TOXICOLOGICAL PROFILE FOR
 

PROPYLENE GLYCOL
 

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
 

Public Health Service
 

Agency for Toxic Substances and Disease Registry
 

September 1997 
 

PROPYLENE GLYCOL ii 

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. 
 


 


 


 


 


 


 

PROPYLENE GLYCOL iii 

UPDATE STATEMENT
 

A Technical Report for propylene glycol was released in May 1993. This edition supersedes any 

previously released draft or final profile or report. 

Toxicological profiles are revised and republished as necessary, but no less than once every three years. 

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
 
PROPYLENE GLYCOL iv 

This page is intentionally blank. 

vi 

*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). Section 

211 of SARA also amended Title 10 of the U. S. Code, creating the Defense Environmental 

Restoration Program. Section 2704(a) of Title 10 of the U. S. Code directs the Secretary of Defense 

to notify the Secretary of Health and Human Services of not less than 25 of the most commonly found 

unregulated hazardous substances at defense facilities. Section 2704(b) of Title 10 of the U. S. Code 

directs the Administrator of the Agency for Toxic Substances and Disease Registry (ATSDR) to 

prepare a toxicological profile for each substance on the list provided by the Secretary of Defense 

under subsection (b). 

 


 


 


 

	 

	 

	 

	 

PROPYLENE GLYCOL vii 

CONTRIBUTORS 

CHEMICAL MANAGER(S)/AUTHOR(S): 

Ed Murray, Ph.D.
 

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

Julia George, Ph.D.
 

Research Triangle Institute, Research Triangle Park, NC
 

THE PROFILE HAS UNDERGONE THE FOLLOWING ATSDR INTERNAL REVIEWS: 

1.	 Green Border Review. Green Border review assures consistency with ATSDR policy. 

2.	 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. 

3.	 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. 

4.	 Quality Assurance Review. The Quality Assurance Branch assures that consistency 

across profiles is maintained, identifies any significant problems in format or content, 

and establishes that Guidance has been followed. 
PROPYLENE GLYCOL viii 

This page is intentionally blank. 
 

 

 

 

 


 

	 

	 

	 

PROPYLENE GLYCOL ix 

PEER REVIEW
 

A peer review panel was assembled for propylene glycol. The panel consisted of the following members: 

1.	 Dr. Gregory Grauer, Associate Professor, Department of Clinical Sciences, College of Veterinary 

Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado; 

2.	 Dr. Philip Leber, Private Consultant, Chem-Tox Consulting, Akron, Ohio; and 

3.	 Dr. Kenneth McMartin, Professor, Department of Pharmacology and Therapeutics, Section of 

Toxicology, Louisiana State University Medical Center, Shreveport, Louisiana. 

These experts collectively have knowledge of propylene glycol’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. 
PROPYLENE GLYCOL x 

This page is intentionally blank. 
 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 

PROPYLENE GLYCOL xi 

CONTENTS
 

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

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

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

CONTRIBUTORS......................................................................................................................................vii
 

PEER REVIEW ...........................................................................................................................................ix
 

CONTENTS.................................................................................................................................................xi
 

LIST OF FIGURES ....................................................................................................................................xv
 

LIST OF TABLES....................................................................................................................................xvii
 

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

1.1 WHAT IS PROPYLENE GLYCOL?.............................................................................................1
 

1.2 WHAT HAPPENS TO PROPYLENE GLYCOL WHEN IT ENTERS THE 

ENVIRONMENT...........................................................................................................................2
 

1.3 HOW MIGHT I BE EXPOSED TO PROPYLENE GLYCOL?....................................................2
 

1.4 HOW CAN PROPYLENE GLYCOL ENTER AND LEAVE MY BODY?.................................3
 

1.5 HOW CAN PROPYLENE GLYCOL AFFECT MY HEALTH?..................................................3
 

1.6 ARE THERE MEDICAL TESTS TO DETERMINE WHETHER I HAVE BEEN 

EXPOSED TO PROPYLENE GLYCOL?.....................................................................................3
 

1.7 WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT MADE TO 

PROTECT HUMAN HEALTH? ...................................................................................................4
 

1.8 WHERE CAN I GET MORE INFORMATION? ..........................................................................4
 

2. HEALTH EFFECTS................................................................................................................................7
 

2.1 INTRODUCTION..........................................................................................................................7
 

2.2 DISCUSSION OF HEALTH EFFECTS BY ROUTE OF EXPOSURE .......................................7
 

2.2.1 Inhalation Exposure ................................................................................................................9
 

2.2.1.1 Death................................................................................................................................9
 

2.2.1.2 Systemic Effects...............................................................................................................9
 

2.2.1.3 Immunological and Lymphoreticular Effects................................................................15
 

2.2.1.4 Neurological Effects ......................................................................................................16
 

2.2.1.5 Reproductive Effects......................................................................................................16
 

2.2.1.6 Developmental Effects...................................................................................................16
 

2.2.1.7 Genotoxic Effects...........................................................................................................16
 

2.2.1.8 Cancer............................................................................................................................17
 

2.2.2 Oral Exposure........................................................................................................................17
 

2.2.2.1 Death..............................................................................................................................17
 

2.2.2.2 Systemic Effects.............................................................................................................17
 

2.2.2.3 Immunological and Lymphoreticular Effects................................................................27
 

2.2.2.4 Neurological Effects ......................................................................................................28
 

2.2.2.5 Reproductive Effects......................................................................................................29
 

2.2.2.6 Developmental Effects...................................................................................................29
 

2.2.2.7 Genotoxic Effects...........................................................................................................30
 

2.2.2.8 Cancer............................................................................................................................30
 

2.2.3 Dermal Exposure...................................................................................................................30
 

2.2.3.1 Death..............................................................................................................................31
 

2.2.3.2 Systemic Effects.............................................................................................................31
 

2.2.3.3 Immunological and Lymphoreticular Effects................................................................37
 

2.2.3.4 Neurological Effects ......................................................................................................38
 

2.2.3.5 Reproductive Effects......................................................................................................39
 

 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 

PROPYLENE GLYCOL xii 

2.2.3.6 Developmental Effects...................................................................................................39
 

2.2.3.7 Genotoxic Effects...........................................................................................................39
 

2.2.3.8 Cancer............................................................................................................................39
 

2.3 TOXICOKINETICS.....................................................................................................................40
 

2.3.1 Absorption.............................................................................................................................40
 

2.3.1.1 Inhalation Exposure .......................................................................................................40
 

2.3.1.2 Oral Exposure ................................................................................................................40
 

2.3.1.3 Dermal Exposure ...........................................................................................................40
 

2.3.2 Distribution ...........................................................................................................................41
 

2.3.2.1 Inhalation Exposure .......................................................................................................41
 

2.3.2.2 Oral Exposure ................................................................................................................42
 

2.3.2.3 Dermal Exposure ...........................................................................................................42
 

2.3.3 Metabolism............................................................................................................................42
 

2.3.4 Excretion ...............................................................................................................................44
 

2.3.4.1 Inhalation Exposure .......................................................................................................44
 

2.3.4.2 Oral Exposure ................................................................................................................44
 

2.3.4.3 Dermal Exposure ...........................................................................................................44
 

2.3.5 Mechanism of Action............................................................................................................44
 

2.4 RELEVANCE TO PUBLIC HEALTH........................................................................................45
 

2.5 BIOMARKERS OF EXPOSURE AND EFFECT .......................................................................51
 

2.5.1 Biomarkers Used to Identify or Quantify Exposure to Propylene Glycol.............................53
 

2.5.2 Biomarkers Used to Characterize Effects Caused by Propylene Glycol...............................53
 

2.6 INTERACTIONS WITH OTHER CHEMICALS .......................................................................54
 

2.7 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE..................................................54
 

2.8 METHODS FOR REDUCING TOXIC EFFECTS......................................................................55
 

2.8.1 Reducing Peak Absorption Following Exposure ..................................................................55
 

2.8.2 Reducing Body Burden.........................................................................................................55
 

2.8.3 Interfering with the Mechanism of Action for Toxic Effects................................................56
 

2.9 ADEQUACY OF THE DATABASE ..........................................................................................56
 

2.9.1 Existing Information on Health Effects of Propylene Glycol ...............................................56
 

2.9.2 Identification of Data Needs .................................................................................................58
 

2.9.3 Ongoing Studies....................................................................................................................65
 

3. CHEMICAL AND PHYSICAL INFORMATION................................................................................66
 

3.1 CHEMICAL IDENTITY..............................................................................................................67
 

3.2 PHYSICAL AND CHEMICAL PROPERTIES...........................................................................67
 

4. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL............................................................71
 

4.1 PRODUCTION ............................................................................................................................ 71
 

4.2 IMPORT/EXPORT ......................................................................................................................71
 

4.3 USE ..............................................................................................................................................72
 

4.4 DISPOSAL...................................................................................................................................73
 

5. POTENTIAL FOR HUMAN EXPOSURE ...........................................................................................75
 

5.1 OVERVIEW.................................................................................................................................75
 

5.2 RELEASES TO THE ENVIRONMENT.....................................................................................75
 

5.2.1 Air .........................................................................................................................................77
 

5.2.2 Water.....................................................................................................................................77
 

5.2.3 Soil ........................................................................................................................................78
 

5.3 ENVIRONMENTAL FATE ........................................................................................................78
 

5.3.1 Transport and Partitioning.....................................................................................................78
 
 

 

 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 

PROPYLENE GLYCOL xiii 

5.3.2 Transformation and Degradation ..........................................................................................79
 

5.3.2.1 Air..................................................................................................................................79
 

5.3.2.2 Water..............................................................................................................................79
 

5.3.2.3 Sediment and Soil ..........................................................................................................80
 

5.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT....................................80
 

5.4.1 Air .........................................................................................................................................80
 

5.4.2 Water.....................................................................................................................................80
 

5.4.3 Sediment and Soil .................................................................................................................81
 

5.4.4 Other Environmental Media..................................................................................................81
 

5.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE..........................................82
 

5.6 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES ................................................82
 

5.7 ADEQUACY OF THE DATABASE ..........................................................................................82
 

5.7.1 Identification of Data Needs .................................................................................................83
 

5.7.2 Ongoing Studies....................................................................................................................86
 

6. ANALYTICAL METHODS..................................................................................................................87
 

6.1 BIOLOGICAL MATERIALS......................................................................................................87
 

6.2 ENVIRONMENTAL SAMPLES ................................................................................................90
 

6.3 ADEQUACY OF THE DATABASE ..........................................................................................92
 

6.3.1 Identification of Data Needs .................................................................................................92
 

6.3.2 Ongoing Studies....................................................................................................................93
 

7. REGULATIONS AND ADVISORIES .................................................................................................94
 

8. REFERENCES ......................................................................................................................................98
 

9. GLOSSARY ........................................................................................................................................137
 

APPENDICES 

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

B. USER’S GUIDE.................................................................................................................................. B-1
 

C. ACRONYMS, ABBREVIATIONS, AND SYMBOLS...................................................................... C-1
 
PROPYLENE GLYCOL xiv 

This page is intentionally blank. 
 

 


 


 


 


 


 


 

PROPYLENE GLYCOL xv 

LIST OF FIGURES
 

2-1. Levels of Significant Exposure to Propylene Glycol – Inhalation ..................................................... 12
 

2-2. Levels of Significant Exposure to Propylene Glycol – Oral .............................................................. 22
 

2-3. Propylene Glycol Metabolism in Mammals.......................................................................................43
 

2-4. Existing Information on Health Effects of Propylene Glycol.............................................................57
 

5-1. Frequency of NPL Sites with Propylene Glycol Comtamination.......................................................76
 
PROPYLENE GLYCOL xvi 

This page is intentionally blank. 
 

 

 

 


 


 


 


 


 


 


 


 


 


 

PROPYLENE GLYCOL xvii 

LIST OF TABLES
 

2-1. Levels of Significant Exposure to Propylene Glycol – Inhalation ..................................................... 10
 

2-2. Levels of Significant Exposure to Propylene Glycol – Oral .............................................................. 18
 

2-3. Levels of Significant Exposure to Propylene Glycol – Dermal.......................................................... 32
 

2-4. Genotoxicity of Propylene Glycol In Vitro ........................................................................................52
 

3-1. Chemical Identity of Propylene Glycol ..............................................................................................68
 

3-2. Physical and Chemical Properties of Propylene Glycol .....................................................................69
 

6-1. Analytical Methods for Determining Propylene Glycol in Biological Samples.................................88
 

6-2. Analytical Methods for Determining Propylene Glycol in Environmental Samples .........................91
 

7-1. Regulations and Guidelines Applicable to Propylene Glycol ............................................................96
 
PROPYLENE GLYCOL xviii 

This page is intentionally blank. 
 

 

 


 

PROPYLENE GLYCOL 1 

1. PUBLIC HEALTH STATEMENT
 

This statement was prepared to give you information about propylene glycol and to emphasize 

the human health effects that may result from exposure to it. The Environmental Protection 

Agency (EPA) has identified 1,416 hazardous waste sites as the most serious in the nation. 

These sites make up the National Priorities List (NPL) and are the sites targeted for long-term 

federal clean-up activities. Propylene glycol has been identified in at least 5 of the 1,416 NPL 

sites. 

When a chemical is released from a large source, such as an industrial plant, or from a container, 

such as a drum or bottle, it enters the environment as a chemical emission. This emission, which 

is also called a release, does not always lead to exposure. You can be exposed to a chemical 

only when you come into contact with the chemical. You may be exposed to it in the 

environment by breathing, eating, or drinking substances containing the chemical or from skin 

contact with it. 

If you are exposed to a hazardous chemical such as ethylene glycol, several factors will 

determine whether harmful health effects will occur and what the type and severity of those 

health effects will be. These factors include the dose (how much), the duration (how long), the 

route or pathway by which you are exposed (breathing, eating, drinking, or skin contact), the 

other chemicals to which you are exposed, and your individual characteristics such as age, sex, 

nutritional status, family traits, lifestyle, and state of health. 

1.1 WHAT IS PROPYLENE GLYCOL? 

Propylene glycol is a synthetic liquid substance that absorbs water. Propylene glycol is also used 

to make polyester compounds, and as a base for de-icing solutions. Propylene glycol is used by 

the chemical, food, and pharmaceutical industries as an antifreeze when leakage might lead to 

contact with food. The Food and Drug Administration (FDA) has classified propylene glycol as 

an additive that is “generally recognized as safe” for use in food. It is used to absorb extra water 

and maintain moisture in certain medicines, cosmetics, or food products. It is a solvent for food 
 

 

 

 

 

 

 

PROPYLENE GLYCOL 2 

1. PUBLIC HEALTH STATEMENT 

colors and flavors, and in the paint and plastics industries. Propylene glycol is also used to 

create artificial smoke or fog used in fire-fighting training and in theatrical productions. Other 

names for propylene glycol are 1,2-dihydroxypropane, 1,2-propanediol, methyl glycol, and 

trimethyl glycol. 

Propylene glycol is clear, colorless, slightly syrupy liquid at room temperature. It may exist in 

air in the vapor form, although propylene glycol must be heated or briskly shaken to produce a 

vapor. Propylene glycol is practically odorless and tasteless. 

For more information on the sources, properties, and uses of propylene glycol, see Chapters 3 

and 4. 

1.2 WHAT HAPPENS TO PROPYLENE GLYCOL WHEN IT ENTERS THE 

ENVIRONMENT 

Waste streams from the manufacture of propylene glycol are primarily responsible for the 

releases into the air, water, and soil. Propylene glycol can enter the environment when it is used 

as a runway and aircraft de-icing agent. Propylene glycol can also enter the environment through 

the disposal of products that contains it. It is not likely to exist in large amounts in the air. We 

have little information about what happens to propylene glycol in the air. The small amounts 

that may enter the air are likely to break down quickly. If it escapes into the air, it will take 

between 24 and 50 hours for half the amount released to break down. Propylene glycol can mix 

completely with water and can soak into soil. It can break down relatively quickly (within 

several days to a week) in surface water and in soil. Propylene glycol can also travel from 

certain types of food packages into the food in the package. See Chapters 4 and 5 for more 

information on propylene glycol in the environment. 

1.3 HOW MIGHT I BE EXPOSED TO PROPYLENE GLYCOL? 

Propylene glycol has been approved for use at certain levels in food, cosmetics, and 

pharmaceutical products. If you eat food products, use cosmetics, or take medicines that contain 

it, you will be exposed to propylene glycol, but these amounts are not generally considered 
 

 

 

 

 

PROPYLENE GLYCOL 3 

1. PUBLIC HEALTH STATEMENT 

harmful. People who work in industries that use propylene glycol may be exposed by touching 

these products or inhaling mists from spraying them. These exposures tend to be at low levels, 

however. Propylene glycol is used to make artificial smoke and mists for fire safety training, 

theatrical performances, and rock concerts. These artificial smoke products may also be used by 

private citizens. These products are frequently used in enclosed spaces, where exposure may be 

more intense. 

See Chapter 5 for more information on exposure to propylene glycol. 

1.4 HOW CAN PROPYLENE GLYCOL ENTER AND LEAVE MY BODY? 

Propylene glycol can enter your bloodstream if you breathe air containing mists or vapors from 

either compound. It can also enter your bloodstream through your skin if you come in direct 

contact with it and do not wash it off. If you eat products that contain propylene glycol, it may 

enter your bloodstream. Exposure of the general population to propylene glycol is likely since 

many foods, drugs, and cosmetics contain it. 

Propylene glycol breaks down in the body in about 48 hours. However, studies of people and 

animals show that if you have repeated eye, skin, nasal, or oral exposures to propylene glycol for 

a short time, you may develop some irritation. 

1.5 HOW CAN PROPYLENE GLYCOL AFFECT MY HEALTH? 

Propylene glycol breaks down at the same rate as ethylene glycol, although it does not form 

harmful crystals when it breaks down. Frequent skin exposure to propylene glycol can 

sometimes irritate the skin. 

1.6 ARE THERE MEDICAL TESTS TO DETERMINE WHETHER I HAVE BEEN 

EXPOSED TO PROPYLENE GLYCOL? 

Propylene glycol is generally considered to be a safe chemical, and is not routinely tested for, 

unless specific exposure, such as to a medicine or cosmetic, can be linked with the observed bad 
 

 

 

PROPYLENE GLYCOL 4 

1. PUBLIC HEALTH STATEMENT 

symptoms. Since propylene glycol breaks down very quickly in the body, it is very difficult to 

detect. Refer to Chapters 2 and 6 for more information on these tests. 

1.7 WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT MADE TO 

PROTECT HUMAN HEALTH? 

The government has developed regulations and guidelines for propylene glycol. These are 

designed to protect the public from potential adverse health effects. 

The Food and Drug Administration (FDA) has classified propylene glycol as “generally 

recognized as safe,” which means that it is acceptable for use in flavorings, drugs, and cosmetics, 

and as a direct food additive. According to the World Health Organization, the acceptable 

dietary intake of propylene glycol is 25 mg of propylene glycol for every kilogram (kg) of body 

weight. For more information on the regulations and guidelines that apply to propylene glycol, 

see Chapter 7. 

1.8 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. 

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 
 

 

 

 

 

 

 

 

 

 

 

 

 


 


 


 


 


 

PROPYLENE GLYCOL 5 

1. PUBLIC HEALTH STATEMENT 

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/
 
 

PROPYLENE GLYCOL 6 

1. PUBLIC HEALTH STATEMENT 

This page is intentionally blank. 
 

 

 

 

 

 

 

 

 

 

 

 

PROPYLENE GLYCOL 7 

2. HEALTH EFFECTS 

2.1 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 of the toxicology of propylene glycol 

and a depiction of significant exposure levels associated with various adverse health effects. It contains 

descriptions and evaluations of studies and presents levels of significant exposure for propylene glycol 

based on toxicological studies and epidemiological investigations. 

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

The general population may be exposed to propylene glycol. Propylene glycol is designated as a 

Generally Recognized As Safe (GRAS) additive by the Food and Drug Administration (FDA) and is 

widely used in commercial formulations of foods, drugs, and cosmetics (Morshed et al. 1988). Propylene 

glycol is used as a de-icer, and in heat transfer fluids. It is also an ingredient of many products that are 

used to produce artificial smoke or mist for theatrical productions, fire safety training, or rock concerts. 

Oral exposure to the small amounts of propylene glycol found in foods and drugs is unlikely to cause 

toxic effects. Dermal exposure to propylene glycol, through cosmetics or drugs, or inhalation of synthetic 

smoke or mist, may be more frequently associated with reported reactions. Propylene glycol induces 

remarkably fewer adverse effects in both humans and animals than does ethylene glycol. Data describing 

either human or animal effects after exposure to propylene glycol were not as prevalent as those found for 

ethylene glycol. Human data came from case reports of clinical studies, adverse reactions to medical 

treatment, or accidental exposure. Animal data generally support those effects, or lack thereof, observed 

in humans. 

2.2 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 or other areas where they may be exposed to propylene glycol, the information in 

this section is organized by chemical, and then by health effect-death, systemic, immunological and 

lymphoreticular, 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). 
 

 

 

 

PROPYLENE GLYCOL 8 

2. HEALTH EFFECTS 

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 judgement 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. These distinctions are intended to help the users of this document identify 

the levels of exposure at which adverse health effects start to appear. LOAELs or NOAELs should also 

help to determine whether or not the effects vary with dose and/or duration, and place into perspective the 

possible significance of these differences 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 or other sites of exposure may want information on 

levels of exposure associated with more subtle effects in humans or animals or exposure levels below 

which no adverse effects 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. 

Estimates of exposure levels posing minimal risk to humans (Minimal Risk Levels or MRLs) have been 

made for both ethylene glycol and propylene glycol. 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 target organs(s) of effect or the most sensitive health effects(s) for a specific duration 

within a given route of exposure. MRLs are based on noncancer health effects only and do not reflect a 

consideration of carcinogenic effects. MRLs can be derived for 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 
 

 

 

 

 

 

 

PROPYLENE GLYCOL 9 

2. HEALTH EFFECTS 

1988; EPA 1990a), 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 result from repeated acute insuhs, 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. 

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. 

2.2.1 Inhalation Exposure 

Information regarding health effects of propylene glycol following inhalation exposure is limited. No 

studies of health effects in humans were found. Studies in animals were few (Konradova et al. 1978; 

Robertson et al. 1947; Suber et al. 1989). 

2.2.1.1 Death 

No studies were located regarding death in humans following inhalation exposure to propylene glycol. 

Twenty-nine monkeys were continuously exposed to propylene glycol vapor over a period of 13 months, 

at doses of 32-112 ppm (doses not further specified) (Robertson et al. 1947). Thirteen of the monkeys 

died or were killed when ill during the course of the experiment (Robertson et al. 1947). Based on the 

relative lack of data in the literature, it is unlikely that sufficient amounts of propylene glycol would be 

present or inhaled near hazardous waste sites to cause death among people living in the area. The 

LOAEL value from the study by Robertson et al. (1947) for death in monkeys after inhalation exposure to 

propylene glycol is recorded in Table 2-1 and plotted Figure 2-1. 

2.2.1.2 Systemic Effects 

No studies were located regarding respiratory, cardiovascular, gastrointestinal, hematological, 

musculoskeletal, hepatic, renal, endocrine, dermal, ocular, body weight, or metabolic effects in humans, 

or cardiovascular, musculoskeletal, dermal, ocular, or metabolic effects in animals after inhalation 

exposure to propylene glycol. The highest NOAEL values and all reliable LOAEL values for systemic 

effects in each species and duration category for propylene glycol after inhalation exposure are reported 

in Table 2-1 and plotted in Figure 2-1. 
TABLE 2-1. Levels of Significant Exposureto Propylene Glycol -Inhalation 

Key toa 

figure 

Speciesl 

(strain) 

Exposurel 

durationl 

frequency System 

NOAEL 

(ppm) 

Less serious 

(ppm) 

LOAEL 

Serious 

(ppm) Reference 

-0 

:;xJ 

o 

-0 

-< 

rm 

Z 

INTERMEDIATE EXPOSURE m 

G) 

1 

Systemic 

Rat 90 d Resp 51 b (nasal hemorrhaging) Suber etal. 1989 

!< 

n 

o 

r­

(Sprague­ 5 d/wk 

Dawley) 6 hr/d 

Hemato 51 F 321 i= (decreased white blood 

cells, and lymphocytes 

in females) 

51 M 321 M (decreased sorbitol 

dehydrogenase, gamma 

glutamyl transferase) 

Hepatic 707 

Renal 51 321 (decreased kidney 

BdWt 51 F 

weight) 

321 F (decreased body weight) 

!'-' 

::r: 

m 

» Immunological/Lymphoreticular !::i 

::r: 

2 Rat 90 d 707 Suber et al. 1989 m 

(Sprague 5 d/wk "

" m Dawley) 6 hr/d 9 

CHRONIC EXPOSURE 

Systemic 

3 Monkey 

(Macacus 

13 mo 

continuous 

Resp 112 Robertson et al. 

1947 

Rhesus) 

Gastro 112 

Hemato 112 (increased hemoglobin) 

Hepatic 112 

Renal 112 

Endocr 112 

Bd Wt 112 

-'" 

o 
-------------

TABLE 2-1. Levels of Significant Exposure to Propylene Glycol -Inhalation (continued) 

-0 

LOAEL :;xJ

Exposurel o 

Key toa Speciesl durationl NOAEL Less serious Serious -0 

figure (strain) frequency System (ppm) (ppm) (ppm) Reference .­

-< 

m 

Z 

m 

Gl 

4 Rat 18 mo Resp 112 	 Robertson et al. ~ continuous 	 1947 () (NS) o

.­ Hepatic 112 


Renal 112 


Bd Wt 112M 	 (50% increase in body 


weight) 


Immunolog ical/Lymp horeticular 

5 Monkey 13 mo 112 	 Robertson et al. 


1947
 (Macacus continuous 


Rhesus) 


6 Rat 18 mo. 	 112 Robertson et al.

1947 continuous (NS) 	 !'-' 

::r: 

Reproductive m 

» 

!:j 7 Rat 18 mo 112 	 Robertson et al ::r: 1947 (NS) continuous 	 m 

." 

." 

9 

m 

aThe number corresponds to in entries Figure 2-2. 

b Used to derive an intermediate inhalation minimal risk level (MRL) of 0.009 ppm; LOAEL divided an by uncertainty factor of 1,000 (10 for extrapolation from animals to humans, 10 for use of a 

LOAEL, and 10 for human variability) and multiplied by 6/24 and 517 to adjust for intermittent of 6 exposure hours/day, 5 days/week. 

Bd Wt =body weight;d =day(s); Endocr= endocrine; F = female; Gastro= gastrointestinal;Hemato = hematological;hr = hour(s); LOAEL= lowest-observable-adverse-effect level; M= 


male; mo = month(s); NOAEL= no-observable-adverse-effectlevel; NS = notspecified;Resp =respiratory;wk = week(s) 


~ 

~ 
(ppm) 

1000 

Figure 2-1. Levels of Significant Exposure to Propylene Glycol - Inhalation 

Intermediate (15-364 days) 

::-., .il' 

::-.,6$ !<9 

Systemic 

~ 

~ ~;z;.(jj 

!'!'§.~~ .#""'~ ;>,..0 ill q;.6'> !f§ ~~ 

~t:j {;:'li 

~ 

!1i 

~q !is­ 0<::' ~ 0'lS> 

<Q 

#if

,~..:}.~ 

ir 

0 

0 

ir ir 

0 

ir 

o 

o 

2r 

-0 

:;0 

o 

-0 

, 

-<

m 

Z 

m 

G) 

!< 

() 

o, 

100 ir 

o 

ir 

0 

ir 

0 

ir 

o 

!'" 

10 

~ !:i

::r: 

$ 

~ 

1 

0.1 Key 

0.01 

I 

~ 

r rat 

k monkey 

o LOAEL for less serious effects (animals) I 

I 

o NOAEl (animals) • I 

The number next to each point corresponds to entries In Table 2-2. 

I 

\.!J 

Minimal risk level . 

for effects other 

than cancer 

0.001 

I-" 

N 
:;lj Figure 2-1. levels of Significant Exposure to Propylene Glycol -Inhalation (continued) 	 '"0 

o 

~ Chronic (~365 days) 	 .­

m 

Z 

m 

CD 

Systemic 	 ~ 

8.­ .~ ~ (ji 	 ~ ~~ :l:- ~CJ.o~ .~0 ~ ~ o ~ (J" ~0<A .~ ~O 0 ~0.@ i:} &flj ,:;

',l,Qj 	 ~ i§' ~ 0 B - ~o rb' 	 rb' ~ OV ~~ if &0 (ppm) . r,,« 	 ~ ~~ rlJ<$" ~-Q. 0<;;' <vt::-"f3 	 <Q0 ,{:'..j.{:' <#'«

1000 <tP o ~ ~ 

3k 4r 3k 	 3k 3k 4r 3k 4r 3k 3k 4r 5k 6r 7r 

0 0 0 	 () 0 0 0 0 0 0 0 0 0 0 100 I­

:x: '" 

m 

10 l-	 ~ m 

." 

" 

~ 

1 

0.1 

Key 

r rat. o LOAEL for less serious effects (animals) I Minimal risk level 

k monkey 	 . I 

o NOAEL (animals) 	 I for effects other 0.01 I than cancer 

The number next to each point corresponds to entries in Table 2-2. \.!...I 

0.001 

I--' 

UJ 
 

 

 

 

 

 

 

 

 

 

PROPYLENE GLYCOL 14 

2. HEALTH EFFECTS 

Respiratory Effects. Studies assessing adverse respiratory effects after acute or intermediate 

inhalation exposure of animals to propylene glycol are inconclusive. The effects of acute inhalation 

exposure to 10% concentrations of propylene glycol for 20 and 120 minutes in rabbits showed an 

increased number of degenerated goblet cells in tracheal lining (Konradova et al. 1978). However, the 

observations made in rats after an intermediate inhalation exposure to propylene glycol did not support 

those findings. Rats which inhaled 321 ppm of propylene glycol over 90 days had thickened respiratory 

epithelium with enlarged goblet cells (Suber et al. 1989). Nasal hemorrhaging was also present in rats 

exposed to a lower dose of 51 ppm propylene glycol, probably caused by dehydration. In rhesus monkeys 

and rats, continuous exposure to concentrations of propylene glycol up to 112 ppm for 13-18 months 

caused no adverse effects on the respiratory system (Robertson et al. 1947). These studies do not indicate 

a basis for concern because comparable exposure conditions do not occur for the general population. 

Gastrointestinal Effects. In rhesus monkeys and rats, continuous exposure to air concentrations of 

propylene glycol up to 112 ppm for 13-18 months caused no adverse effects on the gastrointestinal 

system (Robertson et al. 1947). 

Hematological Effects. Limited information was available on hematological effects of propylene 

glycol. The results from animal studies indicate that intermediate and chronic exposure to propylene 

glycol may lead to hemolysis of red blood cells (RBC). After intermediate inhalation exposure to 

321 ppm propylene glycol, female rats had decreased white blood cell (WBC) counts, while exposure to 

707 ppm of propylene glycol caused decreased mean corpuscular hemoglobin concentrations and white 

blood cell counts; no dose-related changes in RBCs were observed in male rats under the same regimen 

(Suber et al. 1989). In rhesus monkeys, continuous exposure to concentrations of propylene glycol in air 

up to 112 ppm for 13 months caused increased hemoglobin counts compared to the control animals 

(Robertson et al. 1947). These results indicate that there may, be species differences with regard to the 

effect of propylene glycol on red blood cells. 

Hepatic Effects. The results from animal studies show that there are no adverse hepatic effects in rats 

after intermediate inhalation exposure to 707 ppm of propylene glycol (Suber et al. 1989). In rhesus 

monkeys and rats continuous exposure to air concentrations of propylene glycol up to 112 ppm for 13­

18 months caused no adverse effects on the hepatic system (Robertson et al. 1947). Based on these 

findings, it can be assumed that chronic exposures to moderately high levels of propylene glycol will not 

have adverse hepatic effects in humans. It is not clear if hepatotoxicity would result after an acute 
 

 

 

 

 

 

 

 

 

PROPYLENE GLYCOL 15 

2. HEALTH EFFECTS 

exposure to a high level of propylene glycol. Since levels of propylene glycol in the vicinity of a 

hazardous waste site would probably be low, it is unlikely that propylene glycol would induce adverse 

hepatic effects in people living in the area. 

Renal Effects. Intermediate inhalation exposure of rats to 707 ppm propylene glycol did not cause 

adverse renal effects (Suber et al. 1989), although kidney weight was reduced at 321 ppm in males and 

females. In rhesus monkeys and rats, continuous exposure to concentrations of propylene glycol up to 

112 ppm for 13-18 months caused no adverse effects on the renal system (Robertson et al. 1947). These 

results indicate that exposure to low levels of propylene glycol that may be present at hazardous waste 

sites is not likely to cause adverse renal effects in the human population living in the vicinity. 

Endocrine Effects. In rhesus monkeys and rats, continuous exposure to concentrations of propylene 

glycol up to 112 ppm for 13-18 months caused no adverse effects on the endocrine system (Robertson et 

al. 1947). 

Body Weight Effects. Rhesus monkeys continuously exposed to air concentrations of propylene 

glycol up to 112 ppm for 13 months exhibited no adverse body weight effects, whereas rats exposed for 

18 months under the same conditions exhibited a 50% decrease in body weight (Robertson et al. 1947). 

Intermediate inhalation exposure of female rats to 321 ppm caused decreased body weight (Suber et al. 

1989). 

2.2.1.3 Immunological and Lymphoreticular Effects 

No studies were located specifically regarding adverse immunological effects in humans or animals after 

inhalation exposure to propylene glycol. 

Twenty-nine monkeys were continuously exposed to propylene glycol vapor over a period of 13 months, 

at doses of 32-112 ppm (Robertson et al. 1947). There was no effect on the spleen. Similarly, rats exposed 

to 55-112 ppm propylene glycol vapor continuously for 18 months showed no effect on the spleen 

(Robertson et al. 1947). Young, healthy adult Sprague-Dawley rats divided into 4 groups of 19 males and 

19 females each. Three groups were exposed for 5 days per week, 6 hours per day for 13 weeks by noseonly inhalation to mean target aerosol concentrations of 5 1, 321, or 707 ppm propylene glycol, 

respectively (Suber et al. 1989). The fourth group (control group) was exposed to humidified, filtered 

room air. There was no effect on spleen weight. 
 

 

 

PROPYLENE GLYCOL 16 

2. HEALTH EFFECTS 

The highest NOAEL values and all reliable LOAEL values for immunological and lymphoreticular 

effects in each species and duration category for propylene glycol after inhalation exposure are reported 

in Table 2-1 and plotted in Figure 2-1. 

2.2.1.4 Neurological Effects 

No studies were located regarding neurological effects in humans or animals after inhalation exposure to 

propylene glycol. 

2.2.1.5 Reproductive Effects 

No studies were located regarding reproductive effects in humans after inhalation exposure to propylene 

glycol. 

White rats exposed continuously to a concentration of 55-112 ppm propylene glycol for 18 months 

showed no adverse effects on the ability to produce live young, or on survival of the offspring (Robertson 

et al. 1947). 

The NOAEL value for reproductive effects in rats for the chronic-duration category for propylene glycol 

after inhalation exposure is reported in Table 2-1 and plotted in Figure 2-1. 

2.2.1.6 Developmental Effects 

No studies were located regarding developmental effects in humans or animals after inhalation exposure 

to propylene glycol. 

2.2.1.7 Genotoxic Effects 

No studies were located regarding in viva genotoxic effects in humans or animals after inhalation 

exposure to propylene glycol. 

Genotoxicity studies are discussed in Section 2.4. 
 

 

 

 

 

 

PROPYLENE GLYCOL 17 

2. HEALTH EFFECTS 

2.2.1.8 Cancer 

No studies were located regarding cancer effects in humans or animals after inhalation exposure to 

propylene glycol. 

2.2.2 Oral Exposure 

Propylene glycol is a clear, practically odorless and tasteless liquid that is slightly syrupy at room 

temperature. Oral exposure to propylene glycol occurs through ingestion of foods, since propylene glycol 

is approved for use as a food additive. Ingestion by humans is not frequently associated with adverse 

effects. 

2.2.2.1 Death 

No studies were located regarding death in humans after oral exposure to propylene glycol. 

Oral LD50 values have been reported in rats (range, 8-46 g/kg), mice (range, 25-32 g/kg), and guinea pigs 

(range, 18-20 g/kg) after acute oral exposure to propylene glycol (Clark et al. 1979; EPA 1 987a; Ruddick 

1972). Male Wistar rats (6/group) were orally dosed with saline or 2,942 mg/kg/day , propylene glycol in 

water for 10, 20, or 30 days (Morshed et al. 1991a). No death was observed. A fatal case of propylene 

glycol poisoning occurred in a horse given 3.8 L (7,904 mg/kg) of propylene glycol instead of mineral oil. 

The horse died of respiratory arrest 28 hours after administration (Dorman and Haschek 1991). It is 

unlikely that sufficient amounts of propylene glycol can be present or ingested near hazardous waste sites 

to cause death among people living in the area. 

The LD50 value for death in rats after acute duration oral exposure to propylene glycol are reported in 

Table 2-2 and plotted in Figure 2-2. 

2.2.2.2 Systemic Effects 

No studies were located regarding respiratory, cardiovascular, gastrointestinal, musculoskeletal, hepatic, 

renal, endocrine, dermal, ocular, or body weight effects in humans, or musculoskeletal, dermal, or ocular 

effects in animals after oral exposure to propylene glycol. The highest NOAEL values and all reliable 

LOAEL values for systemic effects in each species and duration category for propylene glycol after oral 

exposure are reported in Table 2-2 and Figure 2-2. 
TABLE 2-2. Levels of Significant Exposure to Propylene Glycol - Oral 

LOAEL 

Durationl 

Exposurel 

a Key to Speciesl Frequency NOAEL Less Serious Serious 

figure (Strain) (Specific Route) System (mg/kg/day) (mg/kg/day) (mg/kg/day) 

ACUTE EXPOSURE 

Death 

1 Rat once 

22800 F (L0 ) (Fischer 344) (G) 	 50

Systemic 

2 Rat once Gastro 23500 F (hemorrhagic enteritis) 

(Fischer344) (G) 

Hemato 23500 F (lymphocyte depletion) 

Endocr 23500 F (adrenocortical hemorrhage) 

3 Cat 14 d Hemato 3600 	 (reticulocytosis, 

increased Heinz bodies, (NS) (F) 

increased severe 

mechanical fragility) 

Immunological/Lymphoreicular 

3600 (decreased haptoglobin 4 Cat 14d concentrations) (NS) (F) 

Neurological 

5 	 Rat once 22800 F (lethargy and coma) 

(Fischer344) (G) 

Reproductive 

6 Mouse 5d 10000 

(CO-1) 1x1d 

(GW) 

Reference 

Clark et al. 1979 

-0 

;:0 

o 

-0 

-<rm 

Z 

m 

Gl 

s:: 

n 

o 

rClark et al. 1979 

Weiss et al. 1992 

Weiss et al. 1992 

!'.l 

:I: 

m 

» 

!:j 

:I: 

m 

" " m 

Cl 

Vl 

Clark et al. 1979 

Kavlock et al. 1987 

p 

00 
TABLE 2-2. Levels of Significarit Exposure to Propylene Glycol· Oral (continued)· 

LOAEL 

Durationl 

Exposurel 

a Key to Speciesl Frequency NOAEL Less Serious Serious 

figure (Strain) (Specific Route) System (mg/kg/day) (mg/kg/day) (mg/kg/day) 

Developmental 

7 Mouse 5d 10000 

(CD-1) 1x/d 

(GW) 

INTERMEDIATE EXPOSURE 

Systemic 

8 Cat 13wk Hemato 1260 (increased Heinz bodies, 

(F) decreased RBC survival) 

9 Cat 13 wk 

(F) 

Hemato 2750 (increased Heinz bodies, 

increased punctate 

reticulocytes, decreased 

RBC survival) 

10 Cat 5wkD Hemato 1600 (Heinz body formation) 

(F) 

Renal 1600 

11 Cat 3wk Hemato 8000 

(F) 

Renal 8000 (polyuria, polydipsia) 

12 Cat 22-35 d Renal 1600 8000 (polyuria, polydipsia) 

Mongrel (F) 

Metab 1600 (increasedanion gap, 

increased O-Iactate) 

13 Cat 17wk 

(F) 

Hemato 2400 (Heinz body formation) 

Reference 

Kavlocket al. 1987 

Bauer etal. 1991 

Bauer et al. 1992 

Christopher et al. 

1989a 

Christopher et al. 

1989a 

Christopheret al. 

1990b 

Weiss et al. 1990 

!'.J 

:r: 

m 

» 

Cj

:r: 

m 

"TI 

"TI 

m 

q 

Vl 

"'0 

:;:0 

0 

"'0 

-<, 

m 

Z 

m 

G') 

~ (') 

0, 

f-> 

U) 
TABLE 2-2. Levels of Significant Exposure to Propylene Glycol - Oral (continued) 

""\J 

;:0

Exposure/ LOAEL 0 

Duration/ ""\J 

Key to a Species/ Frequency NOAEL Less Serious Serious •

-< 

m 
 figure (Strain) (Specific Route) System (mg/ltg/day) (mg/kg/day) (mg/kg/day) Reference Z 


m 

G)

•-< 

Neurological 	 n 

0

• 

14 	 Cat 22-35 d 1600 

8000 (ataxia, CNS depression, Christopher et al. 

Mongrel (F) decreased activity) 1990b 

Reproductive 

15 	 Mouse 15-18 wk 10118 NTP 1985 


(swiss CD-i) daily 


(W) 

Developmental 

16 	 Mouse 15-18 wk 10118 NTP 1985 !'-' 

:::r: 

(Swiss CD-i) daily 	 m 

» (W) 	 Cj

:::r: 

m CHRONIC EXPOSURE ."

." 

m 

Systemic q 

VI 

17 	 Rat 2 yr Resp 2500 Gaunt etal.1972 

(F) 	 Cardio 2500 


,Hemato 2500 


Hepatic 2500 


Renal 2500 


Endocr 2500 


18 Dog 2 yr Hemato 2000 5000 	 (decreased Weil et al. 1971 


erythrocytes,
 (F) 
 hemoglobin, hematocrit) 


Hepatic 5000 


Renal 5000 


BdWt 5000 


N 

0 
TAaLE 

Exposurel 

Duration/ 

Key to' Speciesl Frequency 

figure (Strain) (Specific Route) System 

Immunological/Lymphoreticular 

19 Dog 2 yr 

(F) 

2-2. Levels of Significant Exposure to Propylene Glycol - Oral (continued) 

LOAEL 

NOAEL Less Serious Serious 


(mg/kg/day) (mg/kg/day) (mg/kg/day) 


5000 

"'1j 

:::0 

o 

"'1j 

-< 

Reference r

m 

Z 

m 

G) 

!< 

n 

o Wei! et al. 1971 r 

aThe number corresponds to entries in Figure 2-4. 

Bd Wt = body weight; Cardio = cardiovascular; CNS = central nervous sytem; d = day(s}; Endocr = endocrine; F = female; (F) = feed; (G) = gavage; Gastro =' gastrointestinal; (GW) = gavage 

in water; Hemato = hematological; LD50= lethal dose, 50% kill; LOAEL = lowest-observable-adverse-effect level; M = male; metab = metabolic; NOAEL = no-observable-adverse-effect level; 

Resp = respiratory; RBC = red blood cell; (W) = gavage in water; wk =week(s}; x = times; yr = year{s) 

!'" 

:c 

m 

» 

Cj

:c 

m 

-n 

-n 

9 

m 

N 


I-" 

Figure ::>J 2-2. levels of Significant Exposure to· Propylene Glycol - Oral "0 

o 

Acute (~14 days) 

(mg/kg/day) 

100000 

~ 

0Qj 

<:j 

~ ~t::." 

~ §:

t' 0tr:i 

Systemic 

.ff· 

~ ~ fir §' 

~ 

10000 

1r 

III 

2r

• 

2r

• 

3c 

() 

1000 

100 

10 

r 

m 

d 

c 

rat 

mouse 

dog 

cat 

1 

~":,..r{;

~~cl ::".

:...O~flj .il' .~ ~o o~ 6 ;s~ '& ~~.f rlY l§ '.;::" ~ 

2r 5r 

e· • 

4c 

() 

Key 

ill LDso (animals) 

• LOAEL for serious effects (animals) 

o LOAEL for less serious effects (animals) 

o NOAEL (animals) 

.. eEL: cancer effect level (animals) 

~0 

,f 

{?'6 

tf1. ~ 

;;; 

~ t? 

o'i. 

..!:! ~ 

<:)0 

"0 

-< 

r 

m 

Z 

m 

G) 

!< 

n 

o 

r 

Bm 

0 

7m 

0 

!" 

::r: 

~. rn 

:::l 

m 

UJ 

The number next to 

each point 

corresponds to 

entries in Table 2·4. 

tv 

tv 
Figure 2-2. ::0 levels of Significant Exposure to Propylene Glycol - Oral (continued) 	 -0 

o 

-0 

•

-< Intermediate (15-364 days) m 

Z 

m 

Gl 

Systemic 	 !< 

n 

o 

~ Q) • 

.,!).0 (5;& 	 .!jQ) rJ 

if 

t;:-ei .go ~Cl ;:s)0 ~oC§ ~ -::,.o<:$. (mg/kg/day) (Ii 18 ,:§-O &(5 ,!).0 .:fP$' 	 </!'~ ~0 ~ 

~ ~<:$. <:;)0

100000 

15m 16m 11e 	

•

11e 12e 	 14e 10000 I-	 .. 	 0 0 0 0 ~ 

:x: ge 13e ~ 0 () 10e 10e 12e 12e 14e 	 ~ 8e 	 m 0 	 0 0 0 0 "T\ 0 "T\

m 

1000 '" ~ 

100 

Key 

r rat 18 .LDso (animals) The number next to 

m mouse • 	 LOAEL for serious effects (animals) each point 

corresponds to d dog o LOAEL for less serious effects (animals) 10 entries In Table 2-4. 


c cat 
 o NOAEL (animals) 


.. ~EL: cancer effect level (animals) 


1 

IV 

W 
(mg/kg/day) 

10000 

Figure 2-2. Levels of Significant Exposure to Propylene Glycol - Oral (continued) 

Chronic (~365 days) 

:S~ .I".qj 

0r-j ~ 

~ 

~ ;:f 

!l:Jo 

~qj 

&~ t§ (j 

~ if oP iii ~~. 

Systemic 

~Cl 

!'Ii 

~t:{ ~ 0~ 

~ 

.0 

~ 0

0 

~"$ 

.§ 

.~ 

~0 

~ Q;)0 

·CJ ~~ .~ 

~.cI" :fj~ ifCi 

i'~ ~.:;.~ 

-0 

::0 

o 

-0 

-< 

rm 

Z 

m 

Gl 

~ n 

o 

r18d 

() 

18d 

o 

18d 

o 

18d 

o 

19d 

o 

17r 

o 

17r 

o 

17r 

o 18d 

o 

17r 

o 

17r 

o 

17r 

o 

1000 !" 

:r: 

m 

~ 

~ ~ CD 

100 

Key 

10 

r rat 

m mouse 

d dog 

o oat 

III lDso (animals) 

• lOAEl for serious effects (animals) 

o lOAEl for less serious effects (animals) 

o NOAEl (animals) 

• eEL: cancer effect level (animals) 

The number next to 

each point 

corresponds to 

entries in Tabie 2-4. 

1 

tv

.,. 
 

 

 

 

 

 

 

 

 

PROPYLENE GLYCOL 25 

2. HEALTH EFFECTS 

Respiratory Effects. In rats there were no changes in any of the respiratory parameters after 2 years 

of chronic oral exposure to 2,500 mg/kg/day propylene glycol (Gaunt et al. 1972). 

Cardiovascular Effects. The heart histopathology of rats after a 2-year oral exposure to 

2,500 mg/kg/day of propylene glycol revealed no changes (Gaunt et al. 1972). A similar lack of 

cardiovascular effects was observed in rats by Morris et al. (1942) after a 23-month exposure to 

49,500 mg/kg/day propylene glycol in the feed. 

A horse developed myocardial edema prior to death caused by accidental oral administration of 

7,904 mg/kg propylene glycol (Dorman and Haschek 1991). 

It appears that acute exposure to very high levels of propylene glycol may cause adverse cardiovascular 

effects, but it is unlikely that such exposures could occur as a result of being in the vicinity of hazardous 

waste sites. 

Gastrointestinal Effects. Fischer 344 rats exhibited hemorrhagic enteritis after a single oral dose of 

23,500 mg/kg propylene glycol (Clark et al. 1979). The effect of orally administered propylene glycol on 

the brush border membrane from the jejuno-ileum portion of the intestines of rats was investigated in vivo 

(Morshed et al. 1991a). In rats receiving 2,942 mg/kg propylene glycol for 10-30 days, brush border 

enzymes including sucrase, lactase, and gamma-glutamyl transpeptidase exhibited a tendency toward 

increased activity. Absorption of D-glucose and calcium was increased after 10 days of treatment, 

whereas absorption of D-glucose, glycine, L-aspartic acid, L-lysine, and calcium were elevated after 20 or 

30 days of treatment. The structural integrity of the jejunal surface was not adversely affected. 

Hematological Effects. Limited information was available on hematological effects of propylene 

glycol in humans after oral exposure. A 39-year-old woman who had ingested propylene glycol and 

ethanol showed no adverse effects on blood chemistry (Lolin et al. 1988). 

The results from animal studies indicate that intermediate and chronic exposure to propylene glycol may 

lead to hemolysis of red blood cells. Increased numbers of Heinz bodies (sign of red blood cell 

degeneration) were observed in cats exposed orally to 1,200, 1,600, 2,400, and 3,600 mg/kg of propylene 

glycol for 2, 5, and 17 weeks, respectively (Christopher et al. 1989a; Weiss et al. 1990, 1992). Other 

studies indicate increased Heinz body formation and decreased RBC survival in kittens and adult cats 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

PROPYLENE GLYCOL 26 

2. HEALTH EFFECTS 

ingesting 3,000 mg/kg and 1,400 mg/kg/day, respectively (Bauer et al. 1992). These findings are further 

supported by results obtained in dogs after chronic oral exposure to 5,000 mg/kg/day (Weil et al. 1971). 

Red blood cell hemolysis was evidenced by decreased hemoglobin and hematocrit levels, and decreased 

total red blood cell counts. In rats, however, there were no changes in any of the hematological 

parameters after 2 years of chronic oral exposure to 2,500 mg/kg/day propylene glycol (Gaunt et al. 

1972). These results indicate that there may be species differences with regard to the effect of propylene 

glycol on red blood cells. Fischer 344 rats exhibited lymphocyte depletion after a single oral dose of 

23,500 mg/kg propylene glycol (Clark et al. 1979). Hypocellularity of the bone marrow was observed in 

cats after intermediate oral exposure to 8,000 mg/kg/day of propylene glycol (Christopher et al. 1989a). 

Hepatic Effects. The results from chronic-duration animal studies show that there are no adverse 

hepatic effects in rats fed a diet delivering 2,500 mg/kg/day of propylene glycol for 2 years (Gaunt et al. 

1972). Based on these findings, it can be assumed that chronic oral exposures to moderately high levels of 

propylene glycol will not have adverse hepatic effects in humans. It is not clear if hepatotoxicity would 

result after an acute exposure to a high level of propylene glycol. Since levels of propylene glycol in the 

vicinity of a hazardous waste site would probably be low, it is unlikely that propylene glycol would 

induce adverse hepatic effects would occur in people living in the area. 

Renal Effects. No adverse renal effects were observed in cats fed a diet delivering a dose of 

1,600 mg/kg/day of propylene glycol for 5 weeks (Christopher et al. 1989a). In the same study, however, 

cats exposed to 8,000 mg/kg/day of propylene glycol for 3 weeks developed polyuria, considered a less 

serious adverse effect. In another study, an equal number (5-6) of cats of both sexes w.ere fed 

1,600 mg/kg/day propylene glycol for 5 weeks or a high dose diet containing 8,000 mg/kg/day for 

22 days (Christopher et al. 1990b). Cats fed the low dose had no adverse clinical signs. Cats fed the high 

dose had moderate polyuria and polydipsia. Chronic exposure of both rats and dogs to 2,500 and 

5,000 mg/kg/day, respectively, for 2 years, had no nephrotoxic effects in either species (Gaunt et al. 1972; 

Weil et al. 1971). These results indicate that exposure to low levels of propylene glycol that may be 

present at hazardous waste sites are not likely to cause adverse renal effects in the human population 

living in the vicinity. 

Body Weight Effects. Rats given 2,942 mg/kg propylene glycol by gavage for 10 days exhibited a 

41% reduction in body weight, whereas exposure for 20-30 days caused an increase body weight 

(Morshed et al. 1991a). Dogs exposed to 5,000 mg/kg/day oral propylene glycol for 2 years showed no 

adverse effect on body weight (Weil et al. 1971). 
 

 

 

 

 

 

 

 

 

 

PROPYLENE GLYCOL 27 

2. HEALTH EFFECTS 

Metabolic Effects. High levels of propylene glycol in the plasma can lead to an increase in the 

osmolal gap. Propylene glycol is oxidatively converted to lactic and pyruvic acids which, if present in 

sufficient amounts, contribute to a metabolic acidosis. However, acidosis from propylene glycol is not as 

severe as that due to ethylene glycol. In a case of acute propylene glycol poisoning (the amount ingested 

not specified), the patient developed metabolic acidosis (pH of 7.29) with an osmolal gap of 51 mmol/kg 

(reference concentration is <l0 mmol/kg) (Lolin et al. 1988). There is a possibility that this patient also 

ingested a large amount of ethanol since the serum ethanol level was 90 mg/dL. The level of propylene 

glycol was 400 mg/dL in the serum and 10 mg/dL in urine. 

Rats given oral doses of propylene glycol up to 5,885 mg/kg showed an increase of blood lactate of 

2.7 mmol/L, which was prevented by inhibition of propylene glycol metabolism (Morshed et al. 1989). 

Rabbits given an oral dose of 2,942 mg/kg showed a similar increase in blood lactate of 2.6 mmol/L 

(Morshed et al. 1991b). In neither study was there a decrease in blood pH, probably because lactic 

acidosis in clinical situations occurs only when lactate levels rise more than 5 mmol/L (Morshed et al. 

1989). An equal number (5-6) of cats of both sexes were fed a diet containing 12% propylene glycol (low 

dose, 1,600 mg/kg/day) for 5 weeks, a dose equivalent to that found in commercial soft-moist cat foods, 

or a high-dose diet containing 41% propylene glycol (8,000 mg/kg/day) for 22 days (Christopher et al. 

1990b). Pre-dosing observations were made such that each group of cats served as its own control. In the 

low dose cats, anion gap increased from 15.5 Meq/liter during the control period to 22.2 Meq/liter on day 

24 of exposure. Total CO2, decreased at the end of the dosing period. Plasma D-lactate increased 24-fold 

during the dosing period and was significantly correlated with anion gap. L-lactate decreased significantly 

but in a less dramatic fashion to 31% of control values. Serum sodium increased slightly with dosing, but 

there were no other notable changes in serum chemistry. In high-dose cats, plasma D-lactate increased 

rapidly (44-fold) during dosing. 

2.2.2.3 Immunological and Lymphoreticular Effects 

No studies were located regarding immunological and lymphoreticular effects in humans after oral 

exposure to propylene glycol. 

Cats fed 1.2 mg propylene glycol per gram of feed for 14 days showed increased haptoglobin 

concentration (Weiss et al. 1992). Dogs fed 5,000 mg/kg/day propylene glycol for 2 years showed no 

adverse immunological effects (Weil et al. 1971). 
 

 

 

 

PROPYLENE GLYCOL 28 

2. HEALTH EFFECTS 

The highest NOAEL value and the LOAEL value for immunological and lymphoreticular effects in dogs 

and cats for each duration category for propylene glycol after oral exposure are reported in Table 2-2 and 

plotted in Figure 2-2. 

2.2.2.4 Neurological Effects 

Adverse neurological reactions were observed in patients who tested positive in a propylene glycol patch 

test after an acute oral challenge with 2-15 mL of propylene glycol (Hannuksela and Forström 1978). 

Although the observed neurotoxicity is attributed to propylene glycol, the study reports that this response 

was seen in allergic individuals. In a case of acute propylene glycol poisoning, neurotoxic symptoms 

included stupor and repetitive convulsions (Lolin et al. 1988). The study does not specify the amount of 

propylene glycol that caused neurotoxicity. Various degrees of propylene glycol neurotoxicity were also 

observed in a group of 16 outpatients of a neurology clinic after acute oral exposure to 887 mg/kg 3 times 

per day for at least 3 days, using a formulation containing phenytoin and ethanol (Yu et al. 1985). Very 

severe mental symptoms (not specified) were observed in one patient who had the highest overall 

propylene glycol plasma concentration, although patients with lower plasma propylene glycol levels 

showed similar neurotoxicity. The estimated half-life of propylene glycol is 3.8 hours. This means that 

there is a measurable accumulation of propylene glycol if it is ingested in the course of a multiple-dosing 

regimen (Yu et al. 1985). The limitation of the study is that it does not specify if the observed propylene 

glycol effects may have been associated with the neurological problems already present in those patients 

or with concomitant ingestion of ethanol. 

In a study of oral LD50 values using propylene glycol, lethargy and coma were observed prior to death in 

rats (Clark et al. 1979). An equal number (5-6) of cats of both sexes were fed a diet containing 12% 

propylene glycol (low dose, 1,600 mg/kg/day) for 5 weeks, a dose equivalent to that found in commercial 

soft-moist cat foods, or a high dose diet containing 41% propylene glycol (8,000 mg/kg/day) for 22 days 

(Christopher et al. 1990b). Pre-dosing observations were made such that each group of cats served as its 

own control. Animals were observed for signs of toxicity. Cats receiving the low dose showed no clinical 

signs of toxicity. Cats receiving the high dose developed decreased activity, mental depression [author’s 

words], and slight to moderate ataxia. These cats had high levels (44-fold higher than control) of 

D-lactate, thought to contribute to central nervous system toxicity. On the basis of this information, 

adverse neurological reactions due to exposure to low levels of propylene glycol possibly present at 

hazardous waste sites are very unlikely. 
 

 

 

 

 

PROPYLENE GLYCOL 29 

2. HEALTH EFFECTS 

The LOAEL value for neurological effects in rats for acute-duration category oral exposure propylene 

glycol is reported in Table 2-2 and plotted in Figure 2-2. 

2.2.2.5 Reproductive Effects 

No studies were located regarding reproductive effects in humans after oral exposure to propylene glycol. 

Pregnant female Swiss mice were given 10,000 mg/kg/day propylene glycol by mouth on Gd 8-12 

(Kavlock et al. 1987). There was no effect of treatment on their ability to produce live pups, or on the 

survival of those pups. The effects of propylene glycol on reproduction of Swiss (CD-l) mice were tested 

in a protocol which permitted continuous breeding during a specified interval (NTP 1985). Propylene 

glycol in drinking water at doses of 0, 1.0, 2.5, and 5.0% yielded mean exposures of 0, 1,819, 4,796, and 

10,118 mg/kg/day, based on water consumption. Animals were treated during a l-week pre-cohabitation 

period and a 14-week monogamous cohabitation ‘period. Any offspring produced during the cohabitation 

period were examined, sexed, weighed, and killed to allow continuous mating of the parental generation. 

At the end of the cohabitation period, males and females were separated, and the females were allowed to 

deliver and raise the last litter to weaning. Propylene glycol had no adverse effects on any measure of 

reproduction, including number of litters, litter size, pup weight, or sex ratio. There was no effect on the 

reproductive capacity of offspring from the high dose group. 

The highest NOAEL values for reproductive effects in each species and duration category for propylene 

glycol after oral exposure are reported in Tables 2-2 and plotted in Figure 2-2. 

2.2.2.6 Developmental Effects 

No studies were located regarding developmental effects in humans after oral exposure to propylene 

glycol. 

Pregnant female Swiss mice were given 10,000 mg/kg/day propylene glycol by mouth on Gd 8-12 

(Kavlock et al. 1987). There was no effect of treatment on their ability to produce live pups, or on the 

survival of those pups. The effects of propylene glycol on reproduction of Swiss (CD-l) mice were tested 

in a protocol which permitted continuous breeding during a specified interval (NTP 1985). Propylene 

glycol in drinking water at doses of 0, 1.0, 2.5, and 5.0% yielded mean exposures of 0, 1,819, 4,796, and 

10,118 mg/kg/day, based on water consumption. Animals were treated during a l-week pre-cohabitation 

period and a 14-week monogamous cohabitation period. Any offspring produced during the cohabitation 
 

 

 

 

PROPYLENE GLYCOL 30 

2. HEALTH EFFECTS 

period were examined, sexed, weighed, and killed to allow continuous mating of the parental generation. 

At the end of the cohabitation period, males and females were separated, and the females were allowed to 

deliver and raise the last litter to weaning. 

Propylene glycol had no adverse effects on any measure of reproduction, including number of litters, litter 

size, pup weight, or sex ratio. There was no effect on the reproductive capacity of offspring from the high 

dose group. 

The highest NOAEL values for developmental effects in each species and duration category for propylene 

glycol after oral exposure are reported in Table 2-2 and Figure 2-2. 

2.2.2.7 Genotoxic Effects 

No studies were located regarding genotoxic effects in humans or animals after oral exposure to 

propylene glycol. 

Other genotoxicity studies are discussed in Section 2.4. 

2.2.2.8 Cancer 

No studies were located regarding cancer effects in humans after oral exposure to propylene glycol. 

In a dietary study of chronic oral exposure of rats to 2,500 mg/kg/day, there were no treatment-related 

increases in neoplasms (Gaunt et al. 1972). Based on this information, its long history of use in consumer 

products, and structural activity considerations, it is extremely unlikely that exposure to levels of 

propylene glycol near hazardous waste sites would influence the incidence of cancer in the population 

living in the vicinity. 

2.2.3 Dermal Exposure 

Dermal exposure to propylene glycol most likely occurs through contact with cosmetics or drugs. 
 

 

 

 

 

 

PROPYLENE GLYCOL 31 

2. HEALTH EFFECTS 

2.2.3.1 Death 

No studies were located regarding death in humans or animals after dermal exposure to propylene glycol. 

Therefore, no LOAELs for death following dermal exposure could be established. Based on the absence 

of data in the literature, it is unlikely that sufficient amounts of propylene glycol would be present or 

inhaled near hazardous waste sites to cause death among people living in the area. 

2.2.3.2 Systemic Effects 

No studies were located regarding gastrointestinal, hematological, musculoskeletal, hepatic, renal, 

endocrine, ocular, or body weight effects in humans, or respiratory, cardiovascular, gastrointestinal, 

hematological, musculoskeletal, hepatic, renal, endocrine, body weight, or metabolic effects in animals 

after dermal exposure to propylene glycol. 

The highest NOAEL values and all reliable LOAEL values for systemic effects in each species and 

duration category for propylene glycol after dermal exposure are reported in Table 2-3. 

Respiratory Effects. Acute respiratory acidosis and cardiorespiratory arrest occurred in an 8-monthold infant with second- and third-degree burns after acute dermal treatment with silver sulfadiazine 

containing a high amount of propylene glycol. The dose of propylene glycol was 9,000 mg/kg/day 

(Fligner et al. 1985). Due to the high dose of propylene glycol, and the possible concomitant effects of 

both the burn injury and the sulfadiazine therapy, the actual source of the respiratory effect in this infant 

could not be determined, although propylene glycol cannot be ruled out as the causative agent. 

Cardiovascular Effects. Very limited and conflicting information is available for humans on 

cardiovascular effects after dermal exposure to propylene glycol. An 8-month-old infant suffered 

cardiorespiratory arrest after four dermal exposures to propylene glycol in a silver sulfadiazine 

medication (Fligner et al. 1985). Due to the high dose of propylene glycol, and the possible concomitant 

effects of both the burn injury and the sulfadiazine therapy, the actual source of the cardiorespiratory 

effect in this infant could not be determined, although propylene glycol cannot be ruled out as the 

causative agent. Other studies of propylene glycol in humans did not evaluate cardiovascular effects. 

It appears that acute exposure to very high levels of propylene glycol may cause adverse cardiovascular 

effects, but it is unlikely that such exposures could occur as a result of being in the vicinity of hazardous 

waste sites. 
TABLE 2-3. Levels of Significant Exposure to Propylene Glycol - Dermal 

Exposurel 

Durationl 

Speciesl Frequencyl 

(Strain) (Specific Route) 

ACUTE EXPOSURE 

Systemic 

System NOAEL Less Serious 

LOAEL 

Serious Reference 

." 

:::0 

0 

." 

-< 

rm 

z 

m 

(j) 

~ () 

0 

rHuman 5d Hemato 6100 Commens 1990 

1x1d mg/kg 

Human 70 hr 

>1x/d 

Resp 

Cardio 

Metab 

9000 M (acute respiratory acidosis) 

mg/kg 

9000 M (cardiorespiratory arrest) 

mg/kg 

9000 M (increased osmolal gap) 

Fligner eta!. 1985 

Human 

Human 

Human 

20-24h 

48hr 

once 

48hr 

once 

Dermal 

Dermal 

Dermal 

3.2% 

10mg 

0.2 mg 

(irritation reaction) 

(50% solution, skin 

edema and erythema) 

{1% solution, erythema 

and edema) 

mg/kg 

Hannuksela eta!. 

1975 

Kinnunen and 

Hannuksela 1989 

Kinnunen and 

Hannuksela 1989 

!'.l 

:c 

m 

» 

!:i

:c 

m 

.." 

.." 

m 

q 

V'l 

Human 7d 

2x1d 

Dermal 104M 

mg 

Trancik and 

Maibach 1982 

Human once 

48 hrs 

Dermal 2.5% (erythema, induration, 

vesiculation) 

Warshaw and 

Herrmann 1952 

Human 48 hr 

once 

Dermal 15mg M 31 mg M (faint, patchy erythema 

with edema) 

Willis eta!. 1988 

Human 48hr 

once 

Dermal 16 mg M ("basket weave" pattern 

to stratum corneum) 

Willis eta!. 1989 

OJ 

N 
TABLE 2-3. Levels of Significant Exposureto Propylene Glycol - Dermal (continued) 

-0 

Exposure! LOAEL 	 ;;:0 

o 

Duration! 	 -0 

-< Species! Frequency! 	 rm 

(Strain) (Specific Route) System NOAEL Less Serious Serious 	 Reference Z 

m 

G) 

!< 

n 

o 

rRabbit once Dermal 0.52 F 	 Clark et al. 1979 

(New gm 


Zealand) 


Rabbit once Dermal 0.1 gm F 	 Clark et al. 1979 

(New 


Zealand) 


Immunological/Lymphoreticular 

Human 20 -24 hr 3.2% (allergic reaction) 	 Hannuksela et al. !'-' 

1975 :r: 

m 

» Neurological !:j

:r: 

Human 70 hr 9000 M (hypoxic encephalopathy) Fligner etal. 1985 m 

>1x/d 	 mg/kg " " m 

9 

INTERMEDIATE EXPOSURE 

Systemic 

Human 21-22 d Dermal 207 mg M (erythema) 	 Trancik and 


Maibach 1982 


Cardio =cardiovascular; d =day(s); F =female; Hemato =hematological; hr =hour(s); LOAEL =lowest-observable-adverse-affectlevel; M =male; Metab =metabolic; NOAEL = no-observable-adverse-effectlevel; Resp =respiralory;x =times 

OJ 


OJ 

 

 

 

 

PROPYLENE GLYCOL 34 

2. HEALTH EFFECTS 

Dermal Effects. Propylene glycol does not seem to have significant irritative properties. Skin testing 

of 42 healthy volunteers showed that 100% propylene glycol caused faint, patchy erythema with edema in 

40% of the tested subjects (Willis et al. 1988). In another study, an acute dermal exposure of eczema 

patients to 0.2 and 22.8 mg/cm2 of propylene glycol caused skin edema and erythema in 3.8% of the 

823 patients that were skin tested (Kinnunen and Hannuksela 1989). On the basis of-the findings from 

these studies, the authors concluded that propylene glycol has marginal irritant properties. 

However, some cases of sensitivity have been recorded in the literature. A 51-year-old woman developed 

a severe itchy erythematous vesicular dermatitis of the upper lip, nose and adjoining right cheek after 

applying a cream containing 10% propylene glycol (Corrazza et al. 1993). A patch test revealed a 

sensitivity to propylene glycol. In a test of 1,226 patients, applying 5% propylene glycol in Vaseline, or 

10, 30, or 50% in water, caused approximately 208 patients to show some reaction (Aberer et al. 1993). 

Of these 208 patients, 195 exhibited some form of irritation, whereas only 13 exhibited an allergic 

reaction (Aberer et al. 1993). The mechanism of the reaction is not understood, but electron microscopy 

revealed that propylene glycol causes hydration of cornea1 cells producing a characteristic “basket 

weave” pattern in the stratum comeum (Willis et al. 1989). In order to determine if propylene glycol can 

also evoke a hypersensitivity reaction, a total of 15 patients who had positive skin reactions to propylene 

glycol were exposed to an acute oral propylene glycol challenge (Hannuksela and Forström 1978). The 

hypersensitivity reaction that developed consisted of exanthem and cleared within 36-48 hours without 

any medications. 

During 1951 and 1952, propylene glycol was applied in a covered patch test to the normal skin of 

866 patients (Warshaw and Herrmann 1952). The test sites were examined 48 hours after application of 

the patches. Undiluted propylene glycol (Brand A, B, and C), and aqueous dilutions of Brand A (2.5, 10, 

and 50%) were tested. Related compounds, including glycerine, and carbowax 1500, were also tested. 

Propylene glycol was also applied directly to the skin of some individuals with a glass rod for 20 seconds. 

The application site was left uncovered. In many of the patients, the patch tests were repeated, but in 

different locations. When possible, the patients were re-tested after a period of several months. Several 

patients who reacted to propylene glycol were re-tested with exposure to propylene glycol and dry heat; 

female patients who reacted to propylene glycol received lipsticks containing propylene glycol for trial 

use. Positive results were observed in 138 (15.7%) of the skin patch tests of propylene glycol. The 

reactions ranged from simple erythema to erythema with induration and vesiculation. No differences were 

noted in reactions to different brands of propylene glycol. Twenty-three persons with reactions to pure 
 

 

 

 

PROPYLENE GLYCOL 35 

2. HEALTH EFFECTS 

propylene glycol were tested with 50 and 10% dilutions. In general, the reaction to propylene glycol 

decreased with decreasing concentration. Only 5 of 23 showed any reaction to 10% propylene glycol, and 

only showed simple erythema. One of three persons tested with 2.5% propylene glycol had a positive 

reaction. Sixteen patients with positive reactions to the propylene glycol patch test were further patchtested with glycerine and carbowax 1500, yielding 1 positive reaction to carbowax 1500, and a 

questionable positive reaction to glycerine. Sixteen patients with positive reactions to the patch test with 

propylene glycol were retested by simple application of propylene glycol. No positive reactions were 

observed. The incidence of positive reactions to propylene glycol appeared to fluctuate with the season, 

and was significantly higher during the cooler and less humid months (14-22% from October to June, 6% 

from July to September). In 23 of the positive reacting patients, the patch tests with propylene glycol were 

repeated after a period of 2-12 months. Seventeen of 23 patients showed a positive response, while the 

other 6 showed no response. Repeated testing with increased heat and moisture, reactivity tended to 

decrease. One of 15 female patients with a positive reaction to the propylene glycol patch test was also 

reactive to lipstick containing propylene glycol which was applied to the lips. 

Propylene glycol was tested on the skin of 1,556 patients with eczema using a chamber on the back of the 

patients (Hannuksela et al. 1975). Undiluted propylene glycol was applied to the backs of the patients and 

left there for 20-24 hours. Readings of the exposure area were made 1, 2, and 4-5 days after application of 

the chemical. Reactions with redness, with or without infiltration peaking on the first day were considered 

irritant reactions. Reactions with infiltration with or without vesiculation extending to a considerably 

larger area than the test area, with the maximum occurring on the second day or later were considered’ 

allergic. Forty-two positive reactors were subjected to patch tests with 3.2, 10, or 32% aqueous propylene 

glycol. Fifteen patients with allergic reactions to propylene glycol. applied undiluted propylene glycol to 

their armpits 3 times daily for 4 days. Of the patients tested with undiluted propylene glycol, 12.5% 

showed positive reactions. Of these, 70% were of primary irritation, and 30% were allergic in appearance. 

Seasonal variation was observed, with more cases observed in the winter. Forty-two cases of positive 

reactions to undiluted propylene glycol were retested with aqueous dilutions of the compound. Twelve of 

42 showed a positive reaction to 10%, and 9 of 42 had a reaction to 3.2%; 20 of 42 cases reacted to the 

32% solution. Eleven of 15 patients who applied propylene glycol to their armpits had no reaction. The 

4 reacting patients exhibited itching 4-10 hours and eczema within 24 hours. The symptoms reached their 

peak at 48 hours and disappeared after 3-5 days. Three of these patients used undiluted propylene glycol 

and one patient used 10% propylene glycol. In this latter patient, examination of the skin of a lo-hour-old 

reaction revealed no change in the epidermis, but perivascular infiltration in the dermis, indicative of an 

allergic reaction. 
 

 

 

 

 

 

 

 

PROPYLENE GLYCOL 36 

2. HEALTH EFFECTS 

A 21-day cumulative irritation test was conducted using propylene glycol (Trancik and Maibach 1982). 

Ten Caucasian males with healthy skin received dermal applications of 207 mg propylene glycol (USP) 

on their backs in the same spot every day for 21 days. The application site was occluded with gauze and 

tape for 24 hours following application. Daily readings of test site were conducted at the time the patches 

were removed. Scoring ranged from no visible reaction to intense erythema with edema and vesicular 

erosion. In the 21-day cumulative irritation test, only one subject presented with a reaction, which was 

rated as equivocal irritation, on 20 of the test. All other subjects in the test had no reaction. Results of the 

21-day cumulative irritation test indicate that propylene glycol is at least a minimal irritant. 

There are few studies of dermal effects of propylene glycol in animals. New Zealand White rabbits 

exposed to 0.52 g of propylene glycol on skin showed little or no irritation after 72 hours (Clark et al. 

1979). 

These findings, plus a long history of safe use in medicine, indicate that prolonged dermal exposure to the 

low levels of propylene glycol present at hazardous waste sites is very unlikely to cause hypersensitivity 

or other skin reactions in the human population living in the vicinity. 

Metabolic Effects. High levels of propylene glycol in the plasma can lead to an increase in the 

osmolal gap. Propylene glycol is oxidatively converted to lactic and pyruvic acids which, if present in 

sufficient amounts, contribute to a metabolic acidosis. However, acidosis from propylene glycol is not as 

severe as that due to ethylene glycol. Increased osmolal gap was found in two cases of acute dermal 

exposure to propylene glycol. An 8-month-old infant with a severe burnswas topically treated with 

9,000 mg/kg/day of propylene glycol used as a vehicle for silver sulfadiazine (Fligner et al. 1985). The 

osmolal gap reached a maximum of 130 rnilliosmoles/kg 14 days after the treatment started, while serum 

propylene glycol level peaked at 1,059 mg/dL. Due to the high dose of propylene glycol, and the possible 

concomitant effects of both the burn injury and the sulfadiazine therapy, the actual source of the 

metabolic effect in this infant could not be determined, although propylene glycol cannot be ruled out as 

the causative agent. The burn injury may have contributed to the increased absorption of propylene glycol 

and hence, the hyperosmolality. However, in another study of acute dermal propylene glycol exposure of 

12 adults to 6,100 mg/kg/day for 5 days, propylene glycol had no effect on either serum osmolality or 

lactic acid levels (Commens 1990). Although the results of these studies are not conclusive, it seems that 

increased lactate levels leading to acidosis and increased osmolality may develop in humans in the event 

high levels of propylene glycol are absorbed into the blood stream. 
 

 

 

 

 

 

 

 

 

PROPYLENE GLYCOL 37 

2. HEALTH EFFECTS 

2.2.3.3 Immunological and Lymphoreticular Effects 

No studies were located regarding immunological and lymphoreticular effects in animals after dermal 

exposure to propylene glycol. 

Since propylene glycol is widely used as a vehicle for dermally applied medications, several studies 

investigated its potential as both an irritant and contact allergen. Skin testing of 42 healthy volunteers 

showed that 100% propylene glycol caused faint, patchy erythema with edema in 40% of the tested 

subjects (Willis et al. 1988). In another study, an acute dermal exposure of eczema patients to 0.2 and 

22.8 mg/cm2 of propylene glycol caused skin edema and erythema in 3.8% of the 823 patients that were 

skin tested (Kinnunen and Hannuksela 1989). On the basis of the findings from these two studies, the 

authors concluded that propylene glycol has marginal irritant properties. However, some cases of 

sensitivity have been recorded in the literature. A 51-year-old woman developed a severe itchy 

erythematous vesicular dermatitis of the upper lip, nose, and adjoining right cheek after applying a cream 

containing 10% propylene glycol (Corrazza et al. 1993). A patch test revealed a sensitivity to propylene 

glycol. In a test of 1,226 patients applying 5% propylene glycol in Vaseline, or 10, 30, or 50% in water 

resulted in approximately 208 patients showing some reaction (Aberer et al. 1993). Of these 208 patients, 

195 exhibited some form of irritation, whereas only 13 exhibited an allergic reaction (Aberer et al. 1993). 

The mechanism of the reaction is not understood, but electron microscopy revealed that propylene glycol 

causes hydration of corneal cells producing a characteristic “basket weave” pattern in the stratum 

corneum (Willis et al. 1989): In order to determine if propylene glycol can also evoke a hypersensitivity 

reaction, a total of 15 patients who had positive skin reactions to propylene glycol were exposed to an 

acute oral propylene glycol challenge (Hannuksela and Forström 1978). The hypersensitivity reaction that 

developed consisted of exanthem and cleared within 3 6-48 hours without any medications. Propylene 

glycol was tested on the skin of 1,556 patients with eczema using a chamber on the back of the patients 

(Hannuksela et al. 1975). Undiluted propylene glycol was applied to the backs of the patients and left 

there for 20-24 hours. Readings of the exposure area were made 1, 2, and 4-5 days after application of the 

chemical. Reactions with redness, with or without infiltration peaking on the first day were considered 

irritant reactions. Reactions with infiltration with or without vesiculation extending to a considerably 

larger area than the test area, with the maximum occurring on the second day or later were considered 

allergic. Forty-two positive reactors were subjected to patch tests with 3.2, 10, or 32% aqueous propylene 

glycol. Fifteen patients with allergic reactions to propylene glycol applied undiluted propylene glycol to 

their armpits 3 times daily for 4 days. Of the patients tested with undiluted propylene glycol, 12.5% 
 

 

 

 

 

 

 

 

 

PROPYLENE GLYCOL 38 

2. HEALTH EFFECTS 

showed positive reactions. Of these, 70% were of primary irritation, and 30% were allergic in appearance. 

Seasonal variation was observed, with more cases observed in the winter. Forty-two cases of positive 

reactions to undiluted propylene glycol were retested with aqueous dilutions of the compound. Twelve of 

42 cases showed a positive reaction to l0%, and 9 of 42 cases had a reaction to 3.2%; 20 of 42 cases 

reacted to the 32% solution. Eleven of 15 patients who applied propylene glycol to their armpits had no 

reaction. The 4 reacting patients exhibited itching 4-10 hours and eczema within 24 hours. The symptoms 

reached their peak at 48 hours and disappeared after 3-5 days. Three of these patients used undiluted 

propylene glycol and one patient used 10% propylene glycol. In this latter patient, examination of the skin 

of a l0-hour-old reaction revealed no change in the epidermis, but perivascular infiltration in the dermis, 

indicative of an allergic reaction. 

A 22-day sensitization procedure was conducted using propylene glycol (Trancik and Maibach 1982). For 

the sensitization procedure, 203 Caucasian males with healthy skin received dermal doses of 207 mg 

propylene glycol on their backs on Mondays, Wednesdays, and Fridays for 22 days, resulting in a total of 

10 doses. The application site was occluded for 48-72 hours (i.e., covered between doses). The test sites 

were read when the patches were changed. The application site was occluded with gauze and tape for 

24 hours following application. Daily readings of test site were conducted at the time the patches were 

removed. Scoring ranged from no visible reaction to intense erythema with edema and vesicular erosion. 

In addition, minimal glazing of the skin (roughness) was added to the scoring list. Two weeks after the 

sensitization phase, a challenge dose was applied to previously untested skin and occluded for 48­

72 hours. Rechallenge was performed at 2-week intervals. In the sensitization test, equivocal responses 

were noted, but no reaction more than equivocal was observed. At the challenge, 19 of 203 showed a 

positive response. Upon rechallenge, five exhibited an increase in response. The sensitization test 

indicates that propylene glycol might be a sensitizer. 

These findings plus a long history of safe use in medicine indicate that prolonged dermal exposure to the 

low levels of propylene glycol present at hazardous waste sites is very unlikely to cause hypersensitivity 

reactions in the human population living in the vicinity. 

2.2.3.4 Neurological Effects 

No studies were located regarding neurological effects in animals after dermal exposure to propylene 

glycol. 
 

 

PROPYLENE GLYCOL 39 

2. HEALTH EFFECTS 

Adverse neurological reactions were observed in patients who tested positive in a propylene glycol patch 

test after an acute oral challenge with 2-15 mL of propylene glycol (Hannuksela and Forstrom 1978). 

Although the observed neurotoxicity is attributed to propylene glycol, the study reports that this response 

was seen in allergic individuals. An 8-month-old infant with a severe burn was topically treated with 

9,000 mg/kg/day of propylene glycol used as a vehicle for silver sulfadiazine (Fligner et al. 1985). After 

developing respiratory acidosis, the infant experienced cardiac arrest and was resuscitated. Subsequent 

neurological examination revealed hypoxic damage, which was evident by persistent hypoxic 

encephalopathy. Due to the high dose of propylene glycol, and the possible concomitant effects of both 

the bum injury and the sulfadiazine therapy, the actual source of the respiratory effect and subsequent 

neurological damage in this infant could not be determined, although propylene glycol cannot be ruled out 

as the causative agent. 

The LOAEL value for neurological effects in humans for acute effects for propylene glycol after dermal 

exposure is reported in Table 2-3. 

2.2.3.5 Reproductive Effects 

No studies were located regarding reproductive effects in humans or animals after dermal exposure to 

propylene glycol. 

2.2.3.6 Developmental Effects 

No studies were located regarding developmental effects in humans or animals after dermal exposure to 

propylene glycol. 

2.2.3.7 Genotoxic Effects 

No studies were located regarding genotoxic effects in humans or animals after dermal exposure to 

propylene glycol. 

Genotoxicity studies are discussed in Section 2.4. 

2.2.3.8 Cancer 

No studies were located regarding cancer effects in humans after dermal exposure to propylene glycol. 
 

 

 

 

 

 

 

 

 

 

 

 

 

PROPYLENE GLYCOL 40 

2. HEALTH EFFECTS 

No increase in tumors was observed after twice weekly applications of propylene glycol to the skin of 

Swiss mice for 120 weeks, at doses up to 2 mg (Stenback and Shubik 1974). Based on this information, 

its long history of use in consumer products, and structural activity considerations, it is extremely unlikely 

that exposure to levels of propylene glycol near hazardous waste sites would influence the incidence of 

cancer in the population living in the vicinity. 

2.3 TOXICOKINETICS 

The toxicokinetics of propylene glycol is not well defined. Dermal data are most abundant for propylene 

glycol. Due to the relatively nontoxic nature of the compound, kinetic data are somewhat scarce. 

Available information is discussed below. 

2.3.1 Absorption 

2.3.1.1 Inhalation Exposure 

No kinetic data for absorption in humans or animals of propylene glycol after inhalation exposure were 

found in the literature. 

2.3.1.2 Oral Exposure 

The pharmacokinetic properties of propylene glycol are not completely understood, but absorption from 

the gastrointestinal tract is fairly rapid. The maximum plasma concentration of propylene glycol in 

humans is reached within 1 hour after oral exposure (Yu et al. 1985). An equal number (5-6) of cats of 

both sexes were fed a diet containing 12% propylene glycol (low dose, 1,600 mg/kg/day) for 5 weeks, a 

dose equivalent to that found in commercial soft-moist cat foods, or a high dose diet containing 41% 

propylene glycol (8,000 mg/kg/day) for 22 days (Christopher et al. 1990b). Predosing observations were 

made such that each group of cats served as its own control. Plasma levels of propylene glycol were 

measured in 2 cats fed the low dose on day 24 of ingestion, and compared to pre-dosing samples. Plasma 

levels of propylene glycol were 19.1 and 8.4 mmol/liter for the 2 cats. 

2.3.1.3 Dermal Exposure 

Some studies of the dermal absorption of propylene glycol have been conducted. Patients with second and 

third degree burns over more than 20% of their total body surface were studied over a period of 
 

 

 

PROPYLENE GLYCOL 41 

2. HEALTH EFFECTS 

30 months (Kulick et al. 1985). Sulfadiazine preparations containing propylene glycol were applied 

dermally over a period of 3-7 days after admission to the hospital. Serum and urinary levels of propylene 

glycol were measured. Propylene glycol was detected in the serum of 24 of 45 patients, and in the urine of 

40 of 45 patients. Average serum levels were 0.08 mg/mL, with a range of 0-1.3 mg/mL for patient who 

lived, and 0.82 mg/mL with a range of 0-9.8 mg/mL for patients who died. Propylene glycol levels 

correlated with total bum surface area and total third degree burn surface area. 

In vitro studies of the penetration of propylene glycol through rat abdominal stratum corneum have been 

conducted (Takeuchi et al. 1993, 1995). Fresh abdominal skin from male Wistar rats was used in 

experiments in which propylene glycol, or a mixture of propylene glycol and oleic acid were evaluated 

for absorption properties (Takeuchi et al. 1993). When propylene glycol was applied alone for up to 

2 hours, no compound was detected in the dermis. However, when 0.15 M oleic acid was added to the 

propylene glycol, propylene glycol was detected in the dermis after 30 minutes of exposure, but not after 

5 or 15 minutes (Takeuchi et al. 1993). The appearance of propylene glycol seemed to be in three phases 

when in the presence of a skin penetration enhancer such as oleic acid (Takeuchi et al. 1995). The first 

stage was the penetration of propylene glycol into the skin barrier, without any change of the dermal 

structure. The second stage was rapid distribution in and throughout the dermis, presumably accompanied 

by alteration of the dermal structure. In the third stage, propylene glycol was saturated in the dermis. 

Comparison of propylene glycol absorption by skin from humans, hairless mice, and snakes was 

conducted (Rigg and Barry 1990). Shed snake skin tended to underestimate propylene glycol absorption 

in human skin, especially in the presence of enhancers, whereas hairless mouse skin greatly overestimated 

absorption compared to human skin. The authors concluded that human skin should be used for 

absorption studies whenever possible. 

2.3.2 Distribution 

2.3.2.1 Inhalation Exposure 

No kinetic data for distribution in humans or animals of propylene glycol after inhalation exposure were 

found in the literature. 
 

 

 

 

 

 

 

PROPYLENE GLYCOL 42 

2. HEALTH EFFECTS 

2.3.2.2 Oral Exposure 

No studies of the distribution of propylene glycol in humans or animals after oral exposure were found in 

the literature. 

2.3.2.3 Dermal Exposure 

In vitro studies of the penetration of propylene glycol through rat abdominal stratum corneum have been 

conducted (Takeuchi et al. 1993, 1995). Fresh abdominal skin from male Wistar rats was used in 

experiments in which propylene glycol, or a mixture of propylene glycol and oleic acid were evaluated 

for absorption properties (Takeuchi et al. 1993). When propylene glycol was applied alone for up to 

2 hours, no compound was detected in the dermis. However, when 0.15 M oleic acid was added to the 

propylene glycol, propylene glycol was detected in the dermis after 30 minutes of exposure, but not after 

5 or 15 minutes (Takeuchi et al. 1993). The appearance of propylene glycol seemed to be in three phases 

when in the presence of a skin penetration enhancer such as oleic acid (Takeuchi et al. 1995). The first 

stage was the penetration of propylene glycol into the skin barrier, without any change of the dermal 

structure. The second stage was rapid distribution in and throughout the dermis, presumably accompanied 

by alteration of the dermal structure. In the third stage, propylene glycol was saturated in the dermis. 

Additional evaluation indicated that the volume of distribution of propylene glycol in the dermis was 

influenced by the efficiency of the enhancer compound, with oleic acid and oleylamine being the most 

efficient, compared to lauric acid, laurylamine, or azone. 

2.3.3 Metabolism 

The metabolic pathway for propylene glycol in mammals is shown in Figure 2-3. Commercially available 

propylene glycol is usually a mixture of D- and L-isomers. The major route of metabolism for propylene 

glycol is via alcohol dehydrogenase to lactaldehyde, then to lactate, via aldehyde dehydrogenase, and on 

to glucose through gluconeogenic pathways (as summarized in Christopher et al. 1990b; Huff 1961; 

Miller and Bazzano 1965; Morshed et al. 1989, 1991b; Ruddick 1972). Conversion to methylglyoxal is an 

alternate route via alcohol dehydrogenase, ending in metabolism to D-lactate through glyoxalase. 
2. HEALTH EFFECTS 

Figure 2-3. Propylene Glycol Metabolism in Mammals 

CH3CCHO 

Reduced glutathione methylglyoxal D-lactate O 

glyoxaisse I, II 

alcohol 

dehydrogenase 

NAD NADH NAD NADH 

DL-1,2-propanediol DL-lactaldehyde DL-lactate glucose 

alcohol aldehyde CH3CHCH2OH dehydrogenase CH3CHCHO dehydrogenase CH3CHCOOH 

OH OH OH 

PROPYLENE GLYCOL 43 

From Christopher et al. 1980b 
 

 

 

 

 

 

 

 

 

PROPYLENE GLYCOL 44 

2. HEALTH EFFECTS 

2.3.4 Excretion 

2.3.4.1 Inhalation Exposure 

No kinetic data for excretion in humans or animals of propylene glycol after inhalation exposure were 

found in the literature. 

2.3.4.2 Oral Exposure 

The pharmacokinetic properties of propylene glycol are not completely understood, but absorption from 

the gastrointestinal tract is fairly rapid. The maximum plasma concentration of propylene glycol in 

humans is reached within 1 hour after oral exposure, while the elimination half-life is about, 4 hours. The 

total body clearance is about 0.1 L/kg/hour and seems to be serum-concentration dependent (Yu et al. 

1985). Dose-dependent elimination is seen in rats, with saturation of the pathways at doses above 

5,880 mg/kg (Morshed et al. 1988). An apparent maximum elimination rate of 8.3 mmol/kg/hour 

(630 mg/kg/hour) was observed. 

2.3.4.3 Dermal Exposure 

Excretion of propylene glycol has been studied in humans. Patients with second and third degree bums 

over more than 20% of their total body surface were studied over a period of 30 months (Kulick et al. 

1985). Sulfadiazine preparations containing propylene glycol were applied dermally over a period of 3­

7 days after admission to the hospital. Serum and urinary levels of propylene glycol were measured. 

Propylene glycol was detected in the serum of 24 of 45 patients, and in the urine of 40 of 45 patients. 

Average urinary levels were 1.3 mg/mL, with a range of 0-17.9 mg/mL for patient who lived, and 

2.9 mg/mL with a range of 0-23.0 mg/mL for patients who died. Propylene glycol levels correlated with 

total bum surface area and total third degree bum surface area. 

2.3.5 Mechanism of Action 

The mechanism of action of propylene glycol is not well understood. 
 

 

 

 

	 

PROPYLENE GLYCOL 45 

2. HEALTH EFFECTS 

2.4 RELEVANCE TO PUBLIC HEALTH 

Propylene glycol is a colorless, odorless, water-soluble liquid considered safe for use in commercial 

formulations of foods, drugs, and cosmetics. Propylene glycol, like ethylene glycol, is used as an 

antifreeze, de-icing solution, and in various paints and coatings. Unlike ethylene glycol, however, 

propylene glycol has been approved as safe in various food flavorings, drugs, cosmetics, and as a direct 

additive to food. Propylene glycol is commonly used in the pharmaceutical industry as a solvent for 

drugs, as a stabilizer for vitamins, and in ointment for medicinal applications. Propylene glycol may be 

found in canned fruit, packaged coconut, as a solvent in drug and cosmetic preparations, and in flavorings 

and extracts. Propylene glycol is also used in the generation of artificial mists and fogs used in fire safety 

training, and theatrical and stage productions: This widespread use of propylene glycol stems from its low 

level of toxicity. 

Minimal Risk Levels for Propylene Glycol 

Inhalation MRLs 

No MRLs for acute- or chronic-duration inhalation exposure to propylene glycol were derived because 

data are insufficient. Only one acute-duration inhalation exposure study was found in the available 

literature, in which rabbits were exposed to only one dose (10% aerosol) of propylene glycol for 20 and 

120 minutes (Konradova et al. 1978). An increased number of degenerated goblet cells in the tracheal 

lining was observed at both doses. Only a single study was found in the available literature for inhalation 

exposure to propylene glycol for chronic-duration (Robertson et al. 1947) exposure. This study did not 

provided enough information from which to derive an MRL. 

•	 An MRL of 0.009 ppm has been derived for intermediate-duration (15–364 days) inhalation 

exposure to propylene glycol. 

The MRL was based on the LOAEL of 51 ppm for nasal hemorrhaging in rats (Suber et al. 1989). The 

MRL was obtained by dividing the LOAEL value by 1,000 (10 for use of a LOAEL, 10 for extrapolation 

from animals to humans, and 10 for human variability) and multiplying by factors to adjust the exposure 

from 6 hours per day (6 or 24) and 5 days per week (5 of 7) to continuous exposure. Young, healthy adult 

Sprague-Dawley rats were divided into 4 groups of 19 males and 19 females each. Three groups were 

exposed for 5 days per week, 6 hours per day for 13 weeks by nose-only inhalation to mean target aerosol 

concentrations of 51, 321, or 707 ppm propylene glycol. The fourth, the control group, was exposed to 
 

 

 

 

 

 

 

 

PROPYLENE GLYCOL 46 

2. HEALTH EFFECTS 

humidified, filtered room air. Nasal hemorrhaging occurred in all exposed groups of male and female rats 

indicating that propylene glycol can act as a dehydrogenating agent. From week 2 to 14, the average of 

nasal hemorrhaging in male rats was <1, 64, 74, and 75% in controls, low-exposure, medium-exposure, 

and high-exposure groups, respectively. In females, the average indices were <1% in controls, 14% in the 

low-exposure group, and 71% in the medium and high-exposure groups. Animals recovered during nonexposure weekend periods. Similar trends were observed for ocular discharge, with females having 

generally less ocular discharge than males. A significant reduction in body weight of 5-7% starting on day 

50 and continuing until the end of the study was observed in female rats receiving the highest dose of 

707 ppm propylene glycol. Similar observation was made in the group receiving 321 ppm of propylene 

glycol but later in the study starting on day 64. This body weight reduction was correlated with a 

significant reduction in food consumption beginning on study days 43 and 50 for the high- and mediumexposure females, respectively. Female rats exposed to 321 ppm propylene glycol had a significant 

decrease in white blood cell count and lymphocyte numbers. Female rats exposed to 707 ppm propylene 

glycol had a significant decrease in hemoglobin concentration, white blood cell count and lymphocyte 

numbers. Male rats in the medium (321 ppm) and high (707 ppm) groups had a significant decrease in 

serum sorbitol dehydrogenase and gamma-glutamyl transferase. A significant decrease in total serum 

protein was observed in male rats treated with high dose (707 ppm) of propylene glycol while females 

treated with a medium dose (321 ppm) of propylene glycol had an increase in total serum protein. These 

changes were considered to be sporadic. Kidney weight was decreased at 321 ppm in both sexes. 

Although there were no treatment-related gross pathology changes, light microscopy revealed thickening 

of respiratory epithelium with increase in the number of goblet cells and their mucin content in both 

female and male animals receiving medium and high propylene glycol dose. Minute volume, tidal 

volume, and respiratory rates were not significantly altered in rats exposed to 51, 321, or 707 ppm 

propylene glycol for 13 weeks, suggesting that animals adapted to the exposure concentrations. 

Oral MRLs 

No MRLs for acute-, intermediate-, or chronic-duration oral exposure to propylene glycol were derived 

because data are insufficient. 

Death. There were no reports in the literature of human death due to propylene glycol exposure by any 

route, at any level, for any length of time. Lethal oral doses for rats, mice, and guinea pigs range from 

8,000 to 46,000 mg/kg (Clark et al. 1979; EPA 1987a). Monkeys died after inhalation exposure to 
 

 

 

 

 

 

 

 

 

 

 

PROPYLENE GLYCOL 47 

2. HEALTH EFFECTS 

112 ppm propylene glycol after 13 months (Robertson et al. 1947). It is unlikely that sufficient amounts 

of propylene glycol would be inhaled, ingested, or absorbed through the skin to be fatal. 

Systemic Effects 

Respiratory Effects. Acute respiratory arrest was observed in an 8-month-old infant being treated for 

second and third degree bums with an topical antibiotic formulation containing propylene glycol (Fligner 

et al. 1985). The contribution of the bum injury and the antibiotic therapy to the respiratory arrest, 

however, is not known. Anecdotal accounts of respiratory irritation after exposure to propylene glycol as 

a mist or vapor in theatrical productions was found in the literature (Rossol 1990). Studies of laboratory 

animals are inconclusive with respect to the respiratory effects of propylene glycol (Konradova et al. 

1978; Suber et al. 1989). 

Cardiovascular Effects. Very limited information is available in humans and animals on 

cardiovascular effects after exposure to propylene glycol. In the case of the 8-month-old infant mentioned 

above, cardiac arrest accompanied the respiratory arrest (Fligner et al. 1985). The contribution of the 

infant’s injuries to the observed symptoms is not known. No cardiovascular effects were noted in rats 

after 2 years of exposure to oral doses of propylene glycol up to 49,500 ppm (Morris et al. 1942). 

Myocardial edema was observed in a horse prior to death from an accidental oral administration of 

7,904 mg/kg propylene glycol (Dorman and Haschek 1991). 

Gastrointestinal Effects. There were no reports of the effects of propylene glycol on the 

gastrointestinal system of humans. Propylene glycol is approved as a direct food additive. Toxicity to the 

gastrointestinal system has been shown to be negligible. In rats, only a very large oral dose of 

23,500 mg/kg caused hemorrhagic enteritis (Clark et al. 1979). Monkeys and rats exposed by inhalation to 

concentrations of propylene glycol up to 112 ppm for 13-18 months had no gastrointestinal effects 

(Robertson et al. 1947). The effect of orally administered propylene glycol on the brush border membrane 

from the jejuno-ileum portion of the intestines of rats was investigated in vivo and in vitro (Morshed et al. 

1991a). In rats receiving 2,942 mg/kg propylene glycol for 10-30 days, brush border enzymes including 

sucrase, lactase, and gamma-glutamyl transpeptidase exhibited a tendency toward increased activity. 

Absorption of D-glucose and calcium was increased after 10 days of treatment, whereas absorption of 

D-glucose, glycine, L-aspartic acid, L-lysine, and calcium were elevated after 20 or 30 days of treatment. 

The structural integrity of the jejunal surface was not adversely affected. When evaluated in vitro, 

propylene glycol inhibited sucrase, lactase, and maltase, in a non-competitive dose-related manner, with 
 

 

 

 

 

 

 

 

 

 

PROPYLENE GLYCOL 48 

2. HEALTH EFFECTS 

sucrase being the most affected. Nutrient transport was not altered. These studies suggest that ingested 

propylene glycol may influence intestinal digestive and absorptive functions, and that the in vivo and in 

vitro effects are through different mechanisms. 

Hematological Effects. Propylene glycol does not appear to adversely affect hematological 

parameters in humans (Lolin et al. 1988). In animals, however, intermediate- and chronic-duration 

exposure to propylene glycol may lead to hemolysis of red blood cells. For example, propylene glycol is 

used as a moistening agent in cat food. Studies of cats fed 1,200 mg/kg/day and higher doses of propylene 

glycol for 2-17 weeks exhibited hypocellularity of the bone marrow, increased Heinz body formation and 

decreased RBC survival (Christopher et al. 1989a; Weiss et al. 1990, 1992). Similar results were seen in 

dogs after chronic exposure to 5,000 mg/kg/day (Weil et al. 1971). 

Musculoskeletal Effects. No in vivo data on musculoskeletal effects of propylene glycol were found 

in the literature. Propylene glycol was shown to cause damage with subsequent creatine kinase release 

from rat skeletal muscle (Brazeau and Fung 1990). Attempts to elucidate the mechanism of this damage 

suggested that propylene glycol-mediated damage of skeletal muscle may be caused by an intracellular 

mechanism rather than by a direct action on the sarcolernma, and that the mechanism may involve 

calcium. Frog muscle preparations exhibit increased twitch tension in the presence of propylene glycol 

(Hattori and Maehashi 1993). Propylene glycol appears to facilitate transmitter release from the nerve 

terminals and raise the acetylcholine sensitivity of the muscle endplate. 

Renal Effects. No in vivo studies describing frank renal toxicity for propylene glycol alone were 

found (Christopher et al. 1989a; Gaunt et al. 1972; Robertson et al. 1947; Suber et al. 1989). Polyuria and 

polydipsia have been observed in cats ingesting 8,000 mg/kg/day propylene glycol for 3 or more weeks 

(Christopher et al. 1989a, 1990b). Propylene glycol has been shown to damage the membranes of human 

proximal tubule cells in culture (Morshed et al. 1994). Lactate release was increased and glucose 

accumulation decreased in human proximal tubule cells prior to observation of membrane damage, 

indicating that damage was occurring even when the plasma membrane appeared to be unaffected. 

Dermal Effects. Propylene glycol has few irritative properties in humans when applied topically, 

except in the case of unusual sensitivity (Aberer et al. 1993; Corrazza et al. 1993; Hannuksela et al. 1975; 

Kinnunen and Hannuksela 1989; Trancik and Maibach 1982; Warshaw and Herrmann 1952; Willis et al. 

1989). 
 

 

 

 

 

 

 

 

 

 

 

PROPYLENE GLYCOL 49 

2. HEALTH EFFECTS 

Body Weight Effects. Propylene glycol has little effect on body weight. Exposure of rhesus monkeys 

to 112 ppm propylene glycol by inhalation for up to 13 months had no effect on body weight, whereas in 

the same study, rats treated to the same dose for 18 months exhibited a 50% decrease in body weight 

(Robertson et al. 1947). In another study, rats exposed to 321 ppm for an intermediate period of time had 

decreased body weight (Suber et al. 1989). 

Metabolic Effects. Propylene glycol causes acidosis, through conversion to lactic and pyruvic acids. 

However, the acidosis from propylene glycol is not as severe as that caused by ethylene glycol. Evidence 

of this comes from clinical cases of dermal or intravenous treatment with drug formulations containing 

propylene glycol (Fligner et al. 1985; Glasgow et al. 1983; Huggon et al. 1990; Kelner and Bailey 1985). 

Acidosis also occurs after ingestion of large amounts of propylene glycol (Lolin et al. 1988). Increased 

osmolal gap was observed in cats after ingestion of 1,600 mg/kg/day propylene glycol for 5 weeks 

(Christopher et al. 1990b). It seems possible that metabolic acidosis could develop in humans after 

exposure to large doses. 

High levels of propylene glycol in the plasma can lead to an increase in the osmolal gap. Propylene glycol 

is oxidatively converted to lactic and pyruvic acids which, if present in sufficient amounts, contribute to a 

metabolic acidosis. However, acidosis from propylene glycol is not as severe as that due to ethylene 

glycol. An 8-month-old infant with a severe burn was topically treated with 9,000 mg/kg/day of 

propylene glycol used as a vehicle for silver sulfadiazine (Fligner et al. 1985). 

The osmolal gap reached a maximum of 130 milliosmoles/kg 14 days after the treatment started, while 

serum propylene glycol level peaked at 1,059 mg/dL. Due to the high dose of propylene glycol, and the 

possible concomitant effects of both the bum injury and the sulfadiazine therapy, the actual source of the 

metabolic effect in this infant could not be determined, although propylene glycol cannot be ruled out as 

the causative agent. The burn injury may have contributed to the increased absorption of propylene glycol 

and hence, the hyperosmolality. Another infant developed increased osmolality after being exposed 

intravenously to propylene glycol (2.4 mg/kg) used as a vehicle for Enoximone (Huggon et al. 1990). 

However, in another study of acute dermal propylene glycol exposure of 12 adults to 6,100 mg/kg/day for 

5 days, propylene glycol had no effect on either serum osmolality or lactic acid levels (Commens 1990). 

Increased serum propylene glycol levels, increased lactate, and increased total acid (serum lactate and 

pyruvate) were also found in a retrospective study of 35 human sera samples and 8 cerebrospinal fluid 

samples from patients receiving intravenous medications with propylene glycol as the vehicle (Kelner and 

Bailey 1985). The daily dose of propylene glycol ranged from 57 to 771 mg/kg. None of the sera samples 
 

 

 

 

 

 

 

 

 

 

 

 

PROPYLENE GLYCOL 50 

2. HEALTH EFFECTS 

were specifically collected for determination of propylene glycol levels; therefore, the time between 

propylene glycol administration and serum collection varied and was not specified in the report. However, 

statistically significant correlation was found between the lactate levels in serum and cerebrospinal fluid 

samples and the corresponding propylene glycol concentrations (Kelner and Bailey 1985). Although the 

results of these studies are not conclusive, it seems that increased lactate levels leading to acidosis and 

increased osmolality may develop in humans in the event high levels of propylene glycol are absorbed 

into the blood stream. 

Immunological and Lymphoreticular Effects. Since propylene glycol is used in topical 

formulations, it has been investigated as both an irritant and contact allergen (Hannuksela et al. 1975; 

Kinnunen and Hannuksela 1989; Willis et al. 1988). Results indicate that except in rare cases (Corrazza et 

al. 1993; Hannuksela et al. 1975; Tranick and Maibach 1982) the irritative properties of propylene glycol 

are minimal and cannot be classified as allergic reactions (Aberer et al. 1993; Hannuksela and Forström 

1978; Willis et al. 1989). There was no effect on the spleen in rats or monkeys exposed to 112 ppm 

aerosolized propylene glycol for up to 18 months (Robertson et al. 1947; Suber et al. 1989). 

Propylene glycol in a concentration of 0.5-1.0% has been shown to inhibit natural cytotoxicity and 

neutrophil chemiluminescence in human cells in vitro (Denning and Webster 1987). The authors suggest 

that propylene glycol has cytotoxic properties, and should be evaluated in light of this information. 

Neurological Effects. Mild neurological effects have been observed in dermally sensitive individuals 

after an oral challenge dose of 2-15 mL of propylene glycol (Hannuksela and Forström 1978). In the case 

of ingestion of a large amount of propylene glycol, neurotoxic symptoms including stupor and repetitive 

convulsions were noted (Lolin et al. 1988). Neurological effects were also noted in patients receiving 

887 mg/kg propylene glycol 3 times daily, but those effects were complicated by co-ingestion of ethanol 

(Yu et al. 1985). Adverse effects have also been observed in rats prior to death (Clark et al. 1979), and in 

cats (Christopher et al. 1990b). Based on these data, however, it seems unlikely that low level exposure to 

propylene glycol would cause neurotoxicity. 

Reproductive Effects. Studies in humans have not addressed whether propylene glycol adversely 

affects the reproductive system. In rats and mice, no adverse effects on the reproductive competence of 

these animals were observed after oral treatment as high as 10,000 mg/kg/day during gestation, or 

inhalation exposure to 112 ppm for 18 months (Kavlock et al. 1987; NTP 1985; Robertson et al. 1947). 
 

 

 

 

 

 

 

 

 

 

PROPYLENE GLYCOL 51 

2. HEALTH EFFECTS 

Developmental Effects. Specific in vivo studies have not addressed the developmental toxicity of 

propylene glycol in humans or animals. In vitro studies of embryonic development suggest that propylene 

glycol alters the development of mouse zygotes (Damien et al. 1989, 1990). Treatment with propylene 

glycol caused cell membrane damage and altered pH, resulting in a decrease in embryonic development. 

Genotoxic Effects. Studies in humans or animals have not addressed whether adverse genotoxic 

effects occur after in vivo exposure to propylene glycol. Propylene glycol was not mutagenic in 

S. typhimurium strains TA98, TA100, TA1535, TA1537, and TA1538 with and without metabolic 

activation (Clark et al. 1979; Pfeiffer and Dunkelberg 1980). Propylene glycol was negative for sister 

chromatid exchange and changes in alkaline elution rate using Chinese hamster cells or human fibroblasts 

(Sasaki et al. 1980 as cited in Abe et al. 1982; Swenberg et al. 1976). A summary of genotoxic data for 

propylene glycol is presented in Table 2-4. 

Cancer. There is no evidence that propylene glycol is carcinogenic in humans or animals. 

The National Toxicology Program (NTP) has not classified propylene glycol as a carcinogen. The EPA 

(IRIS 1995) has not assigned propylene glycol a weight-of-evidence classification. 

2.5 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). 

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). Biomarkers of exposure have been used by industrial hygienists in 

limited instances as evidence of exposure to certain chemicals. The preferred biomarkers of exposure are 

generally the substance itself or 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 
PROPYLENE GLYCOL 52 

2. HEALTH EFFECTS 

Table 2-4. Genotoxicity of Propylene Glycol In Vitro 

Results 

With Without 

Species (test system) End point activation activation Reference 

Prokaryotic organisms: 

Salmonella typhimurium Gene mutation – – Clark et al. 1979 

Gene mutation – – Pfeiffer and Dunkelberg 

1980 

Mammalian cells 

Human fibroblasts Chromosome – – Sasaki et al. 1980 

aberrations 

Chinese hamster cells Chromosome – – Sasaki et al. 1980 

aberrations 

Chinese hamster lung cells DNA damage – – Swenberg et al. 1976 

– = negative result 
 

 

 

 

 

 

 

 

PROPYLENE GLYCOL 53 

2. HEALTH EFFECTS 

substance and all of its metabolites may have left the body by the time biologic 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 propylene glycol are discussed in Section 2.4.1. 

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 often not substance specific. They also may not be directly adverse, 

but can indicate potential health impairment (e.g., DNA adducts). Biomarkers of effect have been used by 

clinicians to guide them in diagnoses and treatment. Biomarkers of effects caused by propylene glycol are 

discussed in Section 2.4.2. 

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, biologically 

effective dose, or target tissue response. Biomarkers of susceptibility may be defined, for all practical 

purposes, as the susceptibility of the individual, relative to its own population. If biomarkers of 

susceptibility exist, they are discussed in Section 2.6, Populations That Are Unusually Susceptible. 

2.5.1 Biomarkers Used to Identify or Quantify Exposure to Propylene Glycol 

Propylene glycol can also be detected in the blood a short time after exposure to a large amount. There are 

no other specific biomarkers for propylene glycol exposure. Since propylene glycol is considered a safe 

additive for food, cosmetics, and pharmaceuticals, other specific tests of propylene glycol exposure have 

not been developed. 

2.5.2 Biomarkers Used to Characterize Effects Caused by Propylene Glycol 

Propylene glycol is not associated with any specific biomarkers of effect. Dermal irritation may occur 

after repeated exposure, and suspect drug or cosmetic preparations should be examined closely for 

propylene glycol content. 
 

 

 

PROPYLENE GLYCOL 54 

2. HEALTH EFFECTS 

For more information on biomarkers for renal and hepatic effects of chemicals see ATSDR/CDC 

Subcommittee Report on Biological Indicators of Organ Damage (1990) and for information on 

biomarkers for neurological effects see OTA (1990). 

2.6 INTERACTIONS WITH OTHER CHEMICALS 

In the first step of biotransformation, propylene glycol is catalyzed by alcohol dehydrogenase. 4-Methyl 

pyrazole is an inhibitor of propylene glycol metabolism (Morshed et al.1988). 4-methyl pyrazole may 

reduce potential toxic effects of propylene glycol and act as an antidote by interfering with the 

biodegradation of propylene glycol. 

Review of the literature regarding the interaction and influence of other chemicals on the toxicity of 

propylene glycol revealed that propylene glycol is often used as a vehicle for administration of certain 

medications such as Valium, Dilantin, Nembutal (Kelner and Bailey 1985), dihydrotachysterol (DHT) 

(Arulanantham and Genel 1978), Ketoconazole cream (Eun and Kim 1989), and Enoximone (Huggon et 

al. 1990). Among the observed effects were seizures and cerebral irritability (DHT), increased serum 

lactate (Valium, Dilantin, and Nembutal), increased serum osmolality (Enoximone), and skin allergy 

(Ketoconazole cream). All these adverse effects are attributed to propylene glycol and associated with the 

prolonged administration of these medications using propylene glycol as the vehicle. However, the 

precise interaction between propylene glycol and these medications was not investigated. 

In rats, hexobarbital-induced sleeping time was prolonged in the presence of propylene glycol (Dean and 

Stock 1974), probably because of competition for drug-metabolizing enzymes. Studies in rabbits have 

shown that propylene glycol inhibited the elimination of 8-chlorotheophylline and dimenhydrinate from 

the blood, due to a diminished metabolism of the two drugs (Walters et al. 1993). 

2.7 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE 

A susceptible population will exhibit a different or enhanced response to propylene glycol compared to 

most persons exposed to the same level of propylene glycol in the environment. Reasons include genetic 

makeup, developmental stage, health and nutritional status, and chemical exposure history. These 

parameters may result in decreased function of the detoxification and excretory processes (mainly hepatic 

and renal) or compromised function of target organs. For these reasons, the elderly with declining organ 

function, people with unusual chemical exposure history, heavy users of alcohol, and the youngest of the 

population with immature and developing organs will generally be more vulnerable to toxic substances 
 

 

 

 

 

 

 

 

 

PROPYLENE GLYCOL 55 

2. HEALTH EFFECTS 

than healthy adults. Populations who are at greater risk due to their unusually high exposure are discussed 

in Section 5.6, Populations With Potentially High Exposure. 

No information was found on populations with unusual sensitivity to propylene glycol. However, 

populations that may show increased sensitivity include very young children, who have immature hepatic 

detoxification systems, and individuals with impaired liver or kidney function. Studies of burn patients 

indicate the absorption of propylene glycol from antibiotic preparations can be correlated with total bum 

surface area and the severity of the bum (Kulick et al. 1985). Thus, burn patients may be at a higher risk 

for possible adverse effects of propylene glycol. In addition, propylene glycol has been found in the blood 

of alcoholics with cirrhosis of the liver, in the absence of measurable blood alcohol (Casazza et al. 1987). 

Thus, alcoholics with liver disease may comprise a population that is unusually susceptible to the effects 

of propylene glycol. 

2.8 METHODS FOR REDUCING TOXIC EFFECTS 

2.8.1 Reducing Peak Absorption Following Exposure 

No studies on reducing peak absorption of propylene glycol after inhalation exposure were found. The 

pharmacokinetic properties of propylene glycol are not completely understood, but absorption from the 

gastrointestinal tract after oral exposure is fairly rapid. The maximum plasma concentration of propylene 

glycol in humans is reached within 1 hour after oral exposure, while the elimination half-life is about 

4 hours. The total body clearance is about 0.1 L/kg/hour and seems to be serum concentration dependent 

(Yu et al. 1985). Dose-dependent elimination is seen in rats, with saturation of the pathways at doses 

above 5,880 mg/kg (Morshed et al. 1988). However, no studies on reducing peak absorption following 

oral exposure were found. 

Studies on the dermal absorption of propylene glycol in rats indicate that absorption into the dermis is 

enhanced by the addition of fatty acids (Takeuchi et al. 1993, 1995). Thus, cleaning of the skin with a 

defatting solvent, followed by washing with water, may reduce absorption of propylene glycol after 

dermal exposure. 

2.8.2 Reducing Body Burden 

No methods for reducing the body burden of propylene glycol after inhalation, oral, or dermal exposure 

were found. 
 

 

 

 

 

 

 

 

 

 

PROPYLENE GLYCOL 56 

2. HEALTH EFFECTS 

2.8.3 Interfering with the Mechanism of Action for Toxic Effects 

Toxicity studies of propylene glycol in laboratory animals can be found in the literature, but findings of 

adverse effects are rare. Clinical studies in the literature consist of infrequent sensitivity reactions, 

primarily to drug preparations, where pre-existing conditions requiring the drug come into play. There are 

two main reasons for that: 1) propylene glycol biodegradation proceeds via lactate to pyruvate in human 

metabolism, and 2) a significant amount of propylene glycol is excreted unchanged or as glucuronide 

conjugate via the renal pathway (Hannuksela and Forström 1978). Propylene glycol exhibits few of the 

toxic properties of ethylene glycol. Since, however, it does cause metabolic acidosis, albeit to a lesser 

extent that ethylene glycol, correction of the acid-base imbalance would also be helpful in preventing 

subsequent effects. 

2.9 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 propylene glycol 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 propylene glycol. 

The following categories of possible data needs have been identified by scientists from ATSDR. 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 fulfilled. In the future, the identified data needs will be evaluated and prioritized, and a 

substance-specific research agenda will be prepared. 

2.9.1 Existing Information on Health Effects of Propylene Glycol 

Existing information on health effects of propylene glycol is shown in Figure 2-4. The purpose of this 

figure is to illustrate the existing information concerning the health effects of propylene glycol, 

respectively. 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 
2. HEALTH EFFECTS 

Death 

Acute 

Intermediate

Chronic 

Immunologic/Lymphoretic

Neurologic

Reproductive

Developmental

Genotoxic

Cancer 

Figure 2-4. Existing Information on Health Effects of Propylene Glycol 

Death 

Acute 

Intermediate

Chronic 

Immunologic/Lymphoretic

Neurologic

Reproductive

Developmental

Genotoxic

Cancer 

Systemic 

Inhalation 

Oral 

Dermal 

Human 

Inhalation 

Oral 

Dermal 

Systemic 

Animal 

Existing Studies 

PROPYLENE GLYCOL 57 
 

 

 

 

 

 

PROPYLENE GLYCOL 58 

2. HEALTH EFFECTS 

defined in ATSDR’s Decision Guide for Identifying Substance-Specific Data Needs Related to 

Toxicological Profiles (ATSDR 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. 

There is very little data on health effects of propylene glycol in humans. No data for humans were found 

for inhalation exposure of humans. Data exist for inhalation exposure of animals for acute-, intermediate-, 

and chronic-duration exposure. 

Some acute oral data exist for humans, but the information is scanty and includes systemic, and 

neurological effects after acute exposure. Propylene glycol is considered GRAS by the FDA, and thus 

oral exposure through foods is considered safe. With respect to this, animal data for oral exposure are 

more extensive, and all categories of health effects except in vivo genotoxicity are included. 

Propylene glycol is used extensively in topical drug formulations and cosmetics. The majority of reports 

of human dermal studies describe sensitivity reaction (or, lack of reaction) to these preparations. Human 

dermal data includes acute-duration effects, and immunological and neurological effects. Animal data 

describing dermal exposure are limited to acute-duration effects and an evaluation of immunological and 

neurological effects. 

People living near hazardous waste sites or near sites where propylene glycol is manufactured may be 

exposed to propylene glycol by ingestion of contaminated water. Since propylene glycol is an approved 

food additive, ingestion of small amounts would not be considered a health risk. Inhalation exposure is 

not a likely route for toxic health effects. Dermal exposure to propylene glycol has been associated with 

sensitivity reactions, although the data are confusing. Increased use of propylene glycol in foods and 

cosmetics, and as a substitute for ethylene glycol suggests that general exposure to propylene glycol will 

be more frequent and at higher levels than previously experienced by the general population. Therefore, 

additional research in these areas may be warranted. 

2.9.2 Identification of Data Needs 

Acute-Duration Exposure. No information was available for acute-duration inhalation exposure to 

propylene glycol in humans. Only one study in animals was found to provide some information for acuteduration inhalation exposure (Konradova et al. 1978). Rabbits were exposed to only one dose (10% 
 

 

 

 

 

 

 

 

PROPYLENE GLYCOL 59 

2. HEALTH EFFECTS 

aerosol) of propylene glycol for 20 or 120 minutes, and an increased number of degenerated goblet cells 

in the tracheal lining was observed. No other data were available from this study and the importance of 

these findings is unclear. Information regarding acute-duration oral exposure to propylene glycol in 

humans (Frosch et al. 1990; Hannuksella and Forstrom 1978; Lolin et al. 1988; Nelson et al. 1987) and 

animals is more abundant (Clark et al. 1979; Dorman and Haschek 1991; Kavlock et al:1987; Morshed et 

al. 1991a; Ruddick 1972; Studer et al. 1993; Weiss et al. 1992). Acute-duration dermal exposure to 

propylene glycol in humans (Commens 1990; Corazza et al. 1993; Eun and Kim 1989; Fligner et al. 1985; 

Kinnunen and Hannuksela 1989; Kulick et al. 1985; Willis et al. 1988) and animals has been reported 

(Clark et al. 1979), although data are scarce. 

Death has been shown to occur after acute-duration oral exposure to propylene glycol (Clark et al. 1979; 

Dorman and Haschek 1991; Gordon and Hunter 1982; Ruddick 1972). With the exception of 

hematological effects in cats after oral exposure (Weiss et al. 1992), there does not appear to be a target 

system for propylene glycol effects. Sensitization reactions have been reported in humans after acuteduration dermal exposure (Corazza et al. 1993; Hannuksella and Forstrom 1978). 

No acute-duration inhalation MRL could be derived for propylene glycol because no adequate studies 

were found. In the single acute-duration inhalation study found in the literature (Konradova et al. 1978), 

only one dose was used, and sufficient information was not provided on which to base and MRL. No 

acute-duration oral MRL could be derived for propylene glycol because no adequate studies were found. 

With regard to the human studies (Frosch et al. 1990; Hannuksella and Forstrom 1978; Lolin et al. 1988; 

Nelson et al. 1987), only one dose was tested, data were sparse, or the exact dose was not known. Acuteduration oral studies in animals focused on death (Clark et al. 1979; Ruddick 1972), involved a single 

dose (Dorman and Haschek 1991; Kavlock et al 1987; Morshed et al. 1991a; Studer et al. 1993), or 

discussed species-specific effects (Weiss et al. 1992). Thus, none of these studies were adequate for 

deriving an MRL. 

Intermediate-Duration Exposure. No studies of intermediate-duration inhalation exposure of 

humans to propylene glycol were found. One intermediate-duration inhalation study of propylene glycol 

in rats was found in the literature (Suber et al. 1989). No studies of intermediate-duration oral exposure of 

humans to propylene glycol were found. Studies of intermediate-duration oral exposure of animals were 

more abundant (Bauer et al. 1991; Christopher et al. 1989a; Morshed et al. 1991a; NTP 1985; Weiss et al. 

1990). No studies of intermediate-duration dermal exposure to propylene glycol were found in animals. 
 

 

 

 

 

 

 

PROPYLENE GLYCOL 60 

2. HEALTH EFFECTS 

One intermediate-duration dermal exposure study in humans described primarily dermal irritative effects 

of propylene glycol (Trancik and Maibach 1982). 

No reports of death in animals after intermediate-duration exposure to propylene glycol were found. 

Systemic effects after inhalation exposure of rats included nasal hemorrhaging, hematological effects, and 

decreased kidney and body weight (Suber et al. 1989). Cats exhibit characteristic hematotoxicity (Heinz 

body formation) after intermediate-duration oral exposure (Bauer et al. 1991; Christopher et al. 1989a; 

Weiss et al. 1990), although no other targets for toxicity were apparent. 

An intermediate-duration inhalation MRL was derived for propylene glycol based on nasal hemorrhaging 

in rats (Suber et al. 1989). No intermediate-duration oral MRL could be derived due to a lack of suitable 

studies. Of the intermediate-duration oral exposure studies found, none were in humans; animal studies 

included species-specific effects in cats (Bauer et al. 1991; Christopher et al. 1989a; Weiss et al. 1990), 

studies with a single dose (Morshed et al. 1991a), or studies with no adverse effects observed (NTP 

1985). 

Chronic-Duration Exposure and Cancer. No chronic-duration studies of human exposure to 

propylene glycol alone by inhalation, oral, or dermal administration were found in the literature. One 

study of chronic-duration inhalation exposure of animals (Robertson et al. 1947), and one study of dermal 

exposure of animals (Stenback and Shubik 1974) were found. Data for chronic-duration oral exposure of 

animals to propylene glycol is more abundant (Gaunt et al. 1972; Morris et al. 1942; Weil et al. 1971). 

Tumorigenesis was evaluated after inhalation and dermal exposure (Robertson et al. 1947; Stenback and 

Shubik 1974). 

After inhalation exposure to propylene glycol for 13 months, 13 of 29 rhesus monkeys died (Robertson et 

al. 1947). Death was not observed in rats or dogs after exposure to oral doses of propylene glycol of 

2,500 or 5,000 mg/kg/day, respectively, for 2 years (Gaunt et al. 1972; Weil et al. 1971). No reports of 

death after dermal exposure were found. Systemic effects noted after inhalation. exposure of animals to 

propylene glycol were few, and included increased hemoglobin in monkeys and increased body weight in 

rats (Robertson et al. 1947). Similarly, only hematological effects, including decreased erythrocytes, 

hemoglobin, and hematocrit were observed in dogs at 5,000 mg/kg/day (Weil et al. 1971). 
 

 

 

 

 

 

 

 

 

 

PROPYLENE GLYCOL 61 

2. HEALTH EFFECTS 

No evidence of tumorigenesis was noted after oral exposure of rats to doses of propylene glycol up to 

2,500 mg/kg/day for 2 years (Gaunt et al. 1972), or dermal exposure of mice to 20 mg applied twice 

weekly for 120 weeks (Stenback and Shubik 1974). 

No MRLs for chronic-duration inhalation exposure to propylene glycol could be derived due to a lack of 

appropriate studies in the literature. No studies were found for humans, and in the one animal study found 

(Robertson et al. 1947), the effects cited (increased hemoglobin and body weight) were not appropriate 

effects on which to base an MRL. No MRLs for chronic-duration oral exposure to propylene glycol could 

be derived due to a lack of appropriate studies in the literature. In the one study found (Gaunt et al. 1972), 

no adverse effects were noted. 

Immunological and Lymphoreticular Effects. Since propylene glycol is used in topical 

formulations, it has been investigated as both an irritant and contact allergen (Hannuksela et al. 1975; 

Kinnunen and Hannuksela 1989; Tranick and Maibach 1982; Willis et al. 1988). Results indicate that 

except in rare cases (Corrazza et al. 1993; Hannuksela et al. 1975; Trancik and Maibach 1982) the 

irritative properties of propylene glycol are minimal (Aberer et al. 1993; Hannuksela and Forström 1978; 

Willis et al. 1989). There was no effect on the spleen in rats or monkeys exposed to 112 ppm aerosolized 

propylene glycol for up to 18 months (Robertson et al. 1947; Suber et al. 1989). 

Propylene glycol in a concentration of 0.5-1.0% has been shown to inhibit natural cytotoxicity and 

neutrophil chemiluminescence in human cells in vitro (Denning and Webster 1987). The authors suggest 

that propylene glycol has cytotoxic properties and should be evaluated in light of this information. 

The data describing the immunotoxicity of propylene glycol is not clear. Further in vivo animal studies 

would be helpful in defining the immunotoxic effects of propylene glycol. 

Neurological Effects. Mild neurological effects have been observed in dermally sensitive individuals 

after an oral challenge dose of 2-15 mL of propylene glycol (Hannuksela and Forström 1978). In the case 

of ingestion of a large amount of propylene glycol, neurotoxic symptoms including stupor and repetitive 

convulsions were noted (Lolin et al. 1988). Neurological effects were also noted in patients receiving 

887 mg/kg propylene glycol 3 times daily, but those effects were complicated by co-ingestion of ethanol 

(Yu et al. 1985). Adverse effects have also been observed in rats prior to death (Clark et al. 1979) and in 

cats (Christopher et al. 1990b). Based on these data, however, it seems unlikely that low level exposure to 

propylene glycol would cause neurotoxicity. Further studies of the neurological effects of propylene 

glycol would be helpful in defining the toxicity of the compound. 
 

 

 

 

 

 

 

 

 

 

 

PROPYLENE GLYCOL 62 

2. HEALTH EFFECTS 

Genotoxicity. Although propylene glycol has been extensively evaluated in genetic toxicity test 

systems, the existing studies provide convincing evidence that it is not genotoxic. 

Studies in humans or animals have not addressed whether adverse genotoxic effects occur after in vivo 

exposure to propylene glycol. However, propylene glycol was not mutagenic in S. typhimurium strains 

with and without metabolic activation (Clark et al. 1979; Pfeiffer and Dunkelberg 1980). In addition, 

propylene glycol was negative for sister chromatid exchange and changes in alkaline elution rate using 

Chinese hamster cells or human fibroblasts (Sasaki et al. 1980 as cited in Abe et al. 1982; Swenberg et al. 

1976). Based on these results, it seems likely that propylene glycol does not represent a genotoxic risk to 

exposed persons. An in vivo study would complete the database of the genotoxic effects of propylene 

glycol. 

Reproductive Toxicity. Studies in humans have not addressed whether propylene glycol adversely 

affects the reproductive system. In rats and mice, no adverse effects on the reproductive competence of 

these animals were observed after oral treatment at doses as high as 10,000 mg/kg/day during gestation of 

1 generation or for multiple litters and 2 generations of mice (Kavlock et al. 1987; NTP 1985) or 

inhalation exposure to 112 ppm for 18 months (Robertson et al. 1947). Further evaluation of the 

reproductive toxicity of propylene glycol is not necessary. 

Developmental Toxicity. Propylene glycol does not appear to be a developmental toxicant in 

animals. Pregnant female Swiss mice given 10,000 mg/kg/day propylene glycol by mouth on Gd 8-12 

showed no adverse developmental effects (Kavlock et al. 1987). No adverse effects of propylene glycol 

on the development of Swiss (CD-l) mice were noted after doses of approximately 10,000 mg/kg/day 

(NTP 1985). In vitro studies of embryonic development suggest that propylene glycol alters the 

development of mouse zygotes (Damien et al. 1989, 1990). Treatment with propylene glycol caused cell 

membrane damage and altered pH, resulting in a decrease in embryonic development. The relevance of 

these results to in vivo exposure is not clear. Further studies of developmental toxicity of propylene 

glycol do not appear to be necessary. 

Epidemiological and Human Dosimetry Studies. No reliable epidemiological studies of 

propylene glycol exposure are available. Increased use of propylene glycol in food and in drugs and 

cosmetics suggests that oral and dermal exposures are the most important routes of exposure for the 

general population. In addition, the substitution of propylene glycol in applications where ethylene glycol 
 

 

 

 

 

 

 

 

 

 

 

 

PROPYLENE GLYCOL 63 

2. HEALTH EFFECTS 

was previously used will create new subpopulations for exposure. Epidemiological and human dosimetry 

studies of these subpopulations would be helpful in evaluating propylene glycol toxicity in these 

increased applications of use. 

Biomarkers of Exposure and Effect. 

Exposure. Propylene glycol can be detected in the blood a short time after exposure to a large amount. 

There are no other specific biomarkers for propylene glycol exposure. Since propylene glycol is 

considered a safe additive for food, cosmetics, and pharmaceuticals, other specific tests of propylene 

glycol exposure have not been developed. Further evaluation of possible biomarkers of exposure to 

propylene glycol would be helpful, especially in light of increased use of propylene glycol in food, 

cosmetics, and drugs. 

Effect. Propylene glycol is not associated with any specific biomarkers of effect. Dermal irritation may 

occur after repeated exposure, and suspect drug or cosmetic preparations should be examined closely for 

propylene glycol content. In light of the increased use of propylene glycol in foods, cosmetics, and drugs, 

identification of biomarkers of propylene glycol effect would be useful in evaluating biological effects of 

propylene glycol exposure. 

Absorption, Distribution, Metabolism, and Excretion. No kinetic data for absorption, 

distribution, metabolism, or excretion in humans or animals of propylene glycol after inhalation exposure 

were found in the literature. Few data were found in the literature describing the kinetics of propylene 

glycol in humans after oral exposure (Yu et al. 1985), but more data were found for animals (Christopher 

et al. 1990b; Huff 1961; Miller and Bazzano 1965; Morshed et al. 1988, 1989, 1991 a). Since propylene 

glycol is used in topical drug preparations, limited data are available for kinetic parameters in humans 

after dermal exposure (Fligner et al. 1985; Kulick et al. 1985; Rigg and Barry 1990), and in animals (Rigg 

and Barry 1990; Takeuchi et al. 1993, 1995). Most of these data concern acute exposures and are limited 

because propylene glycol is considered a safe and innocuous compound. No data were located regarding 

kinetic parameters of propylene glycol after inhalation exposure. Studies are needed in order to 

adequately assess the rates and extent of the toxicokinetic parameters for this route. In light of increased 

use of propylene glycol as a food additive, and in cosmetics and topically applied drugs, additional studies 

of the absorption, distribution, metabolism, and excretion of propylene glycol after oral and dermal 

exposure for acute-, intermediate-, and chronic-duration exposure would be helpful in assessing the 

kinetic properties of the compound by these routes. 
 

 

 

 

 

 

 

 

 

 

PROPYLENE GLYCOL 64 

2. HEALTH EFFECTS 

Comparative Toxicokinetics. The kinetics of propylene glycol have been studied in animals 

(Morshed et al. 1988; Rigg and Barry 1990; Takeuchi et al. 1993, 1995) and to a lesser extent in humans 

(Fligner et al. 1985; Kulick et al. 1985; Rigg and Barry 1990; Yu et al. 1985). However, information on 

the toxicokinetic properties of propylene glycol are limited, based on its nontoxic status. No specific 

target organs have been identified for propylene glycol, although neurological effects have been noted 

after oral exposure (Clark et al. 1979; Hannuksela and Forström 1978; Lolin et al. 1988; Yu et al. 1985). 

Propylene glycol also causes metabolic acidosis, although to a lesser extent than ethylene glycol (Lolin et 

al. 1988; Morshed et al. 1989, 1991b). Little data exist to assist in interspecies comparison of kinetic 

parameters. In light of increased use of propylene glycol in foods, cosmetics, and drugs, and as a 

substitute for ethylene glycol, additional inhalation, oral, and dermal kinetic studies would be helpful in 

predicting human kinetic response to propylene glycol exposure. 

Methods for Reducing Toxic Effects. No studies related to reducing absorption of propylene 

glycol after inhalation or oral exposure were found. Studies on the dermal absorption of propylene glycol 

in rats indicate that absorption into the dermis is enhanced by the addition of fatty acids (Takeuchi et al. 

1993, 1995). Thus, cleaning of the skin with a defatting solvent, followed by washing with water, may 

reduce absorption of propylene glycol after dermal exposure. 

Toxicity studies of propylene glycol in laboratory animals can be found in the literature, but findings of 

adverse effects are rare. Clinical studies in the literature consist of infrequent sensitivity reactions, 

primarily to drug preparations, where pre-existing conditions requiring the drug come into play. There are 

two main reasons for that: 1) propylene glycol biodegradation proceeds via lactate to pyruvate in human 

metabolism, and 2) a significant amount of propylene glycol is excreted unchanged or as glucuronide 

conjugate via the renal pathway (Hannuksela and Forström 1978). Propylene glycol exhibits few of the 

toxic properties of ethylene glycol. Since it does cause metabolic acidosis, although to a lesser extent that 

ethylene glycol, correction of the acid-base imbalance would also be helpful in preventing subsequent 

effects, and the same therapies that are useful in preventing ethylene glycol acidosis would also be useful 

for propylene glycol. Since propylene glycol is significantly less toxic than ethylene glycol, extensive 

study of methods to reduce the possible toxic effects of exposure does not seem warranted. 
 

 

 

 

 

 

PROPYLENE GLYCOL 65 

2. HEALTH EFFECTS 

2.9.3 Ongoing Studies 

The following ongoing studies regarding the health effects of propylene glycol were reported .in the 

Federal Research in Progress File (FEDRIP 1995) database and in recent literature: 

Regulation of Lipid Metabolism in High Producing Dairy Cattle. The principal investigator is R. 

Grummer from the University of Wisconsin School of Dairy Science in Madison, Wisconsin. The 

objective is to determine the regulation of lipid metabolism in adipose tissue, liver and mammary glands 

of high producing dairy cattle. Propylene glycol will be used for reducing plasma nonesterified fatty acids 

during feed restriction. 

Modifying Milk Fat Composition for Improved Manufacturing Qualities and Consumer Acceptability. 

The principal investigator is D. Palmquist from Ohio State University School of Animal Sciences in 

Wooster, Ohio. The objective is to identify and characterize important regulatory steps in fatty acid 

synthesis and desaturation and their positional distribution on glycerol in milk fat, and to quantify 

modification of milk fat composition by manipulating the diet of the cow. Propylene glycol will be used 

as an oral drench to modify energy balance. 

Microbial Safety Criteria for Foods Contacting Reuse Water in Food. The principal investigator is A. 

Miller from the Eastern Regional Research Center in Wyndmoor, Pennsylvania. The objective is to 

identify microbiological risks to food by reuse water during slaughter and further processing, to study 

bacterial attachment mechanisms and develop approaches to dislodge or prevent adhesion of pathogens to 

food surfaces, and to investigate the potential for expanded applications of reuse water to the food plant 

environment. Propylene glycol will be evaluated in the control of microbial growth. 

The Effect of Vitamin E on the Propylene Glycol-Induced Formation of Heinz Bodies. The principal 

investigator is Diane Hatchell from the Department of Veterans Affairs Medical Center, Durham, North 

Carolina. The objective is to test the efficacy of vitamin E as a means of inhibiting the propylene glycolinduced formation of Heinz bodies in cat blood. 
PROPYLENE GLYCOL 66 

2. HEALTH EFFECTS 

This page is intentionally blank. 
PROPYLENE GLYCOL 67 

3. CHEMICAL AND PHYSICAL INFORMATION 

3.1 CHEMICAL IDENTITY 

Information regarding the chemical identity of propylene glycol is located in Table 3-1. 

3.2 PHYSICAL AND CHEMICAL PROPERTIES 

Information regarding the physical and chemical properties of propylene glycol is located in Table 3-2. 
3. CHEMICAL AND PHYSICAL INFORMATION 

Table 3-1. Chemical Identity of Propylene Glycola 

Characteristic Information 

Chemical name Propylene glycol 

Synonyms and trade names 1,2-Dihydroxypropane; 1,2-propanediol; 1,2-propylene glycol; 

2,3-propanediol; hydroxy-propanol; alpha-propylene glycol; methyl 

glycol; methylethyl glycol; monopropylene glycol; trimethyl glycol. 

Registered trade name(s) PG-12; Sirlene 

Chemical formula C3H8O2 

Chemical structureb 

Identification numbers: 

CAS registry 57-55-6 

NIOSH RTECS TY2000000 

EPA hazardous waste No data 

OHM/TADS 7216877 

DOT/UN/NA/IMDG shipping No data 

HSDB 174 

NCI No data 

CH3 

CH2 OH 

C OH 

H2 

 

PROPYLENE GLYCOL 68 

a

All information obtained from HSDB 1994b, except where noted. b

EPA 1987a 

CAS = Chemical Abstracts Service; DOT/UN/NA/IMDG = Department of Transportation/United Nations/North 

America/International 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 
 

PROPYLENE GLYCOL 69 

3. CHEMICAL AND PHYSICAL INFORMATION 

Table 3-2. Physical and Chemical Properties of Propylene Glycola 

Property Propylene glycol 

Molecular weight 76.11b 

Color Colorlessd 

Physical state Liquidb 

Melting point -60 °Ce,b (forms glass) 

Boiling point 187.6; 188.2 °Cb 

Density: 

at 20 °C (g/cm3) 1.0361c 

Odor Odorless 

Odor threshold No data 

Solubility: 

Water at 20 °C Miscible with water 

Organic solvent(s) Soluble in alcohol, ether, benzene, soluble in acetone, chloroformb . 

Partition coefficients: 

Log Kow -0.92f,g 

Log Koc 0.88f, 0.76g 

Vapor pressure at 20 °C 0.07 mm Hgalso d 

Henry's law constant at 25 °C 1.2x10-8 atm-m3/mole; 1.7x10-8 atm-m3/moleg 

Autoignition temperature 421.26 °Ch; 371 °Ci 

Flashpoint 99.04 °Ch,i 

Flammability limits 2.6–12.5%h,i 

Conversion factors 1 ppm = 3.11 mg/m3j 

1 mg/L = 321.6 ppmj 

Explosive limits No data 

a

All information obtained from HSDB 1995b, except where noted.

b

Merck 1989 

c

Weast 1988 

d

Lewis 1993 

e

Daubert and Danner 1980 

f

EPA 1987a 

g

ASTER 1995 

h

Daubert and Danner 1989 

i

NFPA 1994 

j

Rowe and Wolf 1982 
PROPYLENE GLYCOL 70 

3. CHEMICAL AND PHYSICAL INFORMATION 

This page is intentionally blank. 
 

 

 

 

PROPYLENE GLYCOL 71 

4. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

4.1 PRODUCTION 

Propylene glycol is produced commercially from the hydration of propylene oxide (Merck 1989). 

Propylene glycol also is produced by the liquid-phase high pressure reaction (600 atmospheres) of 

synthetic gas in the presence of a rhodium cluster complex (Kirk-Othmer Encyclopedia of Chemical 

Technology 1978). 

The companies that produce propylene glycol in the United States, their production sites, and the annual 

capacities in millions of pounds for 1993 (the most recent year for which figures are available) are shown 

below (SRI 1993). 

Company Production Site Capacity 

ARCO Chemical Company Bayport, TX 374 

Dow Chemical USA Freeport, TX 250 

Plaquemine, LA 150 

Eastman Chemical Company South Charleston, WV 72 

Olin Corporation Brandenburg, KY 70 

Texaco Chemical Company Port Neches, TX 120 

Total Production 1,036 

Over the past few years, production of propylene glycol has remained relatively constant at a level of 

approximately 1,000 million pounds per year (SRI 1989, 1991, 1993, 1995). The production volumes 

were 935, 1,000, 980, and 1,036 million pounds in 1989, 1991, 1993, and 1995, respectively. 

There is no information on facilities that manufacture or process propylene glycol in the United States 

available in the Toxic Release Inventory because information on this chemical is not required to be 

reported (EPA 1995c). 

4.2 IMPORT/EXPORT 

Propylene glycol has been imported into the United States in ever increasing quantities over the last 

several years. Import volume increased from 198,031 kg (0.4 million pounds) in 1992, to 2,167,664 kg 

(4.8 million pounds) in 1993, to 5,249,265 kg (11.6 million pounds) in 1994 (NTDB 1995). 
 

 

 

 

 

 

 

 

 

 

PROPYLENE GLYCOL 72 

4. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

Propylene glycol also has been exported over the last several years with export volume greatly exceeding 

the import volume in any given year. Export volume for propylene glycol has declined slightly since 

1990, but has averaged 77,000,000 kg per year (170 million pounds per year). Export volumes for 

propylene glycol were 94,606,830 kg (209 million pounds), 64,850,502 kg (143 million pounds), 

62,940,802 kg (139 million pounds), 81,531,357 kg (180 million pounds), and 78,997,747 kg 

(174 million pounds) in 1990, 1991, 1992, 1993, and 1994, respectively (NTDB 1995). 

4.3 USE 

Propylene glycol has been used extensively in many different industrial applications because of its 

chemical and physical properties. Propylene glycol dissolves in water and is miscible with alcohol, 

acetone, chloroform, and other organic solvents; has the capacity to hold large amounts of heat before 

boiling; and lowers the freezing point of water (EPA 1987a; Lewis 1993). In addition, propylene glycol is 

hygroscopic, is suitable for use as an industrial humectant, and possesses excellent solvent properties 

(Lewis 1993; Merck 1989; Rowe and Wolf 1982). Approximately 41% of all propylene glycol produced 

is used for unsaturated polyester resin production, 29% is exported, 11% is used in foods, pharmaceutical 

products, and cosmetics, 7% is used in semi-moist pet food, 4% is used as a humectant for tobacco, 4% is 

used in functional fluids, and 4% is for miscellaneous uses (HSDB 1995b). 

The major use of propylene glycol is as an intermediate in the manufacture of cross-linked polyesters and 

hydroxylated polyester resins. In the airline industry, ethylene glycol has been used as a base component 

of de-icing fluids for aircraft, runways, and taxiways (Klecka et al. 1993; Kirk-Othmer Encyclopedia of 

Chemical Technology 1978). Propylene glycol is a solvent and humectant for various pharmaceuticals, 

hair colorant formulations, and food and tobacco products (Kirk-Othmer Encyclopedia of Chemical 

Technology 1978; Merck 1989). In addition, the use of small amounts of propylene glycol is permitted in 

foods as an anticaking agent, antioxidant, dough strengthener, emulsifier, processing aid, stabilizer and 

thickener, surface active agent or texturizer (EPA 1979). In veterinary medicine, propylene glycol is used 

in oral medications for ruminants and as a solvent for various drugs (Merck 1983). As a nontoxic 

antifreeze, propylene glycol is used in breweries and dairy establishments and as an inhibitor of 

fermentation and mold growth (Merck 1989). The chemical has been used as an emollient in 

pharmaceutical and cosmetic creams because it readily absorbs water. Propylene glycol has even been 

used in vapor form as an air sterilizer in hospitals and public buildings, and in veterinary applications to 

protect animals against the spread of airborne bacteria and influenza virus (Kirk-Othmer Encyclopedia of 

Chemical Technology 1978; Rowe and Wolf 1982). Used as a mist, propylene glycol is deployed as a 
 

 

 

 

 

 

 

PROPYLENE GLYCOL 73 

4. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

special effect fog/smoke during theatrical performances, rock concerts, private parties, and in fire training 

programs to simulate fire fighting conditions (Rossol 1993). 

4.4 DISPOSAL 

Propylene glycol is currently listed as a Generally Recognized as Safe (GRAS) additive in foods (FDA 

1982) and is not listed as a toxic substance under Section 313 of the Emergency Planning and Community 

Right-to Know Act under Title III of the Superfund Amendments and Reauthorization Act (EPA 1995c). 

Two methods for treatment of waste water containing propylene glycol include a methane fermentation 

process and a newly developed biotreatment process that uses mixed cultures of bacteria to degrade the 

compound. The methane fermentation process has proven to be a reliable as well as cost and energy 

efficient method for the treatment of domestic sludges and certain industrial waste water containing 

propylene glycol and other organic compounds (Chou et al. 1979). Propylene glycol in effluents from 

propylene oxide production plants contains both high biological oxygen demand/chemical oxygen 

demand (BOD/COD) loads and high chloride concentrations. The high salinity poses problems to waste 

water treatment such as activated sludge and activated carbon absorption processes A novel and 

economically viable propylene glycol biotreatment process recently has been developed that uses a mixed 

culture of engineered bacterial species from the genera Pseudomonas and Aerobacter. The Pseudomonas 

use propylene glycol to produce volatile acids, while Aerobacter were effective in degrading the volatile 

acids to carbon dioxide and water (Raja et al. 1991). 

A new encapsulated biooxidation method has shown potential for the remediation of soil contaminated 

with propylene glycol (Vesper et al. 1994). The encapsulated biooxidation method proposes that sodium 

percarbonate encapsulated in polyvinylidene chloride be inserted in subsurface soil by a method called 

hydraulic fracturing. Oxygen slowly released from the encapsulated sodium percarbonate increases the 

number of glycol-degrading organisms. In a laboratory experiment conducted over a 30-day period at 

12 °C that simulated subsurface soil temperatures, the concentration of propylene glycol was reduced lofold and the number of propylene glycol degrading organisms increases 10-fold compared to live controls 

without the encapsulated sodium percarbonate. This method is expected to remediate soils contaminated 

with glycols via enhanced aerobic biodegradation in subsurface soils. The hydraulic fracturing technique 

that would be used to deliver the encapsulated sodium percarbonate to the subsurface soils involves 

creating horizontal pancake-shaped fractures that are 5 meters in diameter and 1-2 cm in thickness. These 

fractures are stacked vertically in the subsoil, and granular material is injected into each fracture (Vesper 
 

PROPYLENE GLYCOL 74 

4. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

et al. 1994). The advantage of this method is that oxygen can be delivered deep into contaminated 

subsurface soil and then made available slowly to stimulate bacterial growth. 
 

 

 

 

 

 

 

PROPYLENE GLYCOL 75 

5. POTENTIAL FOR HUMAN EXPOSURE 

5.1 OVERVIEW 

Propylene glycol is released to the environment in manufacturing and processing waste streams and as the 

result of disposal of industrial and consumer products containing this compound. The major sources of 

releases are from the use and disposal of this compound in de-icing solutions. Because of its solubility in 

water and lack of adsorption and partitioning to soils, propylene glycol will have high mobility in soil and 

potential to leach into groundwater. Upon release to the environment, the compound is expected to 

partition to and be transported in surface water and groundwater. Propylene glycol is rapidly degraded in 

all environmental media; it is not expected to persist or bioaccumulate in aquatic organisms. 

Biodegradation is the most important transformation process in surface waters and soils. Assuming first 

order kinetics, the half-life of propylene glycol in water is estimated to be l-4 days under aerobic and 3­

5 days under anaerobic conditions. The half-life of propylene glycol in soil is expected to be equal to or 

slightly less than that for water. Vapors released to the atmosphere readily undergo rapid photochemical 

oxidation via reaction with hydroxyl radicals with an estimated half-life of 0.8 days. Little information 

was found on concentrations of this compound in any environmental media. Propylene glycol is a 

Generally Recognized as Safe (GRAS) food additive that is widely used in food and tobacco products, 

pharmaceuticals, and cosmetics. 

The most important routes of exposure to propylene glycol for members of the general population are 

ingestion and dermal contact with products containing this compound. The general public also may be 

exposed to small amounts of propylene glycol released from newly installed carpet with polyvinyl 

backing. In occupational settings, workers are exposed via dermal contact and possibly inhalation in 

applications involving the heating or spray application of fluids containing this compound. 

Propylene glycol has been identified in at least 5 of 1,416 hazardous waste sites that have been proposed 

for inclusion on the EPA NPL (HazDat 1995). However, the number of sites evaluated for propylene 

glycol is not known. The frequency of these sites within the United States can be seen in Figure 5-1. 

5.2 RELEASES TO THE ENVIRONMENT 

Releases of propylene glycol are not required to be reported under SARA Section 313; consequently there 

are no data for this compound in the 1993 Toxic Release Inventory (EPA 1995c). There are at least 5 NPL 
PROPYLENE GLYCOL 76 

5. POTENTIAL FOR HUMAN EXPOSURE 

Figure 5-1. Frequency of NPL Sites with Propylene Glycol Comtamination* 

*Derived from HazDat 1995 
 

 

 

 

 

PROPYLENE GLYCOL 77 

5. POTENTIAL FOR HUMAN EXPOSURE 

hazardous waste sites where propylene glycol has been identified in some environmental media (HazDat 

1995). 

5.2.1 Air 

Little information was found regarding the release of propylene glycol to the atmosphere. Propylene 

glycol used as a solvent in paints, inks, and coatings will slowly volatilize to the atmosphere (EPA 

1987a). During the application of de-icing solutions to aircraft, an estimated 49-80% of de-icing solutions 

containing both ethylene glycol and propylene glycol are released on airport runway aprons. The 

remainder is retained on the aircraft or is immediately dispersed to the air (Sills and Blakeslee 1992); 

however, release to the atmosphere is expected to be limited by the compound’s low vapor pressure. 

There is no information on releases of propylene glycol to the atmosphere from domestic manufacturing 

and processing facilities because these releases are not required to be reported (EPA 1995c). Propylene 

glycol has not been detected in air samples collected at any hazardous waste sites where it was detected in 

some environmental media (HazDat 1995). 

5.2.2 Water 

Propylene glycol is released to surface waters in waste water from production and processing facilities 

and from spills and in runoff (e.g., through the use of the compound in de-icing fluids). Propylene glycol 

concentrations up to 19,000 mg/L (ppm) were detected in storm water runoff at the Salt Lake City Airport 

in Utah (Sills and Blakeslee 1992). Propylene glycol was detected, but the concentration was not 

quantified in effluents from a chemical manufacturing plant in Memphis, Tennessee (EPA 1976). 

Propylene glycol may also be released to surface waters as a metabolite of propylene glycol dinitrate 

which is a military propellant found in waste water streams from munitions facilities (EPA 1979, 1987a; 

Kaplan et al. 1982; Walker and Kaplan 1992). 

There is no information in the Toxic Release Inventory (TRI) on releases of propylene glycol to surface 

or groundwater from domestic manufacturing and processing facilities because these releases are not 

required to be reported (EPA 1995c). 

Groundwater samples collected from a perched water table at the Ottawa Airport in Canada contained 

4 mg/L (ppm) of propylene glycol (Sills and Blakeslee 1992). Propylene glycol also has been detected in 
 

 

 

 

 

 

 

 

 

 

 

 

PROPYLENE GLYCOL 78 

5. POTENTIAL FOR HUMAN EXPOSURE 

groundwater samples collected at two hazardous waste sites where it was detected in various 

environmental media (HazDat 1995). 

5.2.3 Soil 

The major sources of propylene glycol releases to soil are the disposal of used antifreeze fluids and deicing fluids containing the compounds (EPA 1979, 1987a). 

There is no information in the TRI on releases of propylene glycol to soil from domestic manufacturing 

and processing facilities because these releases are not required to be reported (EPA 

1995c). Propylene glycol has not been detected in any soil samples collected at hazardous waste sites 

although it has been detected in other environmental media (HazDat 1995). 

5.3 ENVIRONMENTAL FATE 

5.3.1 Transport and Partitioning 

Propylene glycol has a low vapor pressure (0.07 mm Hg at 20 °C) and is miscible with water (see 

Table 3-2). If released to the atmosphere (e.g., as vapors generated at elevated temperatures), propylene 

glycol should exist almost entirely in the vapor phase (Eisenreich et al. 1981). The high solubility of 

propylene glycol in water ensures at least partial removal of the compound will occur by wet deposition 

(EPA 1987a). Therefore, upon release to the environment, the compound is expected to be transported 

primarily in aqueous media (EPA 1979). The low Henry’s law constant values for the compound 

(1.2x10-8 to 1.7x10-8 atm-m3

/mole range; see Table 3-2) suggest that releases to surface water will not 

partition to the atmosphere via volatilization (Simmons et al. 1976; Thomas 1990). Adsorption to 

sediment or soil particulates is also not expected to be significant on the basis of the low Koc value (see 

Table 3-2). 

Based on the low Koc value, propylene glycol is expected to have a very high mobility in soil and could 

leach into groundwater (Swarm et al. 1983). The low octanol/water partition coefficient (Kow) (see Table 

3-2) suggests that bioconcentration and biomagnification are also not likely to occur. No measured BCF 

values were located for this compound. 

Propylene glycol is expected to be highly mobile in moist soils and may leach to groundwater upon 

release to surface soils; however, rapid biodegradation is expected to limit the extent of the leaching (see 
 

 

 

 

 

PROPYLENE GLYCOL 79 

5. POTENTIAL FOR HUMAN EXPOSURE 

Section 5.3.2) (EPA 1987a). The compound may also volatilize from dry surface soils (EPA 1979, 1987a; 

Hine and Mookerjee 1975). 

5.3.2 Transformation and Degradation 

5.3.2.1 Air 

Propylene glycol released to the atmosphere is expected to undergo rapid photochemical oxidation via 

reaction with hydroxyl radicals. The half-life for the photochemical oxidation of propylene glycol has 

been estimated to be 20-32 hours (EPA 1987a; Howard et al. 1990). 

5.3.2.2 Water 

Biodegradation by a variety of acclimated and unacclimated microorganisms, under both aerobic and 

anaerobic conditions, is the most important transformation process for propylene glycol in surface waters. 

The half-lives for the biotransformation of propylene glycol generally range from 1 to 4 days under 

aerobic conditions and from 3 to 5 days under anaerobic conditions (EPA 1987a). 

Propylene glycol rapidly disappears from culture flasks containing activated sludge microorganisms 

under both aerobic and anaerobic conditions (Kaplan et al. 1982). Some propylene glycol was lost from 

sterile cultures after 9 days. An 8% and 16% loss of propylene glycol was observed in sterile anaerobic 

and aerobic cultures, respectively. In active cultures, propylene glycol was not detected after 2 days in 

aerobic nutrient broth. When used as a sole carbon source, propylene glycol disappeared after 4 days 

under aerobic and 9 days under anaerobic conditions. Raja et al. (1991) reported a novel biotreatment 

process using Pseudomonas and Aerobacter bacteria. The Pseudomonas were able to use the propylene 

glycol to produce volatile acids, while Aerobacter degraded the volatile acids quickly to carbon dioxide 

and water. 

Propylene glycol is not expected to undergo significant abiotic transformation in surface waters via 

hydrolysis or oxidation (EPA 1979, 1987a). Glycols generally are resistant to hydrolysis (Harris 1990). 

For example, the half-life for reaction of propylene glycol with hydroxyl radicals in aqueous solution has 

been estimated to be 1.3-2.3 years (Harris 1990). 
 

 

 

 

 

 

 

 

PROPYLENE GLYCOL 80 

5. POTENTIAL FOR HUMAN EXPOSURE 

5.3.2.3 Sediment and Soil 

Biodegradation by a variety of microorganisms under both aerobic and anaerobic conditions is the most 

important transformation process for propylene glycol in soils, with half-lives similar to or less than those 

in surface waters (EPA 1 987a). The soil microbe C. glycolicum degraded propylene glycol under 

anaerobic conditions to acid and alcohol end products (Gaston and Stadtman 1963). Ouattara et al. (1992) 

reported anaerobic degradation of propylene glycol by strains of the sulfate-reducing bacteria 

Desulfovibrio isolated from anoxic soil of a rice field. Propylene glycol was degraded to acetate in the 

presence of sulfate with the production of carbon dioxide. The rates of biodegradation of propylene glycol 

in soils are significantly dependent on substrate concentrations, soil types, and ambient soil temperatures, 

but nutritional supplements had minimal effects (Klecka et al. 1993). Generally, the rate of propylene 

glycol biodegradation was faster in soils with low glycol concentrations, high organic carbon content, and 

higher ambient soil temperatures (in the range of -2-25 °C). Propylene glycol present in soils at 

concentrations <6,000 mg/kg (ppm) biodegraded at an average rate of 2.3 mg/kg soil/day at -2 °C, 

27.0 mg/kg (ppm) soil/day at 8 °C and at an average rate of 93.3 mg/kg (ppm) soil/day at 25 °C (Klecka 

et al. 1993). Based on these results, biodegradation is expected to play a major role in removing propylene 

glycol residues from soils adjacent to airport runways and taxiways. 

As in surface waters, abiotic transformation of propylene glycol in soil is not expected to be a significant 

process (EPA 1987a). 

5.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT 

5.4.1 Air 

No information was located on the concentration of propylene glycol in the ambient atmosphere. 

Propylene glycol was detected in air samples collected in a large scale environmental chamber analyzing 

volatile organic emissions. Quasi-steady-state emission rates of the propylene glycol at 24 hours and 

168 hours after the start of the experiment were 690 μg/m2

/hour and 193 μg/m2/hour, respectively from 

newly installed carpet with polyvinylchloride backing (Hodgson et al. 1993). 

5.4.2 Water 

Available information on the environmental impact of de-icing solutions on airport storm water runoff has 

been summarized in a recent review article by Sills and Blakeslee (1992). Monitoring data from several 
 

 

 

 

 

 

 

PROPYLENE GLYCOL 81 

5. POTENTIAL FOR HUMAN EXPOSURE 

contractor and airport authority reports reveal that storm water runoff from airports may contain several 

hundred to several thousand mg/L (ppm) glycols. Propylene glycol levels up to 19,000 mg/L (ppm) were 

detected in storm water from the Salt Lake City International airport. Although the potential for 

groundwater contamination is quite low for many airports with predominantly heavy soil, the movement 

of glycols through unsaturated silty sand can be potentially high (Sills and Blakeslee 1992). At the Ottawa 

International Airport in Canada, groundwater in the perched water table, which contained sandy soil, was 

found to contain propylene glycol at levels up to 4 mg/L (ppm). Peak concentrations occurred in June and 

declined to nondetectable levels by the fall. 

5.4.3 Sediment and Soil 

No information was found on soil concentrations of propylene glycol. 

5.4.4 Other Environmental Media 

Propylene glycol has been identified in negligible amounts in the water-soluble component of cigarette 

smoke (Schumacher et al. 1977). 

Propylene glycol has also been found to migrate into a number of foods from regenerated cellulose films 

containing the compound as a softening agent. The compound was detected in chocolates at 20­

1,460 mg/kg (ppm) after 5.5 months of storage and at 25-1,890 mg/kg (ppm) after 15 months, in fruit 

cakes at 10-154 mg/kg (ppm) after 84-336 days of storage, in meat pies at <10-118 mg/kg (ppm) after 3­

7 days of storage, in toffee at <10-l,530 mg/kg (ppm) after 168-450 days of storage, in madeira cake at 

<10-365 mg/kg (ppm) after 2 1-28 days storage, and in boiled sweets at <10-272 mg/kg (ppm) after 168­

450 days storage (Castle et al. 1988a). 

Propylene glycol is also used in some cosmetic and oral drug formulations and is a GRAS additive in 

foods (FDA 1982), where it is used as an emulsifying and plasticizing agent, humectant, surfactant, and 

solvent. Propylene glycol is added to foods at concentrations ranging from <0.001% in eggs and soups to 

up to 97% in seasonings and flavors (EPA 1979). Propylene glycol is a naturally occurring by-product in 

the fermentation of some beers and has been detected in the concentration range of 1.0-51.0 mg/L (ppm) 

in several commercially packaged beers (Williamson and Iverson 1993). 
 

 

 

 

 

PROPYLENE GLYCOL 82 

5. POTENTIAL FOR HUMAN EXPOSURE 

5.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE 

The general population is exposed to propylene glycol primarily through ingestion of food and 

pharmaceutical products and through dermal contact with cosmetic products containing the compound 

(EPA 1979, 1 987a). The average daily dietary intake of propylene glycol in Japan, where the compound 

is used as a food additive stabilizer, was estimated to be 43 mg per person in 1982 (Louekari et al. 1990). 

Public school children and the general public who participate in fire fighting exercises/demonstrations 

where propylene glycol is used to simulate fire conditions are exposed to small amounts of propylene 

glycol (Rossol 1993). The general public is exposed to low. concentrations of propylene glycol mist from 

propylene glycol-containing theatrical fog/smoke used in producing special effects during theatrical 

performances, rock concerts, and private parties (Rossol 1993). The general public is also exposed to 

small concentrations of propylene glycol from carpets with polyvinyl chloride backing. The quasi-steadystate specific emission rate of propylene glycol from these carpets was calculated to be 690 μg/m2/hour at 

24 hours and 193 μg/m2/hour at 168 hours after carpet installation (Hodgson et al. 1993). 

NOSH estimated that about 2.5 million individuals were potentially exposed to propylene glycol in the 

workplace in 1970; the estimate for 1980 was 80,200 workers (HSDB 1995b). Dennal contact is expected 

to be the main route of worker exposure; however, inhalation of vapors or mists may also occur when the 

compound is heated, agitated, or sprayed (e.g., in de-icing formulations) (Rowe and Wolf 1982). 

5.6 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES 

Workers in industries involved in the manufacture or use of products containing high concentrations of 

propylene glycol (e.g., antifreeze, coolants, de-icing fluids, brakes fluids, solvents) may be exposed to 

concentrations of the compounds at levels higher than the general population, particularly in operations 

involving heating or spraying of these materials. Performers and workers in theatrical productions that use 

propylene glycol-containing fog/smoke for special effects are likely to be exposed to higher 

concentrations of propylene glycol than the general population (Rossol 1993). Fire fighters who 

participate in frequent fire-fighting exercises involving propylene glycol fog/smoke may also belong to 

the high exposure group (Rossol 1993). 

5.7 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 propylene glycol is available. Where adequate information 
 

 

 

 

 

 

 

 

 

PROPYLENE GLYCOL 83 

5. POTENTIAL FOR HUMAN EXPOSURE 

is not available, ATSDR, in conjunction with the 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 propylene glycol. 

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. 

5.7.1 Identification of Data Needs 

Physical and Chemical Properties. As seen in Table 3-2, the relevant physical and chemical 

properties of propylene glycol are known (ASTER 1995b; Daubert and Danner 1989; EPA 1987a; HSDB 

1995b; Merck 1989). No further information is required. 

Production, Import/Export, Use, Release, and Disposal. Production data are available for 

propylene glycol (SRI 1989, 1991, 1993, 1995). Similarly, data on the import/export volumes for 

propylene glycol for the last several years are available (NTDB 1995). Information on the various uses of 

this compound are also available (EPA 1987a; HSDB 1995b; Lewis 1993; Merck 1989; Rowe and Wolf 

1982). Propylene glycol enters the environment primarily during its use as an intermediate in the 

synthesis of polyester fibers and resins, as a component of automotive antifreeze/coolants, and as a deicing fluid for aircraft (Kirk-Othmer Encyclopedia of Chemical Technology 1978; Klecka et al. 1993; 

Lewis 1993; Merck 1989; Rowe and Wolf 1982). Propylene glycol is also used in pharmaceutical 

products, hair colorant formulations, food and tobacco products, as a non-toxic antifreeze in the food 

industry, as an air sterilant in hospitals or animal facilities, and as a special effects fog/smoke in theatrical 

performances or in fire training programs (Kirk-Othmer Encyclopedia of Chemical Technology 1978; 

Klecka et al. 1993; Merck 1989; Rossol 1993; Rowe and Wolf 1982). Information regarding the disposal 

of propylene glycol containing waste waters (Chou et al. 1979; Raja et al. 1991) and for remediation of 

propylene glycol contaminated soils (Drajun 1991; Vesper et al. 1994) is available. 

According to the Emergency Planning and Community Right-to-Know Act of 1986, 42 U.S.C. Section 

11023, industries are required to submit chemical release and off-site transfer information to the EPA. 

The Toxics Release Inventory (TRI), which contains this information for 1988-1993, became available in 
 

 

 

 

 

 

 

 

PROPYLENE GLYCOL 84 

5. POTENTIAL FOR HUMAN EXPOSURE 

May of 1995. This database will be updated yearly and should provide a list of industrial facilities and 

emissions. No TRI data are available for propylene glycol because this chemical is not required to be 

reported by chemical producers (EPA 1995c). 

Environmental Fate. Information regarding the fate of propylene glycol in the air is available that 

suggests the compound would be primarily found in the vapor phase and would likely be removed from 

the atmosphere via wet deposition (Eisenreich et al. 1981; EPA 1979, 1987a). Propylene glycol undergoes 

rapid photochemical oxidation via reaction with hydroxyl radicals with an estimated half-life of 20 hours 

in the atmosphere (EPA 1987a). Because of its high solubility in water, the compound is expected to be 

transported primarily in aqueous media and will not partition to the atmosphere via volatilization from 

water (EPA 1979, 1987a; Thomas 1990). Adsorption to sediment or soil particles is not expected to be 

significant based on the low Koc value and therefore propylene glycol is expected to have a high mobility 

in soil and potential to leach into groundwater (Swarm et al. 1983). Propylene glycol is transformed in 

both water and soil by microorganisms (EPA 1987a; Gaston and Stadtman 1963; Klecka et al. 1993). The 

half-lives for the biotransformation of propylene glycol in surface waters generally range from 1 to 4 days 

under aerobic conditions and from 3 to 5 days under anaerobic conditions, with half-lives in soil similar 

to or less than those in surface waters (EPA 1987a). No additional information on degradation of 

propylene glycol in air or water are required; however, additional quantitative information on the 

degradation of propylene glycol in soil would be useful. 

Bioavailability from Environmental Media. Available information regarding the rate of propylene 

glycol absorption following inhalation, oral, or dermal contact has been discussed in the Toxicokinetics 

section (see Section 2.3). Although no data on propylene glycol’s bioavailability from contaminated air 

are available, the bioavailability from inhalation exposure is expected to be high because propylene glycol 

is likely to be present in the vapor phase (Eisenreich et al. 1981) and not in the particulate phase in the 

adsorbed state. Similarly, no data on the bioavailability of propylene glycol from water, soil or plant 

material are available; however, propylene glycol is readily miscible in water and does not adsorb readily 

to soil. Propylene glycol, therefore, is expected to be readily bioavailable from soil and water. 

Information on the bioavailability of propylene glycol from actual environmental media is not required as 

propylene glycol is a GRAS chemical (FDA 1982). 

Because the FDA (1982) has classified propylene glycol as a GRAS chemical, no monitoring data for 

concentrations of propylene glycol in contaminated media at hazardous waste sites are needed to assess 

the potential risk of adverse health effects in populations living in the vicinity of hazardous waste sites. 
 

 

 

 

 

 

 

 

 

 

PROPYLENE GLYCOL 85 

5. POTENTIAL FOR HUMAN EXPOSURE 

Food Chain Bioaccumulation. Based on its low Koc value, propylene glycol is not expected to 

bioconcentrate in aquatic food chains; however, no measured BCF values were located for any 

invertebrate or fish species. Information is also lacking regarding the biomagnification potential of 

propylene through aquatic food chains although it is unlikely because of the rapid degradation rate for the 

chemical in aquatic systems. No further information on the bioconcentration or biomagnification potential 

of propylene glycol is required as it is a GRAS chemical (FDA 1982). 

Exposure Levels in Environmental Media. No information was located on the concentration of 

propylene glycol in ambient air. Propylene glycol was detected in air samples collected in a large scale 

environmental chamber analyzing volatile organic emissions from newly installed carpet with 

polyvinylchloride backing (Hodgson et al. 1993). No data on the level of propylene glycol in drinking 

water were located, although propylene glycol has been detected at up to 4 mg/L (ppm) in groundwater in 

the vicinity of an airport (Sills and Blakeslee 1992) and at unspecified concentrations in groundwater 

samples collected at two hazardous waste sites (HazDat 1995). Little information on the levels of 

propylene glycol in soils was located. Data on propylene glycol levels in foods, particularly those stored 

in cellulose films or in PET bottles, are available (Castle et al. 1988a; EPA 1979; Kashtock and Breder 

1980; Williamson and Iverson 1993) and a recent estimate of human dietary intake of propylene glycol in 

Japan is available (Louekari et al. 1990). Reliable monitoring data for the levels of propylene glycol in 

various environmental media are not needed as this compound is a GRAS additive in foods (FDA 1982). 

Exposure Levels in Humans. Little quantitative information on propylene glycol levels in various 

human tissues and body fluids of a control population, populations near hazardous waste sites, or 

occupationally exposed groups in the United States is available. Most information is available for oral 

exposures (Yu et al. 1985). Data on the levels of propylene glycol and its metabolites in body tissues and 

fluids are not needed because this chemical is a GRAS food additive (FDA 1982). 

Exposure Registries. No exposure registries for propylene glycol were located. This substance is 

not currently one of the compounds for which a subregistry 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. 
 

 

 

PROPYLENE GLYCOL 86 

5. POTENTIAL FOR HUMAN EXPOSURE 

5.7.2 Ongoing Studies 

No additional information was located on ongoing studies that would fill existing data needs for 

propylene glycol (FEDRIP 1995). 
 

 

 

 


 

PROPYLENE GLYCOL 87 

6. ANALYTICAL METHODS
 

The purpose of this chapter is to describe the analytical methods that are available for detecting and/or 

measuring and monitoring propylene glycol in biological samples or in environmental media. The intent 

is not to provide an exhaustive list of analytical methods that could be used to detect and quantify 

propylene glycol. Rather, the intention is to identify well-established methods that are used as the 

standard methods of analysis. Many of the analytical methods used to detect propylene glycol in 

environmental samples are the methods approved by federal 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 refine 

previously used methods to obtain lower detection limits, and/or to improve accuracy and precision. 

6.1 BIOLOGICAL MATERIALS 

Table 6-1 is a summary of some of the most commonly used methods reported in the literature for 

detecting propylene glycol in biological samples. The primary method for measuring propylene glycol in 

biological samples is derivatization followed by gas chromatography (GC) using either a flame ionization 

detector (FID) or mass spectrometry (MS) for quantification. GC is the preferred analytical method 

because of the ease of sample preparation and the accuracy of the quantification of sample concentrations. 

Alkali flame ionization detectors have also been used for ethylene glycol analysis and give a response 

ratio of 3:l compared with PID (Bogusz et al. 1986). Capillary gas chromatography with a constant 

current 63Ni electron capture detector (ECD) has also been used successfully to detect propylene glycol 

(Needham et al. 1982). 

Sample preparation for GC is important and proceeds through several steps: acidification, esterification, 

and extraction into an organic solvent. The use of internal standards is necessary for quantification. In 

clinical cases involving ethylene glycol poisoning, propylene glycol should not be used as an internal 

standard for quantitation because certain sedatives (Valium and Ativan) may contain propylene glycol 

(Apple et al. 1993). 

Detection of propylene glycol in biological samples using GC with either FID or MS is very sensitive, 

with detection limits ranging from sub to low ppm. The coefficient of variation (CV) varies with the 

concentration of glycol used but typically ranges from 0.4% to 27% and is usually less than 10%. In gas 

chromatographic procedures, the glycols and their acid metabolites are derivatized to form esters in order 
 

 

 


 


 

PROPYLENE GLYCOL 88 

6. ANALYTICAL METHODS 

Table 6-1. Analytical Methods for Determining Propylene Glycol in Biological
 

Samples
 

Sample matrix Preparation method 

Analytical 

method 

Sample 

detection 

limit 

Percent 

recovery Reference 

Human plasma Deproteinization with acetic 

acid; vortex; centrifugation; 

supernatant spiked with 

internal standard; reaction 

HRGC/MS 1 ppm 94–106 Giachetti et 

al. 1989 

with butyl-boronic acid; 

neutralize with NH4OH, 

extraction with 

dichloromethane; 

concentration. 

Human serum Acetonitrile with internal 

standard added to sample; 

centrifugation; concentration; 

extraction with p-bromophenyl boric acid in ethyl 

HRGC/ECD 0.38 ppm >90 Needham et 

al. 1982 

acetate. 

Human blood Deproteinization with HClO4; 

centrifugation; pH adjustment; 

centrifugation 

GC/MS 0.6 ppm NR Sisfontes et 

al. 1986 

Human serum 

and urine 

Internal standard added; 

centrifugation; derivatization 

with phenylboronate in 

methanol. 

HRGC/FID 1.0 ppm 89–98 Houźe et al. 

1993 

Human serum 

(glycolic acid) 

Colorimetric: precipitation of 

protein with trichloroacetic 

acid followed by 

centrifugation, addition of 

chromotropic acid, heating, 

and dilution; gas 

chromatographic: addition of 

internal standard and acetone 

Absorbance at 

580 nm or 

GC/FID as 

appropriate 

1.0 mmol/L 

(60 ppm, 

w/v) for both 

methods; 3– 

6% RSD 

NR Fraser and 

MacNeil 

1993 

followed by centrifugation, 

addition of NaOH, 

evaporation to dryness, and 

formation of methyl ester. 

Humans serum 

(glycolic acid) 

Extraction from salted, 

acidified serum using methyl 

ethyl ketone followed by 

removal of organic phase and 

evaporation to dryness and 

derivatization with PNBDI. 

HPLC/UV 0.05 mmol/L 

(3 ppm, 

w/v); 1% 

RSD 

NR Hewlett et 

al. 1986 
 

 

 

 

 

 


 


 

PROPYLENE GLYCOL 89 

6. ANALYTICAL METHODS 

Table 6-1. Analytical Methods for Determining Propylene Glycol in Biological
 

Samples
 

Sample 

Analytical detection Percent 

Sample matrix Preparation method method limit recovery Reference 

Human plasma, Heparinized blood HPLC/UV Plasma: 85 Brega et al. 

urine (oxalate) deproteinated by addition of 0.15 mg/L 1992 

acetonitrile and phosphate (ppm, w/v); 

buffer (pH=7), centrifugation, 7.5% RSD; 

removal of solvent and urine: 

evaporation to dryness; 0.5 mg/L 

derivatization as for urine; (ppm, w/v); 

urine acidified and derivatized 5% RSD. 

using 1,2-diaminobenzene, 

adjustment of pH to 5-6, 

centrifugation. 

ECD = electron capture detector; FID = flame ionization detector; GC = gas chromatography; HClO4 = chloroform; 

HPLC = high-performance liquid chromatography; HRGC = high resolution gas chromatography; MS = mass 

spectrometry; NH4OH = ammonium hydroxide; NR = not reported; PNBDl = O-p-nitrobenzyl-N,N'-diisopropylisourea; 

RSD = relative standard deviation; UV = ultraviolet detector; w/v = weight:volume 
 

 

 

 

 

 

 

PROPYLENE GLYCOL 90 

6. ANALYTICAL METHODS 

to facilitate quantitative elution from the chromatographic columns (see Table 6-1). Simple and rapid 

methods are also available for the quantitation of the glycols in urine, serum, or deproteinated whole 

blood. These methods use direct sample injection without prior solvent extraction and derivatization 

(Aarstad et al. 1993; Edinboro et al. 1993; Jonsson et al. 1989). However, such methods, particularly 

those that use packed columns may misidentify propionic acid (found in patients with methylmalonic 

acidemia) as ethylene glycol (Shoemaker et al. 1992). 

High-resolution proton nuclear magnetic resonance spectroscopy has potential use in the identification 

and quantification of propylene glycol and other chemicals in cerebrospinal fluid (CSF) and serum 

(Petroff et al. 1986). The technique has two advantages: 1) it requires no pretreatment of the specimens 

prior to analysis and no advance knowledge of possible compounds present in fluids and 2) results are 

extremely rapid. Propylene glycol was detected at 1 ppm in CSF (Petroff et al. 1986). 

No information was located on detecting propylene glycol in feces, adipose tissue, or human milk. 

6.2 ENVIRONMENTAL SAMPLES 

As with biological samples, GC is the major technique used to determine propylene glycol concentrations 

in environmental samples whether in air, water, food, drugs, or other substances. Capillary gas 

chromatography with FTD or ECD, possibly followed by MS, generally gives good quantitative results 

down to the ppm range with recovery usually greater than 80%. The determination of propylene glycol in 

air requires adsorption onto a surface and subsequent extraction. Water samples may be analyzed without 

preparation (EPA 1995a, 1995b). Detection of propylene glycol in foods and drugs may be accomplished 

by chromatography of the sample; for substances with a high fat content, extraction with hexane may be 

used to remove the fat. Table 6-2 is a summary of some of the most commonly used methods reported in 

the literature for detecting propylene glycol in environmental samples. The specific techniques used for 

each analytical method are listed in the table if that information was provided by the author(s). 

The presence of propylene glycol in foods packaged with plastic films containing the compounds has 

been studied, as have ethylene glycol levels in drugs sterilized with ethylene oxide. Sample preparation is 

important because procedures vary depending on the fat content of the food sample. Foods with low fat 

content can be extracted with ethyl acetate, derivatized to a trimethylsilyl ether, and then injected into the 

gas chromatograph. For foods with a high fat content, hexane is used as the defatting agent prior to 

derivatization. Quantifying ethylene glycol or propylene glycol in wines requires no preparation of the 
 

 

 

 

 

 

 


 

PROPYLENE GLYCOL 91 

6. ANALYTICAL METHODS 

Table 6-2. Analytical Methods for Determining Propylene Glycol in 

Environmental Samples
 

Sample 

matrix Preparation method 

Analytical 

method 

Sample 

detection limit 

Percent 

recovery Reference 

Air Sample adsorbed on 

Amberlite® XAD-2 with 

GC/FID NR 75–98 Andersson et al. 1982 

personal sampling pump; 

extraction with diethyl 

ether. 

Water Direct injection (Method 

8015b). 

GC/FID NR NR EPA 1995a 

Water Direct injection (Method 

8430). 

GC/FTIR 120 mg/L (ppm, NR 

w/v) 

EPA 1995b 

Plastics Sample extraction from 

plastic with carbon 

disulfide. 

GC/FID 16.5 ng 58–61 Muzeni 1985 

Plastics Sample extraction with 

solvent of ethylacetatewater-methanol. 

GC/FID 2 ppm NR DeRudder et al. 1986 

Cosmetics Co-distillation with 

isooctane 

GC/FID NR NR Helrich 1990a 

Ground 

tobacco 

Extraction with anhydrous GC/FID 

methanol. 

NR NR Helrich 1990b 

Aqueous 

solution 

Sample concentration, GC/FID 

then dilution with water; 

concentration with helium 

50 ppb 97–103 Kashtock and Breder 

1980 

gas; redilution. 

Beer Addition of ammonium 

sulfate and extract with 

HRGC/FID 0.73 ppm 88 Williamson and 

Iverson 1993 

ethyl acetate. 

Vanilla 

extract 

Refluxing with heptane Titration 

and addition of KIO4, 

NaHCO3, KI, and starch to 

aqeous phase followed by 

titration with KasO2. 

NR NR Helrich 1990c 

Food Addition of hot water to HRGC/FID; 

sample to obtain slurry; GC/MS 

extraction with hexane; 

precipitation of sugars 

with calcium hydroxide; 

concentration; 

derivatization with BSTFA. 

10 ppm 78–107 Castle et al. 1988b 

Anchovies Extraction with methanol 

and concentration. 

HRGC/MS/ 

MS (PICI) 

12.5 ppb NR Matusik et al. 1993 

BSTFA = bis(trimethylsilyl)trifluoroacetamide; FID = flame ionization; GC = gas chromatography; HRGC = high 

resolution gas chromatography; MS = mass spectrometry; MS/MS = tandem mass spectrometry; PICI = positive ion 

chemical ionization 
 

 

 

 

 

 

 

PROPYLENE GLYCOL 92 

6. ANALYTICAL METHODS 

samples prior to analysis (Kaiser and Rieder 1987; Klaus and Fischer 1987). Drugs in aqueous solutions 

may be analyzed directly, water insoluble drugs should be extracted in water, and ointments may be 

dissolved in hexane and then extracted with water. Recovery is between 80 and 114%, with detection 

limits in the low-ppm range (Hartman and Bowman 1977; Manius 1979). The use of ion exchange 

chromatography with sulfuric acid as the mobile phase has also given good recovery (98-101%) with a 

detection limit of 5 μg/mL propylene glycol from pharmaceuticals (Iwinski and Jenke 1987). Although 

the use of TLC (Ballarin 1980) has been recommended, it has been superseded by GC. 

Propylene glycol in cigarette smoke has been detected using electrostatic precipitation or filter pad, with 

extraction and separation with capillary gas chromatography (Borgerding et al. 1990). 

No information was located on techniques for detecting and analyzing propylene glycol in soil. 

6.3 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 ethylene glycol and propylene glycol 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 propylene glycol. 

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. 

6.3.1 Identification of Data Needs 

Methods for Determining Biomarkers of Exposure and Effect. Methods for the determination 

of propylene glycol in blood and urine are available (Giachetti et al. 1989; House et al. 1993; Needham et 

al. 1982; Sifontes et al. 1986) with sensitivities in the sub-ppm range. 

Methods for Determining Parent Compounds and Degradation Products in Environmental 

Media. Methods for the determination of propylene glycol have been reported for air (Andersson et al. 

1982; NIOSH 1984), water or aqueous solutions (EPA 1995a, 1995b; Kashtock and Breder 1980), and 
 

 

 

 

PROPYLENE GLYCOL 93 

6. ANALYTICAL METHODS 

foods (Castle et al. 1988b; Matusik et al. 1993; Williamson and Iverson 1993). Methods have also been 

developed for the determination of glycols that leach from plastics (DeRudder et al. 1986; Muzeni 1985) 

and that can end up in foods stored in containers made from the plastics. An MRL of 0.009 ppm for 

intermediate inhalation exposure to propylene glycol has been defined and none of the methods reported 

would be adequate without modification. It is likely that the LODs of some of the methods could be 

reduced but this remains to be shown. 

6.3.2 Ongoing Studies 

No ongoing research on analytical methods for the determination of propylene glycol was found. 
 

PROPYLENE GLYCOL 94 

6. ANALYTICAL METHODS 

This page is intentionally blank. 

 

PROPYLENE GLYCOL 95 

7. REGULATIONS AND ADVISORIES
 

The international, national, and state regulations and guidelines regarding propylene glycol in air, water, 

and other media are summarized in Table 7-1. An MRL of 0.009 ppm has been derived for intermediateduration inhalation exposure (1.5-364 days) to propylene glycol based on a LOAEL of 51 ppm for nasal 

hemorrhaging (Suber et al. 1989). 

Propylene glycol is regulated under Clean Air Act New Source Performance Standards for the synthetic 

organic chemical manufacturing industry (EPA 1993b). Propylene glycol is regulated by the Clean Water 

Act Effluent Guidelines for organic chemicals, plastics, and synthetic fibers (OCPSF). The waste water 

generated by the production of these chemicals has effluent limitations on biochemical oxygen demand 

(BOD5), total suspended solids (TSS), and pH (EPA 1987d). 
 

 

 

 

 

PROPYLENE GLYCOL 96 

7. REGULATIONS AND ADVISORIES 

Table 7-1. Regulations and Guidelines Applicable to Propylene Glycol 

Agency Description Information Reference 

INTERNATIONAL 

Guidelines: 

WHO Acceptable daily intake 0-25 mg/kg FAO/WHO 1974 

NATIONAL 

Regulations and 

guidelines: 

a. Air 

EPA OAR App. A – Chemicals defining synthetic 

organic chemical and polymer 

manufacturing 

Yes 40 CFR 52 

EPA 1972a 

Subpart VV – Std. of performance for 

equipment leaks of VOC in SOCMI: 

Chemicals produced by affected 

facilities 

Yes 40 CFR 60.489 

EPA 1983 

Definitions of emissions from polymer 

manufacturers: Definition of 

Yes 40 CFR 60.561 

EPA 1990b 

“polymerization reaction section” 

Subpart NNN – Std. of performance for 

VOC emissions from SOCMI distillation 

Yes 40 CFR 60.667 

EPA 1990b 

operations: Chemical affected 

Subpart RRR – Std. of performance for 

VOC emissions from SOCMI process 

reactors: Chemicals affected 

Yes 40 CFR 60.707 

EPA 1993b 

New source performance standard Yes 58 FR45962 

EPA 1993c 

b. Water 

EPA OW Bulk organic chemicals under the Clean 

Water Act 

Yes 40 CFR 414.70 

EPA 1987d 

App. A – Non-complexed metal-bearing 

waste 

Yes 40 CFR 414 

EPA 1987d 

EPA OWRS Pesticide subject to registration and 

reregistration 

Yes 40 CFR 152.146 

EPA 1989b 

EPA 1989a 

c. Food 

FDA Generally recognized as safe Yes 21 CFR 184.1666 

FDA 1982 

2,4-D: Food tolerances for residues 

2,4-D Applied in the form of 

polyethylene glycol and/or propylene 

glycol 

40 CFR 180.142 

EPA 1982 

Max. 2,4-D tolerance: Pasture and 

rangeland grasses 

1,000 ppm 

Min. 2,4-D tolerance: Blueberries and 

rice 

0.1 ppm 
 

	 

	 

	 

PROPYLENE GLYCOL 97 

7. REGULATIONS AND ADVISORIES 

Table 7-1. Regulations and Guidelines Applicable to Propylene Glycol 

Agency Description	 Information Reference 

Inert ingredients exempt from Yes 40 CFR 180.1001 

tolerances EPA 1971 

NATIONAL (cont.) 

d. Other 

EPA OPTS	 Temperature correction factors for 0.043 K°C/mmHg 40 CFR 796.1220 

organic solvents EPA 1985a 

Avian dietary testing procedures – Yes 40 CFR 797.2050 

sample diluents	 EPA 1985b 

Sample Diluents for Bobwhite Yes 40 CFR 797.2130 

reproductive tests EPA 1985b 

Sample diluents for Mallard Yes 40 CFR 797.2150 

reproductive Tests EPA 1985b 

Sample carriers for avian acute toxicity Yes 40 CFR 797.2175 

test EPA 1985b 

STATE 

Regulations and 

guidelines: 

a. Air: Acceptable ambient air concentrations 

VA 24 hours 1.10x103 μg/m3 NATICH 1991 

EPA = Environmental Protection Agency; FDA = Food and Drug Administration; NATICH = National Air Toxics 

Information Clearinghouse; OAR = Office of Air and Radiation; OPTS = Office of Pesticides and Toxic Substances; 

OW = Office of Water; OWRS = Office of Waste Regulations and Standards; SOCMI = Synthetic Organic Chemical 

Manufacturing Industry; VOC = Volatile Organic Compound 
PROPYLENE GLYCOL 98 

7. REGULATIONS AND ADVISORIES 

This page is intentionally blank. 
 

 

 

 

 

 

 

 

_______________________ 


 

PROPYLENE GLYCOL 99 

8. REFERENCES

*Aarstad K, Dale O, Aakervik O, et al. 1993. A rapid gas chromatographic method for 

determination of ethylene glycol in serum and urine. J Anal Toxicol 17(4):218-221. 

Abbondandolo A, Bonatti S, Corsi C, et al. 1980. The use of organic solvent in 

mutagenicity testing. Mutat Res 79:141-150. 

*Abe S, Sasaki M. 1982. SCE as an index of mutagenesis and/or carcinogenesis. Chapter 24 

In: Sister chromatid exchange. Prog Top Cytogenet 2:461-514. 

*Aberer VW, Fuchs T, Peters K-P, et al. 1993. Propylene glycol: Cutaneous side effects and 

test methods. Literature and results of a multicenter study of the German contact allergy group 

(DKG). Dermatosen 41:25-27. [German] 

Aboul-Enein HY, Islam MR. 1989. High performance liquid chromatography determination 

of ethylene glycol in stamp pad ink. Toxicol Environ Chem 24(3):181-184. 

ACGIH. 1994. Threshold limit values and biological exposure indices for 1994-1995. American 

Conference of Governmental Industrial Hygienists. Cincinnati, OH. 

Adams M, Collins M. 1988. Sensitive portable gas chromatograph with data retrieval and 

communications capability for remote surveillance of toxic gases and vapours in plant. 

Analytical Proceedings 25(6): 190-191. 

Adams WH, Toal RL, Breider MA. 1991. Ultrasonographic findings in dogs and cats with 

oxalate nephrosis attributed to ethylene glycol intoxication: 15 cases (1984-1988). J Am Vet 

Med Assoc 199(4):492-496. 

Adams WH, Toal RL, Walker MA, et al. 1989. Early renal ultrasonographic findings in dogs 

with experimentally induced ethylene glycol nephrosis. Am J Vet Res 50(8):1370-1376. 

Agren-Jonsson S, Magnusson B. 1976. Sensitization to propantheline bromide, 

trichlorocarbanilide and propylene glycol in an antiperspirant. Contact Dermatitis 2(2):79-80. 

Ahluwalia P, Amma MKP, Sareen K. 1980. Propane 1,2-diol induced in vivo and in vitro 

changes in rat erythrocytes. Ind J Exp Biol 18:382-284. 

Ahmed MM. 1971. Ocular.effects of antifreeze poisoning. Br J Ophthalmol 55(12):854­

855. AIHA. 1985. Propylene glycol. American Industrial Hygiene Association. Akron, 

OH, 5. 

*Cited in text 
 

 

 

 

 

 

 

 

 

PROPYLENE GLYCOL 100 

8. REFERENCES 

Ambrose D, Hall DJ. 1981. Thermodynamic properties of organic oxygen compounds: I. The 

vapor pressures of l,Zethanediol (ethylene glycol) and bis(2-hydroxyethyl)ether (diethylene glycol). J 

Chem Thermodyn 13:61-66. 

Amoozegar A, Warrick AW, Fuller WH. 1986. Movements of selected organic liquids into dry soils. 

Hazardous Waste and Hazardous Materials 3:29-41. 

Amstrup SC, Gardner C, Myers KC, et al. 1989. Ethylene glycol (antifreeze) poisoning 

in a free-ranging polar bear. Vet Hum Toxicol 31(4):317-319. 

Anbar M, Neta P. 1967. A compilation of specific bimolecular rate constants for the reactions of 

hydrated electrons, hydrogen atoms, and hydroxyl radicals with inorganic and organic compounds in 

aqueous solution. Int J Appl Rad Isotopes 18:493-523. 

*Andersson K, Levin J-O, Lindahl R, et al. 1982. Sampling of ethylene glycol and ethylene glycol 

derivatives in work-room air using Amberlite XAD resins. Chemosphere 1l(11): 1115-1119. 

Andersson K, Levin J-O, Lindahl R, et al. 1984. Influence of air humidity on sampling efficiency 

of some solid adsorbents used for sampling organics from work-room air. Chemosphere 

13(3):437-444 

Andrews LS, Snyder R. 1986. Toxic effects of solvents and vapors. In: Klaassen CD, Amdur 

MO, Doull J, eds. Cassarett and Doull’s toxicology: The basic science of poisons. 3rd ed. New 

York, NY: MacMillan Publishing Co., 654-657. 

Angelini G, Meneghini CL. 1981. Contact allergy from proplene glycol. Contact 

Dermatitis 7: 197-198. 

Anonymous. 1970. Determination of the ethyl alcohol, isopropyl alcohol and propylene 

glycol content of essences and tinctures. Flavour Industry 1:313-315. 

Anonymous. 1987. Ethylene glycol intoxication due to contamination of water systems. 

Atlanta, GA: Centers for Disease Control, Morbidity and Mortality Weekly Report 

36(36):611-614. 

AOAC. 1985. Official methods of analysis. 10th ed. and supplements. Washington, 

DC: Association of Official Analytical Chemists. 

*Apple FS, Googins MK, Resen D. 1993. Propylene glycol interference on gaschromatographic assay of ethylene glycol. Clinical Chemistry 39:167. 

*Arulanantham K, Gene1 M. 1978. Central nervous system toxicity associated with ingestion 

of propylene glycol. J Pediatr 93:515-516. 

*ASTER. 1995a. Assement Tools for the Evaluation of Risk. ASTER output for propylene 

glycol. U. S. Environmental Protection Agency. 
 

 

 

 

 

 

 

 

 

 

PROPYLENE GLYCOL 101 

8. REFERENCES 

*ASTER. 1995b. Assement Tools for the Evaluation of Risk. ASTER output for ethylene 

glycol. U. S. Environmental Protection Agency. 

Atkinson R. 1985. Kinetics and mechanisms of the gas-phase reactions of hydroxyl radical with 

organic compounds under atmospheric conditions. Chem Rev 8569-201. 

Atkinson R. 1987. A structure-activity relationship for the estimation of rate constants for 

the gas-phase reactions of OH radicals with organic compounds. International Journal of 

Chemical Kinetics 19:799-828. 

Atkinson R. 1989. Kinetics and mechanisms of the gas-phase reactions of the hydroxyl radical with 

organic compounds. Journal of Physical and Chemical Referenced Data Monograph 1. 

*ATSDR. 1989. Decision guide for identifying substance-specific data needs related to 

toxicological profiles. Agency for Toxic Substances and Disease Registry, Division of 

Toxicology, Atlanta, GA. 

*ATSDR/CDC. 1990. Subcommittee report on biological indicators of organ damage. Agency 

for Toxic Substances and Disease Registry, Centers for Disease Control and Prevention, 

Atlanta, GA. 

Aungst BJ, Blake JA, Hussain MA. 1990. Contributions of drug solubilization, partitioning, barrier 

disruption, and solvent permeation to the enhancement of skin permeation of various compounds 

with fatty acids and amines. Pharmaceutical Research 7(7):712-718. 

Balikova M, Kohlicek J. 1988. Rapid determination of ethylene glycol at toxic levels in serum 

and urine. Journal of Chromatography 434:469-474. 

Ball NA. 1984. Determination of ethylene oxide, ethylene chlorohydrin and ethylene glycol in 

aqueous solutions and ethylene oxide residues in associated plastics. J Pharm Sci 73(9): 1305­

1307. 

*Ballarin C. 1980. [Studies on the identification of pharmacopeial glycols by thin-layer 

chromatography.] Pharm Prax 35260-264. (German) 

*Barnes DG, Dourson M. 1988. Reference dose (RfD): Description and use in health 

risk assessments. Regul Toxicol Phannacol 8471486. 

Battersby NS, Wilson V. 1989. Survey of the anaerobic biodegradation potential of organic 

chemicals in digesting sludge. Appl Environ Microbial 55(2):433-439. 

Baud FJ, Bismuth C, Gamier R, et al. 1987. 4-Methylpyrazole may be an alternative to ethanol 

therapy for ethylene glycol intoxication in man. J Toxicol Clin Toxicol 24(6):463 -483. 
 

 

 

 

 

 

 

 

PROPYLENE GLYCOL 102 

8. REFERENCES 

Baud FJ, Galliot M, Astier A, et al. 1988. Treatment of ethylene glycol poisoning with 

intravenous 4-methylpyrazole. N Engl J Med 319(2):97-100. 

*Bauer MC, Weiss DJ, Perman V. 1991. Hematologic alterations in adult cats fed 6 or 12% 

propylene glycol. American Journal of Veterinary Research 53:69-72. 

*Bauer MC, Weiss DJ, Perman V. 1992. Hematological alterations in kittens induced by 6 and 

12% dietary propylene glycol. Vet Hum Toxicol 34(2):127-131. 

Beckett SD, Shields RP. 1971. Treatment of acute ethylene glycol (antifreeze) toxicosis in the 

dog. J Amer Vet Med Assoc 158(4):472-476. 

Bedard RG. 1976. Biodegradability of organic compounds. Master of Science Thesis, Connecticut 

University, Storrs, Connecticut. Prepared for Office of Water Research and Technology, 

Washington, DC. NTIS no. PB-264707. 

Berger JR, Ayyar DR. 1981. Neurological complications of ethylene glycol intoxication. Arch 

Neurol 38:724-726. 

Bidmon HJ, Pitts JD, Solomon I-IF, et al. 1990. Estradiol distribution and penetration in rat skin after 

topical application, studied by high resolution autoradiography. Histochemistry 95(1):43-54. 

Bieszkiewicz E, Van Hoi D, Matusiak K. 1979. Effects of methyl alcohol and ethylene glycol 

on the work of activated sludge. Acta Microbial Pol 28(3):255-260. 

Blakeley KR, Rinner SE, Knochel JP. 1993. Survival of ethylene glycol poisoning with profound 

acidemia. New England Journal of Medicine 328(7):515-516. 

Blandford DE, Desjardins PR. 1994. A rapid method for measurement of ethylene glycol. Clinical 

Biochemistry 27(1):25-30. 

Blomstrom DC, Beyer EM. 1980. Plants metabolise ethylene to ethylene glycol. Nature 

283(5742):66-68. 

Blood FR. 1965. Chronic toxicity of ethylene glycol in the rat. Food Cosmet Toxicol 3:229-234. 

Blood FR, Elliot GA, Wright MS. 1962. Chronic toxicity of ethylene glycol in the monkey. 

Toxicol Appl Pharmacol 4:489-491. 

Boatman RJ, Cunningham SL, Ziegler DA. 1986. A method for measuring the biodegradation 

of organic chemicals. Environ Toxicol Chem 5:233-243. 

Boer-mans HJ, Ruegg PL, Leach M. 1988. Ethylene glycol toxicosis in a pygmy goat. J Am 

Vet Med Assoc 193(6):694-696. 
 

 

 

 

 

 

 

 

PROPYLENE GLYCOL 103 

8. REFERENCES 

Bogusz M. 1980. Vitreous humour as reliable material for ethanediol determinations. Forensic 

Sci Int 16( 1):75-76. 

*Bogusz M, Bialka J, Gierz J, et al. 1986. Rapid determination of ethylene glycol in biological 

material. Z Rechtsmed 96(1):23-26. 

Bolbot JA, Anthony C. 1980. The metabolism of l,2-propanediol by the facultative methylotroph 

pseudomnas AMl. J Gen Microbial 120:245-254. 

Bond GG, Shellenberger RJ, Flores GH, et al. 1985. A case-control study of renal cancer 

mortality at a Texas chemical plant. Am J Ind Med 7(2):123-139. 

Bonitenko I, Kutsenko SA, Koposov ES, et al. 1990. [Acute poisoning with ethylene glycol 

esters.] Klin Med 68:126-130. (Russian) 

*Borgerding MF, Milhous LA Jr, Hicks RD, et al. 1990. Cigarette smoke composition: Part 

2. Method for determining major components in smoke of cigarettes that heat instead of bum 

tobacco. J Assoc Off Anal Chem 73(4):610-615. 

Bost RO, Sunshine I. 1980. Ethylene glycol analysis by gas chromatography. J Anal 

Toxicol 4(2):102-103. 

Boublik T, Fried V, Hala E. 1973. The vapour pressures of pure substances: Selected values of 

the temperature dependence of the vapour pressures of some pure substances in the normal and 

low pressure region. New York, NY: Elsevier Scientific Publishing Company, l-5, 99, 119. 

Boyd RD, Haworth C, Stacey TE, et al. 1976. Permeability of the sheep placenta to 

unmetabolized polar non-electrolytes. J Physiol 256(3):617-634. 

*Brazeau GA, Fung JL. 1990. Mechanisms of creatine kinase release from isolated rat 

skeletal muscles damaged by propylene glycol and ethanol. J Pharm Sci 79(5):393-397. 

*Brega AA, Quadri P, Villa ,et al. 1992. Improved HPLC determination of plasma and urine 

oxalate in the clinical diagnostic laboratory. Journal of Liquid Chromatography 15(3):501-511. 

Bridie A, Wolff CJM, Winter M. 1979. BOD and COD of some petrochemicals. Water 

Research 13:627-630. 

Bronaugh RL, Franz TJ. 1986. Vehicle effects on percutaneous absorption: In vivo and in 

vitro comparisons with human skin. Lipids 21(5):309-314. 

Brown DJ, Jain NC, Fomey RB, et al. 1968. Gas chromatographic assay of glycolethanol combinations in biological materials. J Forensic Sci 13(4): 537-543. 

Browning E. 1965. Toxicity and metabolism of industrial solvents. New York, NY: American 

Elsivier, 594-600, 642-644. 
 

 

 

 

 

 

 

PROPYLENE GLYCOL 104 

8. REFERENCES 

Capo MA, Sevil MB, Lopez ME, et al. 1993. Ethylene Glycol action on neurons and 

its cholinomimetic effects. Journal of Environmental Pathology, Toxicology and 

Oncology. 12(3): 155-159. 

Carney E, Liberacki A, Bartels M, et al. 1995. Identification of proximate toxicant for ethylene 

glycol developmental toxicity using rat whole embryo culture. The Toxicologist 15(1):163. 

*Casazza JP, Fretas J, Stambuk D, et al. 1987. The measurement of 1,2Propanediol, 

D, L-2,3-Butanediol and Meso-2,3-Butane&o1 in controls and alcoholic cirrhotics. Alcohol,& 

Alcohoism Suppl 1, 607-609. 

Caskey WH, Taber WA. 1981. Oxidation of ethylene glycol by a salt-requiring bacterium. 

Appl Environ Microbial 42( 1): 180-l 83. 

*Castle L, Cloke HR, Crews C, et al. 1988a. The migration of propylene glycol, mono-, di-, 

and triethylene glycols from regenerated cellulose film into food. Z Lebensm 

Unters Forsch 187(5):463 -467. 

*Castle L, Cloke HR, Star-tin Jr, et al. 1988b. Gas chromatographic determination of monoethylene 

glycol and diethylene glycol in chocolate packaged in regenerated cellulose film. J Assoc Off Anal 

Chem 71(3):499-502. 

Catanzaro JM, Smith JG Jr. 1991. Propylene glycol dermatitis. J Am Acad Dermatol 24(1):90­

95. 

Cate JC, Hedrick R. 1980. Propylene glycol intoxication and lactic acidosis. N Engl J Med 

303:1237. 

CELDs. 1994. Computer-assisted Environmental Legislative Database. University of Illinois at 

Urbana. 

Chemical and Engineering News. 1994. Organics led last years top 50 chemicals production 

increase. 13. 

Cheng JT, Beysolow TD, Kaul B, et al. 1987. Clearance of ethylene glycol by kidneys and 

hemodialysis. J Toxicol Clin Toxicol 25(1-2):95-108. 

Cheng YS, Marshall TC, Kanapilly GM. 1982. Generation and characterization of ethylene 

glycol vapors and aerosols. Am Ind Hyg Assoc J 43(4):250-253. 

Cheung ST, Lin WN. 1987. Simultaneous determination of methanol, ethanol, acetone, 

isopropanol and ethylene glycol in plasma by gas chromatography. J Chromatogr 414(1):248­

250. 
 

 

 

 

 

 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 

PROPYLENE GLYCOL 105 

8. REFERENCES 

Child J, Willetts A. 1978. Microbial metabolism of aliphatic glycols: Bacterial metabolism
 

of ethylene glycol. Biochim Biophys Acta 538(2):316-327.
 

Chou JY, Richardson KE. 1978. The effect of pyrazole on ethylene glycol toxicity and metabolism 

in the rat. Toxicol Appl Pharmacol 43(1):33-44.
 

*Chou WL, Speece RE, Siddiqi RH. 1979. Acclimation and degradation of petrochemical
 

wastewater components by methane fermentation. Biotechnol Bioeng Symp 8:391-414.
 

Christian KL, Moorehead WP. 1985. Ethylene dichloride/ethylene glycol spill in a major water
 

resource in British Columbia. J Environ Health 47:192-196.
 

Christopher MM, Eclcfeldt JH, Eaton JW. 1990a. Propylene glycol ingestion causes D-lactic
 

acidosis. Lab Invest 62:114-118.
 

*Christopher MM, Eckfeldt JH, Eaton JW. 1990b. Propylene glycol ingestion causes D-lactic 

acidosis. Laboratory Investigation. 62(1): 114-118.
 

*Christopher MM, Perman V, Eaton JW. 1989a Contribution of propylene glycol-induced 

Heinz body formation to anemia in cats. J Am Vet Med Assoc 194(8):1045-1056.
 

Christopher MM, Perman V, White JG, et al. 1989b. Propylene glycol-induced Heinz body
 

formation and D-lactic acidosis in cats. Prog Clin Biol Res 319:69-92.
 

Chum A, Amma MKP. 1985. Changes in the hepatic carbohydrate metabolism of propane- 1,2 

diol fed rats. IRCS Med Sci 13:958.
 

Chung PK, Tuso P. 1989. Cerebral computed tomography in a stage IV ethylene glycol
 

intoxication. Conn Med 53(9):513-514.
 

*Clark .CR, Marshall TC, Merickel BS, et al. 1979. Toxicological assessment of heat transfer fluids
 

proposed for use in solar energy applications. Toxicol Appl Pharmacol 51:529-535.
 

Clay KL, Murphy RC. 1977. On the metabolic acidosis of ethylene glycol intoxication. Toxicol
 

Appl Pharmacol 39:39-49.
 

CMR. 1990. Chemical profile: Ethylene glycol. Chemical Marketing Reporter, New York, NY.
 

Colwell RR, Sayler GS. 1978. Microbial degradation of industrial chemicals. Water Pollut
 

Microbial 2:111-134.
 

*Commens CA. 1990. Topical propylene glycol and hyperosmolarity. Br J Dermatol 122(1):77­

80. 

Conway RA, Waggy GT, Spiegel MH, et al. 1983. Environmental fate and effects of ethylene 

oxide. Environ Sci Technol 17(2):107-112. 
 

 

 

 

 

 

 

 

 

PROPYLENE GLYCOL 106 

8. REFERENCES 

Coon RA, Jones RA, Jenkins LJ Jr, et al. 1970. Animal inhalation studies of ammonia, 

ethylene glycol, formaldehyde, dimethylamine, and ethanol. Toxicol Appl Pharmacol 

16:646-655. 

*Corazza M, Virgili A, Mantovani L, et al. 1993. Propylene glycol allergy from acyclovir cream 

with cross-reactivity to hydroxypropyl cellulose in a transdermal estradiol system? Contact 

Dermatitis 29(5):283-284. 

Costa J, Soley J, Mata J, et al. 1985. Biodegradation of ethylene glycol. Effluent and 

Water Treatment Journal 25(12) :429-434. 

Cox DP. 1978. The biodegradation of polyethylene glycols. Adv Appl Microbial 23:173-193. 

Crowell WA, Whitlock RH, Stout RC, et al. 1979. Ethylene glycol toxicosis in cattle. Cornell 

Vet 69(3):272-279. 

Cucuzzella A. 1992. Ethylene glycol poisoning. J Gen Intern Med 7(4):467. 

Curnmings KC, Jatlow PI. 1982. Sample preparation by ultra-filtration for direct gaschromatographic analysis of ethylene glycol in plasma. J Anal Toxicol 6(6):324-326. 

Cunningham KM, Goldberg MC, Weiner ER. 1985. The aqueous photolysis of ethylene glycol 

adsorbed on goethite. Photochem Photobiol 41(4):409-416. 

*Damien M, Luciano AA, Peluso JJ. 1989. Propanediol-induced alterations in membrane intergrity, 

metabolism and developmental potential of mouse zygotes. Human Reproduction 4(8):969­

974. 

*Damien M, Luciano AA, Peluso JJ. 1990. Propanediol alters intracellular pH and developmental 

potential of mouse zygotes independently of volume change. Human Reproduction 5(2):212­

216. 

Danielson JW, Snell RP, Oxborrow GS. 1990. Detection and quantitation of ethylene 

oxide, 2-chloroethanol, and ethylene glycol with capillary gas chromatography. J Chromatogr Sci 

28:97-101. 

*Daubert TE, Danner RP. 1980. Data compilation: Tables of physical and thermodynamic 

properties of pure compounds. American Institute of Chemical Engineers, Design Institute for 

Physical Property Data Project 801, The Pennsylvania State University. 

Daubert TE, Danner RP. 1985. Data compilation tables of properties of pure compounds. New 

York, NY: Design Institute for Physical Property Data, American Institute of Chemical 

Engineers, 450. 
 

 

 

 

 

 

 

 

PROPYLENE GLYCOL 107 

8. REFERENCES 

*Daubert TE, Danner RP. 1989. Physical and thermodynamic properties of pure chemicals: Data 

compilation. Design Institute for Physical Property Data, American Institute of Chemical 

Engineers. New York, NY: Hemisphere Pub Corp, 4 vol. 

*Dean ME, Stock BH. 1974. Propylene glycol as a drug solvent in the study of hepatic 

microsoma] enzyme metabolism in the rat. Toxicol Appl Pharmacol 28:44-52. 

Demey HE, Daelemans R.A, Verpooten GA, et al. 1988. Propylene glycol-induced side effects 

during intravenous nitroglycerin therapy. Intensive Care Med 14(3):221-226. 

*Denning DW, Webster DB. 1987. Detrimental effect of propylene glycol on natural killer cell 

and neutrophil function. J Pharm. Pharmacol. 39:236-238. 

DePass LR, Frank FR, Weaver EV, et al. 1984. Ethylene glycol: Twenty-four month oncogenicity 

feeding study in mice. Bushy Run Research Center. Report 46-89. 

DePass LR, Garman RH, Woodside MD, et al. 1986a. Chronic toxicity and oncogenicity studies 

of ethylene glycol in rats and mice. Fundam Appl Toxicol 7(4):547-565. 

DePass LR, Woodside MD, Maronpot RR, et al. 1986b. Three-generation reproduction and 

dominant lethal mutagenesis studies of ethylene glycol in the rat. Fundam Appl Toxicol 7(4):566­

572. 

*DeRudder D, De Graeve E, Van Severen R, et al. 1986. Quantification of ethylene chlorohydrin and 

ethylene glycol as potential reaction products in gas-sterilized medical-grade plastics. J Clin Hosp 

Pharm 11(2):125-130. 

Dial SM, Thrall MA, Harmar DW. 1989. 4methylpyrazole as treatment for naturally acquired 

ethylene glycol intoxication in dogs. J Am Vet Med Assoc 195(1):73-76. 

Dial SM, Thrall MAH, Harmar DW. 1994. Efficacy of 4-methylpyrazole or treatment of 

ethylene glycol intoxication in dogs. Am J Vet Res 55(12):1762-1770. 

Diamandis EP, Efstathiou CE, Hadjiioannou TP. 1980. Automatic determination of ethylene 

glycol in anti-freeze solutions with a periodate-sensitive flow-through electrode. 

Analyst 105(1257):1203-1207. 

*Dorman DC, Haschek WM. 1991. Fatal propylene glycol toxicosis in a horse. J Am Vet Med 

Assoc 198(9):1643-1644. 

*Drajun J. 1991. Geochemistry and soil chemistry reactions occurring during in situ vitrification. J 

Hazardous Materials 26:343-364. 

Driver J, Tardiff RG, Sedik L, et al. 1993. In vitro percutaneous absorption of [ 14C] 

ethylene glycol. J Expo Anal Environ Epidemiol 3(3):277-284. 
 

 

 

 

 

 

 

 

PROPYLENE GLYCOL 108 

8. REFERENCES 

Dwyer DF, Tiedje JM. 1983. Degradation of ethylene glycol and polyethylene glycols by 

methanogenic’consortia. Appl Environ Microbial 46(1):185-190. 

Ebisuno S, Morimoto S, Yoshida T, et al. 1987. Effect of dietary calcium, and magnesium, on 

experimental renal tublar deposition of calcium oxalate crystal induced by ethylene glycol 

administration and its prevention with phytim and citrate. Urol Int 42:330-337. 

Eckfeldt JH, Light RT. 1980. Kinetic ethylene glycol assay with use of yeast alcohol 

dehydrogenase. Clin Chem 26(9):1278-1280. 

*Edinboro LE, Nanco CR, Soghioan DM, et al. 1993. Determination of ethylene glycol in serum 

utilizing direct injection on a wide-bore capillary column. Therapeutic Drug Monitoring 15:220­

223. 

Eichbaum FW, Yasaka WJ. 1976. Antiarrhythmic effect of solvents: Propylene glycol, benzyl 

alcohol. Basic Res Cardiol 71(4):355-370. 

*Eisenreich SJ, Looney BB, Thornton JD. 1981. Airborne organic contaminants in the Great 

Lakes ecosystem. Environ Sci Technol 15(1):30-38. 

*EPA. 1971. Tolerances and exemptions from tolerances for pesticide chemicals in or on raw 

agricultural commodities. U.S. Environmental Protection Agency. Code of Federal Regulations. 40 

CFR 180.1001. 

*EPA. 1972a. Approval and promulgation of implementation plans. U.S. Environmental Protection 

Agency. Code of Federal Regulations. 40 CFR 52. 

EPA. 1972b. Anaerobic treatment of synthetic organic wastes. Washington, DC: U.S. 

Environmental Protection Agency, Office of Research and Monitoring. 

*EPA. 1976. Frequency of organic compounds identified in water. Athens, GA: U.S. Environmental 

Protection Agency, Office of Research and Development, Environmental Research Laboratory. 

EPA. 1977a. An index of refractory organics. Ada, OK: U.S. Environmental Protection Agency, 

Office of Research and Development, Robert S. Kerr Environmental Laboratory. 

EPA. 1977b. Industrial process profiles for environmental use: Chapter 6. The industrial organic 

chemicals industry. Cincinnati, OH: U.S. Environmental Protection Agency, Office of Research and 

Development, Industrial Environment Research Laboratory. EPA-600/2-77-023f. 

EPA. 1978. Ethylene oxide, ethylene chlorohydrin, and ethylene glycol: Proposed maximum residue 

limits and maximum levels of exposure. Washington, DC: U.S. Environmental Protection Agency. 

Federal Register 43:27474-27483. 
 

 

 

 

 

 

 

 

PROPYLENE GLYCOL 109 

8. REFERENCES 

*EPA. 1979. Investigation of selected potential environmental contaminants: Ethylene glycol, 

propylene glycols and butylene glycols. Washington, DC: U.S. Environmental Protection Agency, 

Office of Toxic Substances. EPA/56011 l-79-00. 

EPA. 1980. Ethylene. glycol. Research Triangle Park, NC: U.S. Environmental Protection 

Agency, Office of Air Quality Planning and Standards, Emissions Standards and Engineering 

Division. EPA-450/3-80-028d. 

*EPA. 1982. Tolerances and exemptions from tolerances for pesticide chemicals in or on raw 

agricultural commodities. U.S. Environmental Protection Agency. Code of Federal Regulations. 

40 CFR 180.142. 

*EPA. 1983. Standards of performance for new stationary sources. U.S. Environmental Protection 

Agency. Code of Federal Regulations. 40 CFR 60.489. 

EPA. 1984a. CC/MS analysis of organics in drinking water concentrates and advanced waste 

treatment concentrates. Volume I: Analysis results for 17 drinking water, 16 advanced waste 

treatment and 3 process blank concentrates. Research Triangle Park, NC: U.S. Environmental 

Protection Agency, Office of Research and Development, Health Effects Research Laboratory. 

EPA-600/l-84-020A. 

EPA. 1984b. Premanufacture notification exemptions: polymers. U.S. Environmental Protection 

Agency. Code of Federal Regulations. 40 CFR 723 .250. 

*EPA. 1985a. Temperature corrections for organic solvents. U.S. Environmental Protection Agency. 

Code of Federal Regulations. 40 CFR 796.1220. 

*EPA. 1985b. Environmental effects testing guidelines. U.S. Environmental Protection 

Agency. Code of Federal Regulations. 40 CFR 797. 

*EPA. 1987a. Health and environmental effects document for propylene glycol. Washington, 

DC: U.S. Environmental Protection Agency, Office of Solid Waste and Emergency Response. 

EPA. 1987b. Toxic chemical release reporting: Community right to know. U.S. Environmental 

Protection Agency. Code of Federal Regulations. 40 CFR 372.65. 

EPA. 1987c. Toxic chemical release reporting: Community right to know. U.S. Environmental 

Protection Agency. Federal Register 52(107):21152-21177. 

*EPA 1987d. Organic chemicals, plastics, and synthetic fibers. U.S. Environmental Protection. 

Agency. Code of Federal Regulations. 40 CFR 414. 

*EPA. 1989a. Pesticides required to be reregistered: List C. U.S. Environmental Protection Agency. 

Federal Register 54(140):30846-30855. 
 

 

 

 

 

 

 

 

 

 

 

 

PROPYLENE GLYCOL 110 

8. REFERENCES 

*EPA. 1989b. Reregistration. U.S. Environmental Protection Agency. Code of Federal 

Regulations. 40 CFR 152.146. 

*EPA. 1990a. Interim methods for development of inhalation reference doses. Washington, 

DC: U.S. Environmental Protection Agency. EPA/600/890/066A. 

* EPA. 1990b. Standards of performance for new stationary sources. U.S. Environmental Protection 

Agency. Code of Federal Regulations. 40 CFR 60. 

EPA. 1993a. Reportable quantity adjustments. U.S. Environmental Protection Agency. Federal 

Register. 58 FR 54836. 

*EPA. 1993b. Standards of performance for new stationary sources. U.S. Environmental Protection 

Agency. Code of Federal Regulations. 40 CFR 60.707. 

*EPA. 1993c. New source performance standards. U.S. Environmental Protection Agency. Federal 

Register. 58 FR 45962. 

*EPA. 1995a. Test methods for evaluating solid waste. Method 8015b, revision 2, January 1995 

“Nonhalogenated Organics Using GCIFTD SW 846. 

*EPA. 1995b. Test methods for evaluating solid waste; Method 8430 revision 0 January 1995; 

“Nonhalogenated Organics Using GCLFID SW 846. 

*EPA 1995c. Toxic Chemical release inventory reporting form R and instructions. Office of 

Pollution, Prevention and Toxics. Washington DC EPA 745-K-95-051. 

*Eun HC, Kim YC. 1989. Propylene glycol allergy from ketoconazole cream. Contact Dermatitis 

21(4):274-275. 

Evans WH David EJ. 1974. Biodegradation of mono-, di-, and triethylene glycols in river waters 

under contrdlled laboratory conditions. Water Research 8(2):97-100. 

Evans WH, Dennis A. 1973. Spectrophotometric determination of low levels in mono-, di-, and 

triethylene glycols in surface waters. Analyst 98(1172):782-791. 

Evmiridis NP. 1989. Periodate determination by FIA with chemiluminescence emission 

detection, and its application to ethylene glycol (ethanediol). Talanta 36(3):357-362. 

Factor SA, Lava NS. 1987. Ethylene glycol intoxication: A new stage in the clinical 

syndrome. NY State J Med 87(3):179-180. 

*FAO/WHO. 1974. Toxicological evaluation of certain food additives with a review of general 

principles and of specifications. In: 17th Report of the Joint FAOAVHO Expert Committee on 

Food Additives, Geneva, Switzerland, June 25-July 4, 1973. Geneva, Switzerland: Food and 

Agricultural Organization of the United Nations/World Health Organization. 
 

 

 

 

 

 

 

 

PROPYLENE GLYCOL 111 

8. REFERENCES 

Farsund T. 1978. Cell kinetics of mouse urinary bladder epithelium: VI. Changes in the 

proportions of cells with various nuclear DNA content after repeated doses of propylene glycol (1, 

2-propanediol). Virchows Arch [B] 27(1): l-6. 

FDA. 1973. Teratologic evaluation of compound FDA 71-56 (propylene glycol) in mice, 

rats, hamsters, and rabbits. PB-223 -822. 

FDA. 1974. Mutagenic evaluation of compound FDA 71-56 (propylene glycol). PB-245450. 

FDA. 1977a. Indirect food additives: Adhesives and components of coatings. Food and Drug 

Administration. Code of Federal Regulations. 21 CFR 175.105. 

FDA. 1977b. Indirect food additives: Adhesive coatings and components. Food and Drug 

Administration. Federal Register 42(50):14534-14554. 

FDA. 1977c. Propylene Glycol and Propylene Glycol Monostearate. Food and Drug 

Administration. Federal Register 42(117):30865-30866. 

*FDA. 1982. Generally recognized as safe. Food and Drug Administration. Code of 

Federal Regulations. 21 CFR 184.1666. 

FEDRIP. 1994. Federal Research in Progress. Dialog Information Service, Inc., Amarillo, TX. 

*FEDRIP. 1995. Federal Research in Progress. Dialog Information Service, Inc., Amarillo. 

TX. Fincher EL, Payne WJ. 1962. Bacterial utilization of ether glycols. Appl Microbial 

10:542-547. 

Flanagan RJ, Dawling S, Buckley BM. 1987. Measurement of ethylene glycol in biological 

specimens using derivatization and gas-liquid chromatography with flame ionization detection. 

Ann Clin Biochem 24(1):80-84. 

*Fligner CL, Jack R, Twiggs GA, et al. 1985. Hyperosmolality induced by propylene glycol: 

A complication of silver sulfadiazine therapy. J Amer Med Assoc 253(11):1606-1609. 

Florida. 1994. Personal conversation with G. Robbins to Marion Deerhake, Research Triangle 

Institute, regarding air quality guidelines. Florida Pine&s County Air Quality Office 

(9/29/94). 

Fait FF Jr, Cowell RL, Brobst DF, et al. 1985. X-ray powder diffraction and microscopic 

analysis of crystalluria in dogs with ethylene glycol poisoning. Am J Vet Res 46(11):2404­

2408. 

Fox LE, Grauer GF, Dubielzig RR, et al. 1987. Reversal of ethylene glycol-induced 

nephrotoxicosis in a dog. J Am Vet Med Assoc 191(11):1433-1435. 
 

 

 

 

 

 

 

 

PROPYLENE GLYCOL 112 

8. REFERENCES 

Frantz SW, Beskitt JL, Grosse CM, et al. 1989. Ethylene glycol: Comparison of 

pharmacokinetics and material balance following single intravenous, oral and cutaneous 

administration to male and female Sprague-Dawley rats. Bushy Run Research Center, Union 

Carbide Corp., Report No. 5 1-543. 

Frantz SW, Tallant MJ, Beskitt JL. 1991. Ethylene glycol: comparisons of pharmacokinetic 

and material balance studies following single intravenous, peroral, and percutaneous 

administrations to female CD-l mice. Bushy Run Research Center, Union Carbide Corp., 

Report No. 53-550. 

*Fraser AD, MacNeil W. 1993. Calorimetric and gas chromatographic procedures for glycolic acid 

in serum: the major toxic metabolite of ethylene glycol. Clinical Toxicology 31(3):397-405. 

Freitag D, Ballhom L, Geyer H, et al. 1985. Environmental hazard profile of organic chemicals: 

An experimental method for the assessment of the behaviour of organic chemicals in the 

ecosphere by means of simple laboratory tests with 14C labeled chemicals. Chemosphere 

14(10):1589-1616. 

*Frosch PJ, Pekar U, Enzmann H. 1990. Contact allergy to propylene glycol: Do we use 

the appropriate test concentration ? Dermatol Clin 8(1): 111-1113. 

FSTRAC. 1990. Summary of state and federal drinking water standards and guidelines. U.S. 

Environmental Protection Agency. Chemical Communication Subcommittee, Federal-State 

Toxicology and Regulatory Alliance Committee (FSTRAC). 

Fuller EW Jr. 1969. Ethylene glycol: A review. Med Leg Bull 18(10):1-8. 

Gabow PA, Clay K, Sullivan JB, et al. 1986. Organic acids in ethylene glycol intoxication. 

Ann Intern Med 105(1):16-20. 

*Gaston LW, Stadtman ER. 1963. Fermentation of ethylene glycol by Clostridium glycolicum. 

J Bacterial 85:356-362. 

*Gaunt IF, Carpanin FMB, Grasso P, et al. 1972. Long-term toxicity of propylene glycol in 

rats. Food Cosmet Toxicol 10(2):151-162. 

Gebhardt DOE. 1986. The teratogenic action of propylene glycol (propanediol-1,2) 

and propanediol- 1,3 in the chick embryo. Teratology 1:153-162. 

Gerhold RM, Malaney GW. 1966. Structural determinants in the oxidation of aliphatic compounds 

by activated sludge. J Water Pollut Contr Fed. 

Gershoff SN, Andms SB. 1962. Effect of vitamin B6 and magnesium on renal disposition 

of calcium oxalate induced by ethylene glycol administration. Proceedings of the Society 

for Experimental Biology and Medicine 109:99-102. 
 

 

 

 

 

 

 

 

 

PROPYLENE GLYCOL 113 

8. REFERENCES 

*Giachetti C, Zanolo G, Assandri A, et al. 1989. Determination of cyclic butylboronate 

esters of some 1,2- and 2,3-diols in plasma by high-resolution gas chromatography/mass 

spectrometry. Biomedical and Environmental Mass Spectrometry 18(8):592-597. 

*Glasgow AM, Boeckx RL, Miller MK, et al. 1983. Hyperosmolality in small Infants due 

to propylene glycol. Pediatrics 72(3): 353-355. 

Godolphin W, Meagher EP, Sanders HD, et al. 1980. Unusual calcium oxalate crystals in 

ethylene glycol poisoning. Clin Toxicol 16(4):479-486. 

Gonzalez CF, Taber WA, Zeitoun MA. 1972. Biodegradation of ethylene glycol by a saltrequiring bacterium. Appl Microbial 24(6):911-919. 

*Gordon HL, Hunter JM. 1982. Ethylene glycol poisoning: A case report. Anaesthesia 17:332­

338. 

Grabinska-Loniewska A. 1974. Studies on the activated sludge bacteria participating in the 

biodegradation of methanol, formaldehyde and ethylene glycol: II. Utilization of various carbon 

and nitrogen compounds. Acta Microbial Pol Ser B Microbial Appl 6(2):83-88. 

Grafton TF, Hansen DK. 1987. In vitro embryotoxic effects of ethylene glycol in 

rats. Teratogenesis, Carcinogenesis, and Mutagenesis 7:483-489. 

Grauer GF, Thrall MA, Henre BA, et al. 1984. Early clinicopathologic findings in dogs ingesting 

ethylene glycol. Am J Vet Res 45(11):2299-2303. 

Grauer GF, Thrall MA, Henre BA, et al. 1987. Comparison of the effects of ethanol 

and 4-methylpyrazole on the pharmacokinetics and toxicity of ethylene glycol in the dog. 

Toxicol Lett 35(2-3):307-314. 

Griffiths AJF. 1979. Neurospora prototroph selection system for studying aneuploid 

production. Environ Health Perspect 31:75-80. 

Griffiths AJF. 1981. Neurospora and environmentally induced aneuploidy. Short-Term Tests 

Chem Carcinog 1981:187-199. 

Grosjean D. 1990. Atmospheric chemistry of toxic contaminants: 2. Saturated aliphatics: 

Acetaldehyde, dioxane, ethylene glycol ethers, propylene oxide. Journal of the Air Waste 

Management Association 40(11):1522-1531. 

Gupta RN. 1982. Liquid-chromatographic determination of ethylene glycol in plasma. Clin 

Chem 28(1):32-33. 

Giisten H, Klasinc L, Marie D. 1984. Prediction of the abiotic degradability of organic 

compounds in the troposphere. Journal of Atmospheric Chemistry 2:83-94. 
 

 

 

 

 

 

 

PROPYLENE GLYCOL 114 

8. REFERENCES 

Haines JR, Alexander M. 1975. Microbial degradation of polyethylene glycols. Appl 

Microbial 29:621-625. 

Hamano T, Mitsuhashi Y, Tanaka K, et al. 1984. Study of enzymic determination of food 

additives: II. Enzymic determination of propylene glycol in commercial foods. Agric Biol 

Chemical 48(10):2517-2521. 

*Hannuksela M, Forström L. 1978. Reactions to peroral propylene glycol. Contact 

Dermatitis 4(1):41-45. 

*Hannuksela M, Pirila V, Salo OP. 1975. Skin reactions to propylene glycol. Contact 

Dermatitis 1:112-116. 

Hansson P. 1990. Kinetic enzymic assay for ethylene glycol. Clin Chim Acta 189(2):243-244. 

Hansson P, Masson P. 1989. Simple enzymatic screening assay for ethylene glycol (ethane-I ,2­

diol) in serum. Clin Chim Acta 182(1):95-101. 

Harada T, Nagashima Y. 1975. Utilization of alklyether compounds by soil bacteria. Journal 

of Fermentation Technology 53(4):218-222. 

*Harris MW, Chapin RE, Lockhart AC, et al. 1992. Assessment of a short-term reproductive and 

developmental toxicity screen. Fundamental and Applied Toxicology 19(2):186-196. 

*Hartman PA, Bowman PB. 1977. Simple GLC determination of ethylene oxide and its reaction 

products in drugs and formulations. J Pharm Sci 66(6):789-792. 

Hatfield R. 1957. Biological oxidation of some organic compounds. Industrial and Engineering 

Chemistry 49:192-196. 

*Hattori T, Maehashi H. 1993. Propylene glycol-induced skeletal muscle excitation. Food Chem 

Toxicol 31(9):647-650. 

*HazDat. 1995. Database. Agency for Toxic Substances and Disease Registry (ATSDR), Atlanta, 

GA. August 21, 1995. 

Heckerling PS. 1987. Ethylene glycol poisoning with a normal anion gap due to occult bromide 

intoxication. Ann Emerg Med 16(12): 1384-1386. 

*Helrich, K. 1990a. Method 970.61; Propylene glycol in cosmetics. Official Methods of Analysis 

of the AOAC, 15th Edition. AOAC, Arlington, VA 

*Helrich, K. 1990b. Method 97 1.02; Glycerol, propylene glycol, and triethylene glycol in cased 

cigarette cut filler and ground tobacco. Official Methods of Analysis of the AOAC, 15th Edition, 

AOAC, Arlington, VA. 
 

 

 

 

 

 

 

 

PROPYLENE GLYCOL 115 

8. REFERENCES 

*Helrich, K. 1990c. Method 947.09; Propylene glycol in vanilla extract. Official Methods of 

Analysis of the AOAC, 15th Edition, AOAC, Arlington, VA. 

Hertz CD, Oxenford JL, Warner JS. 1990. Development of analytical method for compliance 

monitoring of ethylene glycol, n-hexane, methyl ethyl ketone, and formaldehyde in drinking water. 

Proc Water QualTechnol Conf 171651-665. 

Hewlett TP, Jacobsen D, Collins TD, et al. 1989. Ethylene glycol and glycolate kinetics in rats 

and dogs. Veterinary and Human Toxicology 3l(2): 116- 120. 

*Hewlett TP, McMartin KE, Lauro AJ, et al. 1986. Ethylene glycol poisoning: The value of 

glycolic acid determinations for diagnosis and treatment. J Toxicol Clin Toxicol 24(5):389-402. 

*Hewlett TP, Ray AC, Reagor JC. 1983. Diagnosis of ethylene glycol (antifreeze) intoxication in 

dogs by determination of glycolic acid in serum and urine with high pressure liquid 

chromatography and gas chromatography-mass spectrometry. J Assoc Off Anal Chem 

66(2):276-283. 

*Hine J, Mookejee PK. 1975. The intrinsic hydrophilic character of organic 

compounds: Correlations in terms of structural contributions. J Org Chem 

40(3):292-298. 

*Hodgson AT, Wooley JD, Daisey JM. 1993. Emissions of volatile organic compounds from new 

carpets measured in a large-scale environmental chamber. J Air and Waste Management 

Association 43:316-324. 

Holman NW Jr, Mundy RL, Teague RS. 1979. Alkyldiol antidotes to ethylene glycol 

toxicity in mice. Toxicol Appl Pharmacol 49(2):385-392. 

Holopainen JK. 1992. Catch and sex ratio of Carabiae (Coleoptera) in pitfall traps filled with 

ethylene glycol or water. Pedobiologia 36:257-261. 

Hong HL, Canipe J, Jameson CW, et al. 1988. Comparative effects of ethylene glycol and 

ethylene glycol monomethyl ether exposure on hematopoiesis and histopathology in B6C3Fl 

mice. J Environ Pathol Toxicol Oncol 8(7):27-38. 

Horiuti K, Sakoda T, Takei M, et al. 1992. Effects of ethylene glycol on the kinetics of 

contraction on flash photolysis of caged ATP in rat psoas muscle fibres. J Muscle Res Cell Motil 

13(2):199-205. 

*House P, Chaussard J, Harry P, et al. 1993. Simultaneous determination of ethylene glycol, 

propylene glycol, 1,3 -butylene glycol and 2,3 -butylene glycol in human serum and urine by widebore column gas chromatography. J Chromatography 619:251-257. 
 

 

 

 

 

 

 

PROPYLENE GLYCOL 116 

8. REFERENCES 

*Howard PH, Boethling RS, Jarvis WF, et al, eds. 1991. Handbook of environmental 

degradation rates. Chelsea, MI: Lewis Publishers, Inc. 392-393. 

*HSDB. 1995a. Ethylene glycol. Hazardous Substances Data Bank. National Library of 

Medicine, National Toxicology Information Program, Bethesda, MD. 

*HSDB. 1995b. Propylene glycol. Hazardous Substances Data Bank. National Library of 

Medicine, National Toxicology Information Program, Bethesda MD. 

*Huff E. 1961. Metabolism of 1,2-propanediol. Biochim Biophys Acta 48:506-517. 

*Huggon I, James I, Macrae D. 1990. Hyperosmolality related to propylene glycol in an 

infant treated with enoximone infusion. BMJ 301(6742):19-20. 

Hughes RD, Gove CD, Williams R. 1991. Protective effects of propylene glycol, a solvent 

used pharmaceutically, against paracetamol-induced liver injury in mice. Biochem 

Pharmacol 42(3):710-713. 

Hughes S, Meschi PL, Johnson DC. 1981. Amperometric detection of simple alcohols in aqueous 

solutions by application of a triple-pulse potential waveform at platinum electrodes. Anal Chim 

Acta 132: 1-10. 

Hughes TW, Tiemey DR, Khan ZS. 1979. Measuring fugitive emissions from petrochemical 

plants. Chemical Engineering Progress 75:35-39. 

Hylander B, Karlsson K, Person H, et al. 1989. Death and chronic renal failure CFR in severe 

ethylene glycol EG intoxication. Kidney Int 35(1):228. 

Introna F Jr, Smialek JE. 1989. Antifreeze (ethylene glycol) intoxications in Baltimore 

(Maryland, USA): Report of six cases. Acta Morphol Hung 37(3-4):245-264. 

*IRIS. 1995. Integrated Risk Information System (IRIS). Online. Ethylene glycol and 

propylene glycol. U.S. Environmental Protection Agency, Office of Health and Environmental 

Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH, October 3, 

1995. 

*Iwinski G, Jenke DR. 1987. Determination of alcohols in pharmaceuticals by ionexclusion chromatography. J Chromatogr 392:397-405. 

Jacobsen D, Hewlett TP, Webb R, et al. 1988. Ethylene glycol intoxication: Evaluation of 

kinetics and cr-ystalluria. Am J Med 84(1): 145- 152. 

Jacobsen D, McMartin KE. 1986. Methanol and ethylene glycol poisonings: Mechanism 

of toxicity, clinical course, diagnosis and treatment. Med Toxicol 1(5):309-334. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PROPYLENE GLYCOL 117 

8. REFERENCES 

Jacobsen D, Ovrebo S, Ostborg J, et al. 1984. Glycolate causes acidosis in ethylene glycol 

poisoning and is effectively removed by hemodialysis. Acta Med Stand 216:409-416. 

Jacobsen D, Sebastian CS, Barron SK, et al. 1990. Effects of 4-methylpyrazole, 

methanol/ethylene glycol antidote, in healthy humans. J Emerg Med 8(4):455-461. 

Jar-vie DR, Simpson D. 1957. Simple screening test for the emergency identification of methanol 

and ethylene glycol in poisoned patients. Clin Chem 36(11):1957- 1961. 

Jenkins LD, Cook KA, Cain RB. 1979. Microbial degradation of polyethylene glycols. J 

Appl Bacterial 47( 1):75-85. 

Johanson G. 1989. Analysis of ethylene glycol ether metabolites in urine by extractive alkylation and 

electron-capture gas chromatography. Arch Toxicol 63(2):107- 111. 

Johanson G, Michel I, Norback D, et al. 1989. Biological monitoring of exposure to ethylene 

glycol ethers. Arch Toxicol Suppl 13:108-l 11. 

Jones AW, Nilsson L, Gladh A, et al. 1991. 2,3-Butanediol in plasma from an alcoholic mistakenly 

identified as ethylene glycol by gas-chromatographic analysis. Clin Chem 37(8): 1453-1455. 

Jones N, Watson GK. 1976. Ethylene glycol and polyethylene glycol catabolism by a 

sewage bacterium. Biochem Sot Trans 4(5):1-892. 

*Jonsson JA, Eklund A, Molin L. 1989. Determination of ethylene glycol in postmortem blood by 

capillary gas chromatography. J Anal Toxicol 13(1):25-26. 

*Kaiser RE, Rieder RI. 1987. Native ethylene glycol in wine: Application of a dead volume 

free, very fast “deans heart-cut” system on-line with multi-chromatography. J High Resolut 

Chromatogr Comrnun 10(5):240-243. 

*Kaplan DL, Walsh JT, Kaplan AM. 1982. Gas chromatographic analysis of glycols to 

determine biodegradability. Environ Sci Technol 16:723-725. 

Karlson-Stiber C, Persson H. 1992. Ethylene glycol poisoning: Experiences from an epidemic in 

Sweden. Clinical Toxicology 30(4):565-574. 

*Kashtock M, Breder CV. 1980. Migration of ethylene glycol from polyethylene terephthalate 

bottles into 3% acetic acid. J Assoc Off Anal Chem 63(2):168-172. 

Katz M. 1975. Intersociety committee (ISC) methods of air sampling and analysis. Health Lab 

Sci 12:359-422. 

*Kavlock RJ, Short RD, Chemoff N. 1987. Further evaluation of an in vivo teratology 

screen. Teratogenesis, Carcinogenesis, and Mutagenesis 7:7-16. 
 

 

 

 

 

 

 

 

 

PROPYLENE GLYCOL 118 

8. REFERENCES 

*Kelner MJ, Bailey DN. 1985. Propylene glycol as a cause of lactic acidosis. Journal of 

Analytical Toxicology 9(1):40-42. 

Kersters K, Deley J. 1963. The oxidation of glycols by acetic acid bacteria. Biochim Biophys 

Acta 71:311-331. 

Kersting EJ, Nielsen SW. 1965. Ethylene glycol poisoning in small animals. J Amer Vet 

Med Assoc 146(2):113-118. 

Khan SR, Shevock PN, Hackett RL. 1993. Magnesium oxide administration and prevention 

of calcium oxalate nephorolithiasis. J Urol 149:412-416. 

Khera KS. 1991. Chemically induced alterations in maternal homeostasis and histology of conceptus: 

Their etiologic significance in rat fetal anomalies. Teratology 44(3):259-297. 

Khoury GA, Adbelghani AA, Anderson AC. 1993. Bioaccumulation and depuration of 

ethylene glycol by crayfish (Procambarus spp.) Environmental Toxicology and Water 

Quality 8:25-31. 

Kiba N, Goto K, Furusawa M. 1986. Determination of glycerol, propane-1,2-diol and 

triglycerides by high-performance liquid chromatography and a post-column reactor containing 

immobilized glycerol dehydrogenase. Anal Chim Acta 185:287-294. 

*Kinnunen T, Hannuksela M. 1989. Skin reactions to hexylene glycol. Contact 

Dermatitis 21(3):154-158. 

*Kirk-Othmer Encyclopedia of Chemical Technology. 1978. 3rd edition. Vol. 3, 79-95. 

Kirk-Othmer Encyclopedia of Chemical Technology. 1980. 3rd edition. Vol. 11, 933­

956. 

*Klaus R, Fischer W. 1987. A means of analyzing glycols especially ethylene glycol 

and diethylene glycol by a method used for the determination of carbohydrates in 

alcoholic beverages. Chromatographia 23(2): 137-140. 

*Klecka GM, Carpenter CL, Landenberger BD. 1993. Biodegradation of aircraft deicing fluids in 

soil at low temperatures. Ecotoxicology and Environmental Safety 25:280-295. 

*Konradova V, Vavrova V, Janota J. 1978. Effect of the inhalation of a surface tension-reducing 

substance (propylene glycol) on the ultrastructure of the epithelium of the’ respiratory passages 

in rabbits. Folia Morpho 126(1):28-34. 

Kramer JW, Bistline D, Sheridan P, et al. 1984. Identification of hippuric acid crystals in the urine 

of ethylene glycol-intoxicated dogs and cats. J Am Vet Med Assoc 184(5):584. 
 

 

 

 

 

 

 

 

PROPYLENE GLYCOL 119 

8. REFERENCES 

Kring EV, Damrell DJ, Basilio AN Jr, et al. 1984. Laboratory validation and field verification of a 

new passive air monitoring badge for sampling ethylene oxide in air. Am Ind Hyg Assoc J 

45(10):697-707. 

Kukielka E, Cederbaum AI. 1991. Oxidation of ethylene glycol to formaldehyde by rat liver 

microsomes: Role of cytochrome P-450 and reactive oxygen species. Drug Metabolism and 

Disposition 19:1108-l 115. 

*Kulick MI, Wong R, Okarma TB et al. 1985. Prospective study of side effects associated with 

the use of silver sulfadiazine in severely burned patients. Ann Plast Surg 14(5):407-419. 

Lahti A. 1980. Nonimmunologic contact urticaria. Acta Dermato-Vemereol 60(Supp 91):1-49. 

Lamb JC, Maronpot RR, Gulati DK, et al. 1985. Reproductive and developmental toxicity 

of ethylene glycol in the mouse. Toxicol Appl Pharmacol 81:100-112. 

Lang RF. 1986. Determination of polar organic solutes in methanol using hot on-column injection 

capillary gas chromatography. Anal Chem 58(6): 1259-1261. 

Lauwerys R, Bernard A, Viau C, et al. 1985. Kidney disorders and hematotoxicity from organic 

solvent exposure. Stand J Work Environ Health 11(Supp11):83-90. 

LDOTD. 1990. Fate of ethylene glycol in the environment. Baton Rouge, LA: Louisiana 

Department of Transportation and Development, Louisiana Transportation Research 

Center. 

LeGatt DF, Tisdell RH. 1990. Ethylene glycol quantification: Avoid propylene glycol as an internal 

standard. Clin Chem 36(10): 1860-1861. 

Lenk W, Loehr D, Sonnenbichler J. 1989. Pharmacokinetics and biotransformation of 

diethylene glycol and ethylene glycol in the rat. Xenobiotic 19(9):961-979. 

*Lewis RJ. 1993a. Hawley’s Condensed Dictionary, 12th Edition; p 487, ethylene glycol. Van 

Nostrand Reinhold Co., New York. 

*Lewis RJ. 1993b. Hawley’s Condensed Dictionary, 12th Edition; p 970-971, propylene glycol. Van 

Nostrand Reinhold Co., New York. 

Litovitz T. 1986. The alcohols: Ethanol, methanol, isopropanol, ethylene glycol. Pediatr Clin 

North Am 33(2):31l-323. 

Litovitz TL, Schmitz BF, Bailey KM. 1990. 1989 Annual report of the American Association of 

Poison Control Centers national data collection system. Toxicology 8(5):394-431. 

Litovitz TL, Schmitz BF, Bailey KM. 1991. 1990 Annual report of the American Poison Control 

Centers national data collection system. Toxicology 9(5):461-500. 
 

 

 

 

 

 

 

 

 

PROPYLENE GLYCOL 120 

8. REFERENCES 

Loden M. 1986. The in vitro permeability of human skin to benxene, ethylene glycol, 

formaldehyde, and n-hexane. Acta Pharmacol Toxicol 58(5):382-389. 

Lokke H. 1984. Leaching of ethylene glycol and ethanol in subsoils. Water Air Soil 

Pollut 22:373-387. 

*Lolin Y, Francis DA, Flanagan RJ, et al. 1988. Cerebral depression due to propylene glycol 

in a patient with chronic epilepsy the value of the plasma osmolal gap in diagnosis. Postgrad 

Med J 64(754):610-613. 

*Louekari K, Scott AO, Salminen S. 1990. Estimation of food additive intakes. In: Branen AL, 

Davidson P, Salminen S, eds. Food Science Technology. Vol. 35: Food additives. New York, NY: 

Marcel Dekker, Inc., 9-32. 

Lundberg P, Lof A, Johanson G, et al. 1991. New Swedish occupational standards for some organic 

solvents. Am J Ind Med 19(5):559-567. 

Lyman WJ, Reehl WF, Rosenblatt DH. 1982. Handbook of chemical property estimation methods. 

New York, NY: McGraw-Hill, 5 - 4. 

Magerl H, Poelmann E, Hager W. 1983. Determination of ethylene glycol by head-space gas 

chromatography. Z Rechtsmed 90(3):205-209. 

Mallya KB, Mendis T, Guberman A. 1986. Bilateral facial paralysis following ethylene glycol 

ingestion. Can J Neural Sci 13(4):340-341. 

Malrnlund HO, Berg A, Karlman G, et al. 1991. Considerations for the treatment of ethylene glycol 

poisoning based on analysis of two cases. J Toxicol Clin Toxicol 29(2):231-240. 

*Manius GJ. 1979. Determination of ethylene oxide, ethylene chlorohydrin, and ethylene glycol 

residues in ophthalmic solutions at proposed concentration limits. J Pharm Sci 68( 12): 1547­

1549. 

Mantica E, Botta D, Pirri L. 1986. Pollution conditions of the aquifer beneath a plant 

producing alkyd resins. In: Comm Eur Communities, Eur 10388. Org Micropollut Aquat 

Environ, 89-106. 

Marion CV, Malaney GW. 1963. The oxidation of aliphatic compounds by Alcaligenes 

faecalis. J Water Pollut Control Fed 35:1269-1284. 

Maronpot RR, Zelenak JP, Weaver EV, et al. 1983. Teratogenicity study of ethylene glycol in 

rats. Drug and Chemical Toxicology 6(6):579-594. 

Marr MC, Price CJ, Myers CB, et al. 1992. Developmental stages of the CD (Sprague-Dawley) rat 

skeleton after maternal exposure to ethylene glycol. Teratology 46(2): 169- 181. 
 

 

 

 

 

 

PROPYLENE GLYCOL 121 

8. REFERENCES 

Marshall DA, Doty RL. 1990. Taste responses of dogs to ethylene glycol, propylene glycol, and 

ethylene glycol-based antifreeze. J Am Vet Med Assoc 197(12): 1599-1602. 

Marshall TC. 1979. Pharmacokinetics of ethylene glycol following intravenous administration to 

rats. Annual Report on Inhalation Toxicological Research Institute, Lovelace Biomedical 

Environmental Research Institute, 57l-574. 

Marshall TC. 1982. Dose-dependent disposition of ethylene glycol in the rat after intravenous 

administration. J Toxicol Environ Health 10:397-409. 

Marshall TC, Cheng YS. 1983. Deposition and fate of inhaled ethylene glycol vapor 

and condensation aerosol in the rat. Fundam Appl Toxicol 3(3):175-181. 

Martis L, Kroes T, Darby TD, et al. 1982. Disposition kinetics of ethylene oxide, ethylene 

glycol, and 2-chlorethanol in the dog. J Toxicol Environ Health 10:847-856. 

Matsui S, Murakami T, Sasaki T, et al. 1975. Activated sludge degradability of organic 

substances in the waste water of the Kashima petroleum and petrochemical industrial complex in 

Japan. Prog Water Technol 7(3-4):645-650. 

*Matusik JE, Eilers PP, Waldron EM, et al. 1993. Confirmation of identities of propylene and 

ethylene glycols in anchovies by tandem mass spectrometry. J Association of Official Analytical 

Chemistry International 76: 1344-1347. 

Maurer H, Kessler C. 1988. Identification and quantification of ethylene glycol and diethylene 

glycol in plasma using gas chromatography-mass spectrometry. Arch Toxicol 62(1):66-69. 

Maylin GA. 1980. A simple method for detecting ethylene glycol in urine by thin 

layer chromatography. Cornell Vet 70(2) :202-205. 

McCallum NK, Muirhead JM. 1982. Gas-chromatographic determination of propane-1,2-diol 

in flavour bases, flavoured and natural wines. Food Technology in New Zealand 17(8):34­

35. 

McCann J, Choi E, YamasakiE, et al. 1975. Detection of carcinogens as mutagensin the 

Salmonella/microsome test: Assay of 300 chemicals. Proc Nat Acad Sci 72:5135­

5139. 

McCarroll NE, Piper CE, Keech BH. 1981. An E. coli micro-suspension assay for the detection of 

DNA damage induced by direct-acting agents and promutagens. Environ Mutagen 3:429-444. 

McCurdy HH, Solomons ET. 1982. Improved procedure for determination of ethylene 

glycol in blood. J Anal Toxicol 6(5):253-254. 
 

 

 

 

PROPYLENE GLYCOL 122 

8. REFERENCES 

McDonald TO, Kasten K, Hervey R, et al. 1973. Acute ocular toxicity of ethylene oxide, 

ethylene glycol, and ethylene chlorohydrin. Bull Pat-enter Drug Assoc 27(4):153-164. 

McGahey C, Bouwer EJ. 1992. Biodegradation of ethylene glycol in simulated subsurface 

environments. Water Science Technology 26:41-49. 

Means JL, Anderson SJ. 1981. Comparison of five different methods for measuring 

biodegradability in aqueous environments. Water Air and Soil Poll 16:301-315. 

Melnick RL. 1984. Toxicities of ethylene glycol and ethylene glycol mot-methyl ether in Fischer 

344/N rats and B6C3Fl mice. Environ Health Perspect 57:147-155. 

Meola JM, Rosano TG, Swift TA. 1980. Fluorimetry of ethylene glycol in serum. Clin 

Chem 26(12): 1709. 

*Merck Index. 1989a. The Merck index: An encyclopedia of chemicals, drugs, and 

biologicals. 11th ed. Budavari S, ed. Rahway, NJ: Merck and Co., Inc., 379, 7810 

*Merck Index. 1989b. The Merck index: An encyclopedia of chemicals, drugs, and 

biologicals. 11th ed. Budavari S, ed. Rahway, NJ: Merck and Co., Inc., 3759, 7810. 

Mikheev MI, Gorlinskaya Y, Solovyova TV. 1990. The body distribution and biological action 

of xenobiotics. J Hyg Epidemiol Microbial Immunol 34(4):329-336. 

Mill T, Hendry DG, Richardson H. 1980. Free radical oxidants in natural waters. 

Science 207(22):886-887. 

*Miller ON, Bazzano G. 1965. Propanediol metabolism and its relation to lactic acid 

metabolism. Ann NY Acad Sci 119:959-973. 

Miller W. 1990. Ethylene glycol toxicity. Del Med J 62( 10):1267-1272. 

Mitsuhashi Y, Hamano T, Tanaka K, et al. 1985. [Enzymatic analysis of propylene glycol in 

foods by the use of glycerol dehydrogenase.] J Food Hyg Sot Jpn 26:290-294. (Japanese) 

Moffatt EJ, Hagardom AN, Ferslew KE. 1986. A gas-liquid chromatographic method for 

quantitation of 1,3-butylene glycol in whole blood or plasma and the separation of the short chain 

glycols. J Anal Toxicol 10(1):35-37. 

Momont SL, Dahlberg PJ. 1989. Ethylene glycol poisoning. Wis Med J 88(9): 16-20. 

Moriarty RW, McDonald RH Jr. 1974. The spectrum of ethylene glycol poisoning. Clin 

Toxicol 7(6):538-596. 
 

 

 

 

PROPYLENE GLYCOL 123 

8. REFERENCES 

*Morris HJ, Nelson AA, Calvery HO. 1942. Observations on the chronic toxicities of 

propylene glycol, ethylene glycol, diethylene glycol, ethylene glycol mono-ethyl-ether and 

diethylene glycol mono-ethyl-ether. J Pharmacol Exp Therap 74:266-273. 

*Morshed KM, Desjeux JF, Nagpaul JP, et al. 1991a. The effect of propanediols on the 

intestinal uptake of nutrients and brush boder membrane enzymes in the rat. Biochem Med 

Metab Biol 45(2):161-170. 

*Morshed KM, Helgoualch AL, Nagpaul JP, et al. 1991b. The role of propylene glycol 

metabolism in lactatemia in the rabbit. Biochemical Medicine and Metabolic Biology 46:145­

151. 

Morshed KM, Jain SK, McMartin K. 1993. Acute toxicity of propylene glycol: An assessement 

using cultured proximal tuble cells of human origin. Fundam App Toxicol 23:38-43. 

Morshed KM, Nagpaul JP, Amma MKP, et al. 1991. The role of propylene glycol metabolism 

in lactatemia in the rabbit. Biochem Med Metab Biol 46:145-151. 

*Morshed KM, Nagpaul JP, Majumdar S, et al. 1988. Kinetics of propylene glycol elimination 

and metabolism in rat. Biochem Med Metab Biol 39(1):90-97. 

*Morshed KM, Nagpaul JP, Majumdar S, et al. 1989. Kinetics of oral propylene glycolinduced acute hyperlactatemia. Biochem Med Metab Biol 42(2):87-94. 

Murphy MJ, Ray AC, Jones LP, et al. 1984. 1,3-Butanediol treatment of ethylene glycol toxicosis 

in dogs. Am J Vet Res 45(11):2293-2295. 

Mushtaq E, Green LE. 1989. Effect of ethylene glycol on the interaction of different myosin 

subfragment l-Nucleotide complexes with actin. Biochemistry 28:6478-6482. 

*Muzeni RJ. 1985. Rapid gas chromatographic determination of ethylene oxide, ethylene 

chlorohydrin, and ethylene glycol residues in rubber catheters. J Assoc Off Anal Chem 68(3):506­

508. 

Myers VS Jr, Usenik EA. 1969. Propylene glycol intoxication of horses. J Am Vet Med 

Assoc 155(12):1841. 

Nagano K, Nakay ama E, Oobayashi H, et al. 1984. Experimental studies on toxicity of ethylene 

glycol alkyl ethers in Japan. Environ Health Perspect 57:75-84. 

*NAS/NRC. 1989. Biologic markers in reproductive toxicology. National 

Academy of Sciences/National Research Council. Washington, DC: National 

Academy Press, 15-35. 

Nater JP, Baar AJM, Hoedemaeker J. 1977. Histological aspects of skin reactions to 

propylene glycol. Contact Dermatitis 3:181-185. 
 

 

 

PROPYLENE GLYCOL 124 

8. REFERENCES 

*NATICH. 1991. National Air Toxics Information ClearingHouse. Data base report on state, 

local, and EPA air toxics activities. U.S. Environmental Protection Agency, Office of Air Quality 

Planning and Standards, Washington, DC. August 13, 1991. 

*Needham LL, Hill RH Jr, Otti DL, et al. 1982. Electron-capture, capillary column gas 

chromatographic determination of low-molecular-weight diols in serum. J Chromatogr 233:9­

17. 

Neeper-Bradley TL. 1990. Developmental toxicity evaluation of ethylene glycol administered by 

gavage to CD (Sprague-Dawley) rats: Determination of a Bno observed effect level (NOEL). 

Bushy Run Research Center. CMA Project Report 52-656. 

*Nelson EB, Egan JM, Abemethy DR. 1987. The effect of propylene glycol on antipyrine clearance 

in humans. Clin Pharmacol Ther 41(5):571-573. 

Nestrick TJ, Lamparski LL, Peters TL. 1983. Low-splitting-rating injector for capillary 

gas chromatography. Anal Chem 55(12):2009-2011. 

*NFPA. 1994a. Fire Protection Guide to Hazardous Materials, 11th Edition, page 325-50; 

ethylene glycol National Fire Protection Association, Quincy, MA. 

*NFPA. 1994b. Fire Protection Guide to Hazardous Materials, 11th Edition, page 325-82, 

propylene glycol. National Fire Protection Association, Quincy, MA. 

Nguyen TD, Matsuura T, Sourirajan S. 1987. A fundamental approach to reverse-osmosis 

concentration and fractionation of organic chemicals in aqueous solutions for environmental 

analysis. In: Suffet IH, Malaiyandi M, eds. Advances in chemistry series, 214. Organic pollutants 

in water: Sampling, analysis, and toxicity testing. Washington, DC: American Chemical Society, 

139-162. 

NIOSH. 1974. National Occupational Hazard Survey (NOHS). Volume 1: Survey manual. 

Rockville, MD: U.S. Department of Health and Human Services, Public Health Service, Centers 

for Disease Control, National Institute for Occupational Safety and Health, Office of Occupational 

Health Surveillance and Biometrics. 

*NIOSH. 1984. NIOSH manual of analytical methods. 3rd ed. Washington, DC: U.S. 

Department of Health and Human Services, Public Health Service, Centers for Disease Control, 

National Institute for Occupational Safety and Health. NIOSH100184336. 

NIOSH. 1990. National Occupational Exposure Survey (NOES) 1981-1983. Rockville, MD: 

U.S. Department of Health and Human Services, Public Health Service, Centers for Disease 

Control, National Institute for Occupational Safety and Health. 

NIOSH. 1994. Health hazard evaluation report. National Institute for Occupational Safety and 
 

 

 

 

 

 

 

 

 

PROPYLENE GLYCOL 125 

8. REFERENCES 

Health, Centers for Disease Control and Prevention, Public Health Service, U. S. Department of 

Health and Human Services. Heta 90-0355-2449. 

NRC. 1994. Personal conversation with K. Bakshi to Marion Deerhake, Research Triangle 

Institute, regarding the compilation of current EEGLs and CEGLs. National Research Council, 

Committee on Toxicology, National Academy of Sciences. 

NREPC. 1986. New or modified sources emitting toxic air pollutants. Frankfort, KY: 

Department for Environmental Protection, National Resources and Environmental Protection 

Cabinet. 401 KAR 63:022. 

*NTDB. 1995. (CD-ROM) US Dept. of Commerce Census, Economics and 

Statistics Administration. Washington DC. 

*NTP. 1985. Propylene glycol: Reproduction and fertility assessment in CD-l mice when 

administered in drinking water. Final report. National Toxicology Program. NTP-84­

FACB-038. 

NTP. 1988. Developmental toxicity evaluation of ethylene glycol (CAS No. 107-21-1) in CD 

rats. Final report. National Toxicology Program, National Institute of Environmental Health 

Sciences. NTP-88-079. 

NTP. 1992. Toxicology and carcinogenesis studies of ethylene glycol in B6C3Fl mice. 

Document no. NTP TR 413. Washington, DC: U.S. Deparment of Health and Human Services, 

Public Health Service, National Institutes of Health, National Toxicology Program. NTH 

publication no. 91-3144. 

Ochs ML, Glick MR, Ryder WW, et al. 1988. Improved method for emergency screening for 

ethylene glycol in serum. Clin Chem 34(7):1507-1508. 

OHM/TADS. 1985. Oil and Hazardous Materials/Technical Assistance Data System, Chemical 

Information Systems, Inc., Baltimore, MD. December, 1985. 

Oliver JJ. 1993. A comatose man with marked acidosis and crystaluria. Hospital Practice 

28(7):86-88. 

OSHA. 1987. Access to employee exposure and medical records. Occupational Safety and Health 

Administration. Code of Federal Regulations. 29 CFR 1910.20. 

OSHA. 1988. Access to employee exposure and medical records. Occupational Safety and Health 

Administration. Federal Register 53:38140, 38163. 

OSHA. 1989a. Toxic and hazardous substances. Occupational Safety and Health 

Administration. Code of Federal Regulations. 29 CFR 1910.1000. 
 

 

 

 

 

 

 

PROPYLENE GLYCOL 126 

8. REFERENCES 

OSHA. 1989b. Toxic and hazardous substances. Occupational Safety and Health Administration. 

Federal Register 54:2920-2960. 

*OTA. 1990. Neurotoxicity: Identifying and controlling poisons of the nervous system. Office 

of Technology Assessment, Washington, DC. OTA-BA-438. 

*Ouattara AS, Cuzin N, Traore AS, et al. 1992. Anaerobic degradation of 1,2-propanediol by a new 

Desulfovibrio strain and D. alcoholovorans. Arch Microbial 158:218-225. 

Ovrebo S, Jacobsen D, Sejersted OM. 1987. Determination of ionic metabolites from 

ethylene glycol in human blood by isotachophoresis. J Chromatogr Biomed Appl 416(1): 

111-118. 

Pant SK, Thomas KM, Gupta PN, et al. 1989. Detection of presence of diethylene glycol in 

glycerin. Indian J Pharm Sci 51(2):57-58. 

Parry MF, Wallach R. 1974. Ethylene glycol poisoning. Amer J Med 57(1):143-150. 

Pearl RG, Rice SA. 1989. Propylene-glycol-induced pulmonary hypertension in sheep. 

Pharmacology 39(6):383-389. 

Penumarthy L, Oehme FW. 1975. Treatment of ethylene glycol toxicosis in cats. Am J Vet Res 

36(2):209-212. 

PerlW, Silverman F, Delea AC, et al. 1976. Permeability of dog lung endothelium to sodium, diols, 

amides, and water. Am J Physiol 230(6):1708-1721. 

Peterson CD, Collins AJ, Himes JM, et al. 1981. Ethylene glycol poisoning: Pharmacokinetics 

during therapy with ethanol and hemodialysis. New Eng J Med 304:21-23. 

Peterson RL, Rodgerson DO. 1974. Gas-chromatographic determination of ethylene glycol in serum. 

Clin Chem 20(7):820-824. 

*Petroff OA, Yu RK, Ogino T. 1986. High-resolution proton magnetic resonance analysis of 

human cerebrospinal fluid. J Neurochem 47(4): 1270- 1276. 

*Pfeiffer EH, Dunkelberg H. 1980. Mutagenicity of ethylene oxide and propylene oxide and of the 

glycols and halohydrins formed from them during the fumigation of foodstuffs. Food Cosmet 

Toxicol 18:115-118. 

Poikolainen K, Vuori E. 1985. Risk of fatal alcohol poisoning by marital and occupational 

status. Alcohol Alcohol 20(3):329-332. 

Price CJ, Kimmell CA, Tyl RW, et al. 1985. The developmental toxicity of ethylene glycol in 

rats and mice. Toxicol Appl Pharmacol 81(1):113-127. 
 

 

 

 

 

 

 

 

PROPYLENE GLYCOL 127 

8. REFERENCES 

Price KS, Waggy GT, Conway RA. 1974. Brine shrimp bioassay and seawater 

BOD of petrochemicals. J Water Pollut Contr Fed 46(1):63-77. 

Quince JR, Gardner GL. 1982. Recovery and treatment of contaminated groundwater: Part 

II. Ground Water Monitoring Review, Special Issue. Fall 1982:6-13. 

Quinn DA, Robinson D, Hales CA. 1990. Intravenous injection of propylene glycol 

causes pulmonary hypertension in sheep. J Appl Physiol 68(4):1415-1420. 

*Raja LMV, Elamvaluthy G, Palaniappan R, et al. 1991. Novel biotreatment process for 

glycol waters. Appl Biochem Biotechnology (28-29):827-842. 

Rajagopal G, Ramakrishnan S. 1975. A new method for estimation of ethylene glycol in 

biological material. Anal Biochem 65(1-2):132-136. 

Rajagopal G, Ramakrishnan S. 1978. Effect of ethylene glycol toxicity on hepatic 

carbohydrate metabolism in rats. Toxicol Appl Pharmacol 46(2):507-516. 

Rajagopal G, Venkatesan K, Ranganathan P, et al. 1977. Calcium and phosphorus metabolism in 

ethylene glycol toxicity in rats. Toxicol Appl Pharmacol 39(3):543-547. 

Randall PM, Gavaskar AR. 1993. Evaluation of filtration and distillation methods for recycling 

automotive coolants. U.S. Environmental Protection Agency, Risk Reduction Engineering 

Laboratory, Office of Research and Development, Cincinnati, OH. EPA/600/J-931435. PB 94­

101912 

Rice SF, Steeper RR, LaJeunesse CA. 1993. Destruction of representative navy wastes using 

supercritical water oxidation. Sandia National Laboratories, Albuquerque, NM. DE 94­

003139 

Richardson KE. 1973. The effect of partial hepatectomy on the toxicity of ethylene glycol, 

glycolic acid, glyoxilic acid and glycine. Toxicol Appl Pharamacol 24:530-538. 

*Rigg PC, Barry BW. 1990. Shed snake skin and hairless mouse skin as model membranes for 

human skin during permeation studies. J Invest Dex-matol 94(2):235-240. 

*Riley JH, Stahr HM, O’Brien S, et al. 1982. Urine and tissue oxalate and hippurate levels in 

ethylene glycol intoxication in the dog. Veterinary Hum Toxicol 24(5):331-334. 

Roberts JA, Seibold HR. 1969. Ethylene glycol toxicity in the monkey. Toxicol Appl 

Pharmacol 15(3):624-631. 

*Robertson OH, Loosli CG, Puck TT. 1947. Test for chronic toxicity of propylene glycol and 

triethylene glycol on monkeys and rats by vapor inhalation and oral administration. J 

Pharmacol Exper Therap 91:52-76. 
 

 

 

 

 

 

 

 

PROPYLENE GLYCOL 128 

8. REFERENCES 

Robinson D, McCoy CA. 1989. Ethylene glycol toxicity. Crit Care Nurse 9(6):70-74. 

Robinson DW, Reive DS. 1981. A gas chromatographic procedure for quantitation of ethylene 

glycol in postmortem blood. J Anal Toxicol 5(2):69-72. 

Robinson M, Pond CL, Laurie RD, et al. 1990. Subacute and subchronic toxicity of ethylene glycol 

administered in drinking water to Sprague-Dawley rats. Drug Chem Toxicol 13:43-70. 

Rofe AM, Bais R, Conyers RAJ. 1986. The effect of dietary refined sugars and sugar alcohols on 

renal calcium oxalate deposition in ethylene glycol-treated rats. Food Chem. Toxic 24(5):397­

403. 

Romaguera C, Perez AG, Moran M, et al. 1981. Propylene glycol in standard patch tests. Contact 

Dermatitis. 7(6):346. 

Rossa V, Weber U. 1990. Effect of ethylene glycol on rabbit retinas. Ophthalmologica 

200(2):98-103. 

*Rossol M. 1990. Theatrical fogs and smokes: A report on their hazards. American Guild 

of Musical Artists. 

*Rossol M. 1993. Comments on Technical Report for Ethylene Glycol/Propylene Glycol. 

Submitted to ATSDR on Sept. 7, 1993. 

Rothman A, Normann SA, Manoguerra AS, et al. 1986. Short-term hemodialysis in childhood 

ethylene glycol poisoning. J Pediatr 108:153-155. 

*Rowe VK, Wolf MA. 1982. Glycols. In: Clayton GD, Clayton FE, eds. Patty’s industrial 

hygiene and toxicology. Volume 2C: Toxicology. 3rd. ed. New York, NY: John Wiley & Sons, 

3817-3853. 

Rowland J. 1987. Incidence of ethylene glycol intoxication in dogs and cats seen at Colorado State 

University Veterinary Teaching Hospital. Vet Hum Toxicol 29(1):41-44. 

*Ruddick JA. 1972. Toxicology, metabolism, and biochemistry of 1,2-propanediol. Toxicol Appl 

Pharmacol 21(1):102-111. 

Ruegsegger GJ, Schultz LH. 1986. Use of a combination of propylene glycol and niacin for 

subclinical ketosis. J Dairy Sci 69(5):1411-1415. 

Ryder KW, Glick MR, Jackson SA. 1986. Emergency screening for ethylene glycol in serum. 

Clin Chem 32(8):1574-1577. 

Saini M, Meenakshi KM, Amma MKP. 1987. Propane 1,2 diol induced changes in plasma 

proteins and enzymes on acute oral ingestions in female rats. Res Bull Panjab Univ Sci 

38(3):79-86, 
 

 

 

 

 

 

 

 

PROPYLENE GLYCOL 129 

8. REFERENCES 

Sakoda T, Horiuti K. 1992. Effects of ethylene glycol and calcium on the kinetics of contration 

induced by photo-released of low concentrations of ATP in rat psoas muscle fibres. J Muscle Res 

Cell Motil 13(4):464-472. 

Saladino R, Shannon M. 1991. Accidental and intentional poisonings with ethylene glycol in 

infancy: Diagnostic clues and management. Pediatr Emerg Care 7(2):93-96. 

Schramm M, Wanick AW, Fuller WH. 1986. Permeability of soils to four organic liquids and water. 

Hazardous Waste and Hazardous Materials 3(1):21-27. 

Schuler RL, Hardin BD, Niemeier RW, et al.. 1984. Results of testing fifteen glycol ethers 

in a short-term in vivo reproductive toxicity assay. Environmental Health Perspectives 57: 

141-146. 

*Schumacher JN, Green CR, Best FW, et al. 1977. Smoke composition: An extensive 

investigation of the water-soluble portion of cigarette smoke. J Agric Food Chem 25(2):310­

320. 

Sheldon LS, Hites RA. 1979. Environmental occurrence and mass spectral identification of 

ethylene glycol derivatives. Sci Total Environ 11(3):279-286. 

Sherertz EF, Sloan KB, McTieman RG. 1990. Transdermal delivery of 5-fluorouracil through skin 

of hairless mice and humans in vitro: A comparison of the effect of formulations and a prodrug. 

Arch Dermatol Res 282(7):463-468. 

*Shoemaker JD, Lynch RE, Hoffmann JW, et al. 1992. Misidentification of propionic acid as 

ethylene glycol in a patient with methylmalonic acidemia. J Pediatr 120:417-421. 

Siew S, Matta RK, Johnson M. 1975a. Investigation of “crystallosis” in ethylene glycol toxicity. 

Scanning Electron Microscopy 8:555-562. 

Siew S, Matta RK, Johnson M. 1975b. Microanalysis of crystals in biological tissue. In: 

Proceedings from the 10th Annual Conference of the Microbeam Analysis Society, MGM Hotel, Las 

Vegas, Nevada., August 11-15, 1975. Bethlehem, PA: Lehigh University, Metallurgy and 

Materials Science Department, 48-A - 48-D. 

*Sills RD, Blakeslee PA. 1992. The environmental impact of deicers in airport stormwater runoff. In: 

Chemical Deicers and the Environment. Boca Raton, FL: Lewis Publishers, 323-340. 

*Simmons P, Branson D, Bailey R. 1976. 1,2,4-Trichlorobenzene: Biodegradable or not? In: 

Book pap, Int Tech Conf. Research Triangle Park, NC: American Association Text, 212-217, 

Simpson E. 1985. Some aspects of calcium metabolism in a fatal case of ethylene glycol 

poisoning. Ann Clin Biochem 2290-93. 
 

 

 

 

 

 

 

 

 

 

 

 

PROPYLENE GLYCOL 130 

8. REFERENCES 

*Sisfontes L, Nyborg G, Jones AW, et al. 1986. Occurrence of short chain aliphatic diols in 

human blood: Identification by gas chromatography-mass spectrometry. Clin Chim Acta 

155(2):117-122. 

Slave T, Mihail A, Burmaz N. 1974. [Degradation of some organic impurities in residual 

waters.] Rev Chim 25:666-670. (Hungarian) 

Smith BJ, Anderson BG, Smith SA, et al. 1990. Early effects of ethylene glycol on the 

ultrastmcture of the renal cortex in dogs. Am J Vet Res 51(1):89-96. 

*Smith NB. 1984. Determination of serum ethylene glycol by capillary gas chromatography. 

Clin Chim Acta 144(2-3):269-272. 

Smith NB. 1987a. Identification and elimination of an ethylene glycol determination artifact. 

Clin Chim Acta 162(1):105-108. 

Smith NB. 1987b. Measurement of ethylene glycol in biological specimens. Ann Clin 

Biochem 24:639-640. 

Smith NB, Rawal N. 1987. Lack of interference of tris(hydroxymethyl)methylarnine with the 

determination of volatile alcohols or ethanediol in serum by capillary gas chromatography. 

Clin Chem 33(12):2324. 

Speece RE. 1983. Anaerobic biotechnology for industrial wastewater treatment. Environ Sci 

Technol 17(9):416A-427A. 

Speth PA, Vree TB, Neilen NP, et al. 1987. Propylene glycol pharmacokinetics and effects after 

intravenous infusion in humans. Ther Drug Monit 9(3):255-258. . 

Spillane L, Roberts JR, Meyer AE. 1991. Multiple cranial nerve deficits after ethylene glycol 

poisoning. Ann Emerg Med 20(2):208-210. 

Spitz HD, Weinberger J. 1971. Determination of ethylene oxide, ethylene chlorohydrin, and 

ethylene glycol by gas chromatography. J Pharm Sci 60(2):271-274. 

*SRI. 1989. Directory of Chemical Producers -United States of America. Stanford 

Research Institute International Menlo Park, Ca. 

*SRI. 1991. Directory of Chemical Producers -United States of America. Stanford 

Research Institute International Menlo Park, Ca. 620-621; 936 

*SRI. 1993. Directory of Chemical Producers -United States of America. Stanford 

Research Institute International Menlo Park, Ca. 598; 890 

*SRI. 1995. Directory of Chemical Producers -United States of America. Stanford 

Research Institute International Menlo Park, Ca. 590; 875 
 

 

 

 

 

 

 

 

PROPYLENE GLYCOL 131 

8. REFERENCES 

Stein ZLG, Bar-kin RL, Lipscomb JW, et al. 1983. Ethylene glycol toxicity and treatment. 

Drug IntellClin Pharm 17:376-377. 

Steinhart B. 1990. Case report: Severe ethylene glycol intoxication with normal osmolal gap­

“a chilling thought.” J Emerg Med 8(5):583-585. 

Steinke W, Arendt G, Mull M, et al. 1989. Good recovery after sublethal ethylene glycol 

intoxication: Serial EEG and CT findings. J Neurol 236(3):170-173. 

*Stenback F, Shubik P. 1974. Lack of toxicity and carcinogenicity of some commonly used 

cutaneous agents. Toxicol Appl Pharmacol 30:7-13. 

Stevens HM. 1986. The detection of some non-drug poisons in simulated stomach contents by 

diffusion into various color reagents. J Forensic Sci 26:(2)137-145. 

*Studer VA, Grummer RR, Bertics SJ, et al. 1993. Effect of prepartum propylene 

glycol administration’on periparturient fatty liver in dairy cows. J Dairy Sci 

76(10):2931-2939. 

*Suber RL, Deskin R, Nikiforov I, et al. 1989. Subchronic nose-only inhalation study of 

propylene glycol in Sprague-Dawley rats. Food Chem Toxicol 27(9):573-584. 

*Swarm RL, Laskowaski DA, McCall PJ, et al. 1983. A rapid method for the estimation of the 

environmental parameters octanol water partition coefficient, soii sorption constant, water to air 

ratio, and water solubility. Dow Chemical Company, Springer-Verlag New York Inc. Residue 

Reviews 85: 18-28. 

*Swenberg JA, Petzold GL, Harbach PR. 1976. In vitro DNA damage/alkaline elution assay for 

predicting carcinogenic potential. Biochemical and Biophysical Research Communications 

72(2):732-738. 

*Takeuchi Y, Yasukawa H, Yamaoka Y, et al. 1993. Effects of Oleic Acid/propylene glycol on rat 

abdominal stratum corneum: Lipid extraction and appearance of propylene glycol in the dermis 

measured by fourier tranforrn infrared/attenuated total reflectance (FT-IR/ATR) spectroscopy. Chem 

Pharm. Bull 41(8):1434-1437. 

*Takeuchi Y, Yasukawa H, Yamaoka Y, et al. 1995. Behavior of Propylene Gycol (PG) in 

dermis after treatment of rat intact skin surface with fatty acids, fatty amines or azone dissolve 

in PG. Biol Pharm Bull 18(2):304-309. 

Tarr BD, Winters LJ, Moore MP, et al. 1985. Low-dose ethanol in the treatment of ethylene glycol 

poisoning. J Vet Pharmacol Ther 8(3):254-262. 

Texas. 1994. Personal conversation with M. Aponte-Pons to Marion Deerhake, Research Triangle 

Institute, regarding screening levels. Texas Conservation Commission (7/19/94). 
 

 

 

 

 

 

 

 

 

PROPYLENE GLYCOL 132 

8. REFERENCES 

Thrall MA, Grauer GF, Mero KN. 1984. Clinicopathologic findings in dogs and cats with 

ethylene glycol intoxication. J Am Vet Med Asso 184(1):37-41. 

*Trancik RJ, Maiback HI. 1982. Propylene glycol irritation or sensitization? Contact 

Dermatitis, 8:185-189. 

*TRI90. 1992. Toxic Chemical Release Inventory. National Library of Medicine, 

National Toxicolgy Information Program, Bethesda, MD. 

*TRI91. 1993. Toxic Chemical Release Inventory. National Library of Medicine, 

National Toxicolgy Information Program, Bethesda, MD. 

*TRI92. 1994. Toxic Chemical Release Inventory. National Library of Medicine, 

National Toxicolgy Information Program, Bethesda, MD. 

*TRI93. 1995. Toxic Chemical Release Inventory. National Library of Medicine, 

National Toxicolgy Information Program, Bethesda, MD. 

Triosi FM. 1950. Chronic intoxication by ethylene glycol vapour. Brit J Industr Med 7:65-69. 

Tsukamura M. 1966. Utilization of glycols and certain other carbohydrates by mycobacteria as sole 

carbon sources. Amer Rev Resp Dis 94:796-798. 

Tucker SP, Deye GJ. 1981. Sampling and analytical method for ethylene glycol in air. Anal Lett 

14(A12):959-976. 

Turpeinen M. 1991. Absorption of hydrocortisone from the skin reservoir in atopic dermatitis. Br J 

Dermatol 124(4):358-360. 

Tyl RW. 1985. Evaluation of the teratogenic potential of ethylene glycol aerosol in the CD rat 

and CD-l mouse. Bushy Run Research Center, Union Carbide Corp., Report No. 48-100. 

Tyl RW. 1988a. Ethylene glycol: Developmental toxicity evaluation of the aerosol in CD-l mice 

by nose-only or whole-body exposure. Bushy Run Research Center, Union Carbide Corp., 

Report No. 50-121. 

Tyl RW. 1988b. Developmental toxicity evaluation of ethylene glycol applied cutaneously to CD-l 

mouse. Bushy Run Research Center. CMA Project Report 50-597. 

Tyl RW. 1989. Developmental toxicity evaluation of ethylene glycol administrated by gavage to 

CD-l mice: Determination of a “no-observed-effect-level” (NOEL). Bushy Run Research 

Center, CMA Project Report 51-591. 
 

 

 

 

 

 

 

 

 

PROPYLENE GLYCOL 133 

8. REFERENCES 

Tyl RW, Price CJ, Mar-r MC, et al. 1993. Developmental toxicity evaluation of ethylene glycol by 

gavage in New Zealand White (NZW) rabbits. Fundamental and Applied Toxicology 20:402­

412. 

Underwood F, Bennett WM. 1973. Ethylene glycol intoxication: Prevention of renal failure by 

aggressive management. J Am Med Asso 226(12):1453-1454. 

Vale JA. 1979. Ethylene glycol poisoning. Vet Hum Toxicol 21: 118-120. 

Van Rillaer WG, Beemaert H. 1983. Determination of residual propane-Zdiol and propane-1,2­

diol in soft drinks by glass-capillary gas chromatography. Z Lebensm-Unters-Forsch 

177(3):196-199. 

Van Stee EW, Harris AM, Horton ML, et al. 1975. The treatment of ethylene glycol toxicosis with 

pyrazole. J Pharmacol Exp Ther 192(2):251-259. 

VANR. 1988. Vermont Agency of Natural Resources. Department of Environmental Conservation 

and Groundwater Protection. Washington, DC: Bureau of Affairs. 

Vassalli L, Harris DM, Gradini R, et al. 1988. Inflammatory effects of topical antibiotic suspensions 

containing propylene glycol in chinchilla middle ears. Am J Otolaryngol 9(1):1-5. 

Vernon J, Brummett R, Walsh T. 1978. The ototoxic potential of propylene glycol in guineapigs. Arch Otolaryngol 104(12):726-729. 

Verschueren K. 1977. Handbook of environmental data on organic chemicals. New York, NY: Van 

Nostrand Reinhold Company, 646-647, 1029. 

*Vesper SJ, Murdoch LC, Hayes S, et al. 1994. Solid oxygen source for bioremediation in 

subsurface soils. J Hazardous Materials 36: 265-274. 

Vincent R, Cicolelia A, Poirot P. 1990. Determination of glycol ethers in working atmospheres. 

Analusis 18( 10):591-596. 

von Sonntag C. 1984. Carbohydrate radicals: From ethylene glycol to DNA strand breakage. Int J 

Radiat Biol Relat Stud Phys Chem Med 46(5):507-519. 

*Walker JE, Kaplan DL. 1992 . Biological degradation of explosives and chemical agents. 

Biodegradation 3(2-3):369-385. 

*Walters KM, Mason WD, Badr MZ. 1993. Effect of propylene glycol on the disposition 

of dramamine in the rabbit. Drug Metabolism and Disposition 21:305-308. 

Walton EW. 1978. An epidemic of antifreeze poisoning. Med Sci Law 18(4):231-237. 
 

 

 

 

PROPYLENE GLYCOL 134 

8. REFERENCES 

Wang F, Cassidy K, Lum B. 1993. Incineration alternatives for combustible waste. 

Ultraviolet/hydrogen peroxide process. Final Report to Rocky Flats Plant, Lawrence Livermore 

National Laboratory, CA. DE 93 018905. 

Ware GW. 1988. Ethylene Glycol. Review of Environmental Contamination and Toxicology 

106:133-141. 

*Warshaw TG, Herrmann F. 1952. Studies of skin reactions to propylene glycol. J Invest 

Dermatol 19:423-429. 

Watson GK, Jones N. 1977. The biodegradation of polyethylene glycols by sewage bacteria. Water 

Research 11:95-100. 

*Weast RC. 1988a. CRC Handbook of Chemistry and Physics, 69th Edition, entry 6680, 

ethanediol CRC Press, Boca Raton, FL. 

*Weast RC. 1988b. CRC Handbook of Chemistry and Physics, 69th Edition, entry 

11898, l,2-propanediol CRC Press, Boca Raton, FL. 

*Weil CS, Woodside MD, Smyth HF Jr, et al. 1971. Results of feeding propylene glycol in the 

diet to dogs for two years. Food Cosmet Toxicol 9(4):479-490. 

*Weiss DJ, Bauer MC, Murphy MJ, et al. 1992. Increased mechanical fragility and intravascular 

lysis of erythrocytes in cats fed a propylene glycol-containing diet. Comparative Haematology 

International 2:157-161. 

*Weiss DJ, McClay CB, Christopher MM, et al. 1990. Effects of propylene glycol-containing 

diets on acetaminophen-induced methemoglobinemia in cats. J Am Vet Med Assoc 196(11):1816­

1819. 

Wiener HL, Richardson KE. 1988. The metabolism and toxicity of ethylene glycol. Res Commun 

Subst Abus 9(2):77-87. 

Wierda A, Verhoeff J, van Dijk S, et al. 1985. Effects of trenbolone acetate and propylene glycol on 

pregnancy toxaemia in ewes. Vet Ret 116(11):284-287. 

Willets A. 1981. Bacterial metabolism of ethylene glycol. Biochim Biophys Acta 677(2):194-199. 

*Williamson SA, Iverson WG. 1993. Determination of short-chain diols and selected 

fermentation by-products in beer. J American Society of Brewery Chemists 51:114-118. 

*Willis CM, Stephens CJ, Wilkinson JD. 1989. Epidermal damage induced by irritants in man: 

A light and electron microscopic study. J Invest Dermatol 93(5):695-699. 

*Willis CM, Stephens CJM, Wilkinson JD. 1988. Experimentally-induced irritant contact dermatitis: 

Determination of optimum irritant concentrations. Contact Dermatitis 18(1):20-24. 
 

 

 

 

 

 

 

 

 

PROPYLENE GLYCOL 135 

8. REFERENCES 

Wills JH, Coulston F, Harris ES, et al. 1974. Inhalation of aerosolized ethylene glycol by 

man. Clin Toxicol 7(5):463-476. 

Willson JE. 1970. Ethylene oxide sterilant residues. Bull Parenter Drug Assoc 24(5):226-234. 

Winek CL, Shingleton DP, Shanor SP. 1978. Ethylene and diethylene glycol toxicity. Clin 

Toxicol 13(2):297-324. 

*Winter ML, Ellis MD, Snodgrass WR. 1990. Urine fluorescence using a Wood’s lamp to detect the 

antifreeze additive sodium fluorescein: A qualitative adjunctive test in suspected ethylene glycol 

ingestions. Ann Emer Med 19:663-667. 

Wittman JS III, Bawin RR. 1974. Stimulation of gluconeogenesis by propylene glycol in the 

fasting rat. Life Sci 15(3):515-524. 

Wittman JS III, Bawin RR, Miller ON. 1975. Inhibition of propylene glycol stimulated 

gluconeogenesis by quinolinic acid in the fasting rat. Arch Biochem Biophys 170(1):294­

299. 

Woodside MD. 1982. Ethylene glycol: Twenty-four month feeding in the diet of rats. Bushy Run 

Research Center, Union Carbide Chemicals and Plastics Co., Inc., Report No. 44-109. 

Woolf AD, Wynshaw-Boris A, Rinaldo P, et al. 1992. Intentional infantile ethylene glycol 

poisoning presenting as an inherited metabolic disorder. Pediatrics 120(3):421-424. 

Wright CG, Bird LL, Meyerhoff WL. 1991. Tympanic membrane microstructure in experimental 

cholesteatoma. Acta Otolaryngol 111(1):101-111. 

*Wu NM, Malinin TI. 1987. High performance liquid chromatography determination of 

ethylene glycol and ethylene chlorohydrin in tissues. J Anal Toxicol 11(2):63-66. 

Yaws CL, Yang HC, Hoppier JR, et al. 1990. Organic chemicals: Water solubility data. Chem 

Engineering 97:115-118. 

*Yu DK, Elmquist WF, Sawchuk RJ. 1985. Pharmacokinetics of propylene glycol in humans during 

multiple dosing regimens. J Pharm Sci 74(8):876-879. 

Yu DK, Sawchuck RJ. 1983. Gas-liquid chromatographic determination of propane-1,2-diol in 

plasma and urine. Clin Chem 29(12):2088-2090. 

Yu DK, Sawchuk RJ. 1987. Pharmacokinetics of propylene glycol in the rabbit. J Pharmacokinetic 

Biopharm 15(5):453-471. 

Zeiger E, Anderson B, Haworth S, et al. 1987. Salmonella mutagenicity tests: III. Results from the 

testing of 255 chemicals. Environ Mutagen 9(Suppl 9):1-109. 
 

 

PROPYLENE GLYCOL 136 

8. REFERENCES 

Zeiss J, Velasco ME, McCann KM, et al. 1989. Cerebral CT of lethal ethylene glycol intoxication 

with pathologic correlation. Am J Neuroradiol 10(2):440-442. 

Zimina LN, Budarina LS, Nazarenko AF. 1977. Morphological changes in the liver and kidneys in 

ethylene glycol poisoning. Arkh Patol 39(2):51-58. 
 

 

 

 

 

 

 

 

PROPYLENE GLYCOL 137 

9. 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. 
 

 

 

 

 

 

 

 

 

 

PROPYLENE GLYCOL 138 

9. 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. 
 

 

 

 

 

 

 

PROPYLENE GLYCOL 139 

9. GLOSSARY 

Immunological Effects—Functional changes in the immune response. 

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(LO) (LDLo)—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. 
 

 

 

 

 

 

 

 

PROPYLENE GLYCOL 140 

9. 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. 

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 
 

 

 

 

 

 

 

 

 

 

PROPYLENE GLYCOL 141 

9. GLOSSARY 

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. 

Risk—The possibility or chance that some adverse effect will result from a given exposure to a chemical. 
 

 

 

 

 

 

 

PROPYLENE GLYCOL 142 

9. GLOSSARY 

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. 
 

 

 

 

 

 

 

 

 

PROPYLENE GLYCOL A-1 

APPENDIX A. ATSDR MINIMAL RISK LEVELS AND WORKSHEETS 

MINIMAL RISK LEVEL (MRL) WORKSHEET 

Chemical Name: Propylene glycol 

CAS Numbers: 57-55-6 

Date: December 1995 

Profile Status: Third Draft Post Public Comment 

Route: [X] Inhalation [ ] Oral 

Duration: [ ] Acute [X] Intermediate [ ] Chronic 

Graph Key: 1 

Species: Rat 

Minimal Risk Level: 0.009 [ ] mg/kg/day [X] ppm 

Reference: Suber et al. 1989 

Experimental design: Young, healthy adult Sprague-Dawley rats were divided into 4 groups of 19 males 

and 19 females each. Three groups were exposed for 5 days per week, 6 hours per day for 13 weeks by 

nose-only inhalation to mean target aerosol concentrations of 51, 321, or 707 ppm propylene glycol. The 

fourth, the control group, was exposed to humidified, filtered room air. Nasal hemorrhaging occurred in 

all exposed groups of male and female rats indicating that propylene glycol can act as a dehydrogenating 

agent. From week 2-14, the average of nasal hemorrhaging in male rats was <1%, 64%, 74%, and 75% in 

controls, low-exposure, medium-exposure, and high-exposure groups, respectively. In females, the 

average indices were < 1% in controls, 14% in the low-exposure group, and 71% in the medium and highexposure groups. Animals recovered during non-exposure weekend periods. Similar trends were observed 

for ocular discharge, with females having generally less ocular discharge than males. A significant 

reduction in body weight of 5-7% starting on day 50 and continuing until the end of the study was 

observed in female rats receiving the highest dose of 707 ppm propylene glycol. Similar observation was 

made in the group receiving 321 ppm of propylene glycol but later in the study starting on day 64. This 

body weight reduction was correlated with a significant reduction in food consumption beginning on 

study day 43 and 50 for the high- and medium-exposure females, respectively. Female rats exposed to 

321 ppm propylene glycol had a significant decrease in white blood cell count and lymphocyte numbers. 

Female rats exposed to 707 ppm propylene glycol had a significant decrease in hemoglobin concentration, 

white blood cell count and lymphocyte numbers. Male rats in the medium (321 ppm) and high (707 ppm) 

groups had a significant decrease in serum sorbitol dehydrogenase and gamma-glutamyl transferase. A 

significant decrease in total serum protein was observed in male rats treated with high (707 ppm) dose of 

propylene glycol while females treated with a medium (321 ppm) dose of propylene glycol had an 

increase in total serum protein. These changes were considered as being sporadic. Kidney weight was 

decreased at 321 ppm in both sexes. Although there were no treatment-related gross pathology changes, 

light microscopy revealed thickening of respiratory epithelium with increase in the number of goblet cells 

and their mucin content in both female and male animals receiving medium and high propylene glycol 

dose. Minute volume, tidal volume, and respiratory rates were not significantly altered in rats exposed to 

51, 321, or 707 ppm propylene glycol for 13 weeks, suggesting that animals adapted to the exposure 

concentrations. 
 

 

 

 

 

 

 


 


 


 


 


 


 


 


 


 


 


 


 


 


 

PROPYLENE GLYCOL A-2 

APPENDIX A 

Effects noted in study and corresponding doses: Nasal hemorrhaging was observed in all PG-treated 

groups:
 

51 ppm PG = low dose (64% in males, 14% in females; less serious LOAEL)
 

321 ppm PG = mid dose (74% in males, 71% in females)
 

707 ppm PG = high dose (75% in males, 71% in females)
 

Dose and end point used for MRL derivation: 

[ ] NOAEL [X] LOAEL
 

Uncertainty Factors used in MRL derivation: 

[ ] 1 [ ] 3 [X] 10 (for use of a LOAEL)
 

[ ] 1 [ ] 3 [X] 10 (for extrapolation from animals to humans)
 

[ ] 1 [ ] 3 [X] (10 for human variability)
 

Was a conversion factor used from ppm in food or water to a mg/body weight dose? If so, explain: No 

conversion was used. 

If an inhalation study in animals, list conversion factors used in determining human equivalent dose: 

Doses were converted from mg/L to ppm: 

0.16 mg/L x 1,000 = 160 mg/m3. 160 mg/m3 x 24.45/76.09 (MW PG) = 51.4 ppm 

1.0 mg/L = 321.3 ppm 

2.2 mg/L = 706.9 ppm 

Was a conversion used from intermittent to continuous exposure? 

If so, explain: Animals were exposed for 6 hours per day, 5 days per week. Since the effect (nasal
 

hemorrhaging) subsided when exposure was discontinued during the weekend periods, it seemed
 

relevant to adjust the exposure period not only to a continuous 24 hour, but also to a 7-day exposure.
 

Therefore conversion factors of 6/24 and 5/7 were used:
 

51 ppm x 6/24 x 5/7 = 9 ppm
 

Other additional studies or pertinent information that lend support to this MRL: This was the only 

suitable intermediate-duration inhalation exposure study available
 

Agency Contacts (Chemical Managers): Ed Murray 
 

 

 

 

 

 

 

 

	 

	 

	 

PROPYLENE GLYCOL 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. 
 

 

 

 

 

 

 

 

 

 

PROPYLENE GLYCOL 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. 
 

 

 

 

 

	 

	 

	 

	 

	 

	 

	 

	 

PROPYLENE GLYCOL 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"). 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

	 

	 

	 

	 

	 

	 

	 

	 

	 

PROPYLENE GLYCOL 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. 
 

 

	 

	 

PROPYLENE GLYCOL 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. 
1 2 3 4 12 

→

SAMPLE 

Table 3-1. Levels of Significant Exposure to [Chemical x] – Inhalation 

→→

Exposure 

Key to frequency/ figurea Species duration 

INTERMEDIATE EXPOSURE 

5 6 

Systemic ↓ ↓

NOAEL 

System (ppm) 

7 8 ↓ ↓

LOAEL (effect) Less serious (ppm) 

9 

↓

Serious (ppm) 

Re

10 

↓

→→

18 Rat 13 wk Resp 3b 10 (hyperplasia) 

5 d/wk Nit

6 hr/d 

CHRONIC EXPOSURE 

Cancer 11 

↓

38 Rat 18 mo 20 (CEL, multiple Wo

5 d/wk organs) 7 hr/d 

39 Rat 89–104 wk 10 (CEL, lung tumors, NT

5 d/wk nasal tumors) 6 hr/d 

40 Mouse 79–103 wk 10 (CEL, lung tumors, NT

5 d/wk hemangiosarcomas) 6 hr/d 

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 ex

by an uncertainty factor of 100 (10 for extrapolation from animal to humans, 10 for human variability). 

PROPYLENE GLYCOL B-8 

APPENDIX B 

This page is intentionally blank. 
PROPYLENE GLYCOL 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/C benchmark dose or benchmark concentration 

BMDX dose that produces a X% change in response rate of an adverse effect 

BMDLX 95% lower confidence limit on the BMDX 

BMDS Benchmark Dose Software 

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 
 

 

 

PROPYLENE GLYCOL C-2 

APPENDIX C 

DOT Department of Transportation 

DOT/UN/ Department of Transportation/United Nations/ 

NA/IMDG North America/Intergovernmental Maritime Dangerous Goods Code 

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 
 

 

 

PROPYLENE GLYCOL C-3 

APPENDIX C 

MCL maximum contaminant level 

MCLG maximum contaminant level goal 

MF modifying factor 

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 
 

 

PROPYLENE GLYCOL C-4 

APPENDIX C 

OW Office of Water 

OWRS Office of Water Regulations and Standards, EPA 

PAH polycyclic aromatic hydrocarbon 

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 
 

PROPYLENE GLYCOL 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