detection 

ECG/EKG electrocardiogram 

EEG electroencephalogram 

EEGL Emergency Exposure Guidance Level 

EPA Environmental Protection Agency 

F Fahrenheit 

F1 first-filial generation 

FAO Food and Agricultural Organization of the United Nations 

FDA Food and Drug Administration 

FEMA Federal Emergency Management Agency 

FIFRA Federal Insecticide, Fungicide, and Rodenticide Act 

FPD flame photometric detection 

fpm feet per minute 

FR Federal Register 

FSH follicle stimulating hormone 

g gram 

GC gas chromatography 

gd gestational day 

GLC gas liquid chromatography 

GPC gel permeation chromatography 

HPLC high-performance liquid chromatography 

HRGC high resolution gas chromatography 

HSDB Hazardous Substance Data Bank 

IARC International Agency for Research on Cancer 

IDLH immediately dangerous to life and health 

ILO International Labor Organization 

IRIS Integrated Risk Information System 

Kd adsorption ratio 

kg kilogram 

kkg metric ton 

Koc organic carbon partition coefficient 

Kow octanol-water partition coefficient 

L liter 

LC liquid chromatography 

LC50 lethal concentration, 50% kill 

LCLo lethal concentration, low 

LD50 lethal dose, 50% kill 

LDLo lethal dose, low 

LDH lactic dehydrogenase 

LH luteinizing hormone 

LOAEL lowest-observed-adverse-effect level 

LSE Levels of Significant Exposure 

LT50 lethal time, 50% kill 

m meter 

MA trans,trans-muconic acid 

MAL maximum allowable level 

mCi millicurie 

MCL maximum contaminant level 

MCLG maximum contaminant level goal 

MF modifying factor 
ACROLEIN C-3 

APPENDIX C 

MFO mixed function oxidase 

mg milligram 

mL milliliter 

mm millimeter 

mmHg millimeters of mercury 

mmol millimole 

mppcf millions of particles per cubic foot 

MRL Minimal Risk Level 

MS mass spectrometry 

NAAQS National Ambient Air Quality Standard 

NAS National Academy of Science 

NATICH National Air Toxics Information Clearinghouse 

NATO North Atlantic Treaty Organization 

NCE normochromatic erythrocytes 

NCEH National Center for Environmental Health 

NCI National Cancer Institute 

ND not detected 

NFPA National Fire Protection Association 

ng nanogram 

NHANES National Health and Nutrition Examination Survey 

NIEHS National Institute of Environmental Health Sciences 

NIOSH National Institute for Occupational Safety and Health 

NIOSHTIC NIOSH's Computerized Information Retrieval System 

NLM National Library of Medicine 

nm nanometer 

nmol nanomole 

NOAEL no-observed-adverse-effect level 

NOES National Occupational Exposure Survey 

NOHS National Occupational Hazard Survey 

NPD nitrogen phosphorus detection 

NPDES National Pollutant Discharge Elimination System 

NPL National Priorities List 

NR not reported 

NRC National Research Council 

NS not specified 

NSPS New Source Performance Standards 

NTIS National Technical Information Service 

NTP National Toxicology Program 

ODW Office of Drinking Water, EPA 

OERR Office of Emergency and Remedial Response, EPA 

OHM/TADS Oil and Hazardous Materials/Technical Assistance Data System 

OPP Office of Pesticide Programs, EPA 

OPPT Office of Pollution Prevention and Toxics, EPA 

OPPTS Office of Prevention, Pesticides and Toxic Substances, EPA 

OR odds ratio 

OSHA Occupational Safety and Health Administration 

OSW Office of Solid Waste, EPA 

OTS Office of Toxic Substances 

OW Office of Water 

OWRS Office of Water Regulations and Standards, EPA 

PAH polycyclic aromatic hydrocarbon 
ACROLEIN C-4 

APPENDIX C 

PBPD physiologically based pharmacodynamic 

PBPK physiologically based pharmacokinetic 

PCE polychromatic erythrocytes 

PEL permissible exposure limit 

pg picogram 

PHS Public Health Service 

PID photo ionization detector 

pmol picomole 

PMR proportionate mortality ratio 

ppb parts per billion 

ppm parts per million 

ppt parts per trillion 

PSNS pretreatment standards for new sources 

RBC red blood cell 

REL recommended exposure level/limit 

RfC reference concentration 

RfD reference dose 

RNA ribonucleic acid 

RQ reportable quantity 

RTECS Registry of Toxic Effects of Chemical Substances 

SARA Superfund Amendments and Reauthorization Act 

SCE sister chromatid exchange 

SGOT serum glutamic oxaloacetic transaminase 

SGPT serum glutamic pyruvic transaminase 

SIC standard industrial classification 

SIM selected ion monitoring 

SMCL secondary maximum contaminant level 

SMR standardized mortality ratio 

SNARL suggested no adverse response level 

SPEGL Short-Term Public Emergency Guidance Level 

STEL short term exposure limit 

STORET Storage and Retrieval 

TD50 toxic dose, 50% specific toxic effect 

TLV threshold limit value 

TOC total organic carbon 

TPQ threshold planning quantity 

TRI Toxics Release Inventory 

TSCA Toxic Substances Control Act 

TWA time-weighted average 

UF uncertainty factor 

U.S. United States 

USDA United States Department of Agriculture 

USGS United States Geological Survey 

VOC volatile organic compound 

WBC white blood cell 

WHO World Health Organization 
ACROLEIN C-5 

APPENDIX C 

> greater than ≥ greater than or equal to 

= equal to 

< less than ≤ less than or equal to 

% percent α alpha β beta γ gamma δ delta μm micrometer μg microgram q1 

* cancer slope factor 

– negative 

+ positive 

(+) weakly positive result 

(–) weakly negative result 
ACROLEIN C-6 

APPENDIX C 

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ACROLEIN D-1 

APPENDIX D. INDEX 

absorbed dose..............................................................................................................................................84 

active transport...................................................................................................................................... 77, 79 

adrenals .......................................................................................................................................................69 

adsorption..................................................................................................................................................121 

aerobic....................................................................................................................... 108, 123, 124, 125, 137 

ambient air ........................................................................ 108, 111, 122, 126, 134, 136, 137, 138, 139, 148 

anaerobic................................................................................................................................... 123, 124, 137 

bioaccumulation........................................................................................................................................137 

bioavailability ..................................................................................................................................... 91, 137 

bioconcentration factor .............................................................................................................................121 

biodegradation........................................................................................................... 108, 123, 124, 125, 137 

biomarker .............................................................................................................................................. 83, 84 

biomarkers .......................................................................................... 83, 84, 94, 95, 97, 132, 141, 147, 148 

Body Weight Effects....................................................................................................................... 39, 56, 59 

breast milk.................................................................................................................................................133 

cancer .................................................................................................................. 4, 5, 11, 58, 82, 92, 97, 134
 

carcinogen.................................................................................................................................................153 

carcinogenic .............................................................................................. 13, 19, 41, 58, 63, 70, 90, 92, 153 

carcinogenicity........................................................................................................ 5, 10, 41, 58, 59, 92, 153 

cardiovascular ............................................................................................................... 37, 42, 54, 59, 97, 98
 

cardiovascular effects................................................................................................................ 37, 54, 59, 97 

chromosomal aberrations ............................................................................................................................92 

clearance ................................................................................................................................. 13, 39, 97, 134 

death.................................................................................................... 10, 12, 13, 16, 19, 20, 41, 90, 92, 153 

deoxyribonucleic acid (see DNA)...............................................................................................................66 

dermal effects............................................................................................................................ 35, 56, 60, 91 

DNA (see deoxyribonucleic acid)................................................................... 10, 63, 65, 66, 67, 84, 95, 149 

endocrine............................................................................................................................. 38, 42, 59, 80, 81 

endocrine effects .........................................................................................................................................38 

fetus.............................................................................................................................................................81 

gastrointestinal effects .......................................................................................................................... 12, 54 

general population................................................................................... 9, 83, 111, 130, 131, 132, 134, 153 

genotoxic......................................................................................................................................... 19, 63, 67 

genotoxicity..................................................................................................................................... 63, 67, 92 

groundwater .............................................................................................. 111, 124, 127, 129, 134, 137, 138 

half-life................................................................................................................................ 84, 108, 121, 122 

hematological effects ............................................................................................................................ 37, 55 

Hepatic Effects...................................................................................................................................... 38, 55 

hydrolysis............................................................................................................................................ 72, 123 

hydroxyl radical ................................................................................................................................ 108, 122 

immune system ..................................................................................................................................... 39, 93 

immunological .............................................................................................................. 19, 39, 40, 57, 62, 93
 

immunological effects......................................................................................................... 39, 40, 57, 62, 93
 

Kow .................................................................................................................................................... 102, 121 

LD50................................................................................................................................................. 41, 59, 68 

Metabolic Effects........................................................................................................................................55 

Musculoskeletal Effects ..............................................................................................................................55 

neurobehavioral...........................................................................................................................................81 

neurotransmitter ..........................................................................................................................................40 
ACROLEIN D-2 

APPENDIX D 

nuclear............................................................................................................................................... 144, 146 

ocular effects....................................................................................................................... 11, 39, 42, 56, 62 

pharmacodynamic.......................................................................................................................................75 

pharmacokinetic.................................................................................................................. 75, 76, 77, 91, 93 

pharmacokinetics ............................................................................................................................ 82, 83, 91 

photolysis .......................................................................................................................................... 122, 124 

placenta .......................................................................................................................................................93 

rate constant ...................................................................................................................................... 122, 124 

Renal Effects......................................................................................................................................... 38, 56 

retention ......................................................................................................................................................68 

solubility ...................................................................................................................................................121 

toxicokinetic.......................................................................................................................................... 19, 85 

toxicokinetics ..............................................................................................................................................96 

tumors ............................................................................................................................................. 41, 58, 63 

vapor phase ....................................................................................................................................... 104, 121 

vapor pressure ........................................................................................................................... 121, 122, 148 

volatility ....................................................................................................................................................122 

volatilization ............................................................................................. 108, 113, 119, 121, 122, 123, 137