TOXICOLOGICAL PROFILE FOR
 

PHENOL
 


 


 


 


 

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
 

Public Health Service
 

Agency for Toxic Substances and Disease Registry
 

September 2008 
 

PHENOL 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. 
 

PHENOL iii 

UPDATE STATEMENT
 

A Toxicological Profile for Phenol, Draft for Public Comment was released in October 2006. This 

edition supersedes any previously released draft or final profile. 

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

status of previously released profiles, contact ATSDR at: 

Agency for Toxic Substances and Disease Registry
 

Division of Toxicology and Environmental Medicine/Applied Toxicology Branch
 

1600 Clifton Road NE
 

Mailstop F-32
 

Atlanta, Georgia 30333
 
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PHENOL v 

FOREWORD
 

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

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

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

and republished as necessary. 

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

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

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

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

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

referenced. 

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

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

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

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

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

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

Each profile includes the following: 

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

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

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

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

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

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

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

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

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

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

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

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

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

 

PHENOL vi 

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

this toxicological profile resides with ATSDR. 

Howard Frumkin M.D., Dr.P.H. Julie Louise Gerberding, M.D., M.P.H. 

Director Administrator 

National Center for Environmental Health/ Agency for Toxic Substances and 

Agency for Toxic Substances and Disease Registry 

Disease Registry 

*Legislative Background 

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

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

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

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

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

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

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

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

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

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

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

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

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

the list. 
 

 

 

 

 

 

 

 

 

PHENOL vii 

QUICK REFERENCE FOR HEALTH CARE PROVIDERS 

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

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

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

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

answers to often-asked questions. 

Primary Chapters/Sections of Interest 

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

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

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

the general health effects observed following exposure. 

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

and assesses the significance of toxicity data to human health. 

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

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

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

reported in this section. 

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

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

following exposure. 

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

issues: 

Section 1.6 How Can (Chemical X) Affect Children?
 

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

Section 3.7 Children’s Susceptibility
 

Section 6.6 Exposures of Children
 

Other Sections of Interest: 

Section 3.8 Biomarkers of Exposure and Effect 

Section 3.11 Methods for Reducing Toxic Effects 

ATSDR Information Center 

Phone: 1-800-CDC-INFO (800-232-4636) or 1-888-232-6348 (TTY) Fax: (770) 488-4178 

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

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

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

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

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

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

Toxicity; and numerous chemical-specific case studies. 
 

 

 

 

 

 

 

PHENOL viii 

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

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

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

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

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

professionals treating patients exposed to hazardous materials. 

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

Other Agencies and Organizations 

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

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

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

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

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

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

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

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

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

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

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

• Phone: 800-35-NIOSH. 

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

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

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

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

Referrals 

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

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

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

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

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

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

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

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

PHENOL ix 

CONTRIBUTORS 

CHEMICAL MANAGER(S)/AUTHOR(S): 

Jewel Crawford, M.D.
 

Obaid Faroon, DVM, Ph.D.
 

Jewell Wilson, Ph.D.
 

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

Fernando T. Llados, Ph.D. 

Kristina Garber, M.S.
 

Sari J. Paikoff, Ph.D.
 

Michael H. Lumpkin, Ph.D.
 

Syracuse Research Corporation, North Syracuse, NY
 

Syracuse Research Corporation, Arlington, VA
 

THE PROFILE HAS UNDERGONE THE FOLLOWING ATSDR INTERNAL REVIEWS: 

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

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

end points. 

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

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

profile, and makes recommendations for derivation of MRLs. 

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

consistency across profiles and adherence to instructions in the Guidance. 

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

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PHENOL xi 

PEER REVIEW 

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

1.	 Marlissa Campbell, Ph.D., Private Consultant, Pacifica, California; 

2.	 F. Peter Guengerich, Ph.D., Director, Center in Molecular Toxicology, Professor of 

Biochemistry, Vanderbilt University, School of Medicine, Nashville, Tennessee; and 

3.	 Thomas Zoeller, Ph.D., Professor, Department of Biology, University of Massachusetts at 

Amherst, Amherst, Massachusetts; 

These experts collectively have knowledge of phenol’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. 
PHENOL xii 

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PHENOL	 xiii 

CONTENTS
 

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

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

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

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

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

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

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

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

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

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

1.1 WHAT IS PHENOL? .....................................................................................................................1
 

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

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

1.4 HOW CAN PHENOL ENTER AND LEAVE MY BODY? .........................................................3
 

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

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

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

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

TO PHENOL?................................................................................................................................6
 

1.9 WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT MADE TO 

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

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

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

2.1 BACKGROUND AND ENVIRONMENTAL EXPOSURES TO PHENOL IN THE
 

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

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

2.3 MINIMAL RISK LEVELS (MRLs) ............................................................................................14
 

3. HEALTH EFFECTS..............................................................................................................................21
 

3.1 INTRODUCTION........................................................................................................................21
 

3.2 DISCUSSION OF HEALTH EFFECTS BY ROUTE OF EXPOSURE .....................................21
 

3.2.1 Inhalation Exposure ..............................................................................................................22
 

3.2.1.1 Death..............................................................................................................................22
 

3.2.1.2 Systemic Effects.............................................................................................................23
 

3.2.1.3 Immunological and Lymphoreticular Effects................................................................40
 

3.2.1.4 Neurological Effects ......................................................................................................41
 

3.2.1.5 Reproductive Effects......................................................................................................43
 

3.2.1.6 Developmental Effects...................................................................................................43
 

3.2.1.7 Cancer............................................................................................................................44
 

3.2.2 Oral Exposure........................................................................................................................44
 

3.2.2.1 Death..............................................................................................................................44
 

3.2.2.2 Systemic Effects.............................................................................................................61
 

3.2.2.3 Immunological and Lymphoreticular Effects................................................................69
 

3.2.2.4 Neurological Effects ......................................................................................................70
 

3.2.2.5 Reproductive Effects......................................................................................................71
 

3.2.2.6 Developmental Effects...................................................................................................72
 

3.2.2.7 Cancer............................................................................................................................75
 
 

 

PHENOL xiv 

3.2.3 Dermal Exposure...................................................................................................................75
 

3.2.3.1 Death..............................................................................................................................75
 

3.2.3.2 Systemic Effects.............................................................................................................77
 

3.2.3.3 Immunological and Lymphoreticular Effects................................................................85
 

3.2.3.4 Neurological Effects ......................................................................................................85
 

3.2.3.5 Reproductive Effects......................................................................................................86
 

3.2.3.6 Developmental Effects...................................................................................................86
 

3.2.3.7 Cancer............................................................................................................................86
 

3.3 GENOTOXICITY........................................................................................................................87
 

3.4 TOXICOKINETICS.....................................................................................................................93
 

3.4.1 Absorption.............................................................................................................................93
 

3.4.1.1 Inhalation Exposure .......................................................................................................93
 

3.4.1.2 Oral Exposure ................................................................................................................94
 

3.4.1.3 Dermal Exposure ...........................................................................................................95
 

3.4.1.4 Other Routes of Exposure..............................................................................................97
 

3.4.2 Distribution ...........................................................................................................................97
 

3.4.2.1 Inhalation Exposure .......................................................................................................97
 

3.4.2.2 Oral Exposure ................................................................................................................98
 

3.4.2.3 Dermal Exposure .........................................................................................................100
 

3.4.2.4 Other Routes of Exposure............................................................................................100
 

3.4.3 Metabolism..........................................................................................................................101
 

3.4.4 Elimination and Excretion...................................................................................................105
 

3.4.4.1 Inhalation Exposure .....................................................................................................105
 

3.4.4.2 Oral Exposure ..............................................................................................................106
 

3.4.4.3 Dermal Exposure .........................................................................................................107
 

3.4.4.4 Other Routes of Exposure............................................................................................108
 

3.4.5 Physiologically Based Pharmacokinetic (PBPK)/Pharmacodynamic (PD) Models...........108
 

3.4.5.1 Summary of PBPK Models .............................................................................................109
 

3.4.5.2 Discussion of Models ......................................................................................................111
 

3.5 MECHANISMS OF ACTION ...................................................................................................113
 

3.5.1 Pharmacokinetic Mechanisms.............................................................................................113
 

3.5.2 Mechanisms of Toxicity......................................................................................................114
 

3.5.3 Animal-to-Human Extrapolations.......................................................................................115
 

3.6 TOXICITIES MEDIATED THROUGH THE NEUROENDOCRINE AXIS...........................115
 

3.7 CHILDREN’S SUSCEPTIBILITY............................................................................................117
 

3.8 BIOMARKERS OF EXPOSURE AND EFFECT .....................................................................122
 

3.8.1 Biomarkers Used to Identify or Quantify Exposure to Phenol ...........................................123
 

3.8.2 Biomarkers Used to Characterize Effects Caused by Phenol..............................................123
 

3.9 INTERACTIONS WITH OTHER CHEMICALS .....................................................................124
 

3.10 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE ............................................124
 

3.11 METHODS FOR REDUCING TOXIC EFFECTS................................................................125
 

3.11.1 Reducing Peak Absorption Following Exposure.............................................................125
 

3.11.2 Reducing Body Burden ...................................................................................................126
 

3.11.3 Interfering with the Mechanism of Action for Toxic Effects..........................................126
 

3.12 ADEQUACY OF THE DATABASE.....................................................................................126
 

3.12.1 Existing Information on Health Effects of Phenol ..........................................................127
 

3.12.2 Identification of Data Needs............................................................................................129
 

3.12.3 Ongoing Studies ..............................................................................................................138
 
 

PHENOL xv 

4. CHEMICAL AND PHYSICAL INFORMATION..............................................................................139
 

4.1 CHEMICAL IDENTITY............................................................................................................139
 

4.2 PHYSICAL AND CHEMICAL PROPERTIES.........................................................................139
 

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL..........................................................143
 

5.1 PRODUCTION ..........................................................................................................................143
 

5.2 IMPORT/EXPORT ....................................................................................................................143
 

5.3 USE ............................................................................................................................................143
 

5.4 DISPOSAL.................................................................................................................................147
 

6. POTENTIAL FOR HUMAN EXPOSURE .........................................................................................149
 

6.1 OVERVIEW...............................................................................................................................149
 

6.2 RELEASES TO THE ENVIRONMENT...................................................................................151
 

6.2.1 Air .......................................................................................................................................151
 

6.2.2 Water...................................................................................................................................154
 

6.2.3 Soil ......................................................................................................................................155
 

6.3 ENVIRONMENTAL FATE ......................................................................................................155
 

6.3.1 Transport and Partitioning...................................................................................................155
 

6.3.2 Transformation and Degradation ........................................................................................157
 

6.3.2.1 Air................................................................................................................................157
 

6.3.2.2 Water............................................................................................................................157
 

6.3.2.3 Sediment and Soil ........................................................................................................158
 

6.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT..................................159
 

6.4.1 Air .......................................................................................................................................159
 

6.4.2 Water...................................................................................................................................160
 

6.4.3 Sediment and Soil ...............................................................................................................163
 

6.4.4 Other Environmental Media................................................................................................163
 

6.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE........................................164
 

6.6 EXPOSURES OF CHILDREN..................................................................................................166
 

6.7 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES ..............................................167
 

6.8 ADEQUACY OF THE DATABASE ........................................................................................168
 

6.8.1 Identification of Data Needs ...............................................................................................168
 

6.8.2 Ongoing Studies..................................................................................................................172
 

7. ANALYTICAL METHODS................................................................................................................173
 

7.1 BIOLOGICAL MATERIALS....................................................................................................173
 

7.2 ENVIRONMENTAL SAMPLES ..............................................................................................176
 

7.3 ADEQUACY OF THE DATABASE ........................................................................................176
 

7.3.1 Identification of Data Needs ...............................................................................................181
 

7.3.2 Ongoing Studies ..................................................................................................................182
 

8. REGULATIONS AND ADVISORIES ...............................................................................................185
 

9. REFERENCES ....................................................................................................................................191
 

10. GLOSSARY ......................................................................................................................................221
 
 

 

 

 

PHENOL xvi 

APPENDICES 

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

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

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

D. INDEX ................................................................................................................................................D-1
 
 

 

 

 

 

 

 

PHENOL xvii 

LIST OF FIGURES
 

3-1. Levels of Significant Exposure to Phenol – Inhalation ...................................................................... 30
 

3-2. Levels of Significant Exposure to Phenol - Oral ................................................................................ 58
 

3-3. Metabolism of Phenol.......................................................................................................................102
 

3-4. Conceptual Representation of a Physiologically Based Pharmacokinetic (PBPK) Model for a
 

Hypothetical Chemical Substance....................................................................................................110
 

3-5. Existing Information on Health Effects of Phenol............................................................................128
 

6-1. Frequency of NPL Sites with Phenol Contamination.......................................................................150
 
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PHENOL xix 

LIST OF TABLES
 

3-1. Levels of Significant Exposure to Phenol - Inhalation....................................................................... 24
 

3-2. Levels of Significant Exposure to Phenol - Oral ................................................................................ 46
 

3-3. Levels of Significant Exposure to Phenol - Dermal ........................................................................... 78
 

3-4. Genotoxicity of Phenol In Vivo ..........................................................................................................88
 

3-5. Genotoxicity of Phenol In Vitro .........................................................................................................89
 

4-1. Chemical Identity of Phenol.............................................................................................................140
 

4-2. Physical and Chemical Properties of Phenol....................................................................................141
 

5-1. Facilities that Produce, Process, or Use Phenol................................................................................144
 

5-2. Current U.S. Producers of Phenol.....................................................................................................146
 

6-1. Releases to the Environment from Facilities that Produce, Process, or Use Phenol ........................152
 

6-2. Estimated Exposure To Phenol At Various Industry Sites...............................................................169
 

7-1. Analytical Methods for Determining Phenol in Biological Samples................................................174
 

7-2. Analytical Methods for Determining Phenol in Environmental Samples ........................................177
 

8-1. Regulations and Guidelines Applicable to Phenol ...........................................................................186
 
PHENOL xx 

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PHENOL 1 

1. PUBLIC HEALTH STATEMENT 

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

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

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

federal clean-up activities. Phenol has been found in at least 595 of the 1,678 current or former NPL 

sites. Although the total number of NPL sites evaluated for this substance is not known, the possibility 

exists that the number of sites at which phenol is found may increase in the future as more sites are 

evaluated. This information is important because these sites may be sources of exposure, and exposure to 

this substance may be harmful. 

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

such as a drum or bottle, it enters the environment. Such a release does not always lead to exposure. You 

can be exposed to a substance only when you come in contact with it. You may be exposed by breathing, 

eating, or drinking the substance, or by skin contact. 

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

include the dose (how much), the duration (how long), and how you come in contact with it. You must 

also consider any other chemicals you are exposed to and your age, sex, diet, family traits, lifestyle, and 

state of health. 

1.1 WHAT IS PHENOL? 

Description Phenol is a colorless-to-white solid when pure. Commercial phenol is a 

liquid that evaporates more slowly than water. 

Phenol has a distinct odor that is sickeningly sweet and tarry. 

Uses 

 • Manufacturing 

 • Consumer 

products 

Phenol is both a manufactured chemical and produced naturally. Large 

amounts of phenol are produced in the United States. 

Phenol is used to make plastics. Phenol is also used as a disinfectant in 

household cleaning products and in consumer products such as: 

 • mouthwashes 

 • gargles 

 • throat sprays 
PHENOL 2 

1. PUBLIC HEALTH STATEMENT 

For more information on the physical and chemical properties of phenol, and its production, disposal and 

use, see Chapters 4 and 5. 

1.2 WHAT HAPPENS TO PHENOL WHEN IT ENTERS THE ENVIRONMENT? 

Sources Phenol can be found in air and water after release from the manufacture, use, 

and disposal of products containing phenol. Phenol in soil is likely to move to 

groundwater. 

Break down 

 • Air 

 • Water 

 • Soil 

Phenol is quickly broken down in the air, usually within 1–2 days. 

Phenol may persist in water for a week or more. 

Phenol that remains in soil may be broken down by bacteria or other 

microorganisms. 

For more information on phenol in the environment, see Chapter 6. 

1.3 HOW MIGHT I BE EXPOSED TO PHENOL? 

Air The primary way you can be exposed to phenol is by breathing air 

containing it. Releases of phenol into the air occur from: 

 • industries using or manufacturing phenol 

 • automobile exhaust 

 • cigarette smoke, and 

 • wood burning 

Recent data on levels of phenol in air are lacking. 

Water and soil Phenol has been detected in surface waters, rainwater, sediments, drinking 

water, groundwater, industrial and urban runoff, and at hazardous waste 

sites. Phenol in soil is likely to move to groundwater. 

Workplace Workers in the following industries may be exposed to phenol: 

 • petroleum industry 

 • manufacture of nylon, epoxy resins and polycarbonates, herbicides, wood 

preservatives, hydraulic fluids, heavy-duty surfactants, lube-oil additives, 

tank linings and coatings, and intermediates for plasticizers and other 

specialty chemicals 

Exposure occurs through breathing and dermal contact with contaminated 

air or by skin contact with products containing phenol. 
PHENOL 3 

1. PUBLIC HEALTH STATEMENT 

Food Low levels of phenol have been found in foods such as smoked summer 

sausage, smoked pork belly, mountain cheese, fried bacon, fried chicken, 

and black fermented tea. 

Consumer 

products 

Dermal contact can occur through the use of general disinfectants and 

ointments containing phenol. 

Ingestion can occur through the use of products such as throat lozenges or 

sore throat sprays that contain phenol. 

For more information on human exposure to phenol, see Chapter 6. 

1.4 HOW CAN PHENOL ENTER AND LEAVE MY BODY? 

Enter your body 

 • Inhalation 

 • Ingestion 

 • Dermal contact

When you breathe air containing phenol, most of the phenol will rapidly 

enter your body through your lungs. 

Phenol in food or water may also rapidly enter your body through the 

digestive tract. 

A significant amount may enter through your skin when you come into 

contact with phenol vapor, liquid phenol or liquids containing phenol. 

Leave your body Once in your body, phenol is transformed into other chemicals called 

metabolites. Most of these other chemicals leave your body in the urine 

within few days. 

For more information on how phenol enters and leaves the body, see Chapter 3. 
PHENOL 4 

1. PUBLIC HEALTH STATEMENT 

1.5 HOW CAN PHENOL AFFECT MY HEALTH? 

This section looks at studies concerning potential health effects in animal and human studies.

Workers 

 • Inhalation/ 

dermal 

Long-term exposure to phenol at work has been associated with 

cardiovascular disease, but the workers were also exposed to other 

chemicals at the same time. 

General 

population 

 • Oral 

Ingestion of liquid products containing concentrated phenol can cause 

serious gastrointestinal damage and even death. 

General 

population 

 • Dermal 

Application of concentrated phenol to the skin can cause severe skin 

damage. 

Laboratory 

animals 

 • Inhalation 

Short-term exposure to high levels of phenol has caused irritation of the 

respiratory tract and muscle twitching in animals. 

Longer-term exposure to high levels of phenol caused damaged to the 

heart, kidneys, liver, and lungs in animals. 

Laboratory 

animals 

 • Oral 

Drinking water with extremely high concentrations of phenol has caused 

muscle tremors, difficulty walking, and death in animals.

Laboratory 

animals 

 • Dermal 

Short-term application of phenol to the skin has produced blisters and burns 

in animals. 

Cancer There is no evidence that phenol causes cancer in humans. 

The International Agency for Research on Cancer (IARC) and the EPA 

determined that phenol is not classifiable as to human carcinogenicity. 

Further information on the health effects of phenol in humans and animals can be found in 

Chapters 2 and 3. 
PHENOL 5 

1. PUBLIC HEALTH STATEMENT 

1.6 HOW CAN PHENOL AFFECT CHILDREN? 

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

conception to maturity at 18 years of age. 

Effects in children Vomiting and lethargy were the main symptoms observed in children 

following accidental ingestion of a disinfectant containing phenol. We do not 

know whether children would be more sensitive than adults to the effects of 

phenol. 

Birth defects Two studies of women exposed to phenol and other chemicals during 

pregnancy did not provide evidence of birth defects. 

Some birth defects have been observed in animals born to females exposed 

to phenol during pregnancy. This generally occurred at exposure levels that 

were also toxic to the mothers. 

Breast milk There is no information on levels of phenol in human breast milk. 

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

Tobacco smoke Phenol is a component of tobacco smoke. Avoid smoking in enclosed 

spaces like inside the home or car in order to limit exposure to children and 

other family members. 

Consumer 

products 

Household products and over-the-counter medications containing phenol 

should be stored out of the reach of young children to prevent accidental 

poisonings and skin burns. 
PHENOL 6 

1. PUBLIC HEALTH STATEMENT 

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

PHENOL? 

Detecting 

exposure 

Phenol can be measured in blood and urine. Phenol is a normal constituent 

of human urine. 

Measuring 

exposure 

A higher-than-normal concentration of phenol in the urine may suggest 

recent exposure to phenol or to substances that are converted to phenol in 

the body. 

The detection of phenol and/or its metabolites in your urine cannot be used 

to predict the kind of health effects that might develop from that exposure. 

Information about tests for detecting phenol in the body is given in Chapters 3 and 7. 

1.9 WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT MADE TO 

PROTECT HUMAN HEALTH? 

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

can be enforced by law. The EPA, the Occupational Safety and Health Administration (OSHA), and the 

Food and Drug Administration (FDA) are some federal agencies that develop regulations for toxic 

substances. Recommendations provide valuable guidelines to protect public health, but cannot be 

enforced by law. The Agency for Toxic Substances and Disease Registry (ATSDR) and the National 

Institute for Occupational Safety and Health (NIOSH) are two federal organizations that develop 

recommendations for toxic substances. 

Regulations and recommendations can be expressed as “not-to-exceed” levels. These are levels of a toxic 

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

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

these not-to-exceed levels differ among federal organizations because they used different exposure times 

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

Recommendations and regulations are also updated periodically as more information becomes available. 

For the most current information, check with the federal agency or organization that provides it. 
PHENOL 7 

1. PUBLIC HEALTH STATEMENT 

Some regulations and recommendations for phenol include the following: 

Drinking water The EPA has determined that exposure to phenol in drinking water at a 

concentration of 6 milligrams per liter (mg/L) for up to 10 days is not 

expected to cause any adverse effects in a child. 

The EPA has determined that lifetime exposure to 2 mg/L phenol in drinking 

water is not expected to cause any adverse effects. 

Bottled water The FDA has determined that the phenol concentration in bottled drinking 

water should not exceed 0.001 mg/L. 

Workplace air OSHA set a legal limit of 5 parts per million (ppm) phenol in air averaged 

over an 8-hour work day. 

For more information on regulations and advisories, see Chapter 8. 

1.10 WHERE CAN I GET MORE INFORMATION? 

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

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

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

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

substances. 

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

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

assistance number at 1-800-CDCINFO (1-800-232-4636), by e-mail at cdcinfo@cdc.gov, or by writing 

to: 

 Agency for Toxic Substances and Disease Registry 

 Division of Toxicology and Environmental Medicine 

 1600 Clifton Road NE 

 Mailstop F-32 

 Atlanta, GA 30333 

 Fax: 1-770-488-4178 
PHENOL 8 

1. PUBLIC HEALTH STATEMENT 

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/ 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PHENOL 9 

2. RELEVANCE TO PUBLIC HEALTH
 

2.1 BACKGROUND AND ENVIRONMENTAL EXPOSURES TO PHENOL IN THE UNITED 

STATES 

Phenol is a naturally occurring and manufactured chemical that is widely distributed in the environment. 

It is found in various consumer products including throat lozenges, mouthwashes, and antiseptic lotions. 

The most likely route of exposure to phenol is through dermal contact either in the work environment or 

at home using ointments and other household products containing phenol. 

Phenol is a product of combustion of coal wood and municipal solid waste; therefore, residents near coal 

and petroleum fueled facilities as well as residents near municipal waste incinerators may have increased 

exposure to phenol. Phenol is also a product of auto exhaust, and therefore, areas of high traffic likely 

contain increased levels of phenol. Recent data on concentrations of phenol in air are lacking; it was 

found at a median concentration of 30 parts per trillion (ppt) in 7 samples from one U.S. urban/suburban 

site in 1974 and at a median concentration of 5,000 ppt in 83 samples from seven sites between 1974 and 

1978. The individual medians of the seven source sites ranged from 520 to 44,000 ppt. Higher phenol 

concentrations may occur when there is smog or in highly contaminated air. 

Phenol has been detected in surface waters, rainwater, sediments, drinking water, groundwater, industrial 

effluents, urban runoff, and at hazardous waste sites. Levels of up to 1 ppb have been detected in 

unpolluted groundwater and concentrations ranging from 0.01 to 1 ppb were detected in unpolluted rivers. 

Phenol has been detected in Lake Huron water at 3–24 ppb and industrial rivers in the United States at 0– 

5 ppb. 

Phenol generally does not adhere very strongly to soils and tends to filter rapidly through soil, which may 

account for the lack of monitoring data, since any phenol released to soils is likely to move to 

groundwater. In addition, phenol is readily biodegraded under both aerobic and anaerobic conditions, 

which is expected to attenuate its levels in soil. 

Phenol is degraded rapidly in air (half-life of approximately 15 hours), but may persist in water for a 

somewhat longer period. In soil, phenol will biodegrade rapidly; the half-life in soil is generally <5 days. 

Although low levels of phenol have been detected in certain foods and tap water, these levels do not 

constitute major sources of exposure for most people. Phenol has been reported at concentrations of 
 

 

 

 

 

 

 

 

 

PHENOL 10 

2. RELEVANCE TO PUBLIC HEALTH 

7 and 28.6 ppm in smoked summer sausage and smoked pork belly, respectively, and was identified but 

not quantified in mountain cheese, fried bacon, fried chicken, and black fermented tea. 

Since plants can metabolize phenol readily, exposure through eating food derived from plants grown in 

phenol-containing soil is probably minimal. Due to rapid biodegradation in water and soil, this 

contamination should be limited. People with contaminated tap water can be exposed from drinking the 

water or eating foods prepared with it. In addition, inhalation can occur during showering, bathing, and 

cooking with contaminated water. People can also be exposed to phenol through dermal contact due to 

bathing or showering with contaminated water. 

There are no known unique sources of exposure to children. No reports of phenol in breast milk or baby 

foods were found. Children are likely to be exposed to phenol through inhalation of contaminated air 

from wood, coal, and waste incineration as well as from second-hand smoke. Nonsmokers who live with 

smokers may be exposed to 6–14 μg/day of phenol. 

2.2 SUMMARY OF HEALTH EFFECTS 

Information about the health effects of phenol in humans is derived from studies of workers and members 

of the general population following inhalation, oral, and dermal exposure. These studies indicate that 

phenol is an irritating and corrosive substance, making the skin and mucosal membranes targets of 

toxicity, but other effects have also been reported. However, the data for humans exposed to phenol by 

inhalation or ingestion are inadequate to establish concentration-response relationships, which are needed 

to identify adverse effects levels. Fatalities due to ingestion or contact with a significant area of the skin 

have been reported. A minimal lethal oral dose of approximately 70 mg/kg has been estimated in adults. 

Other estimates indicate that an oral dose as low as 1,000 mg could be fatal in humans, but patients 

occasionally survived doses as high as 65,000 mg. Postmortem examination typically showed serious 

mucosal alterations in the gastrointestinal tract. Other than the skin and mucosal membranes, the liver 

and cardiovascular system might by considered targets for phenol toxicity. In an epidemiological study of 

workers from the rubber industry exposed to multiple chemicals (phenol among them), phenol showed the 

strongest association with mortality due to ischemic heart disease. Electrocardiographic alterations have 

been reported following acute oral and dermal exposure to phenol, as well as vomiting and lethargy. 

Studies of populations whose drinking water was contaminated with phenol found increased incidences of 

nausea and diarrhea, but exposure to chlorophenols may have also occurred. Also, liver effects, as judged 

by increased serum activities of alanine aminotransferase (ALT) and aspartate amino transferase (AST), 
 

 

 

 

 

 

 

 

 

 

PHENOL 11 

2. RELEVANCE TO PUBLIC HEALTH 

were reported in a case of prolonged inhalation exposure to phenol and in workers in an oil-refining plant, 

but exposure to other solvents could not be ruled out in the latter case. An increased incidence of 

headaches was reported among people who used drinking water contaminated with phenol and probably 

chlorophenols also. There is no evidence that phenol is a reproductive or developmental toxicant in 

humans. The Development and Reproductive Toxicant Identification Committee of the California EPA’s 

Office of Environmental Health Hazard Assessment examined the weight of evidence on the reproductive 

toxicity of phenol and concluded that phenol had not been clearly shown to cause reproductive toxicity. 

There is only one modern study of inhalation exposure of animals to phenol. The rest of the inhalation 

database for phenol is outdated and not useful for risk assessment, although it serves to identify some 

targets for phenol toxicity. However, no single especially sensitive target emerged from these studies. 

Short-term (5 minutes) exposure of mice to phenol caused respiratory irritation, as judged by the animals’ 

reflex reduction in respiratory rate; a lowest-observed-effect level (LOEL) was not defined; but the 

exposure concentration that reduced the respiratory rate by 50% was 166 ppm. In rats exposed nose-only 

intermittently to concentrations up to 25 ppm for 2 weeks, phenol caused no gross or microscopic 

alterations in major tissues and organs, including the nasal cavity, but some rats showed an increased 

incidence in a red nasal discharge possibly due to the irritating properties of phenol. Phenol caused 

pneumonia, necrosis of the myocardium, centrilobular degeneration, and necrosis of the liver and renal 

lesions in rabbits and guinea pigs, but not in rats, exposed whole-body intermittently to 26 ppm phenol for 

intermediate durations. In yet another study in rats, continuous whole-body exposure to 26 ppm phenol 

for 15 days caused signs of neurological impairment including muscle tremors, twitching, and gait 

disturbances during the first 3–5 days of exposure. At termination, serum transaminases were elevated 

suggesting liver damage, but no histological examination was conducted. Neurological effects, including 

loss of coordination and tremors, were also observed in rats exposed to 234 ppm phenol for 8 hours. In 

summary, inhaled phenol can affect several organs and tissues and produce neurological effects, but few 

generalizations can be made from the available studies due to the different exposure protocols used (i.e., 

nose-only vs. whole-body; intermittent vs. continuous) and incomplete reporting. Toxicokinetics 

information indicates that phenol is readily absorbed through the skin of humans and animals, so that 

whole-body exposure may result in considerably more absorbed phenol than in nose-only exposures. 

Application of phenol to the skin of animals has caused edema, erythema, necrosis, and death; the cause 

of death was not provided in the studies available. The effects of phenol on the skin are due to its 

property to impair the stratum corneum and produce coagulation necrosis by denaturing and precipitating 

proteins. Lethality is influenced by the surface area exposed as well as the concentration of the applied 
 

 

 

 

 

 

 

 

 

 

 

PHENOL 12 

2. RELEVANCE TO PUBLIC HEALTH 

solution. Systemic effects also have been described in animals following dermal exposure to phenol. 

Rabbits that received a dose of phenol of 24 mg/cm2

/kg suffered cardiac arrhythmia. Tremors leading to 

convulsions were reported in rats following application of 107 mg/kg of phenol to an unspecified surface 

area. 

In contrast to the limited inhalation database, there is an extensive database of oral studies in animals; yet, 

it is not easy to characterize the toxicity of orally administered phenol. A key factor contributing to the 

inability to do so is that phenol administered by oral gavage is much more toxic than when it is 

administered in the drinking water, a phenomenon that is related to the toxicokinetics of phenol. Studies 

have shown that the toxicity of phenol is correlated with peak blood concentration rather than with total 

dose, such as the area under the blood concentration curve (AUC). Thus, end points that appear sensitive 

to phenol administered by oral gavage are not affected by the same total daily dose given via the drinking 

water. 

Results from a 28-day drinking water study in mice provided the lowest effect levels in the oral database 

for phenol and suggested that hematological, neurochemical, and immunological end points may be 

particularly sensitive to phenol toxicity. However, since the effects reported in that study occurred at 

dose levels much lower than in any other study available, these findings should be interpreted with 

caution until supporting results are available. In one study, phenol induced a significant decrease in red 

blood cell counts in mice at ≥1.8 mg/kg/day. While this finding could have been due to macrocytosis, the 

study did not provide enough information to evaluate this possibility. Only two additional studies 

provided information on hematological parameters after phenol exposure. In pregnant mice, a single 

gavage dose of 265 mg/kg of phenol (only dose tested) on gestation day (GD) 13 induced a reduction in 

the ratio of poly/normochromatic erythrocytes in the bone marrow, whereas phenol administered to rats in 

doses of up to 320 mg/kg/day in the drinking water for 10 weeks did not significantly affect a 

comprehensive number of hematological parameters monitored. Other long-term drinking water studies 

in rats and mice did not evaluate hematological parameters. 

The neurochemical effects caused by phenol in a study also occurred at ≥1.8 mg/kg/day and consisted of 

alterations in the levels of neurotransmitters in various brain areas. This is difficult to interpret in light of 

the absence of clinical signs and lack of supporting evidence from other studies. Phenol, however, did 

induce neurological effects in other studies. Short-term oral gavage administration of doses 

≥120 mg/kg/day of phenol caused muscle twitching and tremors in rats and mice, but no effects were 

observed at <40 mg/kg/day. Decreased motor activity was reported in female rats dosed with 
 

 

 

 

 

 

 

 

 

 

 

 

 

PHENOL 13 

2. RELEVANCE TO PUBLIC HEALTH 

360 mg/kg/day of phenol in the drinking water for 13 weeks, but no effects were seen at 107 mg/kg/day. 

No neurochemical evaluations were conducted in these studies. Other long-term drinking water studies in 

rats and mice that used much higher doses of phenol did not observe significant changes in gross or 

microscopic appearance of the brain of the animals, but no neurological tests or neurochemical 

evaluations were conducted in these studies. 

Phenol caused a significant decrease in antibody response to immunization with sheep red blood cells 

(SRBC) in mice at ≥6.2 mg/kg/day in a drinking water study. Lymphoproliferative responses to T and 

B cell mitogens were also significantly suppressed at 33.6 mg/kg/day. A study in which the plaqueforming cell assay to SRBC (but not the antibody titer) and lymphoreticular organs of rats exposed to up 

to 321 mg/kg/day of phenol in the drinking water for 10 weeks were evaluated found no significant 

alterations. In another study, a single dose of 224 mg/kg of phenol administered to rats by oral gavage 

caused necrosis or atrophy of the spleen or thymus, but no other immunological end point was evaluated. 

Long-term drinking water studies in rats and mice did not report any significant gross and histological 

alteration in lymphoreticular organs and tissues at phenol doses >1,000 mg/kg/day. 

Other effects of phenol observed in oral studies include renal tubular necrosis in rats treated with a single 

gavage dose of 224 mg/kg or with 40 mg/kg/day for 14 days. However, long-term drinking water studies 

in rats and mice that received much higher doses of phenol do not suggest that the kidney is a particularly 

sensitive target for phenol. Phenol also induced decreases in body weight in rats and mice in 13-week 

and 2-year drinking water studies that were associated with significant reductions in water consumption 

due probably to poor palability. Phenol reduced body weight gain in pregnant mice treated by oral 

gavage with 280 mg/kg/day, a dose level that also caused frank neurotoxicity. Doses of 120 mg/kg/day of 

phenol administered to pregnant rats during GDs 6–15 using a divided dosing protocol to minimize the 

adverse effects of a bolus dose caused a significant reduction in weight gain in the dams; the no-observedadverse-effect level (NOAEL) was 60 mg/kg/day. The latter findings suggest that weight gain during 

pregnancy is a sensitive end point for phenol toxicity and the dose of 120 mg/kg/day was the lowest 

LOAEL in acute-duration oral studies in which no overt signs of toxicity (other than reduced maternal 

weight gain) were observed following administration of phenol. 

Phenol has induced developmental effects in rodents, but, with one exception, it appears that this occurs 

at dose levels that also affect the mothers. In one study, doses of 120 mg/kg/day of phenol on GDs 6–15 

produced a 7% decrease in average fetal body weight in the absence of maternal effects. In the study that 

used the divided dosing protocol mentioned above, there were no developmental effects at 
 

 

 

 

 

PHENOL 14 

2. RELEVANCE TO PUBLIC HEALTH 

120 mg/kg/day, but decreased ossification sites were seen at the highest dose level, 360 mg/kg/day. In a 

two-generation reproductive study in which the parental generation received doses of up to 301– 

321 mg/kg/day of phenol via the drinking water, decreased pup weight and percent live pups on postnatal 

day 4 was reported at a dose level that also significantly decreased maternal water consumption, including 

during gestation and lactation. In pregnant mice, doses of 280 mg/kg/day on GDs 6–15 produced a 

significant decrease in fetal weight and also caused tremors and ataxia in the dams. 

A study of phenol-exposed wood industry workers reported a small, nonsignificant excess of respiratory 

cancers and a study of phenol production workers reported a small, non-significant excess of Hodgkin’s 

disease and of lung, esophageal, rectal, and kidney cancers. However, the interpretation of these findings 

is complicated due to lack of dose-response and potential for confounding. Phenol has been tested for 

carcinogenicity in long-term drinking water bioassays in rats and mice. Statistically significant increased 

incidences of pheochromocytomas of the adrenal gland and leukemia or lymphomas were observed in 

male rats exposed to the low dose of phenol, but not to the high dose of phenol. No significant effects 

were seen in female rats or in mice. Phenol has consistently been found to be a promoter in initiationpromotion studies in mouse skin. Based on inadequate evidence in humans and in animals, EPA assigned 

phenol to Group D, not classifiable as to human carcinogenicity. Under updated guidelines, the data 

regarding carcinogenicity of phenol are: “inadequate for an assessment of human carcinogenic potential.” 

2.3 MINIMAL RISK LEVELS (MRLs) 

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

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

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

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

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

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

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

methodology does not exist to develop MRLs for dermal exposure. 

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

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

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

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

 

 

 

 

 

 

 

 

 

 

 

 

PHENOL 15 

2. RELEVANCE TO PUBLIC HEALTH 

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

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

significant human exposure improve, these MRLs will be revised. 

Inhalation MRLs 

An acute-duration inhalation MRL was not derived for phenol due to inadequacies of the limited database 

available. The database includes a few animal studies of limited scope (Aranyi et al. 1986; De Ceaurriz et 

al. 1981; Flickinger 1976) and a well-conducted study that used modern methodology to evaluate a 

number of relevant end points (Hoffman et al. 2001). No relevant human studies were located. In the 

animal studies, a target for phenol toxicity was not clearly defined; however, for an irritant substance such 

as phenol, it is reasonable to assume that portals of entry, such as the respiratory tract, could be potential 

targets. Of the studies mentioned above, only Hoffman et al. (2001) conducted a careful evaluation of the 

respiratory tract. Hoffman et al. (2001) exposed rats to various exposure levels for 2 weeks and evaluated 

a number of end points including histopathology, hematology, and clinical chemistry and reported no 

adverse effects. De Ceaurriz et al. (1981) exposed mice to various concentrations of phenol in air for 

5 minutes and determined an RD50 (concentration that reduced the respiratory rate by 50%, a protective 

reflex response in rodents) of 166 ppm. Aranyi et al. (1986) also exposed mice to 5 ppm phenol 

3 hours/day for 5 days and reported no significant changes in susceptibility to airborne bacterial agents 

relative to mice exposed to filtered air. Flickinger (1976) observed loss of coordination and tremors in 

rats exposed to 234 ppm phenol for 8 hours; a 1-hour exposure was without effect. No other exposure 

concentration was tested and no control group was used. Fourteen days later, the rats were sacrificed and 

subjected to gross necropsy. Flickinger (1976) indicated that no gross lesions were observed, but the 

scope of the examination was not specified. Of all the studies available, the one conducted by Hoffman et 

al. (2001) is the most complete, better-reported, and used modern methodology, but, as indicated above, 

because no adverse effects were reported, it is not a suitable basis for an MRL. 

An intermediate-duration inhalation MRL was not derived for phenol due to lack of adequate data. No 

relevant human data were located and the available animal studies had numerous limitations including 

poor control of exposure levels, unclear scope of the evaluations, and limited reporting. The 

intermediate-duration database consists of only three studies (Dalin and Kristoffersson 1974; Deichmann 

et al. 1944; U.S. Air Force 1961). Dalin and Kristoffersson (1974) exposed a small number of rats to 0 or 

26 ppm phenol continuously for 15 days and reported mild motor disorders (impaired balance, abnormal 

gait, muscle twitching) during the first few days of exposure. At termination, the activities of serum 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

PHENOL 16 

2. RELEVANCE TO PUBLIC HEALTH 

transaminases were significantly increased indicating liver damage, but no histopathology examination 

was conducted. Because the exposure chamber was not of modern design, there is some uncertainty as to 

the actual exposure levels. Deichmann et al. (1944) exposed guinea pigs, rats, and rabbits intermittently 

for 6–12 weeks to a concentration of phenol in air that apparently could not be controlled with any 

precision, but could have ranged from 26 to 52 ppm. No controls were used and no actual data were 

presented; the paper contains only a narrative of the results. Exposure to phenol caused serious 

histological alterations in the lungs, heart, liver, and kidneys in rabbits and guinea pigs, but no significant 

changes were reported in rats. U.S. Air Force (1961) exposed monkeys, rats, and mice continuously to 

0 or 5 ppm phenol for 90 days. No information was provided regarding the frequency of monitoring the 

test atmosphere, but the concentration of phenol was reported to remain in the range of 4.5–5.5 ppm after 

the first few days of the experiment. Although the report indicates that there were no significant 

histological alterations in organs and tissues, incomplete reporting of the results suggests that there may 

have been some lung, liver, and kidney pathology. In addition, no data were presented to support the 

assertion that there were no effects on hematology (three species), blood chemistry (monkeys only), 

urinalysis (three species), and kidney function tests (monkeys and rats). 

A chronic-duration inhalation MRL for phenol was not derived due to lack of data for this duration. 

Occupational studies in humans are limited by lack of exposure data and simultaneous exposure to 

multiple chemicals. No chronic inhalation study in animals was located. 

Oral MRLs 

No reliable human data were located for derivation of oral MRLs for phenol. As mentioned in 

Section 2.2, effects of phenol administered to animals by oral gavage are different than those observed in 

drinking water studies. Administration of phenol by oral gavage, as was done in almost all acute-duration 

oral studies, results in adverse effect levels that are much lower than those identified in drinking water 

studies. For example, tremors were reported in rats administered a single gavage dose of 120 mg/kg 

(Berman et al. 1995) and in pregnant mice administered 140 mg/kg/day during gestation (NTP 1983b), 

but no adverse neurological signs were reported in rats administered 360 mg/kg/day in the drinking water 

for 13 weeks (Beyrouty 1998) or in rats or mice administered phenol in the drinking water in doses 

exceeding 700 mg/kg/day for up to 103 weeks (NCI 1980). This differential toxicity is related to the 

toxicokinetics of phenol. A study by Hiser et al. (1994) showed that the toxicity of phenol is correlated 

with peak blood concentration rather than with total dose, such as the AUC. Hiser et al. (1994) observed 

that rats given phenol by oral gavage developed a cluster of behaviors that the investigators termed 
 

 

 

 

 

 

 

 

 

 

 

PHENOL	 17 

2. RELEVANCE TO PUBLIC HEALTH 

“phenol twitching behavior” consisting of tremors, sudden jerks, hyper-reactivity to stimulus, and 

excessive blinking, none of which occurred in groups dosed via the drinking water. Hiser et al. (1994) 

also noticed that the twitching behavior developed almost immediately after gavage dosing, a time that 

also coincided with peak blood levels of phenol, and disappeared by 37 minutes after dosing. Also, for a 

given daily dose, peak levels of phenol in blood were much higher following gavage dosing than 

following continuous administration in the drinking water. Additional information that supports the idea 

of toxicity being associated with peak blood levels of phenol was provided by experiments done by NTP 

(1983a). These investigators treated pregnant rats with phenol by gavage in different volumes during 

GDs 6–15. In a group dosed with 125 mg/kg/day in a volume of 1 mL/kg, 7 of 10 rats died. Deaths were 

preceded by dose-related signs of toxicity, including tremors, convulsions, and respiratory distress, and 

necropsy revealed mottled liver and congested lungs. However, in a group treated with 160 mg/kg/day in 

a volume of 5 mL/kg only one of six rats died, as a larger dosing volume would be expected to decrease 

the absorption rate. Based on the information discussed in this paragraph, only drinking water studies and 

divided dose gavage studies were considered appropriate for MRL derivation. 

•	 An MRL of 1 mg/kg/day has been derived for acute-duration oral exposure (1–14 days) to 

phenol. 

All of the acute-duration oral studies available administered phenol to the animals by gavage. As 

indicated in the preceding paragraph, dosing volume in oral gavage studies is important in the 

manifestation of phenol toxicity. Acute-duration studies that used a relatively low dosing volume of 

1 mL/kg are those by Berman et al. (1995), Moser et al. (1995), and Narotsky and Kavlock (1995). These 

studies were not considered for MRL derivation even though they identified adverse effects at dose levels 

lower than studies that used divided gavage dosing or drinking water studies. The remaining database is 

essentially limited to two developmental studies, which were considered for MRL derivation. In one of 

these studies, rats were gavaged with phenol in doses of up to 120 mg/kg/day in a dosing volume of 

5 mL/kg during GDs 6–15 (NTP 1983a). There was no maternal toxicity, but mean fetal body weight at 

this dose level was approximately 7% lower than controls. However, since historical control data showed 

that the concurrent control fetal weight for the CD rat was much higher (22%) than the historical control 

weight and a larger litter size in the high-dose group may have contributed to the smaller fetal weight in 

the high-dose group, the dose of 120 mg/kg/day can be considered an equivocal LOAEL for 

developmental effects; the NOAEL was 60 mg/kg/day. In the other developmental study, which used a 

divided dosing protocol and a dosing volume of 10 mL/kg, there was a dose-related decrease in maternal 

body weight gain during treatment days and beyond, which achieved statistical significance at 

120 mg/kg/day (York 1997). Maternal body weight was also reduced, but differences with control 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PHENOL 18 

2. RELEVANCE TO PUBLIC HEALTH 

achieved statistical significance only at 360 mg/kg/day (see details below). No fetal toxicity was seen at 

120 mg/kg/day. The decrease in maternal body weight gain during gestation was the most sensitive end 

point and the dose level of 120 mg/kg/day is considered a LOAEL; the NOAEL is 60 mg/kg/day. Since 

the York (1997) study identified the most sensitive end point and utilized a dosing protocol that resembles 

more closely a potential environmental exposure scenario to phenol, it was selected as the principal study 

for the derivation of an acute-duration oral MRL for phenol. 

In the York (1997) study, groups of pregnant Sprague-Dawley rats (25/dose group) were dosed 3 times 

daily with 0, 20, 40, or 120 mg phenol/kg in water (total daily doses of 0, 60, 120, or 360 mg/kg) by 

gavage on GDs 6–15; the dosing volume was 10 mL/kg. Maternal end points evaluated included clinical 

signs, body weight, and food consumption. Dams were also observed for abortions and premature 

deliveries. Dams were sacrificed on GD 20 and a gross necropsy was conducted. The uterus was 

examined for pregnancy, number and distribution of implantations, live and dead fetuses, and early and 

late resorptions. Fetuses were weighed and examined for sex and gross external alterations. Half of the 

fetuses were examined for soft tissue alterations and the remaining fetuses were examined for skeletal 

alterations. One dam in the 360 mg/kg/day group died on GD 11 and the death was attributed to phenol 

treatment. Clinical signs considered treatment-related included excess salivation and tachypnea in rats 

exposed to 360 mg/kg/day. Gross necropsy of the dams did not reveal any treatment-related alterations. 

In the 120 mg/kg/day group, maternal body weight gain was significantly reduced for GDs 6–16 (11%) 

and for GDs 12–16 (19%), whereas in the 360 mg/kg/day group, body weight gain was reduced 38% for 

GDs 6–16. Maternal final body weight in the 360 mg/kg/day group was reduced, but <10% relative to 

controls. Food consumption was reduced in the 360 mg/kg/day group by 16% for GDs 6–20 and by 15% 

for GDs 0–20; in the 120 mg/kg/day group, food consumption for GDs 6–16 was reduced 11%. Fetal 

body weight at the 360 mg/kg/day level was reduced 5–7% relative to controls. There was a significant 

decrease in ossification sites on the hindlimb metatarsals in the 360 mg/kg/day group, which was 

considered of minimal biological significance. At the 120 and 360 mg/kg/day dose levels, there were 

increases in litters with fetuses with "any alteration" and with "any variation", but neither reached 

statistical significance and there were no clear dose-response relationships. There were no significant 

effects on corpora lutea, implantations, litter sizes, live fetuses, early and late resorptions, or percent 

resorbed conceptuses. Based on decreased fetal body weight and delayed ossification, the dose of 

360 mg/kg/day is a LOAEL for developmental effects; the NOAEL is 120 mg/kg/day. Based on 

decreased weight gain during gestation, the dose of 120 mg/kg/day is a LOAEL for decreased maternal 

body weight gain; the NOAEL is 60 mg/kg/day. 
 

 

 

 

 

 

 

 

 

 

 

PHENOL 19 

2. RELEVANCE TO PUBLIC HEALTH 

Data from York (1997) were analyzed using the BMD approach for MRL derivation. BMD models in the 

EPA Benchmark Dose Software (BMDS version 2.0) (linear, polynomial, power, and Hill models) were 

fit to the maternal body weight gain data to determine potential points of departure for the MRL (details 

of the modeling are presented in Appendix A). The linear model with homogeneous variance (which was 

identical to the power model), was selected because it was the simplest model and provided the best fit. 

In the absence of a clear criteria as to what level of change in weight gain during pregnancy should be 

considered adverse, the BMR was defined as a change in mean body weight gain equal to one standard 

deviation from the control mean (EPA 2000c). The corresponding BMD was 152 mg/kg/day; the 

corresponding benchmark dose limit (BMDL) was 125 mg/kg/day. Applying an uncertainty factor of 100 

(10 for animal to human extrapolation and 10 for human variability) to the BMDL results in an acuteduration oral MRL of 1 mg/kg/day. 

An intermediate-duration oral MRL for phenol was not derived. Several studies are available that provide 

information on the effects of phenol following intermediate-duration exposure and all of them used 

drinking water to administer the test material. With the exception of one study (Hsieh et al. 1992, see 

below), doses tested in intermediate-duration oral studies were higher than doses tested in acute-duration 

oral studies. A 13-week drinking water study in rats and mice evaluated clinical signs and gross and 

microscopic appearance of a number of organs and tissues and found little evidence of toxicity (NCI 

1980). Reduction in body weight gain was observed in both rats and mice at the highest dose levels 

tested (1,556 mg/kg/day in rats, 2,468 mg/kg/day in mice), which was most likely due to significant 

decreases in water consumption. Also available is a two-generation reproduction study that found no 

evidence of reproductive effects in male and female rats (301 and 321 mg/kg/day, respectively), but 

reported decreased pup weight and reduced viability at 301/321 mg/kg/day (Ryan et al. 2001). 

Significantly reduced water consumption was also reported in the Ryan et al. (2001) study, particularly in 

the 301/321 mg/kg/day males and females. A specialized 13-week neurotoxicity study in rats reported 

decreased motor activity in females dosed with 360 mg/kg/day, but not with 107 mg/kg/day (Beyrouty 

1998). However, the most significant findings among the intermediate-duration database were reported in 

a 28-day study in mice (Hsieh et al. 1992). These investigators found hematological and neurochemical 

effects in mice at 1.8 mg/kg/day and immunological effects at ≥6.2 mg/kg/day. Hsieh et al. (1992) dosed 

CD-1 mice (five per dose group) with phenol in the drinking water for 28 days. At termination, there was 

a dose-related decrease in red cell counts, statistically significant at all dose levels. The hematocrit was 

decreased only at the highest dose level. In the absence of a change in hematocrit, the decrease in red 

blood cells may have been due to macrocytosis, but the study did not provide sufficient information to 

evaluate this possibility. Ryan et al. (2001), in a two-generation study, conducted a comprehensive 
 

 

 

 

PHENOL 20 

2. RELEVANCE TO PUBLIC HEALTH 

evaluation of hematological parameters in rats exposed to up to 321 mg/kg/day for 10 weeks and found 

no significant alterations. Similarly, in the inhalation experiments of U.S. Air Force (1961) in mice 

exposed continuously for 90 days, no hematological alterations were observed. Hsieh et al. (1992) also 

reported significant dose-related alterations in various neurotransmitters in the brain (i.e., dopamine, 

norepinephrine). In the absence of clinical effects, this is difficult to interpret. Beyrouty (1998) exposed 

rats to doses of 308 mg/kg/day of phenol for 13 weeks and found no significant neurological alterations, 

although neurochemical evaluations were not conducted. Hsieh et al. (1992) also found a significant 

decrease in antibody response to immunization with SRBCs at ≥6.2mg/kg/day, detected by two different 

assays (plaque-forming cell assay and antibody titer). At the highest dose level tested, 33.6 mg/kg/day, 

lymphoproliferative responses to T and B cell mitogens were also significantly suppressed. Ryan et al. 

(2001) also conducted the plaque-forming cell assay to SRBC (but not the antibody titer) and evaluated 

lymphoreticular organs of rats in the two-generation study and found no significant alterations, although it 

is not uncommon to find differences in immune responses between rats and mice. The Hsieh et al. (1992) 

study was not used for derivation of an intermediate-duration oral MRL largely due to the unconfirmed 

nature of findings observed at relatively very low doses and because only five mice comprised each dose 

group. Hsieh’s findings need to be replicated before the data can be used for risk assessment. 

A chronic-duration oral MRL for phenol was not derived. The only chronic-duration animal studies are 

the NCI (1980) 103-week studies in rats and mice. NCI (1980) evaluated clinical signs, organ weights, 

and gross and microscopic appearance of organs and tissues. The lowest doses tested were 

322 mg/kg/day in rats and 590 mg/kg/day in mice. Under the conditions of the study, phenol showed 

essentially no systemic toxicity, but neither hematology nor clinical chemistry tests were conducted. The 

only reported effect was a significant decrease in body weight in male ( ≥322mg/kg/day) and female 

(≥721 mg/kg/day) rats associated with significant decreases in water intake; food consumption was 

comparable among all groups. It would not be appropriate to use the LOAEL of 322 mg/kg/day as the 

basis for an MRL since the effect (reduced final body weight) was likely due to decreased water intake. 

An additional reason for not deriving a chronic-duration oral MRL for phenol is the intermediate data 

from Hsieh et al. (1992) suggesting that immunosuppression may be the most sensitive effect, which 

leaves open the possibility that it could do the same in longer-term studies. Tests of immunocompetence 

were not conducted in the standard 2-year bioassays available. 
 

 

 

 

 

 

 

 

PHENOL 21 

3. HEALTH EFFECTS 

3.1 INTRODUCTION 

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

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

contains descriptions and evaluations of toxicological studies and epidemiological investigations and 

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

It should be noted that phenol is the simplest form, or parent compound, of the class of chemicals 

commonly referred to as phenols or phenolics, many of which are natural substances widely distributed 

throughout the environment. There is some confusion in the literature as to the use of the term ‘phenol’; 

in some cases, it has been used to refer to a particular phenolic compound that is more highly substituted 

than the parent compound (Doan et al. 1979), whereas in other cases, it has been used to refer to the class 

of phenolic compounds (Beveridge 1997). This chapter, however, addresses only those health effects that 

can be directly attributable to the parent compound, monohydroxybenzene, or phenol. As Deichmann and 

Keplinger (1981) note: “It cannot be overemphasized that the structure-activity relationships of phenol 

and phenol derivatives vary widely, and that to accept the properties of individual phenolic compounds as 

being those of phenol is a misconception and leads to error and confusion.” 

A glossary and list of acronyms, abbreviations, and symbols can be found in Appendix C at the end of 

this profile. 

3.2 DISCUSSION OF HEALTH EFFECTS BY ROUTE OF EXPOSURE 

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

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

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

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

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

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

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

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

 

 

 

 

 

 

PHENOL 22 

3. HEALTH EFFECTS 

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

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

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

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

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

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

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

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

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

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

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

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

effects to human health. 

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

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

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

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

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

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

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

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

3.2.1 Inhalation Exposure 

3.2.1.1 Death 

A cohort mortality study of workers in five formaldehyde-resin manufacturing facilities was conducted to 

evaluate whether excess mortality could be attributed to occupational exposure to phenol (Dosemeci et al. 

1991). Workers (exposed and non-exposed) had a mortality rate, from all causes, similar to that of the 

general U.S. population. Compared to either the general population or unexposed workers, exposed 

workers had small statistically non-significant excesses in mortality due to Hodgkin’s disease 

(standardized mortality ratio [SMR], 1.7; 95% confidence interval [CI], 0.8–3.1) and esophageal (SMR, 

1.6; 95% CI, 0.9–2.6), renal (SMR, 1.3; 95% CI, 0.7–2.1), and rectal (SMR, 1.4; 95% CI, 0.8–2.2) 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PHENOL 23 

3. HEALTH EFFECTS 

cancers. They also had small reductions in mortality due to: cancer of the stomach, testes, pancreas, 

buccal cavity/pharynx and brain; lymphosarcoma; liver cirrhosis; emphysema; diseases of the 

cardiovascular, circulatory, and digestive systems; motor vehicle accidents; and all accidents. The 

ambiguity of these data, as well as the fact that dose-related trends occurred only for those diseases 

showing reductions in mortality, makes it difficult to assess the impact on mortality of long-term 

occupational exposure to phenol. 

Deichmann et al. (1944) exposed guinea pigs, rabbits, and rats to phenol vapor at levels ranging from 

26 to 52 ppm for 28–88 days. After 28 days of exposure, 5 of 12 guinea pigs died, but no deaths occurred 

in rabbits or rats. Since only a range was given for the exposure level, the exact level of phenol in air that 

resulted in death of guinea pigs was not established and may be as low as 26 ppm or as high as 52 ppm. 

Interpretation of this study is further complicated by an apparent lack of controls. However, since the 

effects observed in guinea pigs and rabbits (described in subsequent sections in Chapter 3) were so 

severe, it is difficult to ascribe the mortality to any source other than the phenol exposure. The lower 

limit of the exposure range, 26 ppm, is recorded as a serious LOAEL in Table 3-1 and plotted in 

Figure 3-1. No deaths were reported in Rhesus monkeys, rats, or mice exposed to 5 ppm phenol 

continuously for 90 days (U.S. Air Force 1961). 

3.2.1.2 Systemic Effects 

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

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

Respiratory Effects. Slight increases in mortality associated with respiratory cancers were seen in 

two epidemiological studies of workers exposed to phenol (Dosemeci et al. 1991; Kauppinen et al. 1986). 

However, after adjusting for smoking-related behavior, these increases became nonsignificant in the 

Kauppinen et al. (1986) study, and neither study showed a dose-related trend; thus, the relevance of these 

findings to respiratory disease per se is somewhat uncertain. Indeed in the latter study, there were slight, 

yet nonsignificant reductions in mortality associated with emphysema among exposed workers, leading 

the investigators to suggest that exposure to phenol could have a protective effect for diseases involving 

free radical damage. 

A case-control study of office workers was conducted by Baj et al. (1994) to evaluate the risks of 

chronic exposures to “inhaled formaldehyde, phenol, and isomers of organic chlorohydrocarbons from 

KsylamitTM ...” which is a widely used liquid wood preservative. It should be noted that in the report, 
252

2525252525

086

166

253

25

098

5

1

234

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

a 

Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) 

ACUTE EXPOSURE Systemic 

1 Rat 

(Fischer- 344) 

2 wk 5 d/wk 6 hr/d 

System 

Resp 

NOAEL 

(ppm) 

25 

Less Serious 

(ppm) 

LOAEL 

Serious 

(ppm) 

Reference Chemical Form 

Hoffman et al. 2001 

Hemato 25 Hepatic Renal 

25 25 

Bd Wt 25 

2 Mouse 

(Swiss OF1) 

5 min Resp 166 M (50% decrease in 

respiration rate) 

De Ceaurriz et al. 1981 

Immuno/ Lymphoret 

3 Rat 

(Fischer- 344) 

2 wk 5 d/wk 6 hr/d 

25 Hoffman et al. 2001 

4 Mouse 

(CD-1) 

5 d 3 hr/d 5 F Aranyi et al. 1986 

Neurological 

5 Rat 

HarlanWistar 

1 hr 234 F Flickinger 1976 
2

234

065

26

106

55555

145

26

26

26

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

a 

Key to 

Figure 

Species 

(Strain) System 

Exposure/ 

Duration/ 

Frequency 

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

LOAEL 

Serious 

(ppm) 

Reference Chemical Form 

6 Rat 

(HarlanWistar) 

8 hr 234 F (loss of coordination and Flickinger 1976

tremors) 

INTERMEDIATE EXPOSURE Death 

7 Gn Pig 

(NS) 

6 wk 5 d/wk 7 hr/d 

Systemic 

8 Resp Monkey (Rhesus) 90 d 24 hr/d 5 M 

26 (5/12 deaths) Deichmann et al. 1944

U.S. Air Force 1961 

Hemato Hepatic Renal Bd Wt 

5 M 5 M 5 M 5 M 

9 Hemato Rat (White) 15 d 24 hr/d 26 Dalin and Kristoffersson 

Hepatic 26 (serum activities of ALT, 

AST, LDH, and GLDH 

increased 2-6-fold; increased serum magnesium) 

Bd Wt 26 
064

26262626

107

55555

108

55555

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

a 

Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

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

LOAEL 

Serious 

(ppm) 

Reference Chemical Form 

10 Rat 

(NS) 

10 wk 5 d/wk 7 hr/d 

Resp 26 Deichmann et al. 1944 

Cardio Hepatic Renal 

26 26 26 

11 Rat 

(SpragueDawley) 

90 d 24 hr/d Resp 5 M U.S. Air Force 1961 

Hemato Hepatic Renal Bd Wt 

5 M 5 M 5 M 5 M 

12 Mouse 

(NS) 

90 d 24 hr/d Resp 5 M U.S. Air Force 1961 

Hemato Hepatic Renal Bd Wt 

5 M 5 M 5 M 5 M 
068

26262626

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

Exposure/ LOAEL 

Duration/ 

a 

Key to Species Frequency NOAEL Less Serious Serious Reference (Route) Figure (Strain) System (ppm) (ppm) (ppm) Chemical Form 

13 Gn Pig 

(NS) 

6 wk 5 d/wk 7 hr/d 

Resp 26 (acute lobular pneumonia Deichmann et al. 1944

with occasional abscesses and vascular damage) 

Cardio 26 (necrosis of the 

myocardium, extensive reactive inflammation) 

Hepatic 26 (fatty changes, 

centrolobular degeneration and necrosis) 

Renal 26 (edema of the convoluted 

tubules, slightly advanced focal cortical lesions, glomerular degeneration) 
063

26262626

224

5

146

26

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

a 

Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

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

LOAEL 

Serious 

(ppm) 

Reference Chemical Form 

14 Rabbit 

(NS) 

12 wk 5 d/wk 7 hr/d 

Resp 26 (confluent lobular 

pneumonia, chronic purulent bronchitis, hyperplastic peribronchial tissue, degenerative changes in pulmonary vessels) 

Deichmann et al. 1944 

Cardio 26 (myocardial 

degeneration, necrosis of muscle bundles, interstitial fibrosis, lymphocytic infiltration) 

Hepatic 26 (centrilobular 

degeneration and necrosis) 

Renal 26 (edema of the convoluted 

tubules, focal cortical lesions, glomerular degeneration) 

Neurological 

15 Monkey 

(Rhesus) 

90 d 24 hr/d 5 M U.S. Air Force 1961 

16 Rat 

(White) 

15 d 24 hr/d 26 (mild motor disorders during the first 4 days of 

exposure, 4.4 degrees decrease in sliding angle) 

Dalin and Kristoffersson 
226

5

228

5

154

26

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

a 

Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

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

LOAEL 

Serious 

(ppm) 

Reference Chemical Form 

17 Rat 

(SpragueDawley) 

90 d 24 hr/d 5 M U.S. Air Force 1961 

18 Mouse 

(NS) 

90 d 24 hr/d 5 M U.S. Air Force 1961 

19 Gn Pig 

(NS) 

6 wk 5 d/wk 7 hr/d 

26 (hindlimb paralysis) Deichmann et al. 1944 

a The number corresponds to entries in Figure 3-1. ALT = alanine aminotransferase; AST = aspartate aminotransferase; Bd Wt = body weight; Cardio = cardiovascular; d = day(s); Endocr = endocrine; F = Female; G

gastrointestinal; GLDH = glutamate dehydrogenase; Gn pig = guinea pig; Hemato = hematological; hr = hour(s); Immuno = immunological; LDH = lactate dehydroglowest-observed-adverse-effect level; M = male; min = minute(s); NOAEL = no-observed-adverse-effect level; NS = not specified; Resp = respiratory; wk = week(s)
Respiratory 

Hematological Hepatic Body Weight Immuno/Lymphor Neurological 

1000 

Renal 

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

Acute (≤14 days)
	

Systemic
	

PHENOL

ppm 

5r 6r 

2m 

100 

1r 1r 1r 1r 1r 3r 

10 

4m 

1 

3. HEALTH EFFECTS

c-Cat 

d-Dog

r-Rat 

p-Pig

q-Cow

 -Humans 

k-Monkey

m-Mouse 

h-Rabbit 

a-Sheep 

f-Ferret 

j-Pigeon

e-Gerbil 

s-Hamster 

g-Guinea Pig 

n-Mink 

o-Other

 Cancer Effect Level-Animals

 LOAEL, More Serious-Animals

LOAEL, Less Serious-Animals

NOAEL - Animals

 Cancer Effect Level-Humans

 LOAEL, More Serious-Humans

LOAEL, Less Serious-Humans

NOAEL - Humans

 LD50/LC50

Minimal Risk Level

 for effects

 other than

 Cancer 

30
Death 

Respiratory Cardiovascular Hematological Hepatic Renal Body Weight 

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

Intermediate (15-364 days)
	

Systemic 

PHENOL

ppm

100 

7g 13g 10r 14h 13g 10r 14h 9r 13g 9r 10r 14h 13g 10r 14h 9r 

10 

8k 12m 11r 8k 12m 11r 8k 12m 11r 8k 12m 11r 8k 12m 11r 

1 

3. HEALTH EFFECTS

c-Cat 

d-Dog

r-Rat 

p-Pig

q-Cow

 -Humans 

k-Monkey

m-Mouse 

h-Rabbit 

a-Sheep 

f-Ferret 

j-Pigeon

e-Gerbil 

s-Hamster 

g-Guinea Pig 

n-Mink 

o-Other

 Cancer Effect Level-Animals

 LOAEL, More Serious-Animals

LOAEL, Less Serious-Animals

NOAEL - Animals

 Cancer Effect Level-Humans

 LOAEL, More Serious-Humans

LOAEL, Less Serious-Humans

NOAEL - Humans

 LD50/LC50

 for effects

 other than

 Cancer 

Minimal Risk Level 

31
Neurological 

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

Intermediate (15-364 days)
	

ppm

PHENOL

100 

19g 16r 

10 

15k 18m 17r 

1 

3. HEALTH EFFECTS

c-Cat 

d-Dog

r-Rat 

p-Pig

q-Cow

 -Humans 

k-Monkey

m-Mouse 

h-Rabbit 

a-Sheep 

f-Ferret 

j-Pigeon

e-Gerbil 

s-Hamster 

g-Guinea Pig 

n-Mink 

o-Other

 Cancer Effect Level-Animals

 LOAEL, More Serious-Animals

LOAEL, Less Serious-Animals

NOAEL - Animals

 Cancer Effect Level-Humans

 LOAEL, More Serious-Humans

LOAEL, Less Serious-Humans

NOAEL - Humans

 LD50/LC50

 for effects

 other than

 Cancer 

Minimal Risk Level 

32
 

 

 

 

 

 

 

 

 

PHENOL 33 

3. HEALTH EFFECTS 

KsylamitTM is indicated to consist of “...a mixture of chlorinated benzenes, pentachlorophenol, 

alpha-chloronaphthalene, chloroparaffin and kerosene...”, and that the authors provide no discussion of 

how phenol and formaldehyde are produced through the use of such a mixture. Twenty-two workers 

(18 women and 4 men) exposed for at least 6 months were the cases, and 29 non-exposed, nonsmoking 

volunteers matched for age, sex, and place of residence were the controls. The investigators indicate that 

all exposed workers developed chronic complaints, among them cough and sore throat, but that no 

remarkable increase in morbidity was found during the 6 months of exposure to KsylamitTM nor during 

the 3-year follow-up study (details of which were not provided). The investigators attribute these 

symptoms to the irritant effect of the inhaled KsylamitTM probably (based on the references provided) due 

to the formaldehyde vapor they assert emanates from the wood-preserving liquid. 

In laboratory animals, phenol is a respiratory irritant. De Ceaurriz et al. (1981) reported a dose-response 

function for reflex apnea, an index of respiratory irritation, in mice exposed to phenol vapor. From the 

log dose-response function for decreased breathing rate, the RD50 (RD designates respiratory depression), 

or level of phenol in air that resulted in a 50% decrease in breathing rate during a 5-minute head-only 

exposure, was established as 166 ppm. Based on the RD50, the study authors estimated that a 

concentration of 17 ppm (0.1xRD50) would be a LOAEL for respiratory irritation in humans, and a 

concentration of 2 ppm (0.01xRD50) would be a NOAEL. 

In a study in which female Harlan Wistar rats were exposed for 1 hour to a phenol aerosol at a 

concentration of 234 ppm, then held for 2 weeks postexposure, Flickinger (1976) observed signs of nasal 

irritation during exposure. However, all animals exhibited normal behavior by postexposure day 1, and 

no abnormal lesions were observed upon gross autopsy. No histopathology was performed; thus, this 

study is not presented as a LOAEL for rats. A more recent study in which rats were exposed 

intermittently nose-only to up to 25 ppm phenol for 2 weeks found no significant gross or microscopic 

alterations in the respiratory tract, including the nasal turbinates (Hoffman et al. 2001). 

Inflammation, cellular infiltration, pneumonia, bronchitis, endothelial hyperplasia, and capillary 

thrombosis occurred in guinea pigs exposed by inhalation to 26–52 ppm phenol for 41 days (Deichmann 

et al. 1944). Rabbits exhibited qualitatively similar but less severe effects after 88 days of similar 

exposure. Rats exposed similarly showed no gross or microscopic alterations in the respiratory tract. 

Since only a range was given for the exposure level (26–52 ppm), the exact level of phenol in air that 

resulted in respiratory effects was not established and may be as low as 26 ppm or as high as 52 ppm. 

Interpretation of this study is further complicated by an apparent lack of controls. However, the lung 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PHENOL 34 

3. HEALTH EFFECTS 

pathology was so severe, particularly in the guinea pigs, that it is difficult to ascribe the effects to any 

source other than the phenol exposure. The lower limit of the exposure range, 26 ppm, can be considered 

a LOAEL for respiratory effects in guinea pigs and rabbits and a NOAEL for rats. 

No significant histological abnormalities of the lungs were detected in Rhesus monkeys, rats, or mice 

exposed to 5 ppm phenol continuously for 90 days (U.S. Air Force 1961). 

Cardiovascular Effects. In a cohort mortality study of workers in a large rubber and tire 

manufacturing plant, Wilcosky and Tyroler (1983) found a significant increase in mortality from ischemic 

heart disease in phenol exposed workers. Of the 25 solvents used in the plant, phenol exposure showed 

the strongest association with mortality from heart disease, greater even than that observed for exposure 

to carbon disulfide, the only known occupational cause of atherosclerosis. 

In a cohort-mortality study of workers from five phenol-formaldehyde resin plants, Dosemeci et al. 

(1991) found a slight reduction in mortality due to heart disease. These investigators hypothesized a 

protective effect of phenol exposures; however, these results clearly conflict with those of Wilcosky and 

Tyroler (1983). As a consequence, without more definitive studies, it is difficult to assess the 

cardiovascular risk to humans, if any, posed by occupational exposure to phenol. 

Myocardial injury was reported in guinea pigs exposed to 26–52 ppm for 41 days, rabbits exhibited 

qualitatively similar but less severe effects after 88 days of similar exposure, and rats showed no 

significant alterations after 54 exposures (Deichmann et al. 1944). The injury was characterized by 

myocardial inflammation, degeneration, and necrosis, interstitial fibrosis, and lymphocyte infiltration. 

Since only a range was given for the exposure level (26–52 ppm), the exact level of phenol in air that 

resulted in myocardial injury was not established and may be as low as 26 ppm or as high as 52 ppm. 

Interpretation of this study is further complicated by an apparent lack of controls. However, the heart 

pathology was so severe that it is difficult to ascribe the effects to any source other than the phenol 

exposure. The lower limit of the exposure range, 26 ppm, can be considered a LOAEL for myocardial 

injury in guinea pigs and rabbits and a NOAEL for rats. 

Gastrointestinal Effects. Historical information in a case report (Merliss 1972) indicates that 

‘carbol marasmus’ was a common occupational disorder of physicians and their assistants during the mid19th Century when carbolic acid sprays (1:40 phenol in water) were commonly used for antisepsis in 

operating rooms. Among the characteristics of this disorder was anorexia leading to progressive weight 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PHENOL 35 

3. HEALTH EFFECTS 

loss and excess production of saliva. Similar gastrointestinal effects were observed in one of the author’s 

patients who was involved in the daily distillation of phenol over a 13.5-year period. Exposed both via 

inhalation of the vapors and dermally from frequent spills, the patient’s symptoms included both loss of 

appetite and weight loss. 

A cohort mortality study of workers in five phenol-formaldehyde resin manufacturing plants found that 

exposed workers showed a slight reduction in death rate due to cancers of the digestive system as 

compared to both non-exposed workers and the general population (Dosemeci et al. 1991). 

In a study of rats exposed continuously for 15 days to 26 ppm phenol vapor, Dalin and Kristoffersson 

(1974) noted the absence of alterations in the digestive system and attributed this to the relatively low 

exposure levels (as compared to studies using oral dosing), but no further discussion was provided. 

Hematological Effects. A case-control study of office workers was conducted by Baj et al. (1994) to 

evaluate the risks of chronic exposures to “inhaled formaldehyde, phenol and isomers of organic chlorohydrocarbons from KsylamitTM” which is a widely used liquid wood preservative. It should be noted that 

in the report, KsylamitTM is indicated to consist of “a mixture of chlorinated benzenes, pentachlorophenol, 

alpha-chloronaphthalene, chloroparaffin and kerosene,” and that the authors provide no discussion of how 

phenol and formaldehyde are produced through the use of such a mixture. Twenty-two workers 

(18 women and 4 men) exposed for at least 6 months were the cases, and 29 non-exposed, nonsmoking 

volunteers matched for age, sex, and place of residence were the controls. Using blood and urine samples 

drawn after 6 months of exposure, cases and controls were compared on a variety of biochemical, 

hematological, and immunological parameters. The exposed group showed no differences in any of the 

blood chemistry parameters examined, serum bilirubin, alanine, and aspartate aminotransferase activity, 

but had about a 30% increase in eosinophils, a 25% increase in monocytes, and a 70% decrease in 

erythrocytes. Measurement of the office air at the end of the 6-month period revealed a level of phenol of 

0.34 ppm. Although the authors contend that their observations support the concern that chronic exposure 

to phenol could adversely affect the hematopoietic system, it is important to consider not only that other 

volatile chemicals, chlorinated organics, were present in the wood-preserving liquid, but also that the 

chemical composition provided for KsylamitTM opens up the possibility that the effects being evaluated 

result from exposure to pentachlorophenol rather than to phenol. This is particularly true since it was not 

possible to determine from the information presented if the analytical methods used would differentiate 

between phenol and pentachlorophenol. 
 

 

 

 

 

 

 

 

 

 

 

 

PHENOL 36 

3. HEALTH EFFECTS 

Workers (n=20) at an oil-refining plant in Egypt exposed to a time-weighted mean concentration of 

5.4 ppm of phenol in air for a mean exposure period of 13.15 years showed small but significant increases 

in hemoglobin, hematocrit, mean corpuscular hemoglobin, and mean corpuscular volume, but red blood 

cell counts were not significantly altered relative to a group of 30 unexposed controls (Shamy et al. 1994). 

Other small, but significant changes relative to controls included increased basophils and neutrophils, 

decreased monocytes, and increased clotting time. 

Hematocrit and hemoglobin concentrations were not affected in rats exposed to 26 ppm phenol in air 

continuously for 15 days (Dalin and Kristoffersson 1974). Detailed hematological evaluations including 

red and white blood cell, reticulocyte, and platelet counts; white cell differential; hemoglobin and 

sulfhemoglobin, and red cell fragility tests, as well as corpuscular volume, corpuscular hemoglobin, and 

corpuscular hemoglobin concentrations, did not reveal any effects in Rhesus monkeys, rats, or mice 

exposed continuously to 5 ppm phenol in air for 90 days (U.S. Air Force 1961). Comprehensive 

hematology testing of rats exposed nose-only to up to 25 ppm of phenol 6 hours/day, 5 days/week for 

2 weeks showed no significant exposure-related deviations from control values (Hoffman et al. 2001). 

Musculoskeletal Effects. A case of muscle pain and weakness was described in an individual after 

intermittent chronic inhalation and dermal exposure to vapors and solutions of phenol, cresol, and xylenol 

for >10 years (Merliss 1972). The symptoms lessened when the subject was removed from exposure. 

Although the exposure concentrations were not reported, the study author stated that the patient often 

detected heavy odors, and that phenol was often spilled on his clothes resulting in skin irritation. Since 

phenol is absorbed readily from the skin, dermal absorption of phenol may have contributed to the 

systemic effects that were observed. The above symptoms may represent neurological effects rather than 

injury to the muscle tissue. 

Hepatic Effects. Enlarged liver and elevated serum levels of hepatic enzymes indicative of liver 

injury (lactate dehydrogenase, 2 times above normal; aspartate aminotransferase (AST), 21 times above 

normal; alanine aminotransferase (ALT), 100 times above normal) were observed in an individual 

following chronic daily exposure to vapors and spills of phenol for >10 years (Merliss 1972). The 

symptoms lessened when the individual was removed from the site of exposure. Although the exposure 

concentrations were not reported, the study author stated that the patient often detected heavy odors and 

that phenol was often spilled on his clothes resulting in skin irritation. Since phenol is absorbed readily 

from the skin, dermal absorption may have contributed to the systemic effects that were observed. A 

study of 20 workers at an oil-refining plant in Egypt exposed to a time-weighted average concentration of 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PHENOL 37 

3. HEALTH EFFECTS 

phenol of 5.4 ppm for a mean exposure duration of 13.15 years found small, but significant increases in 

ALT and AST activities (approximately 65 and 54%, respectively) in serum collected at the end of the 

shift of the last working day of the week relative to 30 unexposed controls (Shamy et al. 1994). 

No effects on activities of liver enzymes (ALT, AST, γ-glutamyltranspeptidase, alkaline phosphatase) in 

the serum or changes in serum bilirubin or ceruloplasmin were noted in 22 workers exposed for 6 months 

to vapors from a wood-treatment liquid containing phenol, formaldehyde, and organic chlorohydrocarbons (Baj et al. 1994). Although the study authors considered a significant increase in serum iron to 

reflect an adverse effect on the liver that they attributed to phenol exposure, it is important to consider not 

only that other volatile chemicals, chlorinated organics, were present in the wood-preserving liquid, but 

also that the chemical composition provided for KsylamitTM opens up the possibility that the effects being 

evaluated result from exposure to pentachlorophenol rather than phenol. Dosemeci et al. (1991) saw a 

dose-related decrease in mortality from liver cirrhosis in a cohort of workers occupationally exposed to 

phenol during their employment at five phenol-formaldehyde resin plants. These findings are 

complicated by the fact that workers were also exposed to other chemicals; however, the authors 

hypothesize that exposure to phenol could have a protective effect for diseases involving free radical 

damage. 

Centrilobular degeneration and necrosis of the liver were reported in guinea pigs exposed intermittently 

by inhalation to 26–52 ppm phenol for 41 days, rabbits exhibited qualitatively similar but less severe 

effects after 88 days of similar exposure, whereas rats showed no significant alterations after 54 exposures 

(Deichmann et al. 1944). Since only a range was given for the exposure level (26–52 ppm), the exact 

level of phenol in air that resulted in hepatic injury was not established and may be as low as 26 ppm or as 

high as 52 ppm. Interpretation of this study is further complicated by an apparent lack of controls. 

However, the liver pathology was so severe, particularly in the guinea pigs, that it is difficult to ascribe 

the effects to any source other than the phenol exposure. 

Elevated activities of liver enzymes (lactate dehydrogenase, AST, ALT, glutamate dehydrogenase) were 

found in the serum of rats exposed continuously to 26 ppm phenol vapor for 15 days (Dalin and 

Kristoffersson 1974). Increased concentration of these enzymes in serum is often associated with liver 

injury, but is not conclusive evidence for the type or severity of injury. Therefore, 26 ppm can be 

considered a less serious LOAEL in rats. Serum levels of magnesium were also increased in these rats, an 

effect the study authors suggested may also be a sign of liver injury. In a more recent study, rats exposed 

nose-only to up to 25 ppm of phenol 6 hours/day, 5 days/week for 2 weeks showed no evidence of liver 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PHENOL 38 

3. HEALTH EFFECTS 

effects as monitored by clinical chemistry tests and histopathological examination of the liver (Hoffman 

et al. 2001). No significant histological abnormalities were detected in the livers of Rhesus monkeys, 

rats, or mice exposed continuously to 5 ppm phenol in air for 90 days (U.S. Air Force 1961). 

Renal Effects. In a case of chronic phenol poisoning, dark urine and glucose in the urine were noted 

in a man following intermittent exposure to vapors and solutions of phenol (Merliss 1972). The urine 

tested negative for protein and urobilinogen. The urine cleared 2–3 months after removal from exposure. 

Although the exposure concentrations were not reported, the study author stated that heavy odors were 

often detectable, and that phenol was often spilled on the patient’s clothes resulting in skin irritation. 

Since phenol is absorbed readily from the skin, dermal absorption may have contributed to the systemic 

effects that were observed. 

Renal proximal tubule and glomerular injury was reported in guinea pigs exposed intermittently by 

inhalation to 26–52 ppm phenol for 41 days, and rabbits exhibited qualitatively similar but less severe 

effects after 88 days of similar exposure; rats exposed similarly for 54 days showed no significant effects 

(Deichmann et al. 1944). Since only a range was given for the exposure level (26–52 ppm), the exact 

level of phenol in air that resulted in renal injury was not established and may be as low as 26 ppm or as 

high as 52 ppm. Interpretation of this study is further complicated by an apparent lack of controls. 

However, the kidney pathology was so severe, particularly in the guinea pigs, that it is difficult to ascribe 

the effects to any source other than the phenol exposure. The lower limit of the exposure range, 26 ppm, 

can be considered a LOAEL for renal injury in guinea pigs and rabbits. No significant histological 

abnormalities were detected in the kidneys of Rhesus monkeys, rats, or mice exposed continuously to 

5 ppm phenol in air for 90 days (U.S. Air Force 1961). No kidney pathology was reported in a study in 

rats exposed intermittently nose-only to up to 25 ppm of phenol for 2 weeks (Hoffman et al. 2001); 

specific end points monitored included kidney histopathology, blood urea nitrogen (BUN), and serum 

creatinine and electrolytes. 

Dermal Effects. Historical information in a case report (Merliss 1972) indicates that ‘carbol 

marasmus’ was a common occupational disorder of physicians and their assistants during the mid-19th 

Century. Among the characteristics of this disorder was an odd form of pigmentation, which commonly 

occurred in the urine, but also occasionally colored the sclera of the eyes, the skin over the nose, and the 

cheek bones. NIOSH (1983) conducted a survey in an Oregon hospital in response to concerns about 

respiratory problems and contact dermatitis in housekeeping staff members who were exposed frequently 

to germicidal solutions containing phenol and other solvents (formaldehyde, cellosolve, ethanolamine). 
 

 

 

 

 

 

 

 

 

 

 

PHENOL 39 

3. HEALTH EFFECTS 

According to the survey, the housekeeping staff reported significantly more symptoms of cough, itching, 

sinus problems, and dermatitis than other employees. Air concentrations of phenol in the work areas were 

below the limit of detection (<0.01 ppm). Urinary phenol levels in housekeeping staff were not 

significantly different from those of other employees. Thus, while it is likely that the employees came 

into contact with irritants, the cause of the reported symptoms could not be assigned to phenol or any 

other specific substance in the work environment. 

No studies were located regarding dermal effects in animals following inhalation exposure to phenol. 

Ocular Effects. A case-control study of office workers was conducted by Baj et al. (1994) to evaluate 

the risks of chronic exposures to “inhaled formaldehyde, phenol and isomers of organic 

chlorohydrocarbons from KsylamitTM” which is a widely used liquid wood preservative reported to 

consist of “a mixture of chlorinated benzenes, pentachlorophenol, alpha-chloronaphthalene, 

chloroparaffin, and kerosene.” Twenty-two workers (18 women and 4 men) exposed for at least 6 months 

were the cases, and 29 non-exposed, nonsmoking volunteers matched for age, sex, and place of residence 

were the controls. The authors indicate that all of the exposed workers developed chronic complaints, 

among them burning eyes, but that no remarkable increase in morbidity was found during the 6 months of 

exposure to KsylamitTM, nor during the 3-year follow-up study (details of which were not provided). The 

authors attribute these symptoms to the irritant effect of the inhaled KsylamitTM probably (based on the 

references provided) due to the formaldehyde vapor they assert emanates from the wood-preserving 

liquid. 

In a study in which female Harlan Wistar rats were exposed for 1 hour to a phenol aerosol at a 

concentration of 234 ppm, then held for 2 weeks postexposure, Flickinger (1976) observed signs of ocular 

irritation during exposure. However, all animals were normal by postexposure day 1, and no abnormal 

lesions were observed upon gross autopsy. 

Body Weight Effects. Historical information in a case report (Merliss 1972) indicates that ‘carbol 

marasmus’ was a common occupational disorder of physicians and their assistants during the mid-19th 

Century. Among the characteristics of this disorder were anorexia accompanied by progressive weight 

loss. The author reported that his patient, a 44-year-old man involved in the daily distillation of phenol, 

showed many of the symptoms of this condition, including lack of appetite and severe weight loss, 

probably due to his daily workplace exposures to phenol vapors. Although the exposure concentrations 

were not reported, the report indicated that the patient often detected heavy odors, and that phenol was 
 

 

 

 

 

 

 

 

 

 

 

 

 

PHENOL 40 

3. HEALTH EFFECTS 

often spilled on his clothes resulting in skin irritation. Since phenol is absorbed readily from the skin, 

dermal absorption may have contributed to the systemic effects that were observed. 

Body weight effects were not observed in adult female Harlan Wistar rats exposed to an aerosol 

containing 234 ppm phenol for 8 hours (Flickinger 1976), in rats exposed continuously to 26 ppm phenol 

in air for 15 days (Dalin and Kristoffersson 1974), in Rhesus monkeys, rats, or mice exposed 

continuously to 5 ppm phenol in air for 90 days (U.S. Air Force 1961), or in rats exposed intermittently 

nose-only for 2 weeks to up to 25 ppm of phenol vapor (Hoffman et al. 2001). 

Metabolic Effects. Dalin and Kristoffersson (1974) reported elevated serum concentrations of 

potassium and magnesium in rats exposed to 26 ppm phenol vapor continuously for 15 days. While not 

necessarily adverse, this effect may be related to the muscle tremors and neurological effects observed 

following inhalation exposure to phenol (see Section 3.2.1.4). No further information was located 

regarding metabolic effects of inhaled phenol in animals. 

3.2.1.3 Immunological and Lymphoreticular Effects 

A case-control study of office workers was conducted by Baj et al. (1994) to evaluate the risks of chronic 

exposures to “inhaled formaldehyde, phenol and isomers of organic chlorohydrocarbons from 

KsylamitTM” which is a widely used liquid wood preservative. Twenty-two workers (18 women and 

4 men) exposed for at least 6 months were the cases, and 29 non-exposed, nonsmoking volunteers 

matched for age, sex, and place of residence were the controls. Using blood samples drawn after 

6 months of exposure, cases and controls were compared on a variety of immunological parameters. The 

exposed group showed significantly decreased (p<0.05) levels of the CD3+, CD4+, and CD8+ subsets of 

T-lymphocytes, a significant decrease (p<0.001) in lymphocyte responsiveness to the mitogen 

phytohemagglutinin (PHA), a significant decrease (p<0.05) in natural killer (NK) cell cytotoxicity, and a 

significant decrease (p<0.0001) in the mixed lymphocyte response assay. Measurement of the office air 

at the end of the 6-month period revealed a level of phenol of 0.34 ppm. Although the authors contend 

that their observations support the concern that chronic exposure to phenol could adversely affect the 

immune system, it is important to consider not only that other volatile chemicals, chlorinated organics, 

were present in the wood-preserving liquid, but also that the chemical composition provided for 

KsylamitTM opens up the possibility that the effects being evaluated resulted from exposure to 

pentachlorophenol rather than phenol. This is particularly true since it was not possible to determine from 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

PHENOL 41 

3. HEALTH EFFECTS 

the information presented if the analytical methods used would differentiate between phenol and 

pentachlorophenol. 

An increased susceptibility to Streptococcus zooepidemicus aerosol was not observed in mice exposed to 

5 ppm phenol for 3 hours, or for 5 daily 3-hour periods (Aranyi et al. 1986). Neither did the phenol 

exposures affect pulmonary bactericidal activity towards Klebsiella pneumonia. Although tests for 

vulnerability to infectious agents do not represent a comprehensive evaluation of immunological 

competence, the 5-ppm level can be considered a NOAEL for this specific immunological effect, and is 

recorded in Table 3-1 and plotted in Figure 3-1. Gross and microscopic examination of the spleen of rats 

exposed nose-only to up to 25 ppm phenol intermittently for 2 weeks did not reveal any significant 

exposure-related alterations (Hoffman et al. 2001). This exposure concentration is listed as a NOAEL for 

lymphoreticular effects in Table 3-1. 

3.2.1.4 Neurological Effects 

Historical information in a case report (Merliss 1972) indicates that ‘carbol marasmus’ was a common 

occupational disorder of physicians and their assistants during the mid-19th Century. Among the 

characteristics of this disorder were anorexia, headache, and vertigo. The author reported that his patient, 

the subject of the case report, showed many of the symptoms of this condition, although his chief 

complaints were weakness and muscle pain in his arms and legs, progressive weight loss, and excess 

production of saliva. The symptoms lessened when the subject was removed from the site of exposure. 

Although it is possible that these symptoms resulted from injury to the muscle, it is more likely that they 

represent a neurological effect. No information on exposure concentrations was presented; however, the 

report indicated that the patient often detected heavy odors and that phenol was often spilled on his 

clothes resulting in skin irritation. Since phenol is absorbed readily from the skin, dermal absorption may 

have contributed to the systemic effects that were observed. 

A case-control study of office workers was conducted by Baj et al. (1994) to evaluate the risks of chronic 

exposures to “inhaled formaldehyde, phenol and isomers of organic chlorohydrocarbons from 

KsylamitTM” which is a widely used liquid wood preservative. Twenty-two workers (18 women and 

4 men) exposed for at least 6 months were the cases, and 29 non-exposed, nonsmoking volunteers 

matched for age, sex, and place of residence were the controls. The workers complained of a variety of 

chronic symptoms, among them headache and fatigue. Measurement of the office air at the end of the 

6 month period revealed a level of phenol of 0.34 ppm. Although these symptoms could be a sign that 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PHENOL 42 

3. HEALTH EFFECTS 

chronic inhalation exposure to phenol could adversely affect the neurological system, it is important to 

consider not only that other volatile chemicals, chlorinated organics, were present in the wood-preserving 

liquid, but also that the chemical composition provided for KsylamitTM opens up the possibility that the 

effects being evaluated resulted from exposure to pentachlorophenol rather than phenol. This is 

particularly true since it was not possible to determine from the information presented if the analytical 

methods used would differentiate between phenol and pentachlorophenol. 

Female Harlan Wistar rats exposed for 1 or 8 hours to 234 ppm phenol delivered in an aerosol 

demonstrated no neurological effects at 1 hour, a slight loss of coordination with spasm of the muscle 

groups at 4 hours, and frank tremors leading to a severe loss of coordination by 8 hours (Flickinger 1976). 

All animals were normal by postexposure day 1, and no abnormal lesions were observed upon gross 

autopsy performed at the end of a 14-day observation period. These exposure levels are recorded in 

Table 3-1 and are plotted in Figure 3-1 as a NOAEL, a less serious LOAEL, and a serious LOAEL. 

Rats exposed continuously to 26 ppm showed numerous symptoms and signs of neurological impairment, 

including muscle tremors, twitching, and disturbances in walking rhythm and posture during the first 3– 

5 days of exposure, and impaired performance (4.4° decrease in sliding angle) on a tilting plane test after 

15 days of exposure (Dalin and Kristoffersson 1974). These effects are indicative of neurological 

impairment. Because the tremors did not last during the whole exposure period, the effects were not 

considered severe. 

Hindlimb paralysis was reported in guinea pigs exposed to 26–52 ppm phenol for 41 days (Deichmann et 

al. 1944). Rabbits and rats exhibited no overt neurological effects after 88 and 74 days of similar 

exposure, respectively. Since only a range was given for the exposure level (26–52 ppm), the exact level 

of phenol in air that resulted in hindlimb paralysis was not established and may be as low as 26 ppm or as 

high as 52 ppm. Interpretation of this study is further complicated by an apparent lack of controls. 

However, the neurological effect was so severe in the guinea pigs that it is difficult to ascribe the effects 

to any source other than the phenol exposure. The lower limit of the exposure range, 26 ppm, is recorded 

in Table 3-1 and plotted in Figure 3-1 as a LOAEL for serious neurological effects in guinea pigs. Since 

the presence or absence of overt neurological effects such as paralysis is not a sensitive end point for 

detecting neurological effects, 26–52 ppm is not considered a reliable NOAEL for neurological effects in 

rats and rabbits. 
 

 

 

 

 

 

PHENOL 43 

3. HEALTH EFFECTS 

There are several differences in the experimental designs of the Dalin and Kristoffersson (1974) and 

Deichmann et al. (1944) studies that may account for the different results regarding neurological effects in 

rats. Dalin and Kristoffersson (1974) reported subtle effects that may have been overlooked in the 

Deichmann et al. (1944) study. Furthermore, Dalin and Kristoffersson (1974) subjected the rats to a 

specific test for neurological impairment, the tilting plane test. Although exposure concentrations were 

the same in both studies, Dalin and Kristoffersson (1974) exposed rats continuously, while Deichmann et 

al. (1944) exposed rats intermittently. Because phenol is metabolized quite rapidly (see Section 3.4.3), 

rats exposed intermittently may not develop neurological effects. 

Histopathological changes in the brain were not observed in Rhesus monkeys, rats, or mice exposed 

continuously to 5 ppm phenol in air for 90 days (U.S. Air Force 1961). 

The highest NOAEL values and all LOAEL values from each reliable study for neurological effects in 

each species for acute and intermediate-duration exposure are recorded in Table 3-1 and plotted in 

Figure 3-1. 

3.2.1.5 Reproductive Effects 

The only relevant information located is that from a retrospective study of pregnancy outcome among 

university laboratory employees in Sweden (Axelsson et al. 1984). No significant increase in the rate of 

miscarriage was found in a group of 576 women exposed to organic solvent relative to 576 unexposed 

pregnancies. Specific mention of phenol was reported in only five cases, all of which were normal 

deliveries. No relevant information was found in animal inhalation studies. 

3.2.1.6 Developmental Effects 

Neither perinatal death rates nor prevalence of malformations were significantly increased in the study of 

laboratory workers conducted by Axelsson et al. (1984) mentioned above. An abstract by Hernberg et al. 

(1983) on data from personal interviews of 1,047 Finnish mothers exposed to disinfectants (including 

phenol) during early pregnancy did not indicate significant associations between exposure to disinfectants 

and the occurrence of congenital defects. No further relevant information in humans was located. No 

developmental inhalation studies in animals were located. 
 

 

 

 

 

 

PHENOL 44 

3. HEALTH EFFECTS 

3.2.1.7 Cancer 

In a nested case-control study of cancers associated with chemical exposures in the wood industry, 

Kauppinen et al. (1986) found a significantly increased risk of respiratory system cancer associated with 

exposure to phenol and phenol in wood dust. As is often the case in occupational settings, these 

exposures were confounded by smoking and exposures to other materials like pesticides; in addition, 

information on direct phenol measurements was not provided. The increased risk observed for exposure 

to phenol was almost 5-fold (odds ratio of 4.94), but showed no dose-related increase. This risk dropped 

to 4-fold with adjustments for smoking history, and <3-fold (and non-significant) when workers exposed 

to both phenols and pesticides were excluded from the analysis. 

Similar to the findings of Kauppinen et al. (1986), a large (14,861) cohort mortality study of workers in 

the phenol-formaldehyde resin manufacturing industry found nondose-related increases in the risk of 

several respiratory system cancers in workers exposed to phenol (Dosemeci et al. 1991). The authors 

develop a semiquantitative exposure assessment by assigning exposure levels (none, low, medium, and 

high) to each job category. The increased risks were small; for instance, for cancer of the larynx or lung, 

standard mortality ratios (SMRs) of 1.1 were less than those found for non-exposed workers. For a 

number of other cancers, including those of the esophagus, rectum, bladder, kidney, and Hodgkin’s 

disease, the SMRs found for phenol-exposed workers were slightly elevated, but none of the increases 

were statistically significant when compared with those in the general population. Furthermore, none of 

these increases had dose-response relationships with cumulative exposure to phenol. 

No studies were located regarding cancer in animals following inhalation exposure to phenol. 

3.2.2 Oral Exposure 

3.2.2.1 Death 

There have been numerous reports of suicide or suicide attempts involving ingestion of large amounts of 

phenol. However, the lack of accurate documentation of dose levels in these cases makes it difficult to 

identify a minimal dose at which lethality occurs. Deichmann and Keplinger (1981), in summarizing the 

literature, indicated that an oral dose as low as 1 g could be fatal in humans, but that occasionally patients 

had survived doses as high as 65 g. Assuming that these patients were male with an average weight of 

70 kg, the lower limit on the dose for death would be 14 mg/kg and the upper limit would be 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PHENOL 45 

3. HEALTH EFFECTS 

approximately 930 mg/kg. In a review of the toxicology of phenol, Bruce et al. (1987) summarized 

human oral lethality data from numerous case reports and estimated 140 mg/kg to be the minimal dose at 

which death occurs. Stajduhar-Caric (1968) reported a case in which a woman ingested ≈10–20 g of 

phenol and died within hours. The lower limit of the ingested dose was converted to 172 mg/kg, 

assuming a 58 kg body weight, to derive a dose for death, which is recorded in Table 3-2 and plotted in 

Figure 3-2. Boatto et al. (2004) described the case of a male who ingested a solution containing phenol 

and cresol and died approximately 30 minutes after ingestion. Toxicology tests revealed that the stomach 

content, blood, and urine of the individual contained 115.0, 58.3, and 3.3 μg/mL of phenol, respectively. 

Similar blood concentrations (56–130 μg/mL) were measured in fatal cases reported by Tanaka et al. 

(1998), Soares and Tift (1982), and Lo Dico et al. (1989). 

The oral LD50 has been determined in rats treated by gavage with phenol in water; the LD50 was found to 

decrease with increasing concentration of phenol in the gavage fluid. The reported LD50 values were 

340 mg/kg in rats gavaged with a solution of 200,000 ppm phenol and 530 mg/kg in rats gavaged with a 

solution of 20,000 ppm phenol (Deichmann and Witherup 1944). After rats were treated by gavage with 

600 mg/kg in a 5% solution, 9 of 30 5-week-old rats, 18 of 20 10-day-old rats, and 12 of 20 adult rats died 

indicating that the 10-day-old rat is more sensitive to phenol than rats in the other age groups tested 

(Deichmann and Witherup 1944). In pregnant rats treated on gestation days (GDs) 6–15, 7 of 10 rats died 

at a dose of 125 mg/kg/day when treated with a volume of 1 mL/kg, while 1 of 6 rats died at a dose of 

160 mg/kg/day when treated with a volume of 5 mL/kg (NTP 1983a). In a 1-day dosing regimen study, 

female rats were given 0, 12, 40, 120, or 224 mg/kg in order to determine a single-dose oral LD50 of 

400 mg/kg (Berman et al. 1995). Mortality was observed only at the highest dose where two of eight rats 

treated died. All female rats treated for 14 days with a dose of 120 mg/kg/day died (Berman et al. 1995; 

Moser et al. 1995). In a 14-day dosing regimen with the same doses (except the 224 mg/kg), all animals 

died at the dose of 120 mg/kg. 

The oral LD50 of phenol has been estimated as 300 mg/kg in mice (von Oettingen and Sharpless 1946). 

Five of 10 rabbits treated with an oral dose of 420 mg/kg died (Deichmann and Witherup 1944). In 

pregnant mice treated on GDs 6–15, four of 35 mice died at a dose of 280 mg/kg/day (NTP 1983b). 

Flickinger (1976) gave male Harlan-Wistar albino rats single doses of 0, 200, 398, 795, and 1,580 mg/kg 

phenol by gavage and held the animals for 14 days postdosing in order to determine an oral LD50. No 

animals died following the 0, 200, or 398 mg/kg doses; four of five animals died the first day following 
059

172

115

400

119

120

073

340

166

125

100

280

104

300

075

420

Table 3-2 Levels of Significant Exposure to Phenol - Oral 

a 

Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) 

ACUTE EXPOSURE Death 

1 Human once 

System 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

LOAEL 

Serious 

(mg/kg/day) 

172 F (death) 

Reference Chemical Form 

Stajduhar-Caric 1968 

2 Rat 

(Fischer- 344) 

once (GW) 400 F (LD50) Berman et al. 1995 

3 Rat 

(Fischer- 344) 

14 d 1 x/d (GW) 

120 F (8/8 died) Berman et al. 1995 

4 Rat 

(Wistar) 

once (GW) 340 (LD50) Deichmann and Witheru

5 Rat 

(CD) 

10 d Gd 6-15 1 x/d (GW) 

125 F (7/10 maternal deaths) NTP 1983a 

6 Mouse 

(CD-1) 

10 d Gd 6-15 1 x/d (GW) 

280 F (4/35 maternal deaths) NTP 1983b 

7 Mouse 

(NS) 

once (GO) 300 M (5/10 deaths) Von Oettingen and Sha

1946 

8 Rabbit 

(White) 

once (GW) 420 (5/10 deaths) Deichmann and Witheru
117

224120

224

120

224

224

120

4012

40

4040

195

4040

Table 3-2 Levels of Significant Exposure to Phenol - Oral (continued) 

Exposure/ 

Duration/ 

a 

Key to Species Frequency 

Figure (Strain) (Route) 

Systemic 

9 Rat once 

(Fischer- 344) (GW) 

10 Rat 14 d 

1 x/d (Fischer- 344) (GW) 

11 Rat 14 d 

Gd 6-19 (Fischer- 344) (GW) 

System 

Hepatic

RenalEndocrBd WtHepatic

Renal Endocr Bd Wt Resp 

Bd Wt 

LOAEL 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

Serious 

(mg/kg/day) 

Reference Chemical Form 

224 F Berman et al. 1995 

120 F 224 F (renal tubular necrosis, 

protein casts, papillary hemorrhage) 

120 F 224 F (unspecified changes in 

the adrenal gland) 

224 F 

40 F Berman et al. 1995 

12 F 40 F (renal tubular necrosis, 

protein casts, papillary hemorrhage in 3/8) 

40 F 40 F 

40 F (dyspnea, rales) Narotsky and Kavlock 1

40 F (20% decrease in 

maternal body weight gain) 
168

120120

257

60

120

140

265

171

280140

280

118

120

224

Table 3-2 Levels of Significant Exposure to Phenol - Oral (continued) 

a 

Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) System NOAEL (mg/kg/day) Less Serious (mg/kg/day) 

LOAEL 

Serious 

(mg/kg/day) 

Reference Chemical Form 

12 Rat 

(CD) 

10 d Gd 6-15 1 x/d (GW) 

Hepatic 120 F NTP 1983a 

Bd Wt 120 F 

13 Rat 

(SpragueDawley) 

10 d Gd 6-15 3 x/d (GW) 

Bd Wt 

b

60 F 120 F (11% reduced maternal 

body gain on Gd 6-16) 

York 1997 

14 Mouse 

(Swiss CD-1) 

once Gd 13 (GW) 

Hemato 265 F (30-60% reduction in the 

ratio of poly/normo chromatic erythrocytes in the bone marrow of pregnant dams) 

Ciranni et al. 1988 

15 Mouse 

(CD-1) 

10 d Gd 6-15 1 x/d (GW) 

Hepatic 280 F NTP 1983b 

Bd Wt 140 F 280 F (67% decrease in 

absolute maternal body weight gain) 

Immuno/ Lymphoret 

16 Rat 

(Fischer- 344) 

once (GW) 120 F 224 F (necrosis or atrophy of the spleen or thymus) Berman et al. 1995 
121

40

105

207

190

40

120

193

12 40

101

70

140 280

196

40

53.3

Table 3-2 Levels of Significant Exposure to Phenol - Oral (continued) 

a 

Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) System 

LOAEL 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

Serious 

(mg/kg/day) 

Reference Chemical Form 

17 Rat 

(Fischer- 344) 

14 d 1 x/d (GW) 

40 F Berman et al. 1995 

Neurological 

18 Rat 

(SpragueDawley) 

once (G) 207 M (muscle twitching, Liao and Oehme 1981 convulsions, coma) 

19 Rat 

(Fischer- 344) 

once (GW) 40 F 120 F (mild-to-severe Moser et al. 1995 whole-body tremors, 

decreased motor activity) 

20 Rat 

(Fischer- 344) 

14 d 1 x/d (GW) 

12 F 40 F (increased rearing) Moser et al. 1995 

21 Mouse 

(CD-1) 

10 d Gd 6-15 1 x/d (GW) 

Developmental 

22 Rat 

(Fischer- 344) 

14 d Gd 6-19 (GW) 

70 F 140 F (mild tremors on the first NTP 1983b

3 days of dosing) 

280 F (tremors, ataxia in 

pregnant dams) 

40 F 53.3 F (significant decrease in Narotsky and Kavlock 1

the number of live-born pups, associated with severe respiratory effects in the dams) 
103

60

120

254

120

360

046

140

280

Table 3-2 Levels of Significant Exposure to Phenol - Oral (continued) 

Exposure/ LOAEL 

Duration/ 

a Frequency Key to Species NOAEL Less Serious Serious (Route) Figure (Strain) System (mg/kg/day) (mg/kg/day) (mg/kg/day) 

23 Rat 10 d 60 F 120 F (7% decrease in average Gd 6-15 (CD) fetal body weight) 1 x/d

(GW)

24 Rat 10 d 120 360 (decreased fetal weight Gd 6-15 (Sprague- and decrease ossification Dawley) 3 x/d sites) (GW) 

25 Mouse 10 d 140 F 280 F Gd 6-15 (CD-1) 1 x/d

(GW)

(18% decreased fetal 

body weight, cleft palate 8/214) 

Reference Chemical Form 

NTP 1983a York 1997 NTP 1983b 
198

16941694169416941694169416941694467508

1556 1694

251

321321321

Table 3-2 Levels of Significant Exposure to Phenol - Oral (continued) 

Exposure/ 

Duration/ 

a 

Key to Species Frequency 

Figure (Strain) (Route) 

INTERMEDIATE EXPOSURE Systemic 

26 Rat 13 wk 

ad lib (Fischer- 344) (W) 

27 Rat 10 wk 

2-gen (SpragueDawley) ad lib(W) 

System 

Resp 

Cardio Gastro Musc/skel Hepatic Renal Endocr Dermal Bd Wt Hemato 

Hepatic Renal 

LOAEL 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

Serious 

(mg/kg/day) 

Reference Chemical Form 

1694 F NCI 1980 

1694 F 1694 F 1694 F 1694 F 1694 F 1694 F 1694 F 

c

467 M 508 F 

1556 M (16% decrease in body 

weight gain associated with decreased water 

intake) 

1694 F (26% decrease in body 

weight gain associated with decreased water 

intake) 

321 F Ryan et al. 2001 

321 F 321 F 
161

33.633.6

1.8

33.633.633.6

Table 3-2 Levels of Significant Exposure to Phenol - Oral (continued) 

a 

Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) System NOAEL (mg/kg/day) Less Serious (mg/kg/day) 

LOAEL 

Serious 

(mg/kg/day) 

Reference Chemical Form 

28 Mouse 

(CD-1) 

28 d ad lib (W) 

Resp 33.6 M Hsieh et al. 1992 

Cardio 33.6 M Hemato 1.8 M (32% decrease in RBC 

count) 

Hepatic Renal 

33.6 M 33.6 M 

Bd Wt 33.6 M 
203

26422642264226422642264226422642741

2468

250

321

015

1.8

6.2

Table 3-2 Levels of Significant Exposure to Phenol - Oral (continued) 

a 

Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) System NOAEL (mg/kg/day) Less Serious (mg/kg/day) 

LOAEL 

Serious 

(mg/kg/day) 

Reference Chemical Form 

29 Mouse 

(B6C3F1) 

13 wk ad lib (W) 

Resp 2642 F NCI 1980 

Cardio 2642 F Gastro 2642 F Musc/skel 2642 F Hepatic 2642 F Renal 2642 F Endocr 2642 F Dermal 2642 F Bd Wt 741 M 2468 M (80% decrease in body 

weight gain associated with decreased water 

intake) 

Immuno/ Lymphoret 

30 Rat 

(SpragueDawley) 

10 wk ad lib (W) 

321 F Ryan et al. 2001 

31 Mouse 

(CD-1) 

28 d ad lib (W) 

1.8 M 6.2 M (decreased antibody 

production response to SRBC) 

Hsieh et al. 1992 
255

107

360

014

1.8

201

15561694

248

301321

206

24682642

249

93

321

Table 3-2 Levels of Significant Exposure to Phenol - Oral (continued) 

a 

Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) System 

LOAEL 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

Serious 

(mg/kg/day) 

Reference Chemical Form 

Neurological 

32 Rat 

(SpragueDawley) 

13 wk ad lib (W) 

107 F 360 F (decreased motor activity Beyrouty 1998

on week 4) 

33 Mouse 

(CD-1) 

28 d ad lib (W) 

1.8 M (decreased levels of Hsieh et al. 1992

dopamine in the corpus striatum) 

Reproductive 

34 Rat 

(Fischer- 344) 

13 wk ad lib (W) 

NCI 1980 c 1556 M 

1694 F 

35 Rat 

(SpragueDawley) 

10 wk 2-gen ad lib (W) 

Ryan et al. 2001 c 301 M 

321 F 

36 Mouse 

(B6C3F1) 

13 wk ad lib (W) 

NCI 1980 c 2468 M 

2642 F 

Developmental 

37 Rat 

(SpragueDawley) 

10 wk 2-gen ad lib (W) 

93 F 321 F (decreased pup weight Ryan et al. 2001

and percent live on day 4) 
050

721721721721721721721721

322721

Table 3-2 Levels of Significant Exposure to Phenol - Oral (continued) 

Exposure/ 

Duration/ 

a 

Key to Species Frequency 

Figure (Strain) (Route) 

CHRONIC EXPOSURE Systemic 

38 Rat 103 wk 

ad lib (Fischer- 344) (W) 

System 

Resp 

Cardio Gastro Musc/skel Hepatic Renal Endocr Dermal Bd Wt 

LOAEL 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

Serious 

(mg/kg/day) 

Reference Chemical Form 

721 F NCI 1980 

721 F 721 F 721 F 721 F 721 F 721 F 721 F 

c

322 M (about 12% decrease in 

body weight associated with a 20% decrease in water intake) 

721 F (about 17% decrease in 

body weight associated with a 10% decrease in water intake) 
212

120412041204120412041204120412041204

207

721

213

1204

208

721

Table 3-2 Levels of Significant Exposure to Phenol - Oral (continued) 

Exposure/ 

Duration/ 

a 

Key to Species Frequency 

Figure (Strain) (Route) 

39 Mouse 103 wk 

(B6C3F1) ad lib 

(W) 

Immuno/ Lymphoret 

40 Rat 103 wk 

ad lib (Fischer- 344) (W) 

41 Mouse 103 wk 

(B6C3F1) ad lib 

(W) 

Neurological 

42 Rat 103 wk 

ad lib (Fischer- 344) (W) 

System 

Resp 

Cardio Gastro Musc/skel Hepatic Renal Endocr Dermal Bd Wt 

LOAEL 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

Serious 

(mg/kg/day) 

Reference Chemical Form 

1204 F NCI 1980 

1204 F 1204 F 1204 F 1204 F 1204 F 1204 F 1204 F 1204 F 

721 F NCI 1980 

1204 F NCI 1980 

721 F NCI 1980 
214

1204

209

721

215

1204

Table 3-2 Levels of Significant Exposure to Phenol - Oral (continued) 

a 

Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) System NOAEL (mg/kg/day) Less Serious (mg/kg/day) 

LOAEL 

Serious 

(mg/kg/day) 

Reference Chemical Form 

43 Mouse 

(B6C3F1) 

103 wk ad lib (W) 

1204 F NCI 1980 

Reproductive 

44 Rat 

(Fischer- 344) 

103 wk ad lib (W) 

721 F NCI 1980 

45 Mouse 

(B6C3F1) 

103 wk ad lib (W) 

1204 F NCI 1980 

a The number corresponds to entries in Figure 3-2. b Used to derive an acute-duration oral MRL of 1 mg/kg/day; the MRL was derived by dividing the BMDL of 125 mg/kg/day by an uncertainty factor of 100 (10 for aextrapolation and 10 for human variability). c Differences in levels of health effects and cancer effects between male and females are not indicated in Figure 3-2. Where such differences exist, only the levels most sensitive gender are presented. ad lib = ad libitum; Bd Wt = body weight; Cardio = cardiovascular; d = day(s); Endocr = endocrine; F = Female; (G) = gavage; Gastro = gastrointestinal; gd = gestatgeneration; Gn pig = guinea pig; (GO) = gavage in oil; (GW) = gavage in water; Hemato = hematological; hr = hour(s); Immuno = immunological; LD50 = lethal dose= lowest-observed-adverse-effect level; M = male; min = minute(s); Musc/skel = musculoskeletal; NOAEL = no-observed-adverse-effect level; NS = not specified; Rcell; Resp = respiratory; SRBC = sheep red blood cells; x = time(s); (W) = drinking water; wk = week(s); yr = year(s) 
Death 

Respiratory Hematological Hepatic Renal Endocrine Body Weight Immuno/Lymphor Neurological Developmental 

1000 

Figure 3-2 Levels of Significant Exposure to Phenol - Oral
	

Acute (≤14 days)
	

Systemic
	

PHENOL

mg/kg/day 

8h
	

4r

2r 24r 

6m 7m 15m 15m 21m 25m 

9r 

14m 

9r 9r 9r 16r 18r 

1 

15m 21m 25m 3r 5r 12r 9r 9r 12r 13r 16r 19r 23r 24r 

100 

21m

13r 23r 22r 

11r 10r 10r 10r 10r 11r 17r 19r 20r 22r 

10r 20r
	 10
	

1 

0.1 

3. HEALTH EFFECTS

c-Cat 

d-Dog

r-Rat 

p-Pig

q-Cow

 -Humans 

k-Monkey

m-Mouse 

h-Rabbit 

a-Sheep 

f-Ferret 

j-Pigeon

e-Gerbil 

s-Hamster 

g-Guinea Pig 

n-Mink 

o-Other

 Cancer Effect Level-Animals

 LOAEL, More Serious-Animals

LOAEL, Less Serious-Animals

NOAEL - Animals

 Cancer Effect Level-Humans

 LOAEL, More Serious-Humans

LOAEL, Less Serious-Humans

NOAEL - Humans

 LD50/LC50

Minimal Risk Level

 for effects

 other than

 Cancer 

58
Respiratory 

Cardiovascular Gastrointestinal Hematological Musculoskeletal Hepatic Endocrine Dermal Body Weight Immuno/Lymphor Neurological Reproductive Developmental 

10000 

Renal 

Figure 3-2 Levels of Significant Exposure to Phenol - Oral (Continued)
 

Intermediate (15-364 days)
	

Systemic
	

PHENOL

mg/kg/day 

29m 29m 29m 29m 29m 29m 29m 29m 29m 36m 

26r 26r 26r 26r 26r 26r 26r 26r 26r 26r 34r 

1000 

29m 

26r 

32r 27r 27r 27r 30r 37r 35r 

32r 100 37r 

28m 28m 28m 28m 28m 

10
	

31m
	

28m 31m 33m
	

1
	

3. HEALTH EFFECTS

c-Cat 

d-Dog

r-Rat 

p-Pig

q-Cow

 -Humans 

k-Monkey

m-Mouse 

h-Rabbit 

a-Sheep 

f-Ferret 

j-Pigeon

e-Gerbil 

s-Hamster 

g-Guinea Pig 

n-Mink 

o-Other

 Cancer Effect Level-Animals

 LOAEL, More Serious-Animals

LOAEL, Less Serious-Animals

NOAEL - Animals

 Cancer Effect Level-Humans

 LOAEL, More Serious-Humans

LOAEL, Less Serious-Humans

NOAEL - Humans

 LD50/LC50

Minimal Risk Level

 for effects

 other than

 Cancer 

59
Respiratory 

Cardiovascular Gastrointestinal Musculoskeletal Hepatic Renal Endocrine Dermal Body Weight Immuno/Lymphor Neurological Reproductive 

Figure 3-2 Levels of Significant Exposure to Phenol - Oral (Continued)

Chronic (≥365 days) 

Systemic 

mg/kg/day 

PHENOL

10000 

39m 39m 39m 39m 39m 39m 39m 39m 39m 41m 43m 45m 

1000 

38r 38r 38r 38r 38r 38r 38r 38r 40r 42r 44r 

38r 

100 

3. HEALTH EFFECTS

c-Cat 

d-Dog

r-Rat 

p-Pig

q-Cow

 -Humans 

k-Monkey

m-Mouse 

h-Rabbit 

a-Sheep 

f-Ferret 

j-Pigeon

e-Gerbil 

s-Hamster 

g-Guinea Pig 

n-Mink 

o-Other

 Cancer Effect Level-Animals

 LOAEL, More Serious-Animals

LOAEL, Less Serious-Animals

NOAEL - Animals

 Cancer Effect Level-Humans

 LOAEL, More Serious-Humans

LOAEL, Less Serious-Humans

NOAEL - Humans

 LD50/LC50

 for effects

 other than

 Cancer 

Minimal Risk Level 

60
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PHENOL 61 

3. HEALTH EFFECTS 

the 795 mg/kg dose, and five of five animals died within 2 hours following 1,580 mg/kg dose. From 

these data, the investigators estimated an oral LD50 of 650 mg/kg. 

No effect on survival was observed in mice treated with phenol in the drinking water at doses up to 

33.6 mg/kg/day for 28 days (Hsieh et al. 1992). Survival was not affected in rats and mice treated with 

phenol in drinking water for 13 or 103 weeks (NCI 1980). Both species were treated with drinking water 

concentrations up to 10,000 mg/L in the 13-week study (maximum doses in mg/kg/day: 1,694 for female 

rats, 1,556 for male rats; 2,643 for female mice, 2,468 for male mice), and up to 5,000 mg/L in the 

103-week study (maximum doses in mg/kg/day: 721 for female rats, 645 for male rats; 1,204 for female 

mice, 1,180 for female mice). 

In most studies, a specific cause of death was not reported, but common signs preceding death included 

convulsions, coma, and respiratory arrest. The LD50 values and doses resulting in death from each 

reliable study in each species in the acute-duration category are recorded in Table 3-2 and plotted in 

Figure 3-2. 

3.2.2.2 Systemic Effects 

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

species and duration category are recorded in Table 3-2 and plotted in Figure 3-2. 

Respiratory Effects. Stajduhar-Caric (1968) reported on a case in which a woman who ingested 

approximately 10–20 g of phenol, became comatose and died within a matter of hours. During the course 

of the poisoning and treatment, initially an increase in respiration was observed, then irregularities in 

breathing, and finally cessation of respiration. An autopsy revealed marked hyperemia of the tracheal and 

bronchial mucous membranes, as well as pulmonary edema. According to Deichmann and Keplinger 

(1981), the progression of impacts on the respiratory system summarized above are typical of oral 

poisonings in humans, although often the intermediate stages are characterized by a decrease in 

respiration rate and magnitude. According to these authors, in acute intoxication, death usually results 

from respiratory failure. Pulmonary congestion and edema were reported in a man who died following 

phenol poisoning (Soares and Tift 1982). In another case of fatal ingestion of phenol, autopsy reported 

white froth in the nostrils, upper airway, trachea, and bronchi as well as edema and fluid in the lungs (Lo 

Dico et al. 1989). Inflammatory changes in the lungs also were observed in a more recent fatal case of 

ingestion of phenol (Tanaka et al. 1998). 
 

 

 

 

 

 

 

 

 

 

 

 

 

PHENOL 62 

3. HEALTH EFFECTS 

Dyspnea and rales were observed in pregnant rats treated by gavage with phenol in water on GDs 6–19 

(Narotsky and Kavlock 1995). The respiratory effects were observed at both 40 and 53.3 mg/kg/day. 

Gross pathological examinations did not reveal any adverse changes in the lungs of mice treated with 

phenol in drinking water at doses of 1.8, 6.2, or 33.6 mg/kg/day for 28 days (Hsieh et al. 1992). 

In a study reported by the National Cancer Institute (NCI 1980), rats exposed to 16–1,694 mg/kg/day 

(100–10,000 mg/L) and mice exposed to 25–2,642 mg/kg/day (100–10,000 mg/L) phenol in drinking 

water exhibited no indication of histopathological effects on the respiratory system after 13 weeks of 

exposure. No histological abnormalities of the respiratory tract were observed in rats or mice exposed to 

2,500 or 5,000 ppm phenol in drinking water for 103 weeks (mg/kg/day doses: 322 or 645 for male rats; 

360 or 721 for female rats; 590 or 1,180 for male mice; 602 or 1,204 for female mice) (NCI 1980). 

Cardiovascular Effects. In a recent report on the clinical treatment of phenol poisoning, Langford 

et al. (1998) provide a summary of a case report in which a woman accidentally consumed an ounce of 

89% phenol that had mistakenly been given to her in preparation for an in-office procedure. Her 

immediate reaction upon consuming the phenol was to clutch her throat and collapse, and within 

30 minutes, she was comatose and had gone into respiratory arrest. Treatment was initiated with an 

endotracheal intubation. Ventilation with a bag and mask led to the detection of a lamp oil odor. Within 

an hour, she developed ventricular tachycardia, which responded to cardioversion; however, she 

subsequently developed (in the first 24 hours) supraventricular and ventricular dysrhythmias, metabolic 

acidosis, and experienced a grand mal seizure. After a 15-day hospital stay, she was completely 

recovered with no evidence of impaired motility or compromised gastrointestinal or cardiovascular 

systems. 

Gross pathological examinations did not reveal any adverse changes in the hearts of mice treated with 

phenol in drinking water at doses of 1.8, 6.2, or 33.6 mg/kg/day for 28 days (Hsieh et al. 1992). In a 

study reported by the NCI (1980), rats exposed to 16–1,694 mg/kg/day (100–10,000 ppm) and mice 

exposed to 25–2,642 mg/kg/day (100–10,000 ppm) phenol in drinking water exhibited no indication of 

histopathological effects on the heart after 13 weeks of exposure. Histological abnormalities of the heart 

were not evident in rats after 103 weeks of exposure to 322 or 645 mg/kg/day for males or 360 or 

721 mg/kg/day for females (2,500 or 5,000 ppm) or in mice after exposure to 590 or 1,180 mg/kg/day for 

males or 602 or 1,204 mg/kg/day for females (2,500 or 5,000 ppm). Cardiovascular function was not 

evaluated in these studies. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PHENOL 63 

3. HEALTH EFFECTS 

Gastrointestinal Effects. In a study on the clinical treatment of phenol poisoning, Langford et al. 

(1998) provide a summary of a case report in which a woman accidentally consumed an ounce of 89% 

phenol that had mistakenly been given to her in preparation for an in-office procedure. Her immediate 

reaction upon consuming the phenol was to clutch her throat and collapse, and within 30 minutes, she was 

comatose and had gone into respiratory arrest. Treatment was initiated with an endotracheal intubation, 

which revealed her mouth and hypopharynx to be white. Esophagitis and upper gastrointestinal bleeding 

occurred in the first week, and an examination of the esophagus on day 8 revealed hyperkeratosis, 

erythema, and a friable mucosa. After a 15-day hospital stay, she was completely recovered with no 

evidence of impaired motility or compromised gastrointestinal system. A male who ingested a solution 

containing phenol and cresol and eventually died did not show macroscopic lesions of the esophagus and 

stomach, but histological examination revealed exfoliation of the mucosa of the esophagus and 

coagulative necrosis of the gastric mucosa (Boatto et al. 2004). Coagulation of the gastric mucosa was 

also reported in a fatal case of poisoning with phenol (Soares and Tift 1982). Erosive duodenal gastritis 

was also observed in a woman who ingested about 70 mL of a 42–52% phenol solution (Kamijo et al. 

1999). Other fatal cases have described mucous changes in the digestive organs (Tanaka et al. 1998) and 

crusted corrugated appearance of the stomach (Lo Dico et al. 1989). 

In a retrospective study of 158 persons exposed to phenol in drinking water for several weeks following 

an accidental spill of phenol, significantly (p<0.01) increased gastrointestinal symptoms (mouth sores, 

nausea, diarrhea) were reported by 17 of the 39 most highly-exposed individuals (Baker et al. 1978). 

Exposure concentrations for the most highly-exposed group were >0.1 mg/L, and the study authors 

estimated phenol intake during this period as 10–240 mg/person/day (0.14–3.4 mg/kg/day assuming a 

70-kg body weight). Symptom rates were not increased among 61 persons exposed to concentrations of 

≤0.1 mg/L (0.003 mg/kg/day assuming 2 L water per day and a 70-kg body weight). Dermal exposure 

was not considered in these estimates of dose. A similar study was conducted by Jarvis et al. (1985) 

among 344 English households whose drinking water contaminated with phenol. An unexposed group 

(250 households) served as control. The day of the contamination incident, the concentration of phenol in 

a high-exposure area (250 households) was estimated to be 10 μg/L, whereas in a low-exposure area 

(94 households), the concentration was 4.7 μg/L. The day after the incident, the phenol concentration in 

the water from both areas was 4.7 μg/L, and 2 days after the incident, it was 0.9 μg/L. Chlorophenols, 

which formed upon chlorination of the water, were detected at a higher concentration of phenol and 

followed a similar pattern as phenol. Since the concentration of phenol and chlorophenols were similar in 

the two exposed areas, the two exposed areas were combined in the analysis. Exposed individuals had 
 

 

 

 

 

 

 

 

 

PHENOL 64 

3. HEALTH EFFECTS 

significantly higher incidences of gastrointestinal illness (i.e., diarrhea, nausea, vomiting, and abdominal 

pain) than the unexposed group, and the onset of symptoms coincided with the period of elevated 

concentrations of phenol in the drinking water. Moreover, stronger associations were observed among 

those who reported drinking the water in the exposed areas than among those who reported not drinking 

the water in the same areas. The specific contribution of phenol to the adverse signs and symptoms 

reported is difficult to determine. 

A case control study of 6,913 individuals living near a Korean river contaminated with 30 tons of 100% 

phenol found nausea, vomiting, diarrhea, and abdominal pain among 1,824 exposed subjects compared to 

1,064 unexposed subjects (Kim et al. 1994). The level of phenol measured in the two reservoirs that 

served the community was 0.05 mg/L after the spill, while that in the chlorinated tap water was 

0.0084 mg/L. 

In a study reported by the NCI (1980), rats exposed up to 1,694 mg/kg/day and mice exposed up to 

2,642 mg/kg/day phenol in drinking water exhibited no indication of histopathological effects on the 

gastrointestinal system after 13 weeks of exposure. No histological abnormalities of the gastrointestinal 

tract were observed in rats or mice exposed to phenol in drinking water that provided doses of 

approximately 720 and 1,200 mg/kg/day, respectively, for 103 weeks (NCI 1980). 

Hematological Effects. No studies were located regarding hematological effects in humans 

following oral exposure to phenol. 

A 30–60% decrease in the ratio of polychromatic to normochromatic erythrocytes was observed in the 

bone marrow of pregnant mice treated by gavage with a single dose of 265 mg/kg phenol in water on 

GD 13 (Ciranni et al. 1988). Dose-related and significant decreases in red blood cell counts were 

observed in mice treated with phenol in the drinking water at doses of 1.8, 6.2, or 33.6 mg/kg/day for 

28 days (Hsieh et al. 1992). Red blood cell counts in cells x106

/mm3 were 7.17 in controls, 4.9 at the low 

dose, 4.64 at the middle dose, and 3.23 at the high dose. A significant decrease in hematocrit was only 

observed at the high dose (48% control, 44.1% high dose), and no changes were observed in leucocyte 

numbers or leucocyte differentials. 

No significant alterations in hematology parameters were observed in male or female rats dosed with up 

to 301 or 321 mg phenol/kg/day in the drinking water, respectively, for 10 weeks (Ryan et al. 2001). 
 

 

 

 

 

 

 

 

PHENOL 65 

3. HEALTH EFFECTS 

Musculoskeletal Effects. No studies were located regarding musculoskeletal effects in humans 

following oral exposure to phenol. 

Rats exposed up to 1,694 mg/kg/day and mice exposed up to 2,642 mg/kg/day phenol in drinking water 

exhibited no histological abnormalities of the bone after 13 weeks of exposure (NCI 1980). No 

histological abnormalities of the bone were observed in rats or mice up to 721 or 1,204 mg/kg/day, 

respectively, of phenol in drinking water for 103 weeks. (NCI 1980). 

Hepatic Effects. Serum markers of liver effects, bilirubin, glucose, cholesterol, and AST activity 

were not affected in 39 persons exposed to phenol in the drinking water at an estimated dose of 0.14– 

3.4 mg/kg/day for several weeks (Baker et al. 1978). Because these examinations were completed 

7 months after the spill, this study does not provide conclusive evidence that there was no reversible liver 

damage. Autopsy of a fatal case of ingestion of phenol revealed substantial toxic changes in the liver 

including extension of sinusoid lumens and an increase in centrilobular increase of cytoplasmic 

eosinophility (Tanaka et al. 1998). 

Serum markers of liver effects (lactic dehydrogenase, alkaline phosphatase, ALT, bilirubin) and 

histopathological changes in the liver were observed in rats given single gavage doses of 224 mg/kg or 

14 daily gavage doses of 40 mg phenol/kg in water (Berman et al. 1995). Changes in liver weight were 

not observed in pregnant rats treated by gavage with 120 mg/kg/day of phenol in water on GDs 6–15 

(NTP 1983a), or in pregnant mice treated by gavage with 280 mg/kg/day phenol in water on GDs 6–15 

(NTP 1983b). 

Gross pathological examinations did not reveal any lesions in mice treated with phenol in the drinking 

water at a dose of 33.6 mg/kg/day for 28 days (Hsieh et al. 1992). 

In a study sponsored by the National Cancer Institute (NCI 1980), rats exposed up to 1,694 mg/kg/day 

and mice exposed up to 2,642 mg/kg/day phenol in drinking water exhibited no histological abnormalities 

of the liver after 13 weeks of exposure. Similar observations were made in rats dosed with up to 301– 

321 mg phenol/kg/day in the drinking water for 10 weeks (Ryan et al. 2001). No histological 

abnormalities of the liver were observed in rats or mice exposed up to 721 or 1,204 mg/kg/day 

respectively, of phenol in drinking water for 103 weeks (NCI 1980). 
 

 

 

 

 

 

 

 

 

 

 

 

PHENOL 66 

3. HEALTH EFFECTS 

Renal Effects. Although not adverse, dark urine (as a result of oxidation products of phenol or a 

result of hemoglobin or its breakdown products in the urine) is a common symptom observed in humans 

exposed to phenol. In persons exposed to about 0.14–3.4 mg/kg/day phenol in drinking water for several 

weeks after an accidental spill, dark urine was reported by 17.9% of the most highly-exposed individuals, 

while only 3.4% of the controls reported the effect (Baker et al. 1978). This difference was not 

statistically significant. A 3.3-fold increase in the prevalence of dark urine was reported by persons 

exposed to unspecified doses of phenol after an accidental spill in Korea (Kim et al. 1994). Autopsy of an 

individual who ingested phenol showed interstitial edema and renal tubular hemorrhage (Tanaka et al. 

1998). Extensive renal autolysis was also observed in a fatal case of poisoning with phenol (Soares and 

Tift 1982). 

Renal tubular necrosis, protein casts, and papillary hemorrhage were not observed in rats treated with a 

single gavage dose of 120 mg/kg phenol in water, but were seen in 60% of animals examined at the next 

highest dose of 224 mg/kg (Berman et al. 1995). No histopathological changes in the kidney were 

observed after 14 daily doses of 12 mg/kg/day, but were observed in 3 of 8 animals given 14 daily doses 

of 40 mg/kg/day (Berman et al. 1995). 

Gross pathological examinations did not reveal any adverse changes in the kidneys of mice treated with 

phenol in drinking water at doses of 1.8, 6.2, or 33.6 mg/kg/day for 28 days (Hsieh et al. 1992). 

Rats exposed up to 1,694 mg/kg/day and mice exposed up to 2,642 mg/kg/day of phenol in drinking water 

exhibited no indication of histopathological effects on the kidney after 13 weeks of exposure (NCI 1980). 

Rats exposed to up to 301–321 mg phenol/kg/day in the drinking water for 10 weeks showed no 

significant histopathological effects in the kidneys (Ryan et al. 2001). 

No compound-related histological changes in the kidneys were observed in rats or mice exposed up to 

721 or 1,204 mg/kg/day, respectively, of phenol in drinking water for 103 weeks (NCI 1980). A higher 

incidence of inflammation of the kidney was reported in male rats exposed to 624 mg/kg/day (96%) than 

in controls (74%); however, because of the high incidence of inflammation in the controls, it is impossible 

to ascertain whether this was related to the exposure to phenol (NCI 1980). A high age-related incidence 

of inflammation is expected in male rats of the Fischer-344 strain used in this study. Kidney function, 

including glomerular filtration rate and glomerular sieving, however, was not evaluated in this study. 

Furthermore, histological examination was limited to standard light microscopic examinations which 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

PHENOL 67 

3. HEALTH EFFECTS 

would not have detected functionally significant glomerular abnormalities like disruption of the 

glomerular basement membrane or immune complex deposition. 

Endocrine Effects. Autopsy of a subject who died following ingestion of a solution containing 

phenol showed interstitial hemorrhage in the pancreas and adrenal glands (Tanaka et al. 1998). No 

further information regarding effects of phenol on endocrine-related end points was located. 

Unspecified microscopic changes were observed in the adrenal glands of rats given a single gavage dose 

of 224 mg/kg phenol in water, but no changes were described in rats treated similarly with doses 

≤120 mg/kg/day (Berman et al. 1995). No adrenal gland effects were observed in rats 14 daily gavage 

doses of 4, 12, or 40 mg/kg (Berman et al. 1995). 

Rats exposed up to 1,694 mg/kg/day and mice exposed up to 2,642 mg/kg/day phenol in drinking water 

exhibited no histopathological changes in the pancreas, pituitary, adrenal glands, thyroid, or parathyroid 

after 13 weeks of exposure (NCI 1980). Exposure-related histopathological changes in the pancreas, 

pituitary, adrenal glands, thyroid, or parathyroid were also not observed in rats and mice exposed to 

2,500 or 5,000 ppm phenol in drinking water for 103 weeks (NCI 1980). Estimated mg/kg/day doses 

were 322 or 645 for male rats, 360 or 721 for female rats, 590 or 1,180 for male mice, and 602 or 

1,204 for female mice. 

Dermal Effects. Skin rash and mouth sores were reported in persons living near a site with 

contaminated well water resulting from an overturned tanker car carrying 37,900 L of 100% phenol 

(Baker et al. 1978). The level of phenol in the drinking water of this cohort was >0.1 mg/L, and while 

substantial oral exposure probably occurred, dermal exposure cannot be ruled out. Increases in the 

prevalence of skin rashes and sore throats were reported by persons drinking water from a river 

contaminated by an accidental spill of phenol (Kim et al. 1994). Because the water was chlorinated 

before use, the effect may also have been a result of exposure to chlorophenol. Perioral chemical burns 

from phenol were observed in a woman who ingested approximately 70 mL of a 42–52% phenol solution 

(Kamijo et al. 1999). Spiller et al. (1993) also reported oral and esophageal burns in 17 out of 52 patients 

following ingestion of a disinfectant containing 26% phenol. 

Rats exposed up to 1,694 mg/kg/day and mice exposed up to 2,642 mg/kg/day phenol in drinking water 

exhibited no histopathological changes in the skin after 13 weeks of exposure (NCI 1980). Exposure­
 

 

 

 

 

 

 

 

 

 

 

PHENOL 68 

3. HEALTH EFFECTS 

related histopathological changes in the skin were also not observed in rats and mice exposed up to 721 or 

1,204 mg/kg/day, respectively, phenol in drinking water for 103 weeks (NCI 1980). 

Ocular Effects. No studies were located regarding ocular effects in humans or animals following oral 

exposure to phenol. 

Body Weight Effects. No effects on body weight were observed in rats treated with a single gavage 

dose of 224 mg/kg phenol in water or 14 daily gavage doses of 40 mg/kg (Berman et al. 1995; Moser et 

al. 1995). Maternal body weight gain was approximately 20% lower in rats treated by gavage with 40 or 

53.3 mg/kg/day phenol in water on GDs 6–19 (Narotsky and Kavlock 1995). Maternal body weight gain 

was 67% lower than controls in mice treated by gavage with 280 mg/kg/day phenol in water on GDs 6– 

15, with no effects on body weight gain observed at 140 mg/kg/day (NTP 1983b). Body weight gain was 

not affected in pregnant rats treated by gavage with 120 mg/kg/day phenol in water on GDs 6–15 (NTP 

1983a). Body weight gain was significantly reduced in pregnant rats dosed with 120 mg phenol/kg/day 

on GDs 6–15 (11% for GDs 6–16 and 19% for GDs 12–16) (York 1997). Doses of 360 mg/kg/day 

caused a reduction in body weight gain of 38% for GDs 6–16; the NOAEL for maternal weight gain in 

this study was 60 mg/kg/day. The reduction in maternal body weight gain in rats during pregnancy 

reported in the York (1997) study was used as the basis for derivation of an acute-duration oral MRL for 

phenol. 

Body weight was not affected in mice treated with phenol in drinking water at a dose of 33.6 mg/kg/day 

for 28 days (Hsieh et al. 1992). During 13-week studies in rats and mice treated with phenol in drinking 

water, decreased body weight gain was associated with dose-related decreases in water intake, 

presumably due to taste aversion (NCI 1980). In rats provided with the highest concentration 

(10,000 ppm), body weight gain was decreased by 26% in females at 1,694 mg/kg/day, and by 16% in 

males at 1,556 mg/kg/day. An effect on body weight gain was not observed in rats at 3,000 ppm 

(467 mg/kg/day for males, 508 mg/kg/day for females). In mice provided with the highest concentration 

(10,000 ppm), body weight gain was decreased by 33% in females at 2,642 mg/kg/day, and by 80% in 

males at 2,468 mg/kg/day. An effect on body weight gain was not observed in mice at 3,000 ppm 

(741 mg/kg/day for males, 793 mg/kg/day for females). A significant decrease in body weight gain 

associated with a significant decrease in water consumption was also observed in male and female rats 

dosed with 301–321 mg/kg/day phenol in the drinking water for 10 weeks (Ryan et al. 2001). 
 

 

 

 

 

 

 

 

 

 

 

 

 

PHENOL 69 

3. HEALTH EFFECTS 

Decreased mean body weight associated with decreased water intake was also observed in rats in a 

103-week study (NCI 1980). At the high concentration (5,000 ppm), body weight was 19% lower than 

controls in males (645 mg/kg/day) and 17% lower than controls in females (721 mg/kg/day). At the low 

concentration (2,500 ppm), body weight was 12% lower than controls in males (322 mg/kg/day) and 

within 10% of controls in females (360 mg/kg/day). Body weight was not affected in mice treated with 

phenol in drinking water for 103 weeks at doses up to 1,180 for males and up to 1,204 mg/kg/day for 

females (NCI 1980). 

3.2.2.3 Immunological and Lymphoreticular Effects 

No studies were located regarding immunological or lymphoreticular effects in humans following oral 

exposure to phenol. 

Necrosis or atrophy of the spleen or thymus was observed in four of six rats given a single gavage dose of 

224 mg/kg of phenol in water, and one of seven rats given 120 mg/kg/day (Berman et al. 1995). Based on 

this effect, which was not further described, the study authors considered 224 mg/kg to be a LOAEL for 

immunological effects. One of eight animals given 12 mg/kg/day, and two of eight given 40 mg/kg/day 

for 14 days showed these same effects. 

Hsieh et al. (1992) conducted a 28-day study of the immunotoxicologic impact of phenol in which 

CD-1 mice were given drinking water that provided doses of phenol of approximately 0, 1.8, 6.2, or 

33.6 mg/kg/day. When challenged with sheep red blood cells (SRBC), a significant decrease was 

observed in the splenic concentration of anti-erythrocyte antibody-forming cells and in the antierythrocyte antibody titer at the two highest doses, while a significant decrease in the absolute number of 

anti-erythrocyte antibody-forming cells present in the spleen was observed only at the top dose. In 

contrast to the results of Hsieh et al. (1992), Ryan et al. (2001) reported no immunologic alterations in 

male rats in a drinking water study. Rats were dosed for 10 weeks with up to 301 mg phenol/kg/day and 

then immunized intravenously with sheep red blood cells. Eighteen hours later, splenocytes were 

prepared in cell culture medium for enumeration of plaque-forming cells. Treatment with phenol had no 

significant effect on antibody-forming cells, and there were no significant effects on spleen or thymus 

weight, spleen cellularity, or spleen and thymus histology. 

Rats exposed up to 1,694 mg/kg/day and mice exposed up to 2,642 mg/kg/day phenol in drinking water 

exhibited no histopathological changes in the bone marrow, spleen, or lymph nodes after 13 weeks of 
 

 

 

 

 

 

 

 

 

 

PHENOL 70 

3. HEALTH EFFECTS 

exposure (NCI 1980). Exposure-related histopathological changes in the bone marrow, spleen, or lymph 

nodes were also not observed in rats or mice exposed to estimated doses of up to 721 or 1,204 mg/kg/day, 

respectively, for 103 weeks (NCI 1980). 

The highest NOAEL values and all LOAEL values from each reliable study for immunological and 

lymphoreticular effects in each species and duration category are recorded in Table 3-2 and plotted in 

Figure 3-2. 

3.2.2.4 Neurological Effects 

Headaches were reported 6 times more frequently by persons using drinking water contaminated with 

phenol than by controls (Kim et al. 1994). The water was used after chlorination; therefore, chlorophenol 

may have contributed to the observed effects. Fine, rapid, rhythmic, perioral movements, as well as signs 

of Parkinson’s syndrome were observed in a woman who ingested approximately 70 mL of a 42–52% 

solution of phenol (Kamijo et al. 1999). Central nervous system depression was described in 11 out of 

52 patients who ingested amounts ranging from 2 to 90 mL of a disinfectant solution containing 26% 

phenol (Spiller et al. 1993). 

Acute oral phenol poisoning in rabbits and rats was characterized by muscular tremors in the head region, 

which eventually spread to other regions of the body, with the lower extremities being the last affected. 

Loss of coordination and convulsions preceded death at doses of 300–940 mg/kg (Deichmann and 

Witherup 1944). Liao and Oehme (1981) described tremors of the muscles around the eyes, followed by 

convulsions and coma, in rats after a sublethal oral dose of 207 mg/kg phenol. Mild-to-severe wholebody tremors and decreased motor activity were reported in rats given a single gavage dose of 120 mg/kg 

phenol in water (Moser et al. 1995). A dose of 40 mg/kg resulted in no neurological effects following a 

single dose, while increased rearing was reported following 14 daily doses (Moser et al. 1995). Pregnant 

mice treated by gavage with phenol in water on GDs 6–15 exhibited tremors and ataxia at 280 mg/kg/day, 

mild tremors on the first 3 days of dosing at 140 mg/kg/day, and no adverse neurological effects at 

70 mg/kg/day (NTP 1983b). 

In contrast with results from oral gavage studies, phenol administered in the drinking water was much less 

toxic. For example, male rats exposed to up to 309 mg phenol/kg/day in the drinking water for 13 weeks 

showed no significant alterations in tests of motor activity or a functional observation battery conducted 

throughout the exposure period (Beyrouty 1998). However, females dosed with 360 mg phenol/kg/day 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

PHENOL 71 

3. HEALTH EFFECTS 

showed a significant reduction in motor activity on week 4 of the study; no significant alterations were 

seen in females at 107 mg/kg/day. Gross and microscopic evaluation of the brain, spinal cord, and 

peripheral nerves was unremarkable (Beyrouty 1998). 

Mice exposed for 28 days to phenol in drinking water exhibited a significant reduction in dopamine level 

in the corpus striatum at the 1.8 mg/kg/day dose, and significantly decreased levels of norepinephrine, 

serotonin, and 5-hydroxyindoleacetic acid in the hypothalamus at the 6.2 mg/kg/day dose (Hsieh et al. 

1992). Levels of neurotransmitters in other brain regions were also significantly altered at higher doses of 

phenol. 

Rats exposed to 16–1,694 mg/kg/day and mice exposed to 25–2,642 mg/kg/day phenol in drinking water 

exhibited no abnormal histology of the brain after 13 weeks of exposure (NCI 1980). Histopathological 

changes in the brain were not evident after 103 weeks of exposure to 322 or 645 mg/kg/day in male rats, 

360 or 721 mg/kg/day in female rats, 590 or 1,180 mg/kg/day in male mice, and 602 or 1,204 mg/kg/day 

in female mice (NCI 1980). However, this study did not include tests for neurological impairment or 

histopathological examinations of tissues in the nervous system other than the brain. 

The highest NOAEL values and all LOAEL values from each reliable study for neurological effects in 

each species and duration category are recorded in Table 3-2 and plotted in Figure 3-2. 

3.2.2.5 Reproductive Effects 

No studies were located regarding reproductive effects in humans following oral exposure to phenol. 

No evidence of impaired reproduction was found in rats exposed to phenol in drinking water at 

<5,000 ppm (estimated 571 mg/kg/day) for three generations or at <1,000 ppm (estimated 

114 mg/kg/day) for five generations (Heller and Pursell 1938). Data regarding breeding habits, controls, 

and the methods used to evaluate the rats for reproductive impairment were not reported in sufficient 

detail to establish reliable NOAELs or LOAELs for presentation in Table 3-2 and Figure 3-2. 

Rats exposed up to 1,694 mg/kg/day and mice exposed up to 2,642 mg/kg/day of phenol in drinking water 

exhibited no histopathological changes in the prostate, testes, uterus, or ovaries after 13 weeks of 

exposure (NCI 1980). Exposure-related histopathological changes in the prostate, testes, uterus, or 
 

 

 

 

 

 

 

PHENOL 72 

3. HEALTH EFFECTS 

ovaries were also not observed in rats or mice exposed up to 721 or 1,204 mg/kg/day, respectively, phenol 

in drinking water for 103 weeks (NCI 1980). 

In a two-generation study in which rats were administered phenol in the drinking water (up to 301– 

321 mg/kg/day), there was a significant decrease in absolute seminal vesicle weight in parental males at 

301 mg/kg/day and in absolute ovaries weight in parental females at 321 mg/kg/day, but were no 

significant alterations in gross or microscopic appearance of the reproductive organs of males and females 

from the parental and F1 generations (Ryan et al. 2001). In addition, there were no significant effects on 

estrus frequency, testicular sperm count, or sperm motility or morphology. Significant reductions in 

prostate and uterine weights in all F1 treated groups were not considered adverse effects of phenol by 

Ryan et al. (2001) on the basis of the absence of histological alterations and functional reproductive 

effects, and based on the fact that only a few animals had organ weights outside the range of concurrent 

control values. 

Information on the effects of exposure to phenol on the genetic material of germinal cells is presented in 

Section 3.3, Genotoxicity. 

The highest NOAEL values from each reliable study for reproductive effects in each species and duration 

category are recorded in Table 3-2 and plotted in Figure 3-2. 

3.2.2.6 Developmental Effects 

No studies were located regarding developmental effects in humans following oral exposure to phenol. 

In a multi-generational study of the effect of various levels of phenol administered orally in water, Heller 

and Pursell (1938) saw no effect on growth, reproduction, and normal rearing of young over 5 generations 

of rats given concentrations of ≈1,000 mg/L phenol in drinking water (estimated dose of 114 mg/kg/day) 

nor over three generations of rats given concentrations of ≈5,000 ppm (estimated dose 571 mg/kg/day). 

Phenol in water was administered to pregnant rats by gavage (5 mL/kg) at dose levels of 0, 30, 60, or 

120 mg/kg/day on GDs 6–15 (NTP 1983a). A dose-related decrease in fetal body weight with increasing 

dose was observed, with 60 mg/kg/day established as the NOAEL and 120 mg/kg/day as the LOAEL. 

The mean reduction in fetal body weight relative to controls was approximately 7%. Concurrent controls 

provide the most appropriate comparison for experimental data; however, it is worth noting that the 
 

 

 

 

 

 

 

 

 

 

PHENOL 73 

3. HEALTH EFFECTS 

weights of control fetuses in this study were 22% higher than those of historical controls. As litter size is
 

known to influence fetal weight, it is possible that a larger litter size in the high-dose group may have
 

contributed to the smaller fetal weights in that group. The data were not specifically analyzed for that
 

potential effect. Teratogenic effects were not observed and no signs of maternal toxicity were observed at
 

any dose level. In a preliminary range-finding study conducted by NTP (1983a), a decrease in maternal
 

weight gain and an increased incidence of maternal mortality were observed at >160 mg/kg. Tremors, a
 

typical symptom of phenol toxicity, were also observed.
 

In a study of the developmental toxicity of phenol and structurally-related chemicals, Kavlock (1990)
 

examined the effects of 0, 100, 333, 667 and 1,000 mg/kg phenol given by gavage on day 11 of gestation. 

Phenol was administered in a 4:4:1:1 mixture of water, Tween 20, propylene glycol, and ethanol. 

Five variables were examined: maternal weight change (at 24 and 72 hours postdosing), litter size
 

(postnatal day [PND] 1 and 6), perinatal loss, pup weight (on PND 1 and 6), and litter biomass (in g on 

PND 1 and 6). 

Within these five parameters, a significant decrease in maternal weight gain was seen at the two highest
 

doses. At these same doses, malformations involving the limbs and tail were seen. At a dose of
 

667 mg/kg, pups in 21% of the litters were affected. At a dose of 1,000 mg/kg, pups in 27% of the litters
 

were affected. The effect on tails was one of shortening or crimping (i.e., ‘kinky’ tails). The hindlimb 

effect consisted of paralysis and/or palsy. In animals with palsy, the limb function would alternate
 

between normal strides and several, second-long period of tetany. Because limb function matures
 

postnatally, this effect was not evident in the newborn but required 7–10 days to become obvious. 

In a subsequent study, Narotsky and Kavlock (1995) found a significant decrease in the number of
 

liveborn pups associated with severe respiratory effects in pregnant rats treated by gavage with 

53.3 mg/kg/day phenol in water on GDs 6–19. In addition, in one high-dose litter, two of four surviving 

pups had kinked tails; this finding was not analyzed for significance but was consistent with earlier 

observations (Kavlock 1990). Developmental effects were not significant at 40 mg/kg/day. 

Phenol in water was administered to pregnant mice by gavage (10 mL/kg) at dose levels of 0, 70, 140, or 

280 mg/kg/day on GDs 6–15 (NTP 1983b). Decreased maternal weight gain, tremors, and increased 

maternal mortality were observed at 280 mg/kg/day. In the fetuses, growth retardation, decreased 

prenatal viability, abnormal structural development, and an increased incidence of cleft palate were 

observed at 280 mg/kg/day. Developmental effects were not observed at 140 mg/kg/day. In pregnant 
 

 

 

 

 

 

 

 

 

 

PHENOL 74 

3. HEALTH EFFECTS 

mice that received 265 mg/kg phenol by gavage on GD 13, Ciranni et al. (1988) found no evidence of 

fetal cellular toxicity, as measured by a ratio polychromatic erythrocyte/normochromatic erythrocyte. 

York (1997) conducted a study in which phenol was administered in three daily gavage doses in water to 

Sprague-Dawley pregnant rats in dosing volumes of 10 mL/kg on GDs 6–15. The total daily doses were 

0, 60, 120, or 360 mg phenol/kg/day. Maternal end points evaluated included clinical signs, body weight, 

and food consumption. Dams were also observed for abortions and premature deliveries. Dams were 

sacrificed on GD 20 and a gross necropsy was conducted. The uterus was examined for pregnancy, 

number and distribution of implantations, live and dead fetuses, and early and late resorptions. Fetuses 

were weighed and examined for sex and gross external alterations. Half of the fetuses were examined for 

soft tissue alterations and the remaining fetuses were examined for skeletal alterations. In the mid-dose 

group, maternal body weight gain was reduced 11% for GDs 6–16 and 19% for GDs 12–16, whereas in 

the high-dose group, body weight gain was reduced 38% for GDs 6–16. Maternal final body weight in 

the high-dose group was reduced, but <10% relative to controls. Dose-related decreases in food 

consumption were also observed during the dosing period. Mean fetal weight in the high-dose group was 

reduced 5–7% relative to controls. In addition, there was a significant decrease in ossification sites on the 

hindlimb metatarsals in the high-dose group, which the investigators considered of minimal biological 

significance. At the mid- and high-dose levels, there were increases in litters with fetuses with “any 

alteration” and with “any variation”, but neither reached statistical significance and there were no clear 

dose-response relationships. No significant effects were seen regarding corpora lutea, implantations, litter 

sizes, live fetuses, early and late resorptions, and percent resorbed conceptuses. Based on the reduced 

fetal weight and delayed ossification in the high-dose group, the dose of 360 mg/kg/day is a 

developmental LOAEL; the developmental NOAEL is 120 mg/kg/day. Based on the reduction in body 

weight gain, the maternal LOAEL is 120 mg/kg/day and the NOAEL is 60 mg/kg/day. 

In a two-generation reproduction study, administration of phenol in the drinking water to the parental 

generation (301–321 mg/kg/day) resulted in a significant reduction in F1 pup weight (30% by PND 21 

relative to controls) and F2 pup weight (37% by PND 21 relative to controls) (Ryan et al. 2001). There 

was also a decrease in percent live pups on day 4 in both generations and for days 7–21 in the F2 

generation at the high-dose level. In addition, preputial separation and vaginal patency were significantly 

delayed at the high dose in F1 males and females, respectively. In this study, water consumption was 

significantly reduced at the high dose, including in females during gestation and lactation, and this was 

accompanied by reduced food consumption and body weight gain. A LOAEL of 321 mg/kg/day can be 
 

 

 

 

 

 

 

 

 

 

 

 

 

PHENOL 75 

3. HEALTH EFFECTS 

defined in this study for developmental toxicity; the NOAEL for developmental toxicity was 

93 mg/kg/day. 

The highest NOAEL values and all LOAEL values from each reliable study for developmental effects in 

each species in the acute-duration category are recorded in Table 3-2 and plotted in Figure 3-2. 

3.2.2.7 Cancer 

No studies were located regarding carcinogenicity in humans following oral exposure to phenol. 

The carcinogenicity of orally administered phenol was examined in rats and mice in a study reported by 

the NCI (1980). Rats and mice received 0, 2,500, or 5,000 ppm in drinking water for 103 weeks. 

Calculated intakes for rats were 322 and 645 mg/kg/day for males and 360 and 721 mg/kg/day for 

females. Calculated intakes for mice were 590 and 1,180 mg/kg/day for males and 602 and 

1,204 mg/kg/day for females. Statistically significant increased incidences of pheochromocytomas of the 

adrenal gland and leukemia or lymphomas were observed in male rats exposed to 322 mg/kg/day 

(2,500 ppm), but not in male rats exposed to 645 mg/kg/day (5,000 ppm). No significant effects were 

seen in female rats or mice of either sex exposed to either exposure level. Since cancer occurred only in 

males of one of the two species tested and a positive dose-response relationship could not be established, 

these results are inconclusive regarding the carcinogenic potential of orally administered phenol. 

3.2.3 Dermal Exposure 

3.2.3.1 Death 

Application of phenol to the skin can be lethal. Death occurred within 10 minutes after ≈25% of an 

individual's body surface was exposed to liquid phenol (Griffiths 1973). The cause of death was reported 

to be respiratory depression and cardiac arrest. In another report, an individual died after being painted 

with a brush that had been soaked in a solution of phenol and thoroughly washed before use (Lewin and 

Cleary 1982). In neither case was the dose known with sufficient accuracy to establish a lethal dose. 

A 10-year-old boy who was hospitalized with serious burns was treated dermally with 7.5 L of an 

antiseptic solution containing 2% phenol for 2.5 days. During this period his urine became dark and his 

respiration became labored, fell into a coma, and died. Postmortem analysis of urine showed the presence 

of 200 mg/L of conjugated phenol (Cronin and Brauer 1949). Soares and Tift (1982) described two fatal 
 

 

 

 

 

 

 

 

 

 

 

 

PHENOL 76 

3. HEALTH EFFECTS 

cases attributed to absorption of phenol through intact skin. One was a 17-year-old male who died within 

30 minutes of splattering a solution containing 30% phenol over portions of his face, neck, and right 

trunk. The other case was a 4-week-old female who was mistakenly treated with undiluted Castellani’s 

paint (a mixture of phenol, basic fuchsin, resorcinol, acetone, ethanol, and water) to treat seborrheic 

dermatitis and died 5 hours later. 

Lethality associated with dermal exposure to phenol is greatly influenced by the surface area exposed as 

well as the concentration of the applied solution. Mortality can vary depending on concentration; a dose 

of 100% phenol may be less toxic than the same dose of phenol given as a diluted solution. When an 

undiluted dose of 0.5 mL/kg was applied to the shaved backs of groups of five rats; one rat died, a 

1/3 dilution killed three rats, a 1/2 dilution killed four rats, and a 2/3 dilution killed all five rats (Conning 

and Hayes 1970). Conning and Hayes (1970) speculated that an undiluted solution may produce a 

coagulative necrosis, which would slow further penetration of phenol resulting in a smaller number of 

deaths than with more diluted solutions. In rats treated with 3,000 mg/kg phenol in a 6% solution over 

1/6 of the total body surface, all 22 treated animals died (Deichmann and Witherup 1944). Increased 

lethality with decreased concentration has also been observed in rabbits treated dermally with 

2,000 mg/kg; 95% phenol resulted in the death of 53% of treated rabbits, while 10% phenol in water 

resulted in the death of 100% of treated rabbits (Deichmann and Witherup 1944). The cause of death was 

not stated in these studies. 

In rats given a single treatment of 5% phenol in water to achieve a dose of 3,000 mg/kg, 10-day-old rats 

were more sensitive than 5-week-old rats or adult rats (Deichmann and Witherup 1944). Within 2– 

14 hours after dosing, 13 of 20 10-day-old rats died; 5 of 20 5-week-old rats died 2–3 hours after dosing, 

and 9 of 20 adult rats died 30–180 minutes after dosing. 

The dermal LD50 of undiluted phenol in rats was reported to be 669 mg/kg (Conning and Hayes 1970). 

The LD50 of an unspecified concentration of phenol in rabbits was reported to be 1,400 mg/kg (Vernot et 

al. 1977). Flickinger (1976) determined a dermal LD50 by exposing male albino rabbits to 0, 252, 500, 

1,000, or 2,000 mg/kg phenol which was placed “in contact” with “abraded and intact skin for a 

maximum period of 24 hours.” No animals died in the 0, 252, or 500 mg/kg groups whereas three of 

four in the 1,000 mg/kg group and all in the 2,000 mg/kg group died the first day following dosing. From 

these data, the authors estimated a “single dose skin penetration LD50" of 850 mg/kg. 
 

 

 

 

 

 

 

 

 

 

 

 

PHENOL 77 

3. HEALTH EFFECTS 

Among pigs treated with a single dose of 500 mg/kg of undiluted phenol on 35–40% of the total body 

surface (about 1,136 cm2

; 0.44 mg/cm2/kg), two of three died (Pullin et al. 1978). The study authors 

reported that a general state of lethargy, cyanosis, convulsions, and coma were observed 5–7 minutes 

before death. 

No effects on survival were observed in mice treated dermally with an unspecified volume of 5% phenol 

(3 times/week) or 10% phenol (2 times/week) in acetone for 12 months (Wynder and Hoffmann 1961). 

Pretreatment with a single dose of 7,12-dimethylbenz[a]anthracene (7,12-DMBA) followed by phenol 

resulted in increased skin tumors and decreased survival. 

All LOAEL and LD50 values from each reliable study are recorded in Table 3-3. 

3.2.3.2 Systemic Effects 

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

species and duration category are recorded in Table 3-3. 

Respiratory Effects. Pulmonary edema was observed in two fatal cases of dermal poisoning with 

phenol (Soares and Tift 1982). A 79-year-old man who mistakenly instilled into his nose 0.5–10 mL of a 

89% phenol solution (approximately 0.4–9 g) showed erythema and sloughing of the nasal mucosa 3 days 

after the accident (Durback-Morris and Scharman 1999). No further relevant information was located 

regarding respiratory effects in humans following dermal exposure to phenol. 

Dyspnea was reported in pigs treated with a single dose of 500 mg/kg of undiluted phenol over 35–40% 

of the total body surface area (0.44 mg/cm2

/kg) (Pullin et al. 1978). This treatment resulted in the death 

of two of the three treated pigs. 

Cardiovascular Effects. There have been several reports of cardiac arrhythmias associated with 

application of phenol solutions to the skin in connection with the surgical procedure of skin peeling 

(Gross 1984; Truppman and Ellenby 1979; Warner and Harper 1985). In this procedure, a mixture of 

phenol (≈50% w/v), hexachlorophene, and croton oil is applied to the skin while the patient is under

anesthesia. In a series of 54 patients in which the whole face was peeled in 1 day, cardiac arrhythmias 

were reported in 39%, while in a series of patients in which half the face was treated on 1 day, and the 

second half was treated 24 hours later, cardiac arrhythmias were reported in 22% (Gross 1984). The 
141

mg/cm2/d

151

mg/cm2/d

087 mg/cm2/d219

mg/cm2/d

072

mg/cm2/d

Table 3-3 Levels of Significant Exposure to Phenol - Dermal 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) 

ACUTE EXPOSURE 

Death 

(Alderly Park) Rat 24 hr 

System NOAEL Less Serious 

LOAEL 

669.4 F 

mg/cm2/d 

Serious 

(LD50) 

Reference Chemical Form 

Conning and Hayes 197

(Wistar) Rat once 

3000 

mg/cm2/d 

(13/20 deaths 

10-day-old, 5/20 deaths 5-week-old, 9/20 deaths adult) 

Deichmann and Witheru

(New Zealand) Rabbit NS 

1400 F 

mg/cm2/d 

(LD50) Vernot et al. 1977 

(Mixed breed) Pig 24 hr 0.44 F 

mg/cm2/d 

(2/3 died) Pullin et al. 1978 

Systemic 

Human 1 hr Cardio 75 M 

mg/cm2/d 

(cardiac arrhythmia) Warner and Harper 198
142

mg/cm2/d

mg/cm2/d

258

mg/kg

041

mg/cm2/d

mg/cm2/d

238

mg/cm2/d

Table 3-3 Levels of Significant Exposure to Phenol - Dermal (continued) 

Exposure/ LOAEL

Duration/

Species Frequency Reference (Route) (Strain) System NOAEL Less Serious Serious Chemical Form 

(Alderly Park) Rat 24 hr Renal 107.1 F 

mg/cm2/d 

(severe hemoglobinuria, hematin casts in the tubules) 

Conning and Hayes 197

Dermal 107.1 F 

mg/cm2/d 

(severe edema, coagulative necrosis, erythema) 

(B6C3F1) Mouse 

(ICR) Mouse 

(NS) once once 

Dermal Dermal 12 F 

mg/cm2/d 

329 F 

mg/kg 

15 F 

mg/cm2/d 

(skin inflammation) 

(skin irritation indicated by thickening of treated ear) 

Murray et al. 2007 

Patrick et al. 1985 

(NS) Rabbit once Cardio 23.8 M 

mg/cm2/d 

(cardiac arrhythmias, ventricular tachycardia) 

Wexler et al. 1984 
220

mg/cm2/d

mg/cm2/d

143

mg/cm2/d

221

mg/cm2/d

Table 3-3 Levels of Significant Exposure to Phenol - Dermal (continued) 

Exposure/ LOAEL

Duration/

Species Frequency Reference (Route) (Strain) System NOAEL Less Serious Serious Chemical Form 

(Mixed breed) Pig 24 hr Resp 0.44 F 

mg/cm2/d 

(dyspnea) Pullin et al. 1978 

Dermal 0.44 F 

mg/cm2/d 

(necrosis of the skin) 

Neurological 

(Alderly Park) Rat 24 hr 

107.1 F 

mg/cm2/d 

(severe muscle tremors, marked twitching, generalized convulsions, loss of consciousness and prostration) 

Conning and Hayes 197

(Mixed breed) Pig 24 hr 0.44 F 

mg/cm2/d 

(twitching, tremors) Pullin et al. 1978 

Cardio = cardiovascular; d = day(s); F = Female; hr = hour(s); LD50 = lethal dose, 50% kill; LOAEL = lowest-observed-adverse-effect level; M = male; NOAEL = no-observed-adverse-effect level; NS = not specified; Resp = respiratory 
 

 

 

 

 

 

 

 

 

 

 

 

PHENOL 81 

3. HEALTH EFFECTS 

study author also indicated that the arrhythmias were less severe in the patients treated over a longer 

period of time. 

Cardiac arrhythmia and bradycardia were reported in a man that splashed an unspecified concentration of 

a phenol-water solution over his face, chest wall, hand, and both arms (Horch et al. 1994). The cardiac 

effects were noted during the first 6 hours after exposure. The serum levels of phenol in μg/L were

11,400 after 1 hour, 17,400 after 4 hours, and 6,000 after 8 hours. Premature heartbeats and arterial 

fibrillation were reported in a male who experienced a 4.5-hour occlusive exposure to 90% phenol 

(Bentur et al. 1998); the concentration of phenol in serum reached a peak of 21.6 mg/L. 

Cardiac arrhythmia has also been noted in rabbits treated with 2 mL of a 50% phenol solution on a 

15-cm2 area (23.8 mg/cm2

/kg) (Wexler et al. 1984). Reducing plasma concentrations of phenol by forced 

diuresis or a longer application time reduced the cardiac effects. 

Gastrointestinal Effects. During the first few days after a man splashed a phenol-water solution 

(concentration not stated) on his face, chest wall, hand, and both arms, he complained of nausea and 

vomited twice (Horch et al. 1994). A worker who was partially immersed for only a few seconds in a 

shallow vat containing a mixture of 40% phenol in dichloromethane, collapsed after showering and was 

taken to a hospital where he was found to have burns over 50% of his body. Initial observations were 

stable; however, after drinking fluids, he developed nausea and vomiting (Foxall et al. 1989). 

No studies were located regarding gastrointestinal effects in animals following dermal exposure to 

phenol. 

Hematological Effects. No studies were located regarding hematological effects in humans 

following dermal exposure to phenol. 

Hemoglobinuria and hematin casts were reported in the renal tubules of rats treated dermally with 

108 mg/kg phenol (Conning and Hayes 1970). These observations are indicative of red blood cell 

hemolysis; however, this was not confirmed with hematological examinations. 

Musculoskeletal Effects. Muscle pain in the arms and legs was reported in a case of chronic phenol 

poisoning (Merliss 1972). The man worked in a laboratory for 13.5 years where he distilled phenol 
 

 

 

 

 

 

 

 

 

PHENOL 82 

3. HEALTH EFFECTS 

several times a day. During the process, heavy odors were detectable, phenol was often spilled on his 

clothes, and he noted skin irritation. The man recovered after 2–3 months away from the exposure. 

No studies were located regarding musculoskeletal effects in animals following dermal exposure to 

phenol. 

Hepatic Effects. Two days after a man was splashed with a phenol-water solution over his face, chest 

wall, hand, and both arms, serum bilirubin increased 2-fold (Horch et al. 1994). After 5 days, serum 

bilirubin returned to normal. An enlarged and tender liver and increased liver transaminase activity in the 

serum were reported in a case of chronic phenol poisoning (Merliss 1972). Lactate dehydrogenase was 

about 2-fold greater than normal, AST was about 21-fold greater than normal, and ALT was about 

100-fold greater than normal. The man worked in a laboratory for 13.5 years where he distilled phenol 

several times a day. During the process, heavy odors were detectable, phenol was often spilled on his 

clothes, and he noted skin irritation. 

No studies were located regarding hepatic effects in animals following dermal exposure to phenol. 

Renal Effects. Renal tubule cell vacuolization was described in a fatal case of dermal poisoning with 

phenol (Soares and Tift 1982). A case of acute renal failure was reported by Foxall et al. (1989) in a 

worker who accidentally fell into a shallow vat containing a mixture of phenol (40%) in dichloromethane. 

The worker was partially immersed for only a few seconds and avoided ingesting any of the solution. He 

showered immediately, subsequently collapsed and was admitted to the hospital with surface burns over 

50% of his body (involving the face, chest, genitals, and both legs). Following admission he became 

anuric and plasma creatinine levels rose. He was transferred to the regional renal unit where he was 

diagnosed with phenol- induced burns, acute tubular necrosis, and fluid overload. For the first 2 weeks, 

the patient demonstrated amino aciduria, glycosuria, and lactic aciduria consistent with renal cortical 

necrosis. This was followed by a period of polyuria revealing a biochemical pattern consistent with renal 

papillary damage. Treatment consisted of administration of a diuretic intravenously and hemodialysis 

daily for a week followed by an additional 18 days of hemodialysis at gradually increasing intervals. The 

patient was discharged 42 days after admission once renal clinical chemistry values had return to normal, 

although nuclear magnetic resonance (NMR) spectroscopic analysis still revealed abnormalities consistent 

with renal papillary damage. One year after the incident, the patient was still polyuric. 
 

 

 

 

 

 

 

 

 

PHENOL 83 

3. HEALTH EFFECTS 

Dark urine was reported in a case of chronic phenol poisoning (Merliss 1972). The man worked in a 

laboratory for 13.5 years where he distilled phenol several times a day. During the process, heavy odors 

were detectable, phenol was often spilled on his clothes, and he noted skin irritation. The study authors 

indicated that the urine was so dark that it suggested hemoglobinuria. Glucose was present in the urine, 

although the urine was negative for homogentistic acid (a substance whose presence can cause urine to 

darken upon standing) and urobilinogen. The urine cleared 2–3 months after the subject was removed 

from phenol exposure. Dark urine was also observed in a man who spilled 90% phenol over an occluded 

area of the skin and kept the area unattended for 4.5 hours (Bentur et al. 1998). 

Hemoglobinuria and hematin casts in the distal convoluted tubules and tubular lumens located in the 

medulla and papilla were reported in rats after a single dermal exposure to 107 mg/kg liquid phenol 

(Conning and Hayes 1970). These phenomena are probably related to red blood cell lysis and increased 

glomerular filtration of hemoglobin. Hemoglobinuria is characteristic of lethal or near-lethal exposures 

by the dermal route. 

Dermal Effects. Application of phenol to the skin of humans results in dermal inflammation and 

necrosis (Horch et al. 1994; Merliss 1972; Truppman and Ellenby 1979). Data concerning minimal 

effective exposure levels in humans were not found. NIOSH (1983) conducted a survey in an Oregon 

hospital in response to concerns about respiratory problems and contact dermatitis in housekeeping staff 

members who were exposed frequently to germicidal solutions containing phenol and other solvents 

(formaldehyde, cellosolve, ethanolamine). The housekeeping staff reported significantly more symptoms 

of cough, itching, sinus problems, and dermatitis than did other employees. Air concentrations of phenol 

in the work areas were below the limit of detection (<0.01 ppm). Urinary phenol levels in the 

housekeeping staff members were not significantly different from those of the other employees. Thus, 

while it is likely that the employees came into contact with irritants, the cause of the reported symptoms 

could not be attributed to phenol or any other specific substance in the work environment. Therefore, this 

study is not recorded in Table 3-3. 

Application of 0.1 mL of molten phenol/kg (≈100 mg/kg) (Brown et al. 1975) or 107 mg/kg (Conning and 

Hayes 1970) to the skin of rats for 24 hours (surface area not reported) produced severe edema, erythema, 

and necrosis. In pigs, application of 500 mg/kg molten phenol to 35–40% of the body surface 

(0.44 mg/cm2

/kg) resulted in skin discoloration after 20–30 minutes of exposure and severe necrosis after 

8 hours of exposure. Two of three pigs died within 95 minutes after exposure (Pullin et al. 1978). 

Necrosis, hyperemia of superficial dermal vessels, and dense perivascular infiltration of lymphocytes and 
 

 

 

 

 

 

 

 

 

 

 

 

 

PHENOL 84 

3. HEALTH EFFECTS 

neutrophils were noted in the skin of pigs treated dermally with an unspecified amount of 89% phenol 

(Hunter et al. 1992). The dose-effect relationship and time course for skin irritation and inflammation 

have been studied in mice (Patrick et al. 1985). The end point examined was swelling (increased 

thickness) of the ear after dermal application to the ear pinna. Application of 12 mg/cm2

/kg of phenol to 

the ear resulted in swelling in four of nine mice within 1 hour after application. Severity of skin irritation 

increased as the concentration of the applied phenol solution increased. Swelling persisted for 6 weeks 

after application of 18 mg/cm2

/kg. Swelling was observed in only one of eight mice treated with 

12 mg/cm2

/kg phenol. Application of 3.5 mM phenol/kg to a 3-cm2 shaved dorsal area from mice 

resulted in inflammation, as evidenced by an increase in skin bi-fold thickness and recruitment of 

inflammatory cells (Murray et al. 2007). This was accompanied by oxidation of glutathione and protein 

thiols and decreased vitamin E and total antioxidant reserves in the skin. Application of an unspecified 

amount of a 1:6 or 1:9 phenol:water solution to the skin of guinea pigs for 1 minute resulted in erythema 

and increased skin vascular permeability indicated by dye permeability (Steele and Wilhelm 1966). 

Skin crusts were reported on mice exposed repeatedly to 5 mg phenol as a 5% (w/v) solution for 

32 weeks, whereas skin ulceration was observed in mice exposed to 5 mg phenol as a 20% (w/v) solution 

(Salaman and Glendenning 1957). The skin ulceration healed in 4 weeks after the end of the exposure. 

In a 52-week study, mice were exposed 2 times each week to 42 or 83 mg/kg of phenol in a 5 or 10% 

solution in benzene (Boutwell and Bosch 1959). Severe skin damage was reported after 36 weeks in the 

mice exposed to 83 mg/kg. Skin papillomas were reported in mice exposed at 42 mg/kg. Because phenol 

was applied in benzene which is also a skin irritant, this study is not presented in Table 3-3. 

Direct application of phenol to the inner ear of rats has resulted in external otitis, inner ear damage 

(Schmidt et al. 1990), and inflammation of the tympanic membrane (Schmidt and Hellström 1993). 

These studies were conducted because phenol has been used as a topical anesthetic in infected ears. 

Ocular Effects. No studies were located regarding ocular effects in humans following dermal 

exposure to phenol. 

A modified Draize test was used to assess ocular damage resulting from application of 5% phenol to the 

center of the cornea in New Zealand rabbits (Murphy et al. 1982). The eyes of one group of rabbits were 

irrigated with water 30 seconds after exposure, while the eyes of another group were unirrigated. 

Conjunctivitis developed in all treated groups and lasted through the 7 days of observation. Corneal 

opacities became apparent in four of nine rabbits 24 hours after phenol application in unirrigated eyes, but 
 

 

 

 

 

 

 

 

 

 

PHENOL 85 

3. HEALTH EFFECTS 

only 1 hour after application in four of nine rabbits receiving irrigation. The opacities lasted through the 

7-day observation period in the unirrigated eyes, but were cleared by day 7 in the irrigated eyes. Based 

on these observations, phenol was designated as a severe eye irritant in unirrigated eyes, and as a 

moderate eye irritant in irrigated eyes (Murphy et al. 1982). 

Body Weight Effects. A man chronically exposed to phenol at a laboratory where he distilled it 

several times a day was 71.5 inches tall, weighed 135 pounds, and was described as emaciated (Merliss 

1972). Loss of appetite and a slow weight loss were symptoms that the subject reported during the 

13.5 years he worked at the laboratory. During the distillation process, heavy odors were detectable, 

phenol was often spilled on his clothes, and he noted skin irritation. 

No studies were located regarding body weight effects in animals following dermal exposure to phenol. 

3.2.3.3 Immunological and Lymphoreticular Effects 

No studies were located regarding immunological or lymphoreticular effects in humans or animals 

following dermal exposure to phenol. 

3.2.3.4 Neurological Effects 

Fatal dermal exposure to an 80% phenol solution in a 24-year-old man being treated for skin rash was 

characterized by severe convulsions prior to death (Lewin and Cleary 1982). A child who suffered 

accidental dermal poisoning with phenol became listless and developed seizures before death (Soares and 

Tift 1982). Seizures were also reported in a young adult who splattered a solution containing 30% of 

phenol over portions of his face, neck, and right trunk and later died (Soares and Tift 1982). A man who 

spilled 90% phenol over his foot and shoe had hypalgesia and hypoesthesia of the affected area in 

addition to confusion, vertigo, and faintness (Bentur et al. 1998). 

Muscle tremors and convulsions are characteristic effects of acute dermal phenol toxicity in laboratory 

animals. Tremors that developed into convulsions and prostration were reported in rats exposed to 

107 mg/kg liquid phenol; application surface areas were not reported (Conning and Hayes 1970). In pigs, 

application of 500 mg/kg over 35–40% of the body surface (0.44 mg/cm2

/kg) resulted in muscular 

tremors in the head region within 3–5 minutes of exposure (Pullin et al. 1978). This was followed by 

dilation of the pupils, loss of coordination, and excess salivation and nasal discharge within 5 minutes of 

exposure. It was followed by convulsions, coma, and death 5–7 minutes after exposure in two of three 
 

 

 

 

 

 

 

 

PHENOL 86 

3. HEALTH EFFECTS 

pigs. Direct application of a dose of 38 mg/kg phenol to the inner ear resulted in a reduced threshold for 

auditory brainstem response (Schmidt et al. 1990). 

No studies were located regarding the following health effects in humans or animals after dermal 

exposure to phenol: 

3.2.3.5 Reproductive Effects 

3.2.3.6 Developmental Effects 

3.2.3.7 Cancer 

No studies were located regarding cancer in humans following dermal exposure to phenol. 

In a study of the promoting effects of phenol, mice were exposed to 9,10-dimethyl-1,2-benzanthracene 

(9,10-DMBA) (300 μg) followed by weekly dermal exposure to 5 mg phenol in either a 5 or 20% phenol 

solution in acetone for 32 weeks (Salaman and Glendenning 1957). Exposure to 9,10-DMBA followed 

by phenol (5 or 20%) resulted in a significantly greater incidence of tumors, including carcinomas, than 

exposure to 20% phenol alone; tumors, but no carcinomas, resulted from exposure to 20% phenol, and no 

tumors resulted from exposure to 5% phenol. Application of 5% phenol alone resulted in skin "crusting" 

at the site of application, whereas 20% phenol resulted in skin ulceration. The study authors concluded 

that phenol was an effective tumor promoter after a single application of 9,10-DMBA. Although this 

study did not include a group of animals that had been exposed to 9,10-DMBA alone, the authors 

indicated that previous work done in their laboratory provided the data from such animals and that it was 

thus the comparison between such historical information and the information from this study which led to 

their conclusion about the promotional effects of phenol. 

A similar promoting activity was observed when an unspecified volume of 10% phenol in acetone was 

placed on the backs of mice 2 times/week for 12 months and when 5% phenol in acetone was placed on 

the backs of mice 3 times/week for 12 months (Wynder and Hoffmann 1961). 

Additional studies indicate that phenol applied to the skin is a cancer promoter and possibly a complete 

carcinogen (i.e., promoter and initiator) in mice. Boutwell and Bosch (1959) examined the carcinogenic 

effects of phenol in several strains of mice. Mice were exposed to a single dermal application of 

9,10-DMBA (75 mg) followed by repeated dermal applications of a 5 or 10% phenol solution in benzene 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PHENOL 87 

3. HEALTH EFFECTS 

(42 or 83 mg/kg/treatment), twice each week for 52 weeks. Two other experimental groups of mice were 

exposed to 9,10-DMBA alone or phenol alone. Severe skin damage, decreased body weight, and 

increased mortality were observed in phenol-treated animals. Sutter strain mice (inbred for 

three generations for susceptibility to the initiator 9,10-DMBA) treated with 9,10-DMBA followed by 

10% phenol developed papillomas (95% in 13 weeks) and carcinomas (43% in 42 weeks) at a much 

higher incidence than mice treated with 9,10-DMBA alone (14% with papillomas at 42 weeks; no 

carcinomas), or phenol alone (36% with papillomas at 52 weeks; no carcinomas). One fibrosarcoma was 

observed after 52 weeks of exposure to phenol alone. An elevated incidence of papilloma was also 

observed in CAF1, C3H, and Holtzmann mice exposed to 9,10-DMBA followed by phenol, and in 

Holtzmann mice exposed to 10% phenol alone. The promoting effect of phenol was dose related; 

application of 5% phenol (41.7 mg/kg) following 9,10-DMBA treatment resulted in fewer tumors than a 

similar protocol using 9,10-DMBA followed by 10% phenol (83.3 mg/kg). Phenol elicits skin tumors in 

mice even without treatment with 9,10-DMBA. Ten out of 30 albino mice treated twice weekly for 

12 weeks with a 20% phenol solution in dioxane developed papilloma of the skin; also, 8 out of 30 mice 

treated with 10% phenol solution in benzene for 15 weeks developed papilloma, and 3 developed 

carcinoma of the skin (Boutwell and Bosch 1959). Because the phenol was administered in benzene or 

dioxane, both of which are skin irritants and/or de-fatting agents, this study is not presented in Table 3-3. 

The effect of phenol on benzo[a]pyrene (B[a]P) carcinogenicity has been examined (Van Duuren and 

Goldschmidt 1976; Van Duuren et al. 1971, 1973). Dermal application of 3 mg phenol in acetone 

simultaneously with 5 μg B[a]P resulted in significantly fewer tumors than application of B[a]P alone. 

Application surface areas were not reported and could not be estimated from the description of the 

application procedure. Mice treated dermally with B[a]P followed by dermal application of brewed tea 

on alternate days over a period of 55 days developed epithelial cell carcinoma or exhibited various stages 

of squamous cell tumors (Kaiser 1967). The brewed tea contained an unspecified level of phenol, the 

presumed cancer promoter in this experiment, as well as cresols and dimethylphenols. 

3.3 GENOTOXICITY 

Phenol has been evaluated for genotoxicity in both in vivo (Table 3-4) and in vitro (Table 3-5) test 

systems. End points evaluated in in vivo mammalian test systems include chromosomal aberrations, 

micronucleus, and deoxyribonucleic acid (DNA) synthesis. Several different cell types have been 

monitored, including bone marrow, liver, and renal cell. Both positive and negative results have been 

reported for in vivo genotoxicity tests. In vitro studies have been conducted in prokaryotic and eukaryotic 
 

 

 

PHENOL 88 

3. HEALTH EFFECTS 

Table 3-4. Genotoxicity of Phenol In Vivo 

Species (test system) End point Results Reference 

Mammalian cells: 

Mouse bone marrow Chromosomal aberration – Barale et al. 1990; Chen and 

Eastmond 1995a; Pashin et al. 

1987 

Mouse bone marrow Chromosomal aberration + Shelby and Witt 1995 

Mouse spermatocytes Chromosomal aberration + Bulsiewicz 1977 

Bone marrow from pregnant Micronucleus + Ciranni et al. 1988 

mice 

Mouse fetal liver cells Micronucleus – Ciranni et al. 1988 

Mouse bone marrow Micronucleus + Li et al. 2005; Shelby and Witt 

1995 

Mouse bone marrow Micronucleus – Barale et al. 1990; Gocke et al. 

1981 

Mouse tubular renal and liver DNA synthesis + Amlacher and Rudolph 1981 

epithelial 

Rat testes DNA synthesis – Skare and Schrotel 1984 

Rat liver DNA synthesis – Miyagawa et al. 1995 

Insects: 

Drosophila Micronucleus – Gocke et al. 1981; Sturtevant 

1952 

+ = positive response; – = negative response; DNA = deoxyribonucleic acid 
 

 

 

 

 

 

 

 

PHENOL 89 

3. HEALTH EFFECTS 

Table 3-5. Genotoxicity of Phenol In Vitro 

Results 

With Without 

Species (test system) End point activation activation Reference 

Prokaryotic organisms: 

Salmonella typhimurium 

S. typhimurium
 

Escherichia coli
 

E. coli 

Eukaryotic organisms: 

Aspergillus 

V79 Chinese hamster 

cells 

Chinese hamster ovary 

cells 

Chinese hamster ovary 

cells (DNA strand breaks) 

Crucian (goldfish) 

erythrocytes 

Mouse lymphoma (DNA 

strand breaks) 

Mouse spermatocytes 

Rat liver mitochondria 

Syrian hamster embryo 

cells 

Syrian hamster embryo 

cells 

Syrian hamster embryo 

cells 

Syrian hamster embryo 

cells 

Human lymphocytes 

Human lymphocytes 

Human lymphocytes 

Human lymphocytes 

Gene mutation 

Gene mutation 

Gene mutation 

Gene mutation 

Chromosomal 

aberration 

Gene mutation 

Micronuclei 

Chromosomal 

aberration 

DNA damage 

Chromosomal 

aberration 

DNA damage 

DNA synthesis 

Gene mutation 

Chromosomal 

aberration 

Sister chromatid 

exchanges 

Unscheduled DNA 

synthesis 

Sister chromatid 

exchanges 

Sister chromatid 

exchanges 

Sister chromatid 

exchanges 

DNA damage 

– 

+ 

– 

No data 

No data 

+ 

+ 

No data 

No data 

No data 

No data 

No data 

No data 

No data 

No data 

No data 

+ 

No data 

No data 

No data 

– 

– 

– 

+ 

+ 

– 

+ 

– 

+ 

– 

+ 

– 

+ 

+ 

+ 

+ 

+ 

– 

+ 

+ 

Florin et al. 1980; 

Haworth et al. 1983; 

Kubo et al. 2002; Pool 

and Lin 1982 

Gocke et al. 1981 

Nagel et al. 1982 

Demerec et al. 1951 

Crebelli et al. 1987 

Paschin and Bahitova 

1982 

Miller et al. 1995 

Sze et al. 1996 

Li et al. 2005 

Pellack-Walker and 

Blumer 1986 

Li et al. 2005 

Schwartz et al. 1985 

Tsutsui et al. 1997 

Tsutsui et al. 1997 

Tsutsui et al. 1997 

Tsutsui et al. 1997 

Morimoto and Wolff 

1980; Morimoto et al. 

1983 

Jansson et al. 1986 

Erexson et al. 1985 

Li et al. 2005 
 

 

PHENOL 90 

3. HEALTH EFFECTS 

Table 3-5. Genotoxicity of Phenol In Vitro 

Species (test system) End point 

Human diploid fibroblasts DNA synthesis 

HeLa cells DNA synthesis 

Results 

With 

activation 

Without 

activation 

No data + 

+ No data 

Reference 

Poirier et al. 1975 

Painter and Howard 

1982 

+ = positive response; – = negative response; DNA = deoxyribonucleic acid 
 

 

 

 

 

 

 

 

 

PHENOL 91 

3. HEALTH EFFECTS 

test systems. Results for various end points (gene mutation, chromosomal aberration, micronuclei, DNA 

damage, sister chromatid exchanges, and unscheduled DNA synthesis) have been both positive and 

negative. The mixed results in both the in vivo and in vitro assays indicate that under certain conditions, 

especially at higher doses, phenol has the potential to be genotoxic. However, at the exposure levels 

likely to occur near hazardous waste sites, phenol is not anticipated to be genotoxic. 

Positive and negative results have been reported for phenol in in vivo chromosomal aberration tests. 

Increases in chromosomal aberrations have been reported in bone marrow (Shelby and Witt 1995) and in 

spermatocytes (Bulsiewicz 1977) from mice treated with phenol. Chromosomal aberrations were 

reported in the bone marrow of male B6C3F1 mice exposed to phenol through intraperitoneal injection 

(Shelby and Witt 1995). Bulsiewicz (1977) also reported results of a five-generation study with Porton 

strain inbred mice. Chromosomal aberrations were monitored in spermatogonia and spermatocytes of 

gavage treated mice. Dose dependent increases in aberrations were observed with succeeding 

generations. The investigator attributed the observed chromosomal effects to interactions of phenol with 

the spindle apparatus. Other studies have not observed chromosomal aberrations in bone marrow from 

mice treated with phenol (Barale et al. 1990; Chen and Eastmond 1995a; Pashin et al. 1987). In tests of 

feeding and injection exposures of Drosophila to phenol, results were negative in sex-linked recessive 

lethal assays (Gocke et al. 1981; Sturtevant 1952). 

Positive (Ciranni et al. 1988; Li et al. 2005; Shelby and Witt 1995) and negative (Barale et al. 1990; 

Gocke et al. 1981) results were reported for in vivo micronucleus assays in bone marrow isolated from 

mice treated with phenol. Bone marrow micronucleus tests were positive for male B6C3F1 mice exposed 

to phenol through intraperitoneal injection (Shelby and Witt 1995). In a study of pregnant CD-1 mice 

receiving doses of phenol, maternal bone marrow micronuclei were studied. Pregnant mice were treated 

by gavage with a single dose of 265 mg/kg of phenol on GD 13. Observed effects included an increase in 

bone marrow micronuclei and cytotoxicity. Micronuclei were not observed in fetal liver tissue (Ciranni et 

al. 1988). Bone marrow of Kunming mice exposed to concentrations of 20, 40, or 80 mg/kg of phenol 

through intraperitoneal injection showed increased frequency of micronuclei at dose levels of 40 and 

80 mg/kg (Li et al. 2005). However, exposures of male CD-1 mice to maximum intraperitoneal injections 

of 160 mg/kg resulted in negative micronucleus tests (Barale et al. 1990). Results were also negative for 

micronucleus assays in male and female NMRI mice dosed twice by intraperitoneal injections of 

188 mg/kg of phenol (Gocke et al. 1981). 
 

 

 

 

 

 

 

 

PHENOL 92 

3. HEALTH EFFECTS 

Phenol increased DNA synthesis in tubular renal and liver epithelial cells from mice (Amlacher and 

Rudolph 1981). Skare and Schrotel (1984) reported the results of experiments where Sprague-Dawley 

rats were dosed with single intraperitoneal injections of 79 mg/kg or five daily intraperitoneal injections 

of 39.5 mg/kg/day. Single strand breaks were not observed in testicular cells. A DNA synthesis test in 

male B6C3F1 mice dosed by gavage with concentrations of 0, 300, and 600 mg/kg of phenol also was 

negative (Miyagawa et al. 1995). 

In vitro tests with phenol for gene mutations in microorganisms have yielded both negative (Florin et al. 

1980; Haworth et al. 1983; Kubo et al. 2002; Nagel et al. 1982; Pool and Lin 1982) and positive 

(Demerec et al. 1951; Gocke et al. 1981) results. Negative results have been reported in Salmonella 

typhimurium strains TA98, TA100, TA1535, TA1537, and TA1538 with and without S9 activation 

(Haworth et al. 1983; Kubo et al. 2002; Pool and Lin 1982). However, increased mutagenicity was 

observed in S. typhimurium TA98, with S9 activation (Gocke et al. 1981). Paschin and Bahitova (1982) 

also reported positive results at the HGPRT locus of V79 for mutagenicity studies involving exposures of 

Chinese hamster ovary (CHO) cells, with S9 activation. Studies of Syrian hamster embryos (SHE) were 

also positive for mutagenicity (Tsutsui et al. 1997). 

In vitro studies regarding chromosomal aberrations in eukaryotic cells have been positive in Aspergillus 

(Crebelli et al. 1987), and in SHE cells (Tsutsui et al. 1997), and negative in mouse lymphoma cells 

(Pellack-Walker and Blumer 1986) and CHO cells (Sze et al. 1996). Tsutsui et al. (1997) reported dosedependent increases in the frequencies of chromosome aberrations in SHE cells exposed to phenol. 

Single strand breaks were not observed in mouse lymphoma L5178YS cells (Pellack-Walker and Blumer 

1986). 

The report of an in vitro micronucleus study with CHO cells was positive with and without S9 activation, 

with stronger results observed with S9 activation (Miller et al. 1995). 

Results of in vitro sister chromatid exchange tests were reported as positive and negative. Phenol 

produced dose-related increases in sister chromatid exchanges in human lymphocytes at doses of 

≥500 μM (Erexson et al. 1985). In contrast, sister chromatid exchanges were not observed in human 

lymphocytes incubated with 0–2,000 μM phenol (Jansson et al. 1986). Incubation of human lymphocytes

with 1,000,000 μM, but not 200,000 μM phenol for 72 hours resulted in an increase in sister chromatid 

exchanges (Morimoto and Wolff 1980). Exposures of human lymphocytes to 3,000 μM phenol with S9 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

PHENOL 93 

3. HEALTH EFFECTS 

activation also resulted in an increase in sister chromatid exchanges (Morimoto et al. 1983). Phenol 

induced sister chromatid exchanges in SHE cells at doses of 1,000 and 3,000 μM (Tsutsui et al. 1997). 

In vitro assays for DNA synthesis have been negative in rat liver mitochondria (Schwartz et al. 1985), and 

positive in human fibroblasts (Poirier et al. 1975) and HeLa cells (Painter and Howard 1982). However, 

unscheduled DNA synthesis was induced to the same degree in SHE cells incubated with phenol in 

concentrations ranging from 1 to 30 μM (Tsutsui et al. 1997). 

An in vitro study of DNA damage using the comet assay indicated that phenol induced DNA damage in 

human lymphocytes, mouse spermatocytes, and crucian erythrocytes. In these tissues, amounts of DNA 

damage increased in conjunction with increasing doses. Observed DNA damage to mouse spermatocytes 

and crucian erythrocytes was more significant than DNA damage to human lymphocytes (Li et al. 2005). 

3.4 TOXICOKINETICS 

Phenol is readily absorbed and widely distributed following inhalation, oral, and dermal exposure. The 

distribution of phenol is thought to be dependent on blood flow. Conjugates with glucuronic acid and 

sulfate are the major metabolites of phenol, although small amounts of the hydroxylation products 

catechol and hydroquinone are also produced. Sulfotransferase and glucuronyltransferases are present in 

most tissues, although the major sites of phenol conjugation are the gastrointestinal tract, liver, lung, and 

kidney. Because of the large capacity of the intestines and liver to conjugate phenol, the fact that the 

first-pass effect occurs following oral exposure but not following dermal exposure may contribute to the 

greater potential for phenol to result in adverse effects following dermal exposure. Phenol and its 

conjugates are predominantly excreted in the urine. 

3.4.1 Absorption 

3.4.1.1 Inhalation Exposure 

Phenol is absorbed readily after inhalation exposure. Eight subjects were exposed to phenol vapors (1.6– 

5.2 ppm) for 8 hours (Piotrowski 1971). Subjects were exposed through a face mask in order to eliminate 

the possibility of percutaneous absorption. The concentration of phenol in inhaled and exhaled air was 

determined, and urine was analyzed for total phenol (phenol and phenol conjugates). Steady-state 

appeared to be achieved within 3 hours after initiating exposure; steady-state retention was 60–88%. 
 

 

 

 

 

 

 

 

 

 

 

 

PHENOL 94 

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Urinary recovery of phenol that had been retained in the lungs was 99±8% within 24 hours after initiating 

exposure. 

Total urinary phenol was determined at about 7 hours into an 8-hour shift in Bakelite workers exposed to 

airborne phenol at 0.16–32 ppm (Ohtsuji and Ikeda 1972). Daily urinary excretion of total phenol was 

99% of the estimated amount inhaled indicating that phenol is readily absorbed. However, lung retention 

was not measured, and the contribution of percutaneous absorption to urinary phenol could not be 

evaluated in this study. 

Rats exposed by intratracheal instillation to [14C]-labeled phenol also demonstrated rapid absorption 

kinetics, with most of the radioactivity being excreted within 72 hours (Hughes and Hall 1995). Rats 

exposed for 6 hours nose-only to 25 ppm [14C]-labeled phenol demonstrated rapid absorption. Greater 

than 90% of phenol-derived radioactivity was measured in the urine 30 minutes after initiation of 

exposure (Hiser et al. 1994). 

3.4.1.2 Oral Exposure 

Based on the rapid excretion of phenol and its metabolites in urine, it has been concluded that phenol is 

readily absorbed by the oral route in humans (Capel et al. 1972) and a variety of mammalian species 

including monkeys (Capel et al. 1972), rodents (Capel et al. 1972; Edwards et al. 1986; Hughes and Hall 

1995; Kao et al. 1979; Kenyon et al. 1995), dogs (Capel et al. 1972), rabbits (Capel et al. 1972), cats 

(Capel et al. 1972; French et al. 1974), and pigs (Capel et al. 1972; Kao et al. 1979). 

In three men given a single oral dose of 0.01 mg/kg [14C]-labeled phenol in food or drink, about 90% 

(range 85–98%) of the dose was excreted in the urine in 14 hours (Capel et al. 1972). In this same study, 

urinary recovery of orally administered [14C]-labeled phenol was determined in 18 other mammalian 

species; mean 24-hour recoveries of 14C ranged from 95% in the rat to 31% in the squirrel monkey. Rats 

exposed orally to radiolabeled phenol demonstrated rapid absorption and excretion, with most of the 

radioactivity being excreted within 72 hours (Hughes and Hall 1995). The gastrointestinal absorption of 

phenol has also been studied in rats with in situ preparations. The absorption kinetics of [14C]-labeled 

phenol administered directly into the small intestines of rats were described as first-order, with a rate 

constant for intestinal absorption of 0.127±0.003 minute-1 (or half-life of 5.5±0.5 minutes from 

t1⁄2=0.693k) (Humphrey et al. 1980). Two hours after [14C]-labeled phenol was injected into the small 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PHENOL 95 

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intestines of anesthetized rats, recoveries in the urine were 77.9±2% after a 12.5-mg/kg dose, and 

76.9±5.8% after a 25-mg/kg dose (Kao et al. 1979). 

Hiser et al. (1994) reported results of the kinetics of oral doses of phenol in rats. Exposures included 

single and multiple bolus and drinking water doses of different concentrations. Peak blood concentrations 

of free phenol of 0.02 μg/g blood in rats receiving 1.5 mg/kg bolus dose were reached 1–3 minutes after 

receiving the dose. A terminal half-life of about 8 minutes was calculated for phenol following low 

doses. Peak blood concentrations of phenol of 46.4 μg/g blood in rats receiving 150 mg/kg bolus dose 

were reached 1 minute after receiving the dose. Since the doses were separated by only a factor of 

100 and the blood peak concentration by a factor of 2,320, these results suggest saturated absorption or 

saturated metabolism and excretion. After 24 hours, concentrations of administered [14C]-radioactivity 

were >90% in the urine, regardless of the dosing method or concentration. 

3.4.1.3 Dermal Exposure 

Phenol is readily absorbed through the skin, and the skin is considered the primary route of entry during 

occupational exposure (ACGIH 2005). Whole-body skin exposures studies were conducted in volunteers 

lightly clothed and unclothed (Piotrowski 1971). The subjects were exposed to phenol vapor (35% 

humidity, 26 °C) at concentrations of 1.3, 2.6, or 6.5 ppm for 6 hours. Fresh air was supplied to the 

subjects through a face mask in order to prevent absorption of phenol through the lungs. The total 

amount of phenol excreted in urine during and after exposure (minus baseline excretion) was used as a 

measure of absorption. Absorption increased proportionately with exposure level. Percutaneous 

clearance (mg phenol absorbed through the skin per hour/mg phenol per m3 of air) was estimated to be 

0.35 m3

/hour. Thus, an amount of phenol equivalent to that contained in 0.35 m3 of air was absorbed 

through the skin each hour. 

The data reported by Piotrowski (1971) provide a basis for comparing the relative contributions of lung 

and percutaneous absorption during exposures to phenol vapor. Assuming a ventilation rate for the 

human of 0.8 m3

/hour (EPA 1986a) and a steady-state lung retention of inhaled phenol of 0.7 m3/hour 

(Piotrowski 1971), clearance of airborne phenol through the lung is ≈0.6m3

/hour. Thus, an amount of 

phenol equivalent to that contained in 0.6 m3 of air was absorbed through the lungs each hour. It can be 

concluded that at any given exposure level within the range of 5–25 mg/m3 (1.3–6.4 ppm), percutaneous 

absorption (0.35 m3

/hour) will be about half that of absorption through the lungs (0.6 m3/hour). 
 

 

 

 

 

 

 

 

 

 

 

 

PHENOL 96 

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Percutaneous absorption of phenol applied in solution directly to the forearm (15.6 cm2) of volunteers has 

been measured (Baranowska-Dutkiewicz 1981). Absorption rate from a 2-mL reservoir of an aqueous 

phenol solution (2.5, 5.0, or 10.0 g/L) was constant for 60 minutes (0.08 mg/cm2

/hour) and increased 

proportionately with applied concentration. Approximately 13% of the applied dose was absorbed in 

30 minutes, of which 80% (range 58–98%) was recovered in the urine within 24 hours. 

When human skin was treated in vitro with 0.0013–0.0027 mg/cm2 [

14C]-labeled phenol and left 

unoccluded, 20% of the radioactivity was absorbed when analyzed 72 hours later, while 7% remained on 

the skin surface (Hotchkiss et al. 1992). Covering the skin with a teflon cap resulted in the absorption of 

47%, with 3% recovered in the skin. When rat skin was subjected to the same exposure regime in this 

study, 72 hours later, 24% of the radioactivity was absorbed with 22% recovered in the skin when the skin 

was unoccluded, and 36% was absorbed with 3–4% recovered in the skin when the skin was occluded. 

In rats in which a 0.03-mg/kg dose of [14C]-labeled phenol was placed on the skin, only 1–5% of the dose 

remained in the body 72 hours later (Hughes and Hall 1995). The dermal absorption of phenol was also 

studied in three pigs in which undiluted phenol was placed on the skin for 1 minute, and the peak plasma 

level was determined (Pullin et al. 1978). Plasma levels were not measurable in one pig treated with a 

dose of 90 mg/kg over a surface area of 91.6 cm2

. In pigs treated with a dose of 500 mg/kg over surface 

areas of 91.6 and 1,135.5 cm2

, peak plasma levels of 0.9 and 30.5 ppm were reported, respectively. 

Permeability coefficients for phenol in isolated skin patches from nude mice have been determined (Behl 

et al. 1983). The permeability coefficient increased as the concentration of the applied aqueous phenol 

solution increased; doubling the concentration from 20 to 40 g/L resulted in a 12-fold increase in mean 

permeability coefficient (0.007–0.085 cm/hour). The value obtained for the permeability coefficient 

when 60 g/L was applied to the skin patch (0.169 cm/hour) was similar to that obtained for skin patches 

in which the stratum corneum had been removed. It was concluded that phenol concentrations exceeding 

20 g/L may destroy a diffusion barrier normally provided by the intact stratum corneum, permitting 

increased percutaneous absorption. 

Dermal absorption of phenol in the presence of various types of soil was measured in vitro using skin 

patches from pigs (Skowronski et al. 1994). Maximum phenol penetration occurred between 2 and 

4 hours after treatment in all cases. Compared to samples with no soil present, the presence of sandy soil 

reduced the peak penetration by one-half, and the presence of clay soil reduced peak penetration by twothirds. 
 

 

 

 

 

 

 

 

 

 

 

 

 

PHENOL 97 

3. HEALTH EFFECTS 

3.4.1.4 Other Routes of Exposure 

Nomoto et al. (1987) studied the absorption of phenol after injection into 20 patients as part of lumbar or 

thoracic sympathetic blockades. Patients were injected with 5–10 mL 7% phenol. The concentrations of 

unconjugated and conjugated phenol (sulfate esters and glucuronic esters) were monitored in blood and 

urine samples. Unconjugated phenol reached a mean peak concentration in blood of 3.01±0.28 μg/mL

18.8±2.5 minutes after the injection. The mean peak concentration of conjugated phenol in the blood was 

4.15±0.25 μg/mL 54.9±4.5 minutes after the injection. The authors concluded that uptake times indicated 

rapid absorption of phenol after injection. The lag time of unconjugated phenol was 5.3±1.6 minutes, 

indicating that phenol remained at the injection site before being taken up into the blood. The lag time of 

conjugated phenol was 9.9±5.9 minutes. 

There is also indirect evidence of phenol being absorbed following phenol injection sclerotherapy for 

hemorrhoids. Suppiah and Perry (2005) reported the case of a 43-year-old man who developed jaundice 

after an unspecified number of injections of 2 mL of a 5% solution of phenol at hemorrhoidal tissue 

during several months. Liver function tests returned to normal after 6 months. 

3.4.2 Distribution 

3.4.2.1 Inhalation Exposure 

No studies were found regarding tissue distribution of phenol in humans after inhalation exposure. 

Rats exposed by intratracheal instillation to radiolabeled phenol were sacrificed 72 hours later and 

analyzed for tissue distribution of the radioactivity (Hughes and Hall 1995). Of the radioactivity 

remaining in the body (1–5%), a majority was distributed in the lungs (0.13%), skin (0.13%), blood 

(0.07%), muscle (0.03%), fat (0.02%), and liver (0.02%). 

No information was found on the placental transfer and distribution of phenol; however, Ghantous and 

Danielsson (1986) examined this question for benzene, the principal metabolite of which is phenol. Mice, 

at GDs 11, 14, and 17, were exposed by inhalation to [14C]-benzene and the distribution of benzene and 

its volatile and nonvolatile metabolites was examined using whole-body autoradiography and assessment 

of tissue concentrations of 14C (day 17 only). The authors indicated that the exposure regimen (50 μCi of

[

14C]-benzene in maize oil, volatilized by gentle heating) would theoretically produce 2,000 ppm in the 
 

 

 

 

 

 

 

 

 

PHENOL 98 

3. HEALTH EFFECTS 

inhalation chamber. Measurements of the difference between the amount added to the chamber and the 

amount inhaled by the animals indicated an uptake of 90% (i.e., 45 μCi). These authors did not

specifically characterize the metabolites, but were able to show that the [14C]-labeled volatile and 

nonvolatile activity crossed the placental barrier. There was no evidence of preferential accumulation. 

Indeed, the concentration of volatile and nonvolatile radioactivity in fetal tissues was much lower than 

that observed in the corresponding maternal tissues. As a metric of the relative accumulation, the authors 

noted that compared to maternal brain tissue, fetal uptake of benzene was only 8%. 

In a study conducted by Hiser et al. (1994), rats were exposed 6 hours nose-only to 25 ppm [14C]-phenol 

for either 1 or 8 days. Mean percent of administered dose/g were reported for several tissues. 

Radioactivity was quantified in blood, bone, brain, fat, heart, kidney, liver, lung, muscle, skin, spleen, 

testes, ovaries, and carcass 24 hours after exposure. No single tissue seemed to preferentially accumulate 

phenol-derived radioactivity and, in all cases, concentrations were <0.02% administered dose/g tissue. 

No significant differences were seen between the 1- and 8-day exposure experiments. 

3.4.2.2 Oral Exposure 

Limited information in humans is available from cases of accidental or intentional ingestion of phenol 

that resulted in fatalities. One case involved ingestion of a mixture of phenol and cresol. The 

concentrations of phenol measured in the blood, urine, and stomach content were 58.3, 3.3, and 

115 μg/mL, respectively (Boatto et al. 2004). Another case involved ingestion of a mixture of phenol and 

chloroform. Phenol was measured at 60 μg/mL in the blood and 208 μg/mL in the urine. Concentrations 

in the brain, lungs, liver, and kidney were 106, 116, 166, and 874 μg/g, respectively (Tanaka et al. 1998). 

The third case involved ingestion of phenol, which resulted in the following tissue concentrations of 

phenol: blood, 130 μg/mL; urine, 47 μg/mL; bile, 187 μg/mL; brain, 486 μg/g; kidney, 331 μg/g; muscle, 

204 μg/g; liver, 228 μg/g; and stomach content, 668 mg (Lo Dico et al. 1989). 

In animals, information is available for rabbits (Deichmann 1944) and rats (Hiser et al. 1994; Hughes and 

Hall 1995; Liao and Oehme 1981). In rabbits, distribution is rapid, with peak tissue concentrations 

achieved in most tissues within 1 hour after dosing. The highest peak concentrations and fraction of 

administered dose are found in the liver; >90% of the administered dose is eliminated from tissues within 

24 hours. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PHENOL 99 

3. HEALTH EFFECTS 

The levels of phenol in various tissues of five rabbits given a lethal (LD50) oral dose of phenol 

(500 mg/kg) were determined (Deichmann 1944). The rabbits were killed within 1–3 minutes after 

dosing when twitching, the first sign of systemic toxicity, appeared. The highest concentrations of total 

phenol (free plus conjugates) were found in the liver (20.9–30.4 mg/100 g tissue), lungs (5.1– 

17.1 mg/100 g), blood (6.1–12.6 mg/100 g), brain and spinal cord (3.1–10.4 mg/100 g), and kidneys (2.3– 

7.1 mg/100 g). 

The kinetics of tissue distribution of [14C]-labeled phenol in rats given 207 mg/kg of [14C]-labeled phenol, 

a sublethal (≈0.5xLD50) oral dose, were studied (Liao and Oehme 1981). Although all rats survived for 

16 hours, signs of systemic toxicity were observed including twitching of muscles around the eyes and 

ears, convulsions, and coma persisting for 15–30 minutes. Thirty minutes after dosing, 28.4% of 

administered 14C was recovered in tissues (liver, kidney, adrenal, thyroid, spleen, blood, lung, thymus, 

brain, testes, heart, muscle, and fat). Sixteen hours after dosing, 0.3% of the administered dose was 

recovered in tissues. Concentrations of 14C were highest in all tissues 30 minutes after dosing, with the 

exception of the thyroid gland, in which peak concentrations were achieved after 2 hours. The highest 

concentration and fraction of administered dose were found in the liver; 42% (range 29–56%) of the 

administered dose was recovered in the liver 30 minutes after dosing. Approximately 67–85% of the 14C 

in blood was present in the plasma fraction, of which 41–50% was bound to plasma proteins or other 

macromolecules. The elimination half-time for 14C was <4 hours. Based on their results, the study 

authors suggested that blood flow determines the tissue uptake of the radiolabel from phenol. 

Rats exposed orally to radiolabeled phenol were sacrificed 72 hours later and analyzed for tissue 

distribution of the radioactivity (Hughes and Hall 1995). Of the radioactivity remaining in the body, a 

majority was distributed in the muscle (0.08%), skin (0.07%), fat (0.02%), liver (0.02%), and blood 

(0.02%). 

No evidence of exposure-related DNA adduct formation in femur bone marrow, Zymbal gland, liver, or 

spleen was seen in rats treated orally with 75 mg/kg/day phenol for 4 days (Reddy et al. 1990). In this 

study, concurrent in vitro exposures of these tissues did produce adducts, suggesting that efficient 

detoxification and excretion mechanisms may be operating in vivo. 

In a study conducted by Hiser et al. (1994), rats were exposed to [14C]-phenol via single gavage doses of 

1.5, 15, or 150 mg/kg, multiple gavage doses of 1.5 mg/kg/day, 5,000 ppm in drinking water for 1 day, or 

5,000 ppm in drinking water for 8 days. In all cases, phenol-derived radioactivity was detected in blood, 
 

 

 

 

 

 

 

 

PHENOL 100 

3. HEALTH EFFECTS 

bone, brain, fat, heart, kidney, liver, lungs, skin, spleen, testes, ovaries, and carcass 24 hours after 

exposures. Regardless of the dosing method or dose level, no single tissue seemed to accumulate 

radioactivity, with all measured concentrations being <0.02% of the administered dose/g tissue. 

3.4.2.3 Dermal Exposure 

Limited information is available in humans from a fatal case. Tissue samples (liver, blood, lung, urine, 

and stomach contents) from an individual who was painted with benzyl benzoate with a brush that had 

been soaked in 80% phenol were analyzed for phenol. The blood contained 4.7 μg/mL phenol and 

unhydrolyzed and hydrolyzed liver samples contained 3.3 and 7.1 μg/g phenol, respectively. Phenol was

not detected in the lung, urine, or stomach contents (Lewin and Cleary 1982). 

Rats exposed dermally to radiolabeled phenol were sacrificed 72 hours later and analyzed for tissue 

distribution of the radioactivity (Hughes and Hall 1995). Of the radioactivity remaining in the body (1– 

5%), a majority was distributed in the skin (0.021%), muscle (0.02%), fat (0.03%), liver (0.01%), and 

blood (0.02%). 

3.4.2.4 Other Routes of Exposure 

No studies were located regarding distribution of phenol in humans after exposure by other routes. 

Microdialysis sampling has been used in rats infused with phenol (0.181 nmol/minute for 90 minutes) to 

study excretion into the bile (Scott and Lunte 1993). For all phenol metabolites, bile concentrations were 

higher than liver concentrations indicating that the metabolites are actively excreted in the bile. 

The distribution of phenol in the liver has been studied in mice treated intravenously with 31.4 mg/kg 

phenol (Davies and Lunte 1996). Microdialysis probes used to monitor the distribution of phenol 

metabolites in three regions of the liver (anterior, median, posterior) indicated that phenol-glucuronide 

was the most prevalent metabolite in all three regions, but the level was significantly lower in the anterior 

region compared to the other regions. When phenol was delivered to the liver through microdialysis 

probes, no regional differences in the delivery of phenol or metabolite formation were observed, 

indicating that clearance of phenol from the liver is dominated by blood flow rather than metabolism. 
 

 

 

 

 

 

 

 

 

PHENOL 101 

3. HEALTH EFFECTS 

3.4.3 Metabolism 

Figure 3-3 shows the general metabolic pathways that transform phenol prior to its excretion in the urine. 

Three different enzymes systems catalyze the reactions that transform phenol. Cytosolic phenol 

sulfotransferases catalyze the transfer of inorganic sulfur from the activated 3'-phosphoadenosine-5'­

phosphosulfate donor molecule to the hydroxyl group on phenol. Microsomal membrane-located uridine 

diphosphate (UDP) glucuronosyltransferases catalyze the transfer of an activated glucuronic acid 

molecule to the hydroxyl moiety of phenol to form an O-glucuronide conjugate. Cytochrome P4502E1, 

also microsomally located, catalyzes the hydroxylation of phenol to form hydroquinone (and to a much 

lesser extent, catechol), which is then acted upon by the phase II enzymes (Buxton 2006; Campbell et al. 

1987; Gut et al. 1996; Koop et al. 1989; McFadden 1996; Powley and Carlson 2001; Snyder et al. 1993). 

Hydroquinone can, in turn, form conjugates, undergo peroxidation to form benzoquinone, or undergo 

further oxidation to form trihydroxybenzene. All three enzyme systems that metabolize phenol are found 

in multiple tissues and there is competition among them not only for phenol, but also for subsequent 

oxidative products, like hydroquinone. As a consequence, the relative amount of the products formed can 

vary based on species, dose and route of administration. 

Cytochromes other than CYP2E1 also seem to be involved in the metabolism of phenol as demonstrated 

by Powley and Carlson (2001) in experiments utilizing chemical inhibitors of CYP2E1, CYP2B, 

CYP2F2, and CYP2E1 knockout mice. The investigators found that CYP2E1 was responsible for only 

approximately 50% of phenol metabolism in liver, suggesting the participation of other cytochromes. 

Experiments in pulmonary microsomes showed that both CYP2E1 and CYP2F2 played important roles in 

the metabolism of phenol. 

Phenol can also undergo peroxidation to form 4,4’-biphenol and diphenoquinone. This has been 

demonstrated in studies that used in vitro cell preparations with high peroxidase activity (Eastmond et al. 

1986; Post et al. 1986), purified peroxidase enzymes (Smart and Zannoni 1984; Subrahmanyam and 

O'Brien 1985), or cell lines that have high myeloperoxidase activity (Kolachana et al. 1993). Thus far, 

there is no direct evidence that these peroxidation reactions occur in vivo. 

In vivo, the gastrointestinal tract, liver, lung, and kidney appear to be the major sites of phenol sulfate and 

glucuronide conjugation of simple phenols (Cassidy and Houston 1984; Powell et al. 1974; Quebbemann 

and Anders 1973; Tremaine et al. 1984). Experiments conducted by Cassidy and Houston (1984) in rats 

injected intra-arterially, intravenously, or intraduodenally (doses ranged from 0.5 to 15 mg/kg) allowed 
 

 

PHENOL 102 

3. HEALTH EFFECTS 

Figure 3-3. Metabolism of Phenol 

Biphenyl polymers 

Glutathione 

HO OH O O conjugate 

peroxidase
 

Biphenol* Diphenylquinone*
 

peroxidase 

OH 

Sulfate conjugate
 

conjugate UGT
 

Glucuronide 

PST
 

Phenol
 

CYP2E1 

OH
 

OH
 PST 

CYP2E1 

Sulfate and glucuronide conjugation OH UGT PST 

UGT OH
 

Hydroquinone
 Catechol peroxidase 

O CYP2E1 CYP2E1 

Sulfate and 

glucuronide 

conjugates 

OH 

Glutathione conjugate 

OH 

PST 

Sulfate and glucuronide 

conjugates UGT O 

Benzoquinone* 

OH 

Trihydroxybenzene* 

PST = phenol sulfotransferase; UGT = UDP-dependent glucuronosyl transferase
 

*Indicates metabolites identified in vitro only
 

Source: EPA 2002 
 

 

 

 

 

 

 

 

 

PHENOL 103 

3. HEALTH EFFECTS 

them to evaluate the first-pass metabolism by different tissues. It was assumed that phenol that was 

systemically available had not been conjugated or metabolized and, therefore, the doses at which this 

occurred reflected the doses at which metabolic reactions were saturated. The investigators found that 

metabolism became nearly saturated in the liver at doses 10 times lower than in the endothelial lung, 

whereas metabolism in the gut was not saturated even at the highest dose tested. They also observed that 

the endothelial lung had a much lower affinity for phenol than the liver and gut. However, caution should 

be exercised when interpreting the results of the metabolic capacity of the lung because normal exposure 

results in exposure of the epithelial respiratory tract rather than the endothelial surface, as occurred in this 

study. 

Four principal metabolites have been identified in mammals: two phenol and two hydroquinone 

conjugates (of sulfate and glucuronide) (Capel et al. 1972; Hoffmann et al. 1999; Kenyon et al. 1995; 

Wheldrake et al. 1978). In humans, rats, and mice given low doses of phenol orally, sulfate conjugates of 

phenol were found to predominate. However, in guinea pigs, pigs, and fruit bats, the glucuronide 

conjugates were dominant (Capel et al. 1972). In humans given an oral dose of 0.01 mg/kg, 77% of the 

urinary 14C was identified as phenyl sulfate, 16% as phenyl glucuronide, and trace amounts (<1%) as the 

sulfate and glucuronide conjugates of hydroquinone (Capel et al. 1972). 

In mice, phenyl sulfate was the predominant urinary metabolite for low doses (1–21 mg/kg) of phenol 

administered either by gavage and intravenously; however, as the dose increased, a decrease in phenol 

sulfation and a concomitant increase in glucuronidation of both phenol and hydroquinone was seen 

suggesting saturation of the sulfation pathway (Kenyon et al. 1995). The degree of saturation appeared to 

be slightly greater following gavage administration, and intravenous administration resulted in higher 

proportions of the products of oxidative metabolism, with male mice being more prone than female mice. 

These latter observations suggest that the oxidative pathway become more prominent when phenol is 

introduced directly into the circulation, bypassing an initial intestinal sulfate conjugation process, and also 

suggests that the sulfate conjugation process saturates at a lower concentration in males than in females. 

Similarly, in the rat, the ratio of phenyl sulfate/glucuronide conjugates in urine decreased from 2.6 to 

0.7 when the intravenous dose level is increased from 1.2 to 25 mg/kg (Weitering et al. 1979). This 

phenomenon appears to be, at least in part, the result of differences in Km in the two pathways, in relation 

to their respective Vmax (Koster et al. 1981; Weitering et al. 1979). The range of substrate concentrations 

over which the reaction rate remains a linear function of concentration narrows as Vmax/Km decreases. A 

shift toward glucuronide formation as a function of dose would be expected in Vmax/Km, for the sulfation 
 

 

 

 

 

 

 

 

PHENOL 104 

3. HEALTH EFFECTS 

pathway was less significant than the glucuronide pathway. Treatment of rats with an intraperitoneal dose 

of phenol (23–188 mg/kg) has also been shown to result in dose-dependent decreases in hepatic 

3'-phosphoadeonsine 5'-phosphosulfate (PAPS), the co-substrate for the sulfate conjugation of phenol, as 

well as sulfate (Kim et al. 1995). The depletion of PAPS may also contribute to the saturation of sulfation 

at high doses of phenol. In another study of rats exposed to single and multiple bolus and drinking water 

doses of different concentrations, metabolites in the urine were primarily conjugates of phenol, showing 

dose-dependant concentrations (Hiser et al. 1994). For bolus doses, the ratios of glucuronide to sulfate 

phenol conjugates were 0.61 for 1.5 and 15 mg/kg doses and 1.16 for 150 mg/kg doses. Drinking water 

exposures resulted in a similar ratio of glucuronide to sulfate as observed for the 150 mg/kg bolus dose, 

with a ratio of 0.60. For inhalation exposures, ratios ranged from 0.24 to 0.39. Small amounts of an 

unidentified metabolite (2–4% total urinary radioactivity) were also detected. 

All three enzyme systems involved in phenol metabolism have other substrates, which can competitively 

inhibit the metabolism of phenol, thereby changing the balance among metabolites. Inhibition of phenol 

sulfotransferase with chlorinated phenols (e.g., pentachlorophenol) results in increased glucuronide 

conjugation of simple phenols (Mulder and Scholtens 1977). Similarly, benzene is metabolized by 

CYP2E1; thus, high exposures to benzene may competitively inhibit phenol metabolism, resulting in 

decreasing hydroquinone production (and its corresponding sulfate and glucuronide conjugates) 

(Medinsky et al. 1995; Schlosser et al. 1993). Further information regarding the shift between sulfation, 

glucuronidation, and oxidation reactions is presented in Section 3.5.1, Pharmacokinetics Mechanisms. 

Age- and sex-related changes in phenol sulfoconjugation were studied in hepatic cytosolic preparations 

from fetal, newborn, and adult rats (Iwasaki et al. 1993). Phenol sulfoconjugation activity was higher in 

adult males (1.94±0.1 nmol/mg/minute) than females (1.07±0.03 nmol/mg/minute), although there were 

no sex-related differences in the younger rats. Activity in fetal rats was very low 

(0.04±0.01 nmol/mg/minute). Activity at 2 days after birth was half that in adult females and a quarter of 

that in adult males, and remained constant until 25 days after birth. At 2 years of age, activity was 

intermediate between young adult male and female activities, and there were no sex-related differences. 

Heaton and Renwick (1991) found that young rats have a higher production of oxidative metabolism than 

adult rats. If this were the case in humans, children might be potentially more sensitive to the systemic 

effects of phenol, if a reactive intermediate is responsible for phenol toxicity. However, since 

glucuronidation does not appear to be limited in the young, production of oxidative products may be a 

smaller risk than anticipated. Caution should be exercised when extrapolating from adolescent rats to 
 

 

 

 

 

 

 

 

 

 

PHENOL 105 

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children, since rodents are well known to undergo a number of changes in xenobiotic-metabolizing 

enzymes during sexual development (Waxman et al. 1985). 

3.4.4 Elimination and Excretion 

Phenol, in its free and conjugated forms, is a normal constituent of human urine. Piotrowski (1971) 

reported 8.7±2.0 mg/day as the daily excretion rate of total phenol (free plus conjugates) in human 

subjects with no known exposure to phenol. Others have reported a range of values. In a study of 

workers employed in the distillation of high-temperature phenolic fractions of tar, mean values of phenol 

in the urine of 13.8 mg/L in 26 male non-exposed workers and 67.8 mg/L in 89 exposed workers were 

reported (Bieniek 1994). The highest concentration was found 2 hours after the end of the work shift. 

Quint et al. (1998) evaluated the urinary phenol concentration before and after using phenol to chemically 

cauterize the lesion created by excision of chrondroblastoma in 11 patients. Preoperatively, the average 

urinary concentration of phenol was 5.1 mg/L. Ling and Hanninen (1991) studied the effect of phenol on 

serum and urinary concentrations in patients who switched from a conventional diet to an uncooked 

“vegan” diet. Patients were tested at week 0, were on the vegan diet for 4 weeks, and then were on the 

regular diet for the second month. Urinary and serum levels of phenol were measured at weeks 0, 2, 4, 

and 9. A significant decrease in both urinary and serum concentrations of phenol was seen within 

2 weeks of adopting the vegan diet. At 2 weeks, the serum concentration had dropped from about 0.75 to 

0.5 mg/L (about 30%), and levels in urine had dropped from about 7 mg/L to about 3 mg/L (about 60%). 

These data indicate that phenol is a natural product of metabolism that may vary significantly depending 

at least on diet, but probably also due to other factors. 

Horch et al. (1994) make the statement “urine phenol concentrations should be monitored in exposed 

persons to determine if they are within normal range (0.5–81 mg/L),” but they provide no citation for the 

range given. It should be noted that as late as 1980, gas chromatographic analyses of urine used to 

determine phenol levels showed fairly large interlaboratory variation (Van Roosmalen et al. 1981). Thus, 

the range of values given above, if derived from multiple references including the older literature, may be 

artificially broad. 

3.4.4.1 Inhalation Exposure 

Phenol absorbed through the lungs is excreted rapidly in urine in its free and conjugated forms. Within 

24 hours after human subjects inhaled phenol at concentrations of 6–20 mg/m3 (1.5–5.1 ppm), 99±8% of 

the phenol retained in the lungs was excreted (Piotrowski 1971). The urinary excretion of phenol was 
 

 

 

 

 

 

 

 

 

 

PHENOL 106 

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studied in 106 men occupationally exposed to phenol, cresols, xylenols, and other phenolic derivatives, 

and 26 unexposed controls (Bieniek 1994). Urine samples were taken after 4 hours at work, and in 

16 workers every 2 hours for 24 hours after an 8-hour shift. The mean level of phenol in urine of the 

exposed workers was 87.3 mg/L, compared to 11.7 mg/L in controls. The highest phenol concentrations 

were recorded between 8 and 10 hours after the beginning of the exposure. Exposure concentrations were 

not reported in this study. 

A study of workers in a Bakelite factory reported a linear correlation between concentrations of phenol in 

the air (up to 12.5 mg/m3 or 3.25 ppm) and urinary excretion of total phenol (free plus conjugated) 

(Ohtsuji and Ikeda 1972). However, the urinary concentration of free phenol seemed to be independent of 

the environmental phenol, suggesting that under the exposure conditions, the maximum capacity to 

conjugate phenol had not been reached. 

Urinary excretion of total phenol (free and conjugates) is considered a biomarker of exposure for phenol. 

The biological exposure index (BEI) for phenol, for exposure to 5 ppm in air, is 250 mg/g creatinine when 

measured at the end of the shift (ACGIH 2001). 

In rats exposed by intratracheal instillation to radiolabeled phenol, elimination was 95% complete after 

72 hours, with the primary elimination route being through the urine (Hughes and Hall 1995). Fecal 

elimination was slower and accounted for less overall. 

In a study conducted by Hiser et al. (1994), rats were exposed via nose-only inhalation for 6 hours to 

25 ppm 14C-phenol for either 1 or 8 days. Thirty hours after initiation of exposure, mean percentages of 

phenol-derived radioactivity were measured in urine and feces. In rats exposed for 1 day, values in urine 

were 94.48% (males) and 90.92% (females). In rats exposed for 8 days, values in urine were 97.40% 

(males). In rats exposed for 1 day, values in feces were 3.33% (males) and 2.02% (females). In rats 

exposed for 8 days, values in feces were 0.81% (males). Less than 1% remained in tissues and carcass. 

These results indicate rapid elimination of phenol in urine after inhalation exposure. 

3.4.4.2 Oral Exposure 

Phenol absorbed from the gastrointestinal tract is excreted rapidly in urine as free phenol or conjugates 

(Capel et al. 1972; Deichmann 1944; Edwards et al. 1986; French et al. 1974; Kao et al. 1979; Kenyon et 

al. 1995; Liao and Oehme 1981). In three human subjects who received a single oral dose of 0.01 mg/kg 
 

 

 

 

 

 

 

 

 

PHENOL 107 

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[

14C]-labeled phenol, the mean 24-hour urinary recovery of 14C was 90% (range 85–90%) of the 

administered dose (Capel et al. 1972). In this same study, urinary recovery of orally administered 

[

14C]-labeled phenol was determined in 18 other mammalian species; the mean 24-hour recoveries of 14C 

ranged from 95% in the rat to 31% in the squirrel monkey. In three separate fatal cases of ingestion of 

phenol at unknown quantities, phenol was detected in the urine at concentrations of 3.3 μg/mL (Boatto et 

al. 2004), 208 μg/mL (Tanaka et al. 1998), and 47 μg/mL (Lo Dico et al. 1989).

Both urinary and fecal excretion of 14C was determined in rats administered an oral dose of 1.2 mg/kg of 

[

14C]-labeled phenol (Edwards et al. 1986). Rats excreted 80.3±11.2% in the urine and 1.8±1.6% in the 

feces in 24 hours. In rats exposed orally to radiolabeled phenol, elimination was 95% complete after 

72 hours, with the primary elimination route being through the urine (Hughes and Hall 1995). Fecal 

elimination was slower and less overall. 

Hiser et al. (1994) reported results of rats exposed to single and multiple bolus and drinking water doses 

of different concentrations of [

14C]-phenol. After 24 hours, concentrations of administered 14C 

radioactivity were >90% in the urine, regardless of the dose method or concentration. Less than 1% 

remained in tissues and carcass. This indicates rapid elimination of phenol in urine after oral exposure. 

3.4.4.3 Dermal Exposure 

Phenol absorbed through the skin is rapidly excreted in urine as free phenol or conjugates. A 4.5-hour 

occlusive exposure of one foot of an adult male to 90% phenol resulted in an elimination half-life of 

13.86 hours. When admitted to the hospital, the phenol urine concentration was 7,909 mg/g in creatine. 

Over the next 12, 20, 43, 58, and 82 hours, phenol concentrations in the urine were measured at 13,416, 

721, 80, 62.8, and 35.7 mg/g creatine, respectively (Bentur et al. 1998). Following an industrial accident 

in which a phenol-water solution was splashed over a man's face, chest wall, hand, and both arms, phenol 

in the urine decreased from 566 mg/L after 4 hours to 0.75 mg/L 46 hours after the exposure (Horch et al. 

1994). Subjects exposed to dermally applied reservoirs containing phenol solutions (2.5–10 mg/L) 

excreted 80% (range 58–98%) of the absorbed phenol in the urine within 24 hours (BaranowskaDutkiewicz 1981). Another study in which both clothed and unclothed human subjects were dermally 

exposed for 7 hours to phenol vapors while breathing clean air to avoid inhalation exposure, found that 

almost 100% of the absorbed phenol was excreted in the urine within 1 day, with clothing providing no 

apparent protection (Piotrowski 1971). 
 

 

 

 

 

 

 

 

 

 

 

 

 

PHENOL 108 

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In rats exposed dermally to radiolabeled phenol, elimination was 95% complete after 72 hours, with the 

primary elimination route being through the urine (Hughes and Hall 1995). Fecal elimination was slower 

and less overall. 

3.4.4.4 Other Routes of Exposure 

Observations of elimination of phenol (5–10 mL 7%) after injection into 20 patients were carried out as 

part lumbar of lumbar and thoracic sympathetic blockade treatments. Apparent elimination half-lives 

were 30.3±2.8 minutes for unconjugated phenol and 64.0±7.3 minutes for conjugated phenol. Urinary 

excretion of conjugated phenol was 52±5% after 8 hours (Nomoto et al. 1987). 

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

Physiologically based pharmacokinetic (PBPK) models use mathematical descriptions of the uptake and 

disposition of chemical substances to quantitatively describe the relationships among critical biological 

processes (Krishnan et al. 1994). PBPK models are also called biologically based tissue dosimetry 

models. PBPK models are increasingly used in risk assessments, primarily to predict the concentration of 

potentially toxic moieties of a chemical that will be delivered to any given target tissue following various 

combinations of route, dose level, and test species (Clewell and Andersen 1985). Physiologically based 

pharmacodynamic (PBPD) models use mathematical descriptions of the dose-response function to 

quantitatively describe the relationship between target tissue dose and toxic end points. 

PBPK/PD models refine our understanding of complex quantitative dose behaviors by helping to 

delineate and characterize the relationships between: (1) the external/exposure concentration and target 

tissue dose of the toxic moiety, and (2) the target tissue dose and observed responses (Andersen and 

Krishnan 1994; Andersen et al. 1987). These models are biologically and mechanistically based and can 

be used to extrapolate the pharmacokinetic behavior of chemical substances from high to low dose, from 

route to route, between species, and between subpopulations within a species. The biological basis of 

PBPK models results in more meaningful extrapolations than those generated with the more conventional 

use of uncertainty factors. 

The PBPK model for a chemical substance is developed in four interconnected steps: (1) model 

representation, (2) model parameterization, (3) model simulation, and (4) model validation (Krishnan and 

Andersen 1994). In the early 1990s, validated PBPK models were developed for a number of 

toxicologically important chemical substances, both volatile and nonvolatile (Krishnan and Andersen 
 

 

 

 

 

 

 

 

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1994; Leung 1993). PBPK models for a particular substance require estimates of the chemical substancespecific physicochemical parameters, and species-specific physiological and biological parameters. The 

numerical estimates of these model parameters are incorporated within a set of differential and algebraic 

equations that describe the pharmacokinetic processes. Solving these differential and algebraic equations 

provides the predictions of tissue dose. Computers then provide process simulations based on these 

solutions. 

The structure and mathematical expressions used in PBPK models significantly simplify the true 

complexities of biological systems. If the uptake and disposition of the chemical substance(s) are 

adequately described, however, this simplification is desirable because data are often unavailable for 

many biological processes. A simplified scheme reduces the magnitude of cumulative uncertainty. The 

adequacy of the model is, therefore, of great importance, and model validation is essential to the use of 

PBPK models in risk assessment. 

PBPK models improve the pharmacokinetic extrapolations used in risk assessments that identify the 

maximal (i.e., the safe) levels for human exposure to chemical substances (Andersen and Krishnan 1994). 

PBPK models provide a scientifically sound means to predict the target tissue dose of chemicals in 

humans who are exposed to environmental levels (for example, levels that might occur at hazardous waste 

sites) based on the results of studies where doses were higher or were administered in different species. 

Figure 3-4 shows a conceptualized representation of a PBPK model. 

If PBPK models for phenol exist, the overall results and individual models are discussed in this section in 

terms of their use in risk assessment, tissue dosimetry, and dose, route, and species extrapolations. 

3.4.5.1 Summary of PBPK Models 

A PBPK model simulating phenol disposition has been developed as part of the attempt to understand the 

toxicity of benzene, of which phenol is the primary metabolite (Bois et al. 1991). Human exposure to 

benzene is widespread, and much of the toxicity of benzene is due to the action of its metabolites. Thus, 

while no studies were located involving PBPK models developed specifically for phenol exposure, the 

benzene model of Bois et al. (1991) is capable of predicting the pharmacokinetics of phenol and is 

appropriate to this discussion. 
 

 

PHENOL 110 

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Figure 3-4. Conceptual Representation of a Physiologically Based
 

Pharmacokinetic (PBPK) Model for a 

Hypothetical Chemical Substance
 

Inhaled chemical Exhaled chemical 

Ingestion 

 Chemicals in air 

contacting skin 

Lungs 

Liver 

Fat 

Slowly 

perfused 

tissues 

Richly 

perfused 

tissues 

Kidney 

Skin 

V 

E 

N 

O 

U 

S 

B 

L 

O 

O 

D 

A 

R 

T 

E 

R 

I 

A 

L 

B 

L 

O 

O 

D 

Vmax Km 

GI 

Tract 

Feces 

Urine

Source: adapted from Krishnan et al. 1994 

Note: This is a conceptual representation of a physiologically based pharmacokinetic (PBPK) model for a 

hypothetical chemical substance. The chemical substance is shown to be absorbed via the skin, by inhalation, or by 

ingestion, metabolized in the liver, and excreted in the urine or by exhalation. 
 

 

 

 

 

 

 

 

PHENOL 111 

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Two empirical compartmental models for benzene have also been developed, which predict the 

production and subsequent metabolism of phenol. A two-compartment model for quantifying benzene 

hepatic metabolism to phenol and other metabolites in an in vitro microsome system was developed by 

Schlosser et al. (1993) and enhanced by Medinsky et al. (1995). This model does not predict benzene (or 

phenol) absorption, disposition, or excretion from the body of animals or humans. A one-compartment 

model of phenol in humans was developed for assessing the variability of worker biomarkers related to 

occupational exposures (Pierrehumbert et al. 2002). Methods for model calibration and validation data 

were not reported. Both of these models are limited for use in phenol risk assessment since they do not 

reduce uncertainties associated with extrapolation animal internal dosimetry to humans or high exposure 

levels to low levels. 

3.4.5.2 Discussion of Models 

The Bois et al. (1991) Model 

A PBPK model for benzene and phenol was developed by Bois et al. (1991) to explore differences in 

metabolite formation and distribution from benzene or phenol exposures to clarify why benzene, but not 

phenol, is carcinogenic in rats and humans. 

Description of the model. The model represents the male rat as a series of flow-limited 

compartments interconnected by arterial and alveolar blood flow. The disposition of benzene and phenol 

was predicted in the liver, fat, bone marrow, and well- and poorly-perfused tissues. In addition, phenol 

distribution to the gut and lung was included. Routes of exposure included oral gavage dosing, 

inhalation, and intravenous injection of both compounds. Elimination of benzene was accomplished by 

exhalation and metabolism in the liver and bone marrow. Additionally, phenol was conjugated in the 

liver, lung, and gut. Hepatic and bone marrow metabolism of benzene to phenol was described by 

Michaelis-Menten generation of benzene oxide followed by first-order production of phenol. MichaelisMenten kinetics described the transformation of benzene oxide to diols or glutathione conjugates and 

phenol to hydroquinone and sulfo- and glucurono-conjugates. Physiological flow and metabolic rates and 

constants were allometrically scaled to body weight. Instead of using point estimates of physiological and 

metabolic parameters values, uniform or log-uniform distributions (e.g., ranges) of parameter values were 

defined for all 64 model parameters. The model was executed using Monte Carlo techniques, in which 

individual random values were sampled from each parameter distribution during iterative model runs to 

produce distributions of model outputs rather than single values. This was done to accommodate 
 

 

 

 

 

 

 

 

 

 

 

 

 

PHENOL 112 

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variability and uncertainty in the parameter values. The parameter distributions were taken from the 

literature. 

The model was calibrated to rat data for gavage (Sabourin et al. 1987, 1989) or inhalation (Sabourin et al. 

1987, 1989) of benzene and intravenous, intra-arterial, intra-duodenal, and hepatic portal injection of 

phenol (Cassidy and Houston 1984) by adjusting the bounds of alveolar ventilation and other 

nonspecified parameter distributions. Different compartments pertaining to separate metabolic systems 

were assessed by selective injection as follows: jugular vein to assess first-pass metabolism across lung, 

hepatic portal vein to assess hepatic first-pass metabolism, duodenum to assess intestinal mucosa 

metabolism, and carotid artery to assess immediate tissues distribution. 

Validation of the model. Validation of this model against empirical data was not done, introducing 

uncertainty into the ability of the model to predict other data. Of particular interest is the prediction that 

hydroquinone production is greater following phenol administration as compared to benzene 

administration. This is in opposition to the prediction of Medinsky et al. (1995). 

Target tissues. The target tissues were blood and bone marrow. The expected levels of phenol in 

blood and bone marrow, and total hydroquinone were substantially higher after phenol administration 

than after benzene administration. 

Species extrapolation. Extrapolation of this model from rats to other animals or humans has not 

been done. 

Interroute extrapolation. The model included parameter values for intestinal absorption and 

pulmonary partitioning of phenol, which enable simulation of oral and inhalation exposures, respectively. 

However, calibration and validation of these routes was not performed against empirical data. Predictions 

of phenol metabolism and distribution following injection into various sites were used to illustrate 

possible consequences of first-pass metabolism following oral exposure to phenol. 

Risk assessment. This model has not been applied to a quantitative risk assessment of benzene or 

phenol. The predicted blood and bone marrow phenol and total hydroquinone levels were substantially 

higher after phenol administration than after benzene administration. This finding is counter to the 

hypothesis that phenol or hydroquinone plays a direct role in the carcinogenicity of benzene, suggesting 

that other metabolites must be involved. The study authors suggest that catechol, a potentially genotoxic 
 

 

 

 

 

 

 

 

 

 

 

 

 

PHENOL 113 

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oxidation metabolite produced in much larger amounts following benzene, as opposed to phenol 

administration, may contribute to benzene's carcinogenicity. 

3.5 MECHANISMS OF ACTION 

3.5.1 Pharmacokinetic Mechanisms 

Absorption of phenol occurs fairly rapidly via the inhalation (Hughes and Hall 1995; Ohtsuji and Ikeda 

1972; Piotrowski 1971), oral (Capel et al. 1972; Edwards et al. 1986; French et al. 1974; Hughes and Hall 

1995; Kao et al. 1979; Kenyon et al. 1995), and dermal (Baranowska-Dutkiewicz 1981; Hughes and Hall 

1995; Piotrowski 1971) routes. Because it is an irritant, tissue damage, inflammation, or other irritation 

effects may occur at the sites of absorption. Because of its high pKa, ionization will not occur within the 

acid environment of the gut. The action of gut microflora on phenol breakdown is not expected to be 

significant. 

When it is absorbed through the lungs, gut, or skin, phenol conjugated at the portal-of-entry and free 

phenol enter the bloodstream where it can then be distributed throughout the body (if the conjugation 

capacity of the tissue has been saturated by a high dose). The dilution of phenol in water enhances the 

dermal absorption of phenol, as indicated by the greater toxicity of a water-phenol solution compared to 

neat phenol (Conning and Hayes 1970). Conning and Hayes (1970) speculated that an undiluted solution 

may produce a coagulative necrosis, which would slow further penetration of phenol resulting in less 

phenol absorbed than with more diluted solutions. 

As described in Section 3.4.3, Metabolism, conjugation with glucuronic acid and conjugation with sulfate 

are the main routes of detoxification of phenol. In most species tested, including humans, sulfation 

predominates at lower doses. As doses increase, glucuronidation increases, as does the formation of 

oxidative metabolites. Some have suggested that the shift from sulfation to glucuronidation is caused by 

a reduction in the availability of co-substrates in conjugation reaction and/or reduction in the sulfate pool 

(Kim et al. 1995) or due to a difference in Km of the two pathways in relation to their respective Vmax 

(Weitering et al. 1979). An alternative explanation for the dose-dependent metabolic profiles for phenol 

is that the activities of metabolizing enzymes vary across areas of the liver (Medinsky et al. 1995). As 

blood flows into the liver from the periphery of the lobule towards the central vein, it encounters first a 

zone in which both sulfotransferases and glucuronosyltransferases are present (periportal zone 1), the 

former predominating. Glucuronosyltransferases predominate in zone 2, whereas both glucuronosyltranferases and monooxygenases are present in pericentral zone 3. In this zonal arrangement, phenol 
 

 

 

 

 

 

 

 

 

 

 

PHENOL 114 

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would be metabolized first by sulfotransferases, and at low doses, little free phenol would be available for 

glucuronide conjugation and oxidation. However, at increasing phenol doses, unconjugated phenol that 

reaches zone 2 is available for glucuronidation. At even higher doses that exceed the conjugation 

capacities of zones 1 and 2, oxidative metabolites are generated (Kenyon et al. 1995). Studies in isolated 

perfused liver from rats (Ballinger et al. 1995) and mice (Hoffmann et al. 1999) have validated the 

‘enzyme zonation’ model. 

The influence of enzyme localization on intestinal metabolism of phenol has also been studied (Kothare 

and Zimmerman 2002). In an in situ perfused intestine preparation from rat, the investigators showed that 

sulfation was the predominant metabolic pathway after vascular administration of phenol, whereas 

luminal dosing produced greater glucuronidation. These results were consistent with the sulfotransferases 

being cytosolic enzymes (Burchell and Coughtrie 1997) and glucuronyltransferase being located between 

the nuclear and apical membrane of the epithelial cell (Inoue et al. 1999) and showing a decreasing 

expressional gradient from the villus to the crypt (Chowdhury et al. 1985). 

Phenol that is absorbed is rapidly excreted in the urine as free phenol or conjugates (BaranowskaDutkiewicz 1981; Capel et al. 1972; Deichmann 1944; Edwards et al. 1986; French et al. 1974; Hughes 

and Hall 1995; Kao et al. 1979; Kenyon et al. 1995; Liao and Oehme 1981; Piotrowski 1971). 

3.5.2 Mechanisms of Toxicity 

Limited information is available regarding the mechanism(s) of toxicity of phenol. Phenol is irritating 

and corrosive at high concentrations as evidenced by numerous cases of accidental dermal exposure or 

intentional or accidental ingestion of phenol. Phenol impairs the stratum corneum and produces 

coagulation necrosis by denaturing and precipitating proteins. Studies in mice suggest that dermal 

application of phenol increases the formation of free radicals in the skin, and that the redox cycling of 

these radicals reduces antioxidant capacity, leading to significant oxidative damage of protein, DNA, and 

lipids (Murray et al. 2007). 

Phenol is a hydroxylated metabolite of benzene and it further undergoes oxidative metabolism to produce 

other compounds; however, it is still unknown with certainty whether the parent compound or a 

metabolite(s) is responsible for phenol’s systemic toxicity. The major tissues in which metabolism 

appears to occur are the liver, gut, lung, and kidney (Cassidy and Houston 1984; Powell et al. 1974; 

Quebbemann and Anders 1973; Tremaine et al. 1984). A study by Chapman et al. (1994) provided some 
 

 

 

 

 

 

 

 

 

PHENOL 115 

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insight on a possible toxic entity. These investigators found that incubation of whole rat conceptus in 

vitro with phenol resulted in minor dysmorphogenic and embryotoxic effect. However, addition of 

exogenous hepatic bioactivation system greatly increased the toxicity of phenol. The major metabolites 

formed were hydroquinone, catechol, and benzoquinone and these three metabolites exhibited similar 

potency. Chapman et al. (1994) also found that adding together phenol and hydroquinone resulted in 

more-than-additive embryotoxicity which, according to the investigators, suggested the involvement of a 

peroxidative mechanism for phenol bioactivation. 

Several studies in animals have reported tremors following exposure by oral gavage (Moser et al. 1995; 

NTP 1983b). The mechanism by which phenol or metabolites exert this effect is unknown. There is little 

indication from studies in animals or from fatal poisoning cases in humans that phenol distributes 

preferentially to the brain, although tremors also may be caused by actions at the periphery. Injections of 

phenol (2–3%) have been used to block nerve conduction in a number of neurological disorders (i.e., 

spasticity in cerebral palsy, cervical dystonia) or to relieve pain in certain cancers. This occurs by phenol 

physically interrupting the continuity of axons and inducing axonal degeneration. How this may be 

related to tremors caused by gavage dosing of phenol, if at all, is unknown. It has been suggested that 

phenol exposure results in cardiac effects because it blocks the cardiac sodium channel subtype, with little 

effect on sodium channels in skeletal muscle (Zamponi et al. 1994). A preferential block by phenol of 

sodium channels in inhibitory pathways would be consistent with a net result of increased activity or even 

tremors, but there is no experimental support for this hypothesis. 

3.5.3 Animal-to-Human Extrapolations 

Although mammals all metabolize phenol to the same metabolites, the amounts of each metabolite vary 

between species. For example, in the old world monkeys and prosimians, sulfation is the major phenol 

conjugation pathway, while in the new world monkeys, glucuronidation predominates (Mehta et al. 

1978). Cats and pigs have low activities of phenol glucuronyltransferase, and metabolize phenol to 

phenyl sulfate nearly exclusively (Capel et al. 1972; French et al. 1974; Miller et al. 1976). Because 

humans have a greater capacity to glucuronidate phenol, cats and pigs would not be good models for the 

metabolism of phenol by humans. 

3.6 TOXICITIES MEDIATED THROUGH THE NEUROENDOCRINE AXIS 

Recently, attention has focused on the potential hazardous effects of certain chemicals on the endocrine 

system because of the ability of these chemicals to mimic or block endogenous hormones. Chemicals 
 

 

 

 

 

 

 

 

 

 

PHENOL 116 

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with this type of activity are most commonly referred to as endocrine disruptors. However, appropriate 

terminology to describe such effects remains controversial. The terminology endocrine disruptors, 

initially used by Thomas and Colborn (1992), was also used in 1996 when Congress mandated the EPA to 

develop a screening program for “...certain substances [which] may have an effect produced by a 

naturally occurring estrogen, or other such endocrine effect[s]...”. To meet this mandate, EPA convened a 

panel called the Endocrine Disruptors Screening and Testing Advisory Committee (EDSTAC), and in 

1998, the EDSTAC completed its deliberations and made recommendations to EPA concerning endocrine 

disruptors. In 1999, the National Academy of Sciences released a report that referred to these same types 

of chemicals as hormonally active agents. The terminology endocrine modulators has also been used to 

convey the fact that effects caused by such chemicals may not necessarily be adverse. Many scientists 

agree that chemicals with the ability to disrupt or modulate the endocrine system are a potential threat to 

the health of humans, aquatic animals, and wildlife. However, others think that endocrine-active 

chemicals do not pose a significant health risk, particularly in view of the fact that hormone mimics exist 

in the natural environment. Examples of natural hormone mimics are the isoflavinoid phytoestrogens 

(Adlercreutz 1995; Livingston 1978; Mayr et al. 1992). These chemicals are derived from plants and are 

similar in structure and action to endogenous estrogen. Although the public health significance and 

descriptive terminology of substances capable of affecting the endocrine system remains controversial, 

scientists agree that these chemicals may affect the synthesis, secretion, transport, binding, action, or 

elimination of natural hormones in the body responsible for maintaining homeostasis, reproduction, 

development, and/or behavior (EPA 1997). Stated differently, such compounds may cause toxicities that 

are mediated through the neuroendocrine axis. As a result, these chemicals may play a role in altering, 

for example, metabolic, sexual, immune, and neurobehavioral function. Such chemicals are also thought 

to be involved in inducing breast, testicular, and prostate cancers, as well as endometriosis (Berger 1994; 

Giwercman et al. 1993; Hoel et al. 1992). 

Based on the available information, there is no clear evidence that phenol is an endocrine disruptor in 

humans or in animals. Long-term studies in rats and mice treated with phenol in the drinking water did 

not report alterations in the gross or microscopic appearance of the reproductive organs (NCI 1980). In 

the 13-week experiment, rats and mice received approximately up to 1,700 and 2,700 mg phenol/kg/day, 

respectively. In the 2-year study, rats received estimated doses of phenol of up to 600–700 mg/kg/day 

and mice received 1,100–1,200 mg/kg/day. Similar observations were made in a more recent 

two-generation reproductive study in rats (Ryan et al. 2001). In the latter study, the highest doses of 

phenol, 301–321 mg/kg/day, had no significant effect on fertility, estrus frequency, testicular sperm 

count, or sperm motility or morphology. Significant reductions in prostate and uterine weights in all F1 
 

 

 

 

 

 

 

 

 

 

 

 

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treated groups were not considered adverse effects of phenol by Ryan et al. (2001) on the basis of the 

absence of histological alterations and functional reproductive effects, and based on the fact that only a 

few animals had organ weights outside the range of concurrent control values. 

In standard developmental toxicity studies in rats and mice, with one exception, fetotoxicity has only been 

reported at doses that were also toxic to the mothers (Narotsky and Kavlock 1995; NTP 1983b; Ryan et 

al. 2001; York 1997). In the study by NTP (1983a) in rats, a 7% decrease in fetal body weight was 

reported at the high-dose level, 120 mg/kg/day, without any evidence of maternal toxicity. However, 

historical control data showed that the concurrent control fetal weight for the CD rat was much higher 

(22%) than the historical control weight. In addition, a larger litter size in the high-dose group may have 

contributed to the smaller fetal weight in the high-dose group. 

Only two reports were located with relevant information from assays in vitro. In one of them, phenol 

tested negative for estrogenic activity in a reporter gene expression assay using yeast cells (Nishihara et 

al. 2000). A substance was considered positive when its activity was >10% of the activity of 10-7 M 17βestradiol. For phenol, that concentration was >1x10-3 M. The other study found that phenol had very 

weak binding affinity to a purified recombinant human estrogen receptor (Hu and Aizawa 2003). 

3.7 CHILDREN’S SUSCEPTIBILITY 

This section discusses potential health effects from exposures during the period from conception to 

maturity at 18 years of age in humans, when all biological systems will have fully developed. Potential 

effects on offspring resulting from exposures of parental germ cells are considered, as well as any indirect 

effects on the fetus and neonate resulting from maternal exposure during gestation and lactation. 

Relevant animal and in vitro models are also discussed. 

Children are not small adults. They differ from adults in their exposures and may differ in their 

susceptibility to hazardous chemicals. Children’s unique physiology and behavior can influence the 

extent of their exposure. Exposures of children are discussed in Section 6.6, Exposures of Children. 

Children sometimes differ from adults in their susceptibility to hazardous chemicals, but whether there is 

a difference depends on the chemical (Guzelian et al. 1992; NRC 1993). Children may be more or less 

susceptible than adults to health effects, and the relationship may change with developmental age 

(Guzelian et al. 1992; NRC 1993). Vulnerability often depends on developmental stage. There are 
 

 

 

 

 

 

 

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critical periods of structural and functional development during both prenatal and postnatal life, and a 

particular structure or function will be most sensitive to disruption during its critical period(s). Damage 

may not be evident until a later stage of development. There are often differences in pharmacokinetics 

and metabolism between children and adults. For example, absorption may be different in neonates 

because of the immaturity of their gastrointestinal tract and their larger skin surface area in proportion to 

body weight (Morselli et al. 1980; NRC 1993); the gastrointestinal absorption of lead is greatest in infants 

and young children (Ziegler et al. 1978). Distribution of xenobiotics may be different; for example, 

infants have a larger proportion of their bodies as extracellular water, and their brains and livers are 

proportionately larger (Altman and Dittmer 1974; Fomon 1966; Fomon et al. 1982; Owen and Brozek 

1966; Widdowson and Dickerson 1964). The infant also has an immature blood-brain barrier (Adinolfi 

1985; Johanson 1980) and probably an immature blood-testis barrier (Setchell and Waites 1975). Many 

xenobiotic metabolizing enzymes have distinctive developmental patterns. At various stages of growth 

and development, levels of particular enzymes may be higher or lower than those of adults, and 

sometimes unique enzymes may exist at particular developmental stages (Komori et al. 1990; Leeder and 

Kearns 1997; NRC 1993; Vieira et al. 1996). Whether differences in xenobiotic metabolism make the 

child more or less susceptible also depends on whether the relevant enzymes are involved in activation of 

the parent compound to its toxic form or in detoxification. There may also be differences in excretion, 

particularly in newborns who all have a low glomerular filtration rate and have not developed efficient 

tubular secretion and resorption capacities (Altman and Dittmer 1974; NRC 1993; West et al. 1948). 

Children and adults may differ in their capacity to repair damage from chemical insults. Children also 

have a longer remaining lifetime in which to express damage from chemicals; this potential is particularly 

relevant to cancer. 

Certain characteristics of the developing human may increase exposure or susceptibility, whereas others 

may decrease susceptibility to the same chemical. For example, although infants breathe more air per 

kilogram of body weight than adults breathe, this difference might be somewhat counterbalanced by their 

alveoli being less developed, which results in a disproportionately smaller surface area for alveolar 

absorption (NRC 1993). 

Based on a very limited data set, it is likely that most of the effects of phenol exposure, including cardiac 

arrhythmias and central nervous system depression, observed in adults after exposure to high amounts of 

phenol will be observed in children if exposures are comparable. The data are insufficient to determine 

whether children will be especially sensitive to such effects, however. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

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IARC (1989), citing Hinkel and Kintzel (1968), indicated that a newborn infant whose umbilicus had 

been bound with a bandage containing 2% phenol, died after 11 hours. Another newborn whose skin 

ulcer was treated with a solution of 30% phenol/60% camphor developed circulatory failure, cerebral 

intoxication, and methemoglobinemia, but recovered after a blood transfusion. Rogers et al. (1978) 

evaluated the percutaneous absorption of phenol in 16 infants, aged 2–5 months, who were treated for 

seborrhoeic eczema with Magenta Paint B.P.C., a medicine containing 4% phenol. The treatment 

consisted of twice daily painting of the napkin and skin folds (representing about 11–15% of the body 

surface) with the Magenta paint over 48 hours, with an average of 32 mL of paint (approximately 

1,300 mg of phenol) applied to each child. Phenol was detected in the urine of four of the infants; 

however, no information on concentration was presented. Liver function tests run on 8 of the 16 treated 

infants showed no abnormalities. The study was initiated because of the observation of signs of central 

nervous system depression in a 6-month-old who had been treated over a much larger area (all of the body 

except the face). 

A study of 2,075 infants exposed to phenolic disinfectants used to clean hospital nursery surfaces reported 

a significant increase in mean third-day microbilirubin level and an increase in the proportion of infants 

with a microbilirubin level >10 mg/dL (Doan et al. 1979). However, no cases of severe jaundice were 

observed. Since infants did not come into direct contact with the cleaned surfaces, exposure was assumed 

to have occurred by inhalation of fumes. 

In a 5-year (1987–1991) retrospective review of acute exposures to a phenol-containing disinfectant 

(Creolin DisinfectantTM [26% phenol]) reported to a regional poison control center, Spiller et al. (1993) 

identified 96 patients, 16 of which were lost to follow-up. There were 60 oral-only exposures, 7 dermalonly exposures, 12 oral/dermal exposures, and 1 inhalation exposure. Sixty (75%) of the patients were 

under 5 years of age. It was not possible to determine from the information presented the degree of 

concordance between the 60 patients with oral-only exposures and the 60 under the age of 5, but it is clear 

that oral exposure of young children is the predominant characteristic of this population of exposed 

individuals. In this regard, children have clearly been demonstrated to be at greater risk of exposure to 

phenol via the accidental ingestion of phenol-containing disinfectants. Vomiting and lethargy were the 

main signs of toxicity observed in the children. 

Warner and Harper (1985) reported the case of a 10-year-old male developed cardiac arrhythmias 

following a chemical peeling procedure initiated to remove a 12x17 cm hairy nevus of the left scapula 

and nape. An hour into the procedure, which involved the application of a solution of phenol (60% 
 

 

 

 

 

 

 

 

 

 

 

 

 

PHENOL 120 

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phenol, 0.8% croton oil in hexachlorophene soap and water) to the entire surface of the nevus, multifocal 

and coupled premature ventricular complexes developed in the electrocardiogram, but subsided after 

infusion of bretylium sulfate. Although this was a severe reaction, it is difficult to determine, based on 

just one case, whether it reflects a special sensitivity based on age. A 10-year-old boy who was 

hospitalized with serious burns was treated dermally with 7.5 L of an antiseptic solution containing 

2% phenol for 2.5 days. During this period, his urine became dark, his respiration became labored, he fell 

into a coma, and he died. Postmortem analysis of urine revealed 200 mg/L of conjugated phenol (Cronin 

and Brauer 1949). 

In a review of the use of phenol as a neurolytic agent, Wood (1978) summarized the results of a number 

of studies including one in which children with cerebral palsy were given nerve blocks with 3% phenol in 

water as a treatment for spasticity. Out of 150 blocks on 46 children, 9 were associated with 

complications, 8 with muscle weakness, and 1 with painful paresthesia. This degree of complication was 

twice that reported by another group who reported on 98 blocks, presumably in adults, with a 

complication rate of 3% with all complications being transient paresthesia. The first group concluded that 

in children the risk was too great for the benefit of the procedure. These two studies in combination 

suggest that children may be especially sensitive to phenol given by injection. Interestingly, a later study 

(Morrison et al. 1991) involving 24 pediatric patients similarly treated for spasticity with injections of 5% 

phenol in water at the motor point of insertion during halothane anesthesia concluded that there was no 

increase in the incidence of complications. In this study the complications of concern were cardiac 

arrhythmias and the incidence was 19%, yet the authors concluded that the procedure appeared 

“appropriate to perform in the day-surgery context.” The difference in these studies is likely due to the 

fact that the earlier study evaluated the incidence of delayed complications, whereas the Morrison et al. 

(1991) work evaluated the incidence of an immediate complication, e.g., cardiac arrhythmias. There was 

no indication in the Morrison et al. (1991) study that delayed complications such as subsequent muscle 

weakness or paresthesia were evaluated. 

Only one study in animals was located that compared the age-dependency toxicity of phenol. Deichmann 

and Witherup (1944) administered phenol orally and subcutaneously to three age groups of rats: 10 days 

old, 5 weeks old, and adults. At a dose of 600 mg/kg orally, death occurred in 90% of 10-day-old rats, in 

30% of 5-week-old rats, and in 60% of adult rats. Similarly, 3,000 mg/kg administered subcutaneously 

caused death in 65% of 10-day-old rats, 25% of 5-week-old rats, and 45% of adult animals. These results 

suggested that neonates are more sensitive than adults, and that adults are more sensitive than young rats, 

but these findings have not been confirmed. 
 

 

 

 

 

 

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Extremely limited data regarding possible adverse developmental effects in humans exposed to phenol 

provide no evidence for effects. As mentioned in Section 3.6, standard developmental toxicity studies in 

rats and mice, with one exception (NTP 1983a), have reported fetotoxicity at doses that were also toxic to 

the mothers (Narotsky and Kavlock 1995; NTP 1983b; Ryan et al. 2001; York 1997). Results from some 

studies in vivo and in vitro suggest that phenol potentially could affect the germ cells, opening the 

possibility that parental exposure would result in adverse childhood development or cancer (Bulsiewicz 

1977; Li et al. 2005). However, the results of a well-conducted two-generation reproduction study do not 

support that possibility (Ryan et al. 2001). 

There is no information regarding pharmacokinetics of phenol in children. As discussed in Section 3.4.3, 

phenol is metabolized by CYP2E1 isozymes and also forms sulfate and glucuronide conjugates. To the 

extent that the enzymes involved in the metabolism of phenol are developmentally regulated, the 

metabolism, and consequently the toxicity of phenol, in immature humans may be different than in adults. 

If microsomal oxidation transforms phenol into a toxic metabolite, a reduced CYP2E1 activity, as it 

seems to occur in neonates, would result in decreased toxicity. However, the ability of the liver to 

sulfonate phenol, and consequently facilitate elimination, also develops with age (Iwasaki et al. 1993). 

Thus, a lower ability to conjugate could result in more phenol available for oxidative metabolism. Heaton 

and Renwick (1991) found that young rats have a higher production of oxidative metabolism than adult 

rats. If this were the case in humans, children might be potentially more sensitive to the systemic effects 

of phenol. Glucuronide conjugation reactions also are considerably reduced in the young and reach adult 

values only after the age of 3 in humans. This would play a role at high doses where the glucuronide 

metabolites of phenol predominate. As previously mentioned, caution should be exercised when 

extrapolating from adolescent rats to children, since rodents are known to undergo a number of changes in 

xenobiotic-metabolizing enzymes during sexual development (Waxman et al. 1985). 

It is not known whether phenol can cross the placenta and there are no reports on levels of phenol in 

maternal milk. 

There are no biomarkers of exposure or effects for phenol that have been validated in children or in adults 

exposed as children. No relevant studies were located regarding interactions of phenol with other 

chemicals in children or adults. 
 

 

 

 

 

 

 

 

 

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3.8 BIOMARKERS OF EXPOSURE AND EFFECT 

Biomarkers are broadly defined as indicators signaling events in biologic systems or samples. They have 

been classified as markers of exposure, markers of effect, and markers of susceptibility (NAS/NRC 

1989). 

Due to a nascent understanding of the use and interpretation of biomarkers, implementation of biomarkers 

as tools of exposure in the general population is very limited. A biomarker of exposure is a xenobiotic 

substance or its metabolite(s) or the product of an interaction between a xenobiotic agent and some target 

molecule(s) or cell(s) that is measured within a compartment of an organism (NAS/NRC 1989). The 

preferred biomarkers of exposure are generally the substance itself, substance-specific metabolites in 

readily obtainable body fluid(s), or excreta. However, several factors can confound the use and 

interpretation of biomarkers of exposure. The body burden of a substance may be the result of exposures 

from more than one source. The substance being measured may be a metabolite of another xenobiotic 

substance (e.g., high urinary levels of phenol can result from exposure to several different aromatic 

compounds). Depending on the properties of the substance (e.g., biologic half-life) and environmental 

conditions (e.g., duration and route of exposure), the substance and all of its metabolites may have left the 

body by the time samples can be taken. It may be difficult to identify individuals exposed to hazardous 

substances that are commonly found in body tissues and fluids (e.g., essential mineral nutrients such as 

copper, zinc, and selenium). Biomarkers of exposure to phenol are discussed in Section 3.8.1. 

Biomarkers of effect are defined as any measurable biochemical, physiologic, or other alteration within an 

organism that, depending on magnitude, can be recognized as an established or potential health 

impairment or disease (NAS/NRC 1989). This definition encompasses biochemical or cellular signals of 

tissue dysfunction (e.g., increased liver enzyme activity or pathologic changes in female genital epithelial 

cells), as well as physiologic signs of dysfunction such as increased blood pressure or decreased lung 

capacity. Note that these markers are not often substance specific. They also may not be directly 

adverse, but can indicate potential health impairment (e.g., DNA adducts). Biomarkers of effects caused 

by phenol are discussed in Section 3.8.2. 

A biomarker of susceptibility is an indicator of an inherent or acquired limitation of an organism's ability 

to respond to the challenge of exposure to a specific xenobiotic substance. It can be an intrinsic genetic or 

other characteristic or a preexisting disease that results in an increase in absorbed dose, a decrease in the 
 

 

 

 

 

 

 

 

 

 

 

 

 

PHENOL 123 

3. HEALTH EFFECTS 

biologically effective dose, or a target tissue response. If biomarkers of susceptibility exist, they are 

discussed in Section 3.10, Populations That Are Unusually Susceptible. 

3.8.1 Biomarkers Used to Identify or Quantify Exposure to Phenol 

Biological monitoring for exposure to phenol is possible by measuring blood or urine levels of the parent 

compound. However, it should be noted that phenol and metabolites of phenol may also come from other 

sources. For example, phenol is a metabolite of benzene and of protein metabolism. Urine samples taken 

from male workers employed in the distillation of high-temperature phenolic fractions of tar revealed a 

phenol excretion rate of 4.20 mg/hour compared to a control rate of 0.53 mg/hour for non-exposed 

workers (Bieniek 1994). Samples were taken 4 hours into the workers' workday, but the worker exposure 

levels were not reported. A study of workers in a Bakelite factory reported a linear correlation between 

concentrations of phenol in the air (up to 12.5 mg/m3 or 3.25 ppm) and urinary excretion of total phenol 

(free plus conjugated) (Ohtsuji and Ikeda 1972). However, the urinary concentration of free phenol 

seemed to be independent of the environmental phenol, suggesting that under the exposure conditions, the 

maximum capacity to conjugate phenol had not been reached. 

The biological exposure index (BEI) for occupational exposure to 5 ppm phenol is 250 mg total phenol in 

urine/g creatinine (ACGIH 2005). The urine should be collected at the end of the 8-hour work shift. The 

sample can be stored in the refrigerator for 4 days or frozen for at least 3 months before analysis. ACGIH 

(2005) warns that the test is nonspecific and should not be used when workers are exposed to benzene or 

to household products or medications that contain phenol. Dermal exposure may result in overestimation 

of inhalation exposure. 

Phenol can also be measured in the urine after oral exposure, although a dose-response relationship 

between oral exposure to phenol and phenol in the urine has not been established. In persons not exposed 

to phenol or benzene, the total phenol concentration in the urine does not exceed 20 mg/L and is usually 

<10 mg/L (ACGIH 2005). 

3.8.2 Biomarkers Used to Characterize Effects Caused by Phenol 

Specific biomarkers used to characterize effects caused by phenol have not been identified. Dark urine 

has been reported in persons exposed to phenol (orally, dermally, or by inhalation) (Baker et al. 1978; 

Bentur et al. 1998; Cronin and Brauer 1949; Kim et al. 1994; Merliss 1972). The dark urine may be a 

result of an oxidation product of phenol or hemoglobin or hemoglobin breakdown products. Further 
 

 

 

 

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research is required to identify the cause of the dark urine. If it is the result of an oxidation product of 

phenol, it should be considered a biomarker of exposure. 

For more information on biomarkers for renal and hepatic effects of chemicals see ATSDR/CDC 

Subcommittee Report on Biological Indicators of Organ Damage (Agency for Toxic Substances and 

Disease Registry 1990) and for information on biomarkers for neurological effects see OTA (1990). 

3.9 INTERACTIONS WITH OTHER CHEMICALS 

Phenol is a tumor promoter in laboratory animals. In mice, dermal exposure to phenol in benzene 

(Boutwell and Bosch 1959) or in acetone (Salaman and Glendenning 1957; Wynder and Hoffmann 1961) 

increased the incidence of tumors resulting from dermal exposure to the tumor initiator, 9,10-DMBA. 

The mechanism of phenol promotion activity is not known, but may be related to the dermal damage that 

it causes and subsequent rapid cell division that may take place to repair the damage. When injected with 

mixtures of phenol and hydroquinone, a hydroxylated metabolite of phenol, mice exhibited significantly 

depressed bone marrow erythropoiesis compared to injection with phenol alone (Chen and Eastmond 

1995a). The involvement of peripheral acetylcholine in phenol-induced tremors was implicated by 

studies in which mice were injected with phenol and pentobarbital, an inhibitor of acetylcholine release 

(Itoh 1995). 

3.10 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE 

A susceptible population will exhibit a different or enhanced response to phenol than will most persons 

exposed to the same level of phenol in the environment. Reasons may include genetic makeup, age, 

health and nutritional status, and exposure to other toxic substances (e.g., cigarette smoke). These 

parameters result in reduced detoxification or excretion of phenol, or compromised function of organs 

affected by phenol. Populations who are at greater risk due to their unusually high exposure to phenol are 

discussed in Section 6.7, Populations with Potentially High Exposures. 

Potentially, individuals with low activities of the enzymes phenol sulfotransferase and glucuronyltransferase may be more susceptible to phenol toxicity. Persons with ulcerative colitis may have an 

impaired capacity to sulfate phenol (Ramakrishna et al. 1991), which may increase the amount of 

unchanged phenol that is absorbed following oral exposure. Neonates may also be more susceptible to 

toxicity from dermally-applied phenol because of increased skin permeability and proportionately greater 

surface area. A study in which 10-day-old rats were more sensitive to lethality following oral exposure to 
 

 

 

 

 

 

 

 

 

PHENOL 125 

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phenol than 5-week-old or adult rats (Deichmann and Witherup 1944) further suggests that the young 

may be more sensitive to phenol. For a more detailed discussion, please see Section 3.7. Because phenol 

is a vesicant, individuals with sensitive skin or pulmonary incapacity may be more sensitive to phenol. 

Individuals with kidney or liver diseases that impair metabolism or excretion of phenol and phenol 

metabolites may be more susceptible to phenol. 

3.11 METHODS FOR REDUCING TOXIC EFFECTS 

This section will describe clinical practice and research concerning methods for reducing toxic effects of 

exposure to phenol. However, because some of the treatments discussed may be experimental and 

unproven, this section should not be used as a guide for treatment of exposures to phenol. When specific 

exposures have occurred, poison control centers and medical toxicologists should be consulted for 

medical advice. The following texts provide specific information about treatment following exposures to 

phenol: 

Goldfrank LR, Flomenbaum NE, Lewin NA, et al. 2002. Goldfrank’s toxicologic emergencies. 7th ed. 

New York, NY: McGraw-Hill. 

Haddad LM, Shannon MW, Winchester JF. 1998. Clinical management of poisoning and drug overdose. 

3rd ed. Philadelphia, PA: WB Saunders Company. 

Viccellio P. 1998. Emergency toxicology. 2nd ed. Philadelphia, PA: Lippincott-Raven Publishers. 

3.11.1 Reducing Peak Absorption Following Exposure 

Human exposure to phenol may occur by inhalation, ingestion, or dermal contact. Mitigation methods for 

reducing exposure to phenol include the general recommendation of separating contaminated food, water, 

air, and clothing from the exposed individual. Externally, phenol can produce mild irritation; acute 

exposure may produce dermatitis and abnormal pigmentation (HSDB 2008). Dermal exposure to 

relatively low concentrations of phenol (5–6%) over a sufficient surface area can result in death. 

Therefore, speed in removing phenol from the skin is important (HSDB 2008). A study was conducted to 

assess the efficacy of 10 different strategies to decontaminate the skin of anesthetized pigs that were 

exposed to 89% aqueous phenol for 1 minute (Monteiro-Riviere et al. 2001). The treatment included 

plain water washes for different periods of time, as well as soap, polyethylene glycol, and isopropanol 

solutions. The evaluation was based on scoring of erythema, edema, and histological parameters of the 

skin. The result showed polyethylene glycol (PEG 400) and 70% isopropanol were superior to the other 

treatments and equally effective in reducing skin damage. The study also found that PEG 400, 70% 
 

 

 

 

 

 

PHENOL 126 

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isopropanol, and 15-minute water treatments significantly reduced phenol absorption in the isolated 

porcine skin flap relative to no treatment. 

Emesis is not recommended following oral ingestion of phenol because of phenol’s corrosive effects and 

potential for seizures and rapid central nervous system depression. Instead, in the absence of esophageal 

injury, repeated gastric lavage is recommended followed by administration of olive oil or vegetable oil to 

remove surface phenol and prevent deeper penetration. This can be followed by administration of a 

cathartic such as castor oil, sorbitol, or saline. Lavage is contraindicated if esophageal injury is suspected. 

3.11.2 Reducing Body Burden 

Phenol is excreted in the breath, urine, and feces. Mitigation strategies to increase urinary output and 

dilute the chemical once it is in the bloodstream may be useful. One method for this may be increased 

hydration of the individual in order to stimulate diuresis. Hemodialysis is not effective in removing 

phenol. Information on the distribution of phenol is limited and provides little insight on how distribution 

might be altered to facilitate any attempts at mitigation of effects. 

3.11.3 Interfering with the Mechanism of Action for Toxic Effects 

The mechanism of action of phenol in the body is not well understood. Reports of cardiac arrhythmias 

resulting from phenol exposure are not uncommon (Gross 1984; Horch et al. 1994; Truppman and 

Ellenby 1979; Warner and Harper 1985). Specific methods to interfere with the mechanism of action for 

phenol were not identified. Treatment of phenol toxicity is essentially supportive. Patients exposed by 

inhalation should be removed from the contaminated area and given 100% humidified oxygen and 

ventilatory assistance. Cardiovascular support includes the use of intravenous saline and vasopressors to 

support the blood pressure. Lidocaine can be used to treat ventricular dysrhythmias and bretilium for 

lidocaine-refractory arrhythmias. Administration of sodium bicarbonate intravenously may rapidly 

reverse central nervous system depression in the presence of metabolic acidosis. Also, if 

methemoglobinemia is >30%, ingestion of methylene blue may be warranted. 

3.12 ADEQUACY OF THE DATABASE 

Section 104(I)(5) of CERCLA, as amended, directs the Administrator of ATSDR (in consultation with the 

Administrator of EPA and agencies and programs of the Public Health Service) to assess whether 

adequate information on the health effects of phenol is available. Where adequate information is not 
 

 

 

 

 

 

 

PHENOL 127 

3. HEALTH EFFECTS 

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 phenol. 

The following categories of possible data needs have been identified by a joint team of scientists from 

ATSDR, NTP, and EPA. They are defined as substance-specific informational needs that if met would 

reduce the uncertainties of human health assessment. This definition should not be interpreted to mean 

that all data needs discussed in this section must be filled. In the future, the identified data needs will be 

evaluated and prioritized, and a substance-specific research agenda will be proposed. 

3.12.1 Existing Information on Health Effects of Phenol 

The existing data on health effects of inhalation, oral, and dermal exposure of humans and animals to 

phenol are summarized in Figure 3-5. The purpose of this figure is to illustrate the existing information 

concerning the health effects of phenol. Each dot in the figure indicates that one or more studies provide 

information associated with that particular effect. The dot does not necessarily imply anything about the 

quality of the study or studies, nor should missing information in this figure be interpreted as a “data 

need”. A data need, as defined in ATSDR’s Decision Guide for Identifying Substance-Specific Data 

Needs Related to Toxicological Profiles (Agency for Toxic Substances and Disease Registry 1989), is 

substance-specific information necessary to conduct comprehensive public health assessments. 

Generally, ATSDR defines a data gap more broadly as any substance-specific information missing from 

the scientific literature. 

The existing information on the health effects of phenol in humans comes from case reports of people 

who accidentally or intentionally swallowed phenol-containing substances or whose skin came in contact 

with phenol, subjects exposed to phenol (and possibly to other substances at the same time) at work, and 

populations whose drinking water was contaminated with phenol (and other substances). Acute oral and 

dermal exposure to high amounts of phenol caused serious systemic effects and even death in humans due 

phenol’s irritant and corrosive properties. 

Acute- and intermediate-duration inhalation studies in animals are available, but only one of these studies 

can be considered a modern study. Inhalation studies in animals showed adverse respiratory, 

cardiovascular, liver, renal, and neurological effects. Phenol administered by oral gavage is much more 

toxic than in drinking water; this is related to differences in toxicokinetics between the two means of 
 

PHENOL 128 

3. HEALTH EFFECTS 

Figure 3-5. Existing Information on Health Effects of Phenol 

Death

Acute 

Intermediate 

Chronic 

Immunologic/Lymphoretic 

Neurologic 

Reproductive 

Developmental 

Genotoxic 

Cancer 

Systemic 

Inhalation 

Oral 

Dermal 

Human 

Death

Acute 

Intermediate 

Chronic 

Immunologic/Lymphoretic 

Neurologic 

Reproductive 

Developmental 

Genotoxic 

Cancer 

Systemic 

Inhalation 

Oral 

Dermal 

Animal 

Existing Studies 
 

 

 

 

 

 

 

 

 

 

 

 

 

PHENOL 129 

3. HEALTH EFFECTS 

administration. Phenol exhibited relatively little toxicity in drinking water studies, including studies of 

reproductive and developmental end points. Of special interest is a study that reported hematological, 

immunological, and neurological effects in mice exposed to low concentrations of phenol in the drinking 

water for 28 days. Longer-term studies examined mostly systemic end points. Data are extensive 

regarding genotoxicity of phenol in bacterial systems and mammalian systems. Data regarding the oral 

carcinogenicity of phenol in rats and mice are available, as well as data on the dermal carcinogenicity, 

and tumor-promoting and tumor-inhibiting activities of phenol. 

3.12.2 Identification of Data Needs 

Acute-Duration Exposure. Case reports of humans exposed to high doses of phenol, either orally or 

dermally, have provided acute toxicity information. Both ingestion of phenol (Boatto et al. 2004; Soares 

and Tift 1982; Stajduhar-Caric 1968; Tanaka et al. 1998) and contact of phenol with a significant area of 

the skin (Cronin and Brauer 1949; Griffiths 1973; Soares and Tift 1982) have caused deaths in humans. 

The cardiovascular system also might be considered a target for acute phenol toxicity. Supraventricular 

and ventricular dysrhythmias were reported in a case of acute ingestion of phenol (Langford et al. 1998) 

and cardiac arrhythmia and bradycardia were reported following acute dermal exposure to phenol (Gross 

1984; Horch et al. 1994; Truppman and Ellenby 1979; Warner and Harper 1985). Two acute-duration 

inhalation studies in animals of limited scope indicated that the respiratory tract and the nervous system 

are targets for phenol toxicity (De Ceaurriz et al. 1981; Flickinger 1976). A more recent well-conducted 

study that used modern methodology to evaluate a number of relevant end points, including upper and 

lower respiratory tract histology, defined a study NOAEL of 25 ppm, the highest exposure level tested 

(Hoffman et al. 2001). Because no adverse effects were reported in that study, it was considered an 

unsuitable basis for an MRL. Therefore, additional studies may be necessary to establish NOAELs and 

LOAELs that can be used to construct dose-response relationships for acute exposure to phenol. 

Acute-duration oral gavage studies in animals provided information on lethal doses (Berman et al. 1995; 

Deichmann and Witherup 1944; Flickinger 1976; von Oettingen and Sharpless 1946) and other effects, 

including renal (Berman et al. 1995), hematological (Ciranni et al. 1988), neurological (Moser et al. 

1995), and developmental effects (Narotsky and Kavlock 1995; NTP 1983a, 1983b). A study in which 

pregnant rats were administered phenol by oral gavage, but divided in three daily doses and in a relatively 

high volume to minimize the effects of a bolus dose of phenol, reported a significant reduction in body 

weight gain in the dams at ≥120 mg/kg/day, but no significant developmental effects were reported at this 

dose level (York 1997). The maternal NOAEL was 60 mg/kg/day. Decreased fetal weight and decreased 
 

 

 

 

 

 

 

 

 

 

PHENOL 130 

3. HEALTH EFFECTS 

ossification sites were only seen at the highest dose level, 360 mg/kg/day. The reduction in maternal 

weight gain during pregnancy was used as the basis for the derivation of an acute-duration oral MRL of 

1 mg/kg/day for phenol. A need for additional acute-duration oral studies is not apparent at this time. 

Phenol is a well known skin irritant and further acute-duration dermal studies in animals are unlikely to 

provide new key information. 

Intermediate-Duration Exposure. Limited information exists regarding effects of phenol in 

humans exposed for intermediate durations. A study of office workers exposed to vapors of a liquid 

wood preservative containing phenol, among a number of other chlorinated compounds, reported adverse 

respiratory, hematological, hepatic, and ocular effects, but the specific role of phenol, if any, could not be 

ascertained (Baj et al. 1994). Studies of populations whose drinking water was contaminated with phenol 

found increased incidences of nausea and diarrhea, but exposure to chlorophenols may have also occurred 

(Baker et al. 1978; Jarvis et al. 1985; Kim et al. 1994). Only three studies were identified that exposed 

animals to airborne phenol for intermediate durations (Dalin and Kristoffersson 1974; Deichmann et al. 

1944; U.S. Air Force 1961). These studies provided evidence of respiratory, heart, liver, kidney, and 

neurological effects, but had numerous limitations including poor control of exposure levels, unclear 

scope of the evaluations, and limited reporting, and were inadequate for MRL derivation. Therefore, a 

well-conducted 90-day inhalation study that examines a comprehensive number of end points would 

provide valuable information for dose-response analyses and possibly MRL derivation. Since phenol is 

well absorbed through the skin, a nose-only exposure protocol may be considered. 

Several studies provided information on the effects of phenol following intermediate-duration oral 

exposure and all of them used drinking water to administer phenol. A 13-week drinking water study in 

rats and mice evaluated clinical signs and gross and microscopic appearance of a number of organs and 

tissues and found little evidence of toxicity (NCI 1980). A two-generation reproduction study found no 

evidence of reproductive effects in male or female rats, but reported decreased pup weight and reduced 

viability (Ryan et al. 2001). A specialized 13-week neurotoxicity study reported decreased motor activity 

in female rats (Beyrouty 1998). In these three studies, the doses tested were higher than doses tested in 

acute-duration oral studies. The most significant findings in the intermediate-duration oral database were 

those of Hsieh et al. (1992) who reported hematological, neurochemical, and immunological effects in 

mice at dose levels much lower than those used in other studies that tested similar end points. The Hsieh 

et al. (1992) study was not used for derivation of an intermediate-duration oral MRL largely due to the 

unconfirmed nature of findings and because only five mice comprised each dose group. Replication of 

Hsieh’s findings seems necessary before using the data for risk assessment. Skin ulcerations were 
 

 

 

 

 

 

 

PHENOL 131 

3. HEALTH EFFECTS 

reported in mice treated dermally with 20% phenol in acetone once each week for 24–32 weeks (Salaman 

and Glendenning 1957). Because humans are more likely to be dermally exposed to phenol in water, and 

phenol is readily absorbed through the skin, additional intermediate-duration studies examining the 

effects of dermal exposure to different concentrations of phenol in water may fill a data gap. 

Chronic-Duration Exposure and Cancer. There is limited information on health effects in 

humans exposed chronically to phenol. Neither morbidity nor mortality was significantly increased in 

workers in five companies that used formaldehyde and phenol (Dosemeci et al. 1991). In another study 

of workers in the rubber industry, exposure to phenol was associated with an increased incidence of 

cardiovascular disease, independently of being associated with exposure to other solvents such as carbon 

disulfide (Wilcosky and Tyroler 1983). Liver effects, as judged by increased serum activities of ALT and 

AST, were reported in a case of prolonged inhalation exposure to phenol (Merliss 1972) and in workers in 

an oil-refining plant (Shamy et al. 1994), but exposure to other solvents could not be ruled out in the latter 

case. The lack of exposure data and simultaneous exposure to other chemicals precluded using the human 

data for derivation of a chronic-duration inhalation MRL for phenol. No chronic-duration inhalation 

studies in animals were identified. This constitutes a data gap that may need to be filled. 

The only chronic-duration animal studies are the NCI (1980) 103-week studies in rats and mice. NCI 

(1980) evaluated clinical signs, organ weights, and gross and microscopic appearance of organs and 

tissues. Under the conditions of the study, phenol showed essentially no systemic toxicity. A chronicduration oral drinking water study with emphasis on immunological end points may be necessary if the 

intermediate-duration immunotoxicity study that NTP is currently conducting confirms that 

immunocompetence is the most sensitive end point for phenol toxicity. Since, as previously mentioned, 

phenol is readily absorbed through the skin and the possibility exists of dermal exposure via contaminated 

water (bathing or showering) at or near waste sites, a chronic-duration dermal study of phenol in water 

may be considered if the results of a shorter-term study suggest that adverse effects might happen. 

A study of phenol-exposed wood industry workers reported a small, nonsignificant excess of respiratory 

cancers (Kauppinen et al. 1986) and a study of phenol production workers reported a small, 

nonsignificant excess of Hodgkin’s disease and of lung, esophageal, and kidney cancers (Dosemeci et al. 

1991). However, the interpretation of these findings is complicated due to lack of dose-response and 

potential for confounding. Phenol has been tested for carcinogenicity in long-term drinking water 

bioassays in rats and mice (NCI 1980). Statistically significant increased incidences of 

pheochromocytomas of the adrenal gland and leukemia or lymphomas were observed in male rats 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PHENOL 132 

3. HEALTH EFFECTS 

exposed to the low dose of phenol, but not to the high dose of phenol. No significant effects were seen in 

female rats or in mice. Additional bioassays do not seem necessary at this time. 

Genotoxicity. Phenol has been tested extensively for genotoxicity in a variety of in vivo (Amlacher 

and Rudolph 1981; Barale et al. 1990; Bulsiewicz 1977; Chen and Eastmond 1995a; Ciranni et al. 1988; 

Gocke et al. 1981; Li et al. 2005; Miyagawa et al. 1995; Pashin et al. 1987; Shelby and Witt 1995; Skare 

and Schrotel 1984; Sturtevant 1952) and in vitro (Crebelli et al. 1987; Demerec et al. 1951; Erexson et al. 

1985; Florin et al. 1980; Gocke et al. 1981; Haworth et al. 1983; Jansson et al. 1986; Kubo et al. 2002; Li 

et al. 2005; Miller et al. 1995; Morimoto and Wolff 1980; Morimoto et al. 1983; Nagel et al. 1982; 

Painter and Howard 1982; Paschin and Bahitova 1982; Pellack-Walker and Blumer 1986; Poirier et al. 

1975; Pool and Lin 1982; Schwartz et al. 1985; Sze et al. 1996; Tsutsui et al. 1997) tests. The results of 

these assays have been equivocal. Phenol appears to be potentially genotoxic, although this may be more 

a result of the action of its metabolites than the parent compound. Additional genotoxicity studies of 

phenol do not seem to be necessary. 

Reproductive Toxicity. Extremely limited data regarding possible adverse reproductive effects in 

humans following exposure to phenol provide no evidence for effects (Axelsson et al. 1984). Histopathological changes in reproductive organs were not observed in rats or mice treated with phenol in the 

drinking water for 13 or 103 weeks (NCI 1980). In a two-generation study in which rats were 

administered phenol in the drinking water, there were no significant alterations in gross or microscopic 

appearance of the reproductive organs of males and females from the parental and F1 generations (Ryan et 

al. 2001). In addition, there were no significant effects on estrus frequency, testicular sperm count, or 

sperm motility or morphology. Significant reductions in prostate and uterine weights in all F1 treated 

groups were not considered adverse effects of phenol by Ryan et al. (2001) on the basis of the absence of 

histological alterations and functional reproductive effects, and based on the fact that only a few animals 

had organ weights outside the range of concurrent control values. Additional reproductive toxicity 

studies by the oral route do not seem necessary. Studies by the inhalation or dermal route also do not 

seem necessary since there is no indication that reproductive effects would be route-dependent. 

Developmental Toxicity. Extremely limited data regarding possible adverse developmental effects 

in humans following exposure to phenol provide no evidence for effects (Axelsson et al. 1984). Phenol 

has been evaluated for developmental effects in rats and mice exposed by oral gavage (Ciranni et al. 

1988; Kavlock 1990; Narotsky and Kavlock 1995; NTP 1983a, 1983b; York 1997) and in rats dosed 

through the drinking water in a two-generation reproduction study (Ryan et al. 2001). These studies 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

PHENOL 133 

3. HEALTH EFFECTS 

indicated that fetotoxicity occurs only at dose levels that are also toxic to the mother. The study by York 

(1997) was used to derive an acute-duration oral MRL of 1.0 mg/kg/day for phenol. Additional 

developmental studies by the oral route of exposure do not seem necessary at this time. Also, studies by 

the inhalation or dermal route also do not seem necessary since there is no indication that developmental 

effects would be route-dependent. 

Immunotoxicity. Immunological effects were reported in workers exposed for 6 months to a mixture 

of phenol, formaldehyde, and organic chlorohydrocarbons, although there is some question whether the 

exposure was due to phenol or a substituted phenol (Baj et al. 1994). Increased susceptibility to bacteria 

was not observed in mice exposed by inhalation to phenol (Aranyi et al. 1986). Necrosis or atrophy of the 

spleen or thymus, which was not described further, was observed in rats given a single dose of phenol by 

oral gavage (Berman et al. 1995). Effects on the spleen or thymus were not observed in rats given 

14 daily doses of phenol (Berman et al. 1995). Decreased antibody production in response to 

immunization with SRBC was observed in mice treated with relatively low doses of phenol in the 

drinking water for 28 days (Hsieh et al. 1992). Ryan et al. (2001) conducted similar tests in rats in the 

two-generation reproductive study and found no significant effects of phenol. It would be useful to try to 

replicate Hsieh’s findings before the results can be used for risk assessment. In longer-term studies, 

histopathologic changes in the spleen or thymus were not observed in rats or mice exposed to phenol in 

the drinking water for 13 or 103 weeks, but immunocompetence was not assessed (NCI 1980). Studies by 

the inhalation and dermal routes are not necessary since there is no evidence of route-dependency. 

Neurotoxicity. An increase in the number of headaches was reported by persons exposed to phenol in 

drinking water following an accident, but chlorophenols may have contributed to the observed effects 

(Kim et al. 1994). As reported in a retrospective review (Spiller et al. 1993), 11 patients with oral 

exposures to phenol-based disinfectants experienced rapid central nervous system depression, but no 

seizures occurred. Neurological effects (muscle tremor, loss of coordination) have been reported in 

laboratory animals after single exposures to high concentrations of phenol in the air (Flickinger 1976), 

continuous exposure in the air (Dalin and Kristoffersson 1974), repeated intermittent exposures in the air 

(Deichmann et al. 1944), and oral gavage dosing (Deichmann and Witherup 1944; Liao and Oehme 1981; 

Moser et al. 1995; NTP 1983b). In contrast, no such effects were observed in rats and mice in drinking 

water studies of longer durations and with higher doses of phenol (Beyrouty 1998; NCI 1980). These 

neurological effects correlate with peak blood concentrations of phenol achieved during gavage dosing. 

Drinking water studies suggest that the nervous system is not a sensitive target for phenol toxicity by this 
 

 

 

 

 

 

 

 

 

 

 

 

PHENOL 134 

3. HEALTH EFFECTS 

route of exposure. A need to conduct additional toxicity studies is not apparent, but studies aimed at 

elucidating the mechanism(s) of phenol neurotoxicity are needed. 

Epidemiological and Human Dosimetry Studies. As previously mentioned, information about 

the health effects of phenol in humans is derived from studies of workers and members of the general 

population following inhalation, oral, and dermal exposure. Specific effects and references are mentioned 

in previous sections. Doses were generally not available, but Deichmann and Keplinger (1981) estimated 

that an oral dose as low as 1 g could be fatal in humans, but also pointed out that patients occasionally 

survived doses as high as 65 g. Other than the skin and mucosal membranes, the liver and cardiovascular 

system might by considered targets for phenol toxicity. Wilcosky and Tyroler 1983 studied workers in 

the rubber industry and found that exposure to phenol was associated with an increased incidence of 

cardiovascular disease, independently of being associated with exposure to other solvents such as carbon 

disulfide. Cardiac arrhythmia and bradycardia were reported following acute dermal exposure to phenol 

(Gross 1984; Horch et al. 1994; Truppman and Ellenby 1979; Warner and Harper 1985) and 

supraventricular and ventricular dysrhythmias were reported in a case of acute ingestion of phenol 

(Langford et al. 1998). Liver effects were reported in a case of prolonged inhalation exposure to phenol 

(Merliss 1972) and in workers in an oil-refining plant (Shamy et al. 1994), but exposure to other solvents 

could not be ruled out in the latter case. Prolonged exposure to low levels of phenol may occur at or near 

waste sites via contaminated water. Since such contamination may lead to inhalation exposure 

(evaporation of phenol when bathing or showering, particularly if the water is acidic), dermal exposure 

(absorption through the skin), and oral exposure (ingestion of water or cooking with contaminated water), 

a dosimetric model that predicts total exposure and intake of phenol from contaminated water would be 

valuable. The specific end points that should be monitored under such exposure scenario (prolonged low 

level) are not immediately apparent. Phenol administered in the drinking water to rats and mice for 

2 years showed almost no systemic toxicity (NCI 1980). 

Biomarkers of Exposure and Effect. 

Exposure. Measurement of total phenol in the urine is the most useful biomarker following inhalation 

exposure to phenol (ACGIH 2001). The test is nonspecific and should not be used when workers are 

exposed to benzene, to household products, or to medications containing phenol. Dermal exposure may 

also result in overestimation of inhalation exposure. In persons not exposed to phenol or benzene, the 

total phenol concentration in the urine does not exceed 20 mg/L and the mean is usually <10 mg/L 

(ACGIH 2001). Phenol can also be measured in the urine after oral exposure, although a dose-response 
 

 

 

 

 

 

 

 

 

 

 

 

PHENOL 135 

3. HEALTH EFFECTS 

relationship between oral exposure to phenol and phenol in the urine has not been established. Benzene 

metabolism yields not only phenol, 1,4-dihydroxybenzene, and their sulfates and glucuronides, but also 

the benzene-specific t,t-muconic acid. For both t,t-muconic acid and S-phenylmercapturic acid, 

significant correlations were shown with benzene concentrations in air and in blood (Popp et al. 1994; 

Stommel et al. 1989). Thus, determination of urinary concentrations of these metabolites allows 

delineation of the portion of metabolites stemming from phenols and the portion derived from benzene 

exposure. Further research on the relationship between exposure doses and urinary levels of phenol is 

needed. 

Effect. Specific biomarkers used to characterize effects caused by phenol have not been identified. Dark 

urine has been reported in persons occupationally exposed to phenol (inhalation, dermal) (ACGIH 2001; 

Merliss 1972), and following oral exposure (Baker et al. 1978; Kim et al. 1994). The dark urine may be a 

result of an oxidation product of phenol or hemoglobin. Further research is required to identify the cause 

of the dark urine. 

Absorption, Distribution, Metabolism, and Excretion. The toxicokinetics of phenol have been 

studied extensively in laboratory animals and humans. Phenol is readily absorbed from the lungs, 

gastrointestinal tract, and skin. A study that examined the absorption of phenol vapor through the skin 

indicates that it is readily absorbed and clothing does not serve as a barrier (Piotrowski 1971). Dermal 

absorption is considered the primary route of entry for vapor, liquid, and solid phenol (ACGIH 2001). 

Conjugation of phenol with glucuronic acid and sulfate are the main detoxification pathways. 

Conjugation occurs predominantly in the lungs, gastrointestinal tract, liver, and kidneys. The skin has 

relatively low potential to detoxify phenol. Therefore, absorption through the skin may represent the 

greatest hazard from phenol because it readily passes through the skin and because there is no first-pass 

metabolic effect as is observed following oral exposure. Further studies regarding the metabolism of 

phenol following dermal exposure are needed. In vitro studies of phenol metabolism have demonstrated 

that reactive intermediates are produced during the metabolism of phenol (Chapman et al. 1994; 

Eastmond et al. 1986; Lunte and Kissinger 1983; Subrahmanyam and O'Brien 1985). These reactive 

compounds may be involved in mediating phenol toxicity. Further investigation of these compounds in 

tissues suspected of being targets for phenol toxicity (i.e., the lungs, skin, liver, kidney, and heart) are 

needed to provide information for extrapolating from animals to humans. 

There is no PBPK model specifically designed for phenol, although phenol, as a major metabolite of 

benzene, has been considered in a PBPK model of benzene discussed in this profile (Bois et al. 1991). 
 

 

 

 

 

 

 

 

 

 

 

PHENOL 136 

3. HEALTH EFFECTS 

The model does not adequately explain the differences in carcinogenicity observed between benzene and 

phenol, and needs additional refinements in order to incorporate all the observations and be validated. 

Additional efforts to develop a PBPK model for phenol are needed. 

Comparative Toxicokinetics. The metabolism and excretion of orally administered phenol in 

18 animal species have been compared to metabolism and excretion in humans (Capel et al. 1972). The 

rat was the most similar to the human with respect to the fraction of administered dose excreted in urine 

in 24 hours (95%) and the number and relative abundance of the four principal metabolites excreted in 

urine (sulfate and glucuronide conjugates of phenol and 1,4-dihydroxybenzene). The rat excreted a larger 

fraction of the orally administered dose than the guinea pig or the rabbit (Capel et al. 1972) and appears to 

be the least susceptible of the three species to respiratory, cardiovascular, hepatic, renal, and neurological 

effects of inhaled phenol (Deichmann et al. 1944). More rapid metabolism and excretion of absorbed 

phenol may account for the lower sensitivity of the rat to systemic effects of phenol. More information 

on the relative rates of metabolism of phenol in various species is needed to identify the most appropriate 

animal model for studying potential health effects in humans. 

Methods for Reducing Toxic Effects. Removing a person from phenol exposure is the most 

important method for reducing toxic effects of phenol. This is especially important following dermal 

exposure, after which speed in removing phenol from the skin is important (HSDB 2008). Because a 

study has shown that dilution in water increases the dermal absorption of phenol (Conning and Hayes 

1970), it has been recommended that polyethylene be used to remove dermal contamination with phenol 

(Viccellio 1998). Because water is readily available, others believe that its use is more appropriate for the 

decontamination of skin following phenol exposure (Pullin et al. 1978). A study is available that 

evaluated several strategies to decontaminate the skin of pigs following acute dermal exposure to phenol 

(Monteiro-Riviere et al. 2001). The study showed that polyethylene glycol (PEG 400) and 70% 

isopropanol were superior to other treatments and equal effective in reducing skin damage induced by 

phenol. The general recommendations for reducing the absorption of phenol following acute oral 

exposure are well established and have a proven efficiency (HSDB 2008). No additional investigations 

are considered necessary at this time. 

No clinical treatments, other than supportive measures, are currently available to enhance elimination of 

phenol following exposure. Studies designed to assess the potential risks or benefits of increasing 

ventilation to enhance pulmonary elimination or of stimulating excretion of phenol and its metabolic 

products are needed. 
 

 

 

 

 

 

 

 

 

 

PHENOL 137 

3. HEALTH EFFECTS 

Children’s Susceptibility. Data needs relating to both prenatal and childhood exposures, and 

developmental effects expressed either prenatally or during childhood, are discussed in detail in the 

Developmental Toxicity subsection above. 

Deichmann and Witherup (1944) found that 10-day-old rats were more sensitive to lethality following 

oral exposure to phenol than 5-week-old or adult rats; however, this work has never been repeated and 

there was little other information evaluating the toxicity of phenol at various ages. Such studies need to 

be conducted in order to follow up this earlier observation. However, caution should be exercised when 

extrapolating from adolescent rats to children, since rodents are known to undergo a number of changes in 

xenobiotic-metabolizing enzymes during sexual development (Waxman et al. 1985). 

Studies that specifically evaluated age-related changes in the phase I and phase II metabolic 

transformations of phenol are not available. However, in general, it is known that there is a reduced 

capacity to metabolize xenobiotics in the first 15 days of life, and that the different enzyme systems have 

different time courses of development thereafter (Morselli et al. 1980). For example, glucuronide 

conjugation reactions are considerably reduced in young humans, and reach adult values only after the 

age of 3, whereas sulfate conjugations and oxidative reactions catalyzed by the cytochrome 

P450 enzymes apparently develop more rapidly (Buxton 2006; Morselli et al. 1980). Thus, there could be 

age-related differences in the balance among metabolites, particularly at high doses where the glucuronide 

metabolites begin to dominate. While there is agreement that conjugation reactions represent a 

detoxification mechanism for phenol, it is still unknown whether parent compound or an oxidation 

product(s) is the entity responsible for the systemic toxicity of phenol in vivo. Studies are needed to 

examine how age affects the metabolism of phenol, and particularly how age changes the balance 

between phase I and phase II metabolism at either high or low doses. 

There was no information found on the placental transfer of phenol or on the concentrations of phenol 

present in breast milk. There is evidence that benzene and its (not specifically identified) metabolites do 

cross the placenta, although there is no evidence of selective accumulation (Ghantous and Danielsson 

1986). Additional studies of this issue are needed to determine if phenol and its metabolites are among 

the metabolites of benzene that cross the placenta, and if so whether phenol behaves like benzene in the 

lack of accumulation. Information is also needed on the content of phenol in breast milk under various 

conditions (e.g, smoking versus nonsmoking mothers) in order to determine if breast milk could ever be a 

source of phenol exposure for children. 
 

 

 

PHENOL 138 

3. HEALTH EFFECTS 

Child health data needs relating to exposure are discussed in Section 6.8.1, Identification of Data Needs: 

Exposures of Children. 

3.12.3 Ongoing Studies 

No ongoing studies pertaining to phenol were identified in the Federal Research in Progress database 

(FEDRIP 2006). 
 

 

 

PHENOL 139 

4. CHEMICAL AND PHYSICAL INFORMATION 

4.1 CHEMICAL IDENTITY 

Information regarding the chemical identity of phenol is located in Table 4-1. 

4.2 PHYSICAL AND CHEMICAL PROPERTIES 

Information regarding the physical and chemical properties of phenol is located in Table 4-2. 
 

 

 

 

 

 

 

 

PHENOL 140 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-1. Chemical Identity of Phenol 

Characteristic Information Reference 

Chemical name Phenol Lide 2005 

Synonym(s) Benzenol, hydroxylbenzene, Lewis 2000 

monophenol, oxybenzene, phenyl 

alcohol, phenyl hydrate, phenyl 

hydroxide, phenylic acid, phenylic 

alcohol 

Registered trade name(s) Carbolic acid, phenic acid, phenic Gardner et al. 1978 

alcohol 

Chemical formula C6H6O Lide 2005 

Chemical structure OH Budavari et al. 1989 

Identification numbers: 

CAS registry 108-95-2 HSDB 2008 

NIOSH RTECS SJ3325000 RTECS 2006 

EPA hazardous waste U188 EPA 1998; HSDB 2008 

DOT/UN/NA/IMCO shipping UN 1671 (solid) HSDB 2008 

UN 2312 (molten) 

UN 2821 (solution) 

IMO 6.1 (solid, molten, solution) 

HSDB 113 HSDB 2008 

NCI C50124 Lewis 2000 

CAS = Chemical Abstracts Services; DOT/UN/NA/IMCO = 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; RTECS=Registry of Toxic Effects of Chemical Substances 
 

 

 

 

 

 

PHENOL 141 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-2. Physical and Chemical Properties of Phenol 

Property Information Reference 

Molecular weight 94.111 Lide 2005 

Color Colorless to light pink HSDB 2008 

Physical state Crystalline solid liquid (w/ 8% H2O) 

Melting point 40.89 °C Lide 2005 

Boiling point 181.87 °C Lide 2005 

Density at 20 °C/4 °C 1.0545 at 45 °C/4 °C Lide 2005 

Vapor density 3.24 Lewis 2000 

Odor Distinct aromatic, somewhat sickening, sweet HSDB 2008 

and acrid odor 

Odor threshold: 

Water 7.9 ppm (w/v) Amoore and Hautala 1983 

1 ppm (w/v) Baker et al. 1978 

Air 0.040 ppm (v/v) Amoore and Hautala 1983 

Solubility: 

Water at 25 °C 8.28x104 mg/L Southworth and Keller 1986 

Organic solvent(s) Soluble in water and ethanol, very soluble in Lide 2005 

ether, miscible with acetone and benzene 

Partition coefficients: 

Log Kow 1.46 HSDB 2008 

Log Koc 1.21–1.96 Artiola-Fortuny and Fuller 

1982; Boyd 1982; Briggs 

1981; Sacan and Balcioglu 

1996; Scott et al. 1983 

Vapor pressure at 25 °C 0.35 mmHg HSDB 2008 

Henry's law constant 3.0x107 atms m3-mol Gaffney et al. 1987 

Autoignition temperature 715 °C Lewis 2000 

Flashpoint, open cup 85 °C HSDB 2008 

Flashpoint, closed cup 79 °C HSDB 2008 

Flammability limits (in air, 1.7–8.6% HSDB 2008 

by % v) 

Conversion factors: 

ppm (v/v) to mg/m3 in ppm (v/v)x3.92=mg/m3 

air (25 °C) 

mg/m3 to ppm (v/v) in mg/m3x0.225=ppm (v/v) 

air (25 °C) 

atm = atmosphere; v = volume; w = weight 
PHENOL 142
 

4. CHEMICAL AND PHYSICAL INFORMATION 

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PHENOL 143 

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

5.1 PRODUCTION 

Table 5-1 lists the number of facilities in each state that manufacture or process phenol, the intended use, 

and the range of maximum amounts of phenol that are stored onsite. The data listed in Table 5-1 are 

derived from the Toxics Release Inventory (TRI) (TRI05 2007). Only certain types of facilities were 

required to report. Therefore, this is not an exhaustive list. 

Phenol has been obtained by distillation from petroleum and synthesis by oxidation of cumene or toluene, 

and by vapor-phase hydrolysis of chlorobenzene (Wallace 1998). In 2004, nearly 98% of U.S. phenol 

production was based on oxidation of cumene except at one company that used toluene oxidation and a 

few companies that distilled phenol from petroleum (CMR 2005). In 2004, the total annual capacity of 

phenol production approached 6.6 billion pounds (CMR 2005). A list of current U.S. producers of phenol 

is found in Table 5-2. 

5.2 IMPORT/EXPORT 

According to the National Trade Data Bank (USITC 2008), exports of phenol were 503 million kg 

(1,110 million pounds) (USITC 2008). The major importer of phenol from the United States was Canada, 

with an import value of 117 million kg during 2007. The total amount of phenol imported to the United 

States was 1.3 million kg (2.8 million pounds) in 2005. The largest exporter of phenol to the United 

States was South Africa, which exported 1 million kg of phenol (USITC 2008). 

5.3 USE 

The two major uses of phenol in 2004 were the production of bisphenol-A (48%) and the production of 

phenolic resins (25%) (CMR 2005). The largest use for bisphenol-A is as an intermediate in the 

production of epoxy resins (Thurman 1982). Phenol-formaldehyde resins comprise over 95% of this 

market (Thurman 1982). Other major uses of phenol include the production of caprolactam (11%), 

aniline (2%), alkylphenols (4%), xylenols (4%), and miscellaneous uses (6%) (CMR 2005). Phenol is 

used as a slimicide (a chemical toxic to bacteria and fungi characteristic of aqueous slimes) and as a 

general disinfectant in solution or mixed with slaked lime for toilets, stables, cesspools, floors, drains, and 

other areas (Budavari et al. 1989; Hawley 1981). 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PHENOL 144 

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

Table 5-1. Facilities that Produce, Process, or Use Phenol 

Minimum Maximum 

Number of amount on site amount on site 

Statea facilities in poundsb in poundsb Activities and usesc 

AK 1 100 999 1, 13 

AL 93 0 49,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

AR 39 0 49,999,999 1, 2, 3, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

AZ 17 0 9,999,999 1, 5, 6, 7, 8, 11, 12 

CA 122 0 9,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

CO 6 0 99,999 1, 2, 5, 6, 9, 10, 11 

CT 24 0 999,999 2, 3, 6, 7, 8, 10, 11, 12, 14 

DE 10 1,000 999,999 1, 3, 5, 6, 7, 12, 13 

FL 27 0 9,999,999 1, 5, 6, 7, 8, 11, 12, 13 

GA 68 0 49,999,999 1, 2, 3, 4, 5, 6, 7, 8, 10, 11, 12, 13, 14 

GU 2 0 9,999 9 

IA 31 0 999,999 2, 3, 5, 6, 7, 8, 10, 11, 12 

ID 6 0 9,999 1, 2, 3, 5, 7, 11, 13 

IL 105 0 49,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

IN 126 0 49,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

KS 36 0 9,999,999 1, 2, 3, 4, 5, 6, 7, 8, 10, 11, 12, 13 

KY 51 0 9,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 

LA 100 0 99,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

MA 38 0 499,999,999 1, 2, 3, 5, 6, 7, 8, 10, 11, 12, 13 

MD 19 0 999,999 1, 2, 3, 4, 5, 6, 7, 8, 11, 13 

ME 23 0 999,999 1, 2, 3, 5, 6, 7, 8, 10, 12, 13, 14 

MI 88 0 9,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

MN 41 0 9,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 

MO 42 0 9,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 

MS 49 0 49,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

MT 15 0 9,999,999 1, 2, 3, 5, 6, 9, 13, 14 

NC 69 0 49,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

ND 3 0 99,999 1, 5, 7 

NE 9 100 999,999 1, 3, 5, 6, 8, 11, 12 

NH 11 0 999,999 1, 2, 3, 5, 7, 8, 10, 11, 12, 13 

NJ 47 0 49,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

NM 3 10,000 999,999 1, 2, 3, 7, 10, 12, 13 

NV 2 1,000 99,999 7 

NY 62 0 9,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

OH 122 0 499,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

OK 45 0 9,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

OR 50 0 49,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 

PA 108 0 99,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 
 

 

 

 

 

 

 

 

 

 

 

 

PHENOL 145 

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

Table 5-1. Facilities that Produce, Process, or Use Phenol 

Minimum Maximum 

Number of amount on site amount on site 

Statea facilities in poundsb in poundsb Activities and usesc 

PR 15 0 999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 13 

RI 5 100 99,999 6, 7, 8 

SC 53 0 49,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

SD 1 1,000 9,999 3, 6, 10, 11 

TN 72 0 9,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

TX 155 0 10,000,000,000 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

UT 25 0 999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 

VA 41 0 49,999,999 1, 2, 3, 5, 6, 7, 8, 10, 11, 12, 13, 14 

VI 4 100 999,999 1, 2, 3, 4, 5, 6, 7, 9 

VT 6 1,000 9,999 2, 3, 6, 8, 10 

WA 58 0 9,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

WI 60 0 9,999,999 1, 2, 3, 5, 6, 7, 8, 9, 10, 11, 12, 13 

WV 27 0 49,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 13 

WY 13 0 999,999 1, 3, 4, 5, 6, 7, 12, 13 

a

Post office state abbreviations used 

b

Amounts on site reported by facilities in each state 

c

Activities/Uses: 

1. Produce 6. Impurity 11. Chemical Processing Aid 

2. Import 7. Reactant 12. Manufacturing Aid 

3. Onsite use/processing 8. Formulation Component 13. Ancillary/Other Uses 

4. Sale/Distribution 9. Article Component 14. Process Impurity 

5. Byproduct 10. Repackaging 

Source: TRI05 2007 (Data are from 2005) 
 

PHENOL 146 

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

Table 5-2. Current U.S. Producers of Phenol 

Capacity
 

Company Location (millions of pounds)
 

Dakota Gasification Company Beulah, North Dakota 35 

The Dow Chemical Company Oyster Creek, Texas 650 

General Electric Company, GE Advanced Mount Vernon, Indiana 750 

Materials Plastics 

Georgia Gulf Corporation Pasadena, Texas 160 

Georgia Gulf Corporation Plaquemine, Louisiana 500 

INOES Phenol Inc. Theodore, Alabama 1200 

JLM Chemicals Blue Island, Illinois 100 

Merisol USA LLC Houston, Texas 25 

Noveon Inc. Kalama, Washington 75 

Shell Chemical Company Deer Park, Texas 1,180 

Sunoco Inc. Haverhill, Ohio 1,000 

Sunoco Inc. Philadelphia, Pennsylvania 1,115 

Source: Derived from SRI 2006 
 

 

 

 

PHENOL 147 

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

5.4 DISPOSAL 

Phenol is listed as a toxic substance under Section 313 of the Emergency Planning and Community Right 

to Know Act (EPCRA) under Title III of the Superfund Amendments and Reauthorization Act (SARA) 

(EPA 1998c). Disposal of wastes containing phenol is controlled by a number of federal regulations (see 

Chapter 8). 
 

PHENOL 148
 

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

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PHENOL 149 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.1 OVERVIEW 

Phenol has been identified in at least 595 of the 1,678 hazardous waste sites that have been proposed for 

inclusion on the EPA National Priorities List (NPL) (HazDat 2006). However, the number of sites 

evaluated for phenol is not known. The frequency of these sites can be seen in Figure 6-1. Of these sites, 

589 are located within the United States and 4 are located in the Commonwealth of Puerto Rico (not 

shown) and 2 are located in the Virgin Islands (not shown). 

Phenol is released to the air and water as a result of its manufacture, its use in phenolic resins, and organic 

synthesis (Wallace et al. 1996). Phenol is found in petroleum products such as coal tar, and creosote and 

can be released by combustion of wood and auto exhaust (Wallace et al. 1996). Phenol is also produced 

by the natural degradation of organic wastes including benzene. Phenol is a major metabolite of benzene 

(Rothman et al. 1998), which is found extensively in the environment (Agency for Toxic Substances and 

Disease Registry 2006), therefore, phenol may be formed in the environment as a result of the natural 

degradation of benzene. 

Phenol mainly enters the water from industrial effluent discharges. Phenol is degraded rapidly in air by 

gas-phase hydroxyl radical reaction (estimated half-life 14.6 hours), but may persist in water for a 

somewhat longer period. Half-lives for biodegradation range from <1 day in samples of lake water to 

9 days in estuarine water; a typical half-life for photooxidation by photochemically produced peroxyl 

radicals is approximately 19 hours. In soil, phenol will generally biodegrade rapidly; however, 

biodegradation of phenol in water or soil may be hindered or precluded by the presence of high, toxic 

concentrations of phenol or other chemicals, or by other factors such as a lack of nutrients or 

microorganisms capable of degrading phenol. If biodegradation is sufficiently slow, phenol in sunlit 

water will undergo photooxidation with photochemically produced peroxyl radicals, and phenol in soil 

will leach to groundwater. Phenol may remain in air, water, and soil for much longer periods if it is 

continually or consistently released to these media from point sources. Since plants can metabolize 

phenol readily, exposure through eating food derived from plants grown in phenol-containing soil is 

probably minimal. 

Phenol has been measured in effluents (up to 53 ppm), ambient water (1.5–>100 ppb), drinking water (not 

quantified), groundwater (1.9–>10 ppb), rain (0.075–1.2 ppb), sediment (>10 ppb), and ambient air (0.03– 

44 ppb). Occupational exposures occur through inhalation and dermal exposure; air concentrations 

 

 

 

 

 

 

 

 

 

 

 

 

 

PHENOL 151 

6. POTENTIAL FOR HUMAN EXPOSURE 

monitored in various workplaces range from 0.1 to 12.5 mg/m3 (0.03–32 ppm). Occupational as well as 

consumer exposure may also occur through dermal contact with phenol or phenol-containing products. 

6.2 RELEASES TO THE ENVIRONMENT 

The Toxics Release Inventory (TRI) data should be used with caution because only certain types of 

facilities are required to report (EPA 2005). This is not an exhaustive list. Manufacturing and processing 

facilities are required to report information to the TRI only if they employ 10 or more full-time 

employees; if their facility is included in Standard Industrial Classification (SIC) Codes 10 (except 1011, 

1081, and 1094), 12 (except 1241), 20–39, 4911 (limited to facilities that combust coal and/or oil for the 

purpose of generating electricity for distribution in commerce), 4931 (limited to facilities that combust 

coal and/or oil for the purpose of generating electricity for distribution in commerce), 4939 (limited to 

facilities that combust coal and/or oil for the purpose of generating electricity for distribution in 

commerce), 4953 (limited to facilities regulated under RCRA Subtitle C, 42 U.S.C. section 6921 et seq.), 

5169, 5171, and 7389 (limited S.C. section 6921 et seq.), 5169, 5171, and 7389 (limited to facilities 

primarily engaged in solvents recovery services on a contract or fee basis); and if their facility produces, 

imports, or processes ≥25,000 pounds of any TRI chemical or otherwise uses >10,000 pounds of a TRI

chemical in a calendar year (EPA 2005). 

6.2.1 Air 

Estimated releases of 7.6 million pounds (~3,480 metric tons) of phenol to the atmosphere from 

677 domestic manufacturing and processing facilities in 2004, accounted for about 64% of the estimated 

total environmental releases from facilities required to report to the TRI (TRI05 2007). These releases are 

summarized in Table 6-1. 

During manufacturing, phenol is released primarily to the atmosphere from storage tank vents and during 

transport loading (EPA 1979c). Other major sources of release to the atmosphere are residential wood 

burning and automobile exhaust (EPA 1981a). Volatilization from environmental waters and soils has 

been shown to be a slow process (see Section 6.3.1) and is not expected to be a significant source of 

atmospheric phenol. Phenol is released into the atmosphere from industrial combustion processes. For 

example, phenol has been detected at a concentration of 0.36 ppb in the emissions of a waste incinerator 

plant in Germany (Jay and Stieglitz 1995). In Brazil, an estimated 64 kg/year of phenol is released to the 

urban areas located near coal-fired power stations, indicating that people who live near coal-fired power 

stations may have an increased risk of exposure to phenol (Moreira dos Santos et al. 2004). Phenol is also 
PHENOL 152 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-1. Releases to the Environment from Facilities that Produce, Process, or
 

Use Phenola
 

Reported amounts released in pounds per yearb 

Total release 

On- and 

Statec RFd Aire Waterf UIg Landh Otheri On-sitej Off-sitek off-site 

AL 33 407,745 278 0 8,213 0 408,261 7,975 416,236 

AR 15 53,803 136 0 4,781 0 54,241 4,479 58,720 

AZ 2 5,499 No data 0 100 0 5,499 100 5,599 

CA 33 100,135 1,974 0 5,544 305 102,117 5,841 107,958 

CO 2 32 No data 0 0 0 32 0 32 

CT 4 5,631 No data 0 649 728 5,631 1,377 7,008 

DE 2 160 44,595 0 0 0 44,755 0 44,755 

FL 12 114,230 950 0 91 0 115,272 0 115,272 

GA 25 146,687 518 0 1,468 2,102 147,242 3,533 150,775 

IA 5 17,126 36 0 100,501 0 17,162 100,501 117,663 

ID 2 1,005 5 0 4,428 0 1,010 4,428 5,438 

IL 28 614,954 602 0 50,925 251 616,526 50,206 666,732 

IN 32 391,396 3,660 100,000 35,975 5 495,190 35,845 531,035 

KS 7 76,565 54 0 5,869 1,829 76,637 7,680 84,317 

KY 13 108,867 809 0 56,542 0 109,676 56,542 166,218 

LA 36 124,638 15,173 150,002 10,660 120 295,401 5,192 300,593 

MA 6 15,108 No data 0 803 0 15,108 803 15,911 

MD 2 13,004 No data 0 0 0 13,004 0 13,004 

ME 5 25,852 15 0 906 0 25,893 880 26,773 

MI 29 121,520 660 19 78,038 44,762 122,188 122,810 244,998 

MN 8 55,892 150 0 98 3 56,117 26 56,143 

MO 9 15,024 0 0 0 0 15,024 0 15,024 

MS 12 67,983 207 0 1,238 0 68,190 1,238 69,428 

MT 5 3,724 25 0 23 0 3,772 0 3,772 

NC 23 186,812 311 0 164,098 0 187,269 163,952 351,221 

ND 1 220 49 2,100 0 0 2,369 0 2,369 

NE 4 888 No data 0 147 0 896 139 1,035 

NH 2 6,203 No data 0 1 0 6,203 1 6,204 

NJ 10 6,218 1,828 0 10,327 0 16,022 2,351 18,373 

NM 1 1,078 No data 0 0 0 1,078 0 1,078 

NY 23 57,689 62 0 22,704 56,518 57,777 79,196 136,973 

OH 45 522,126 1,219 34 119,210 807 528,880 114,516 643,397 

OK 10 21,713 558 0 17,557 4,855 38,249 6,434 44,683 

OR 22 186,431 189 0 12,935 3,453 187,736 15,272 203,008 

PA 29 424,309 9,699 0 4,994 2,093 434,776 6,319 441,096 

PR 3 4,974 No data 0 4,561 0 4,974 4,561 9,535 

RI 1 724 No data 0 0 0 724 0 724 
 

PHENOL 153 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-1. Releases to the Environment from Facilities that Produce, Process, or
 

Use Phenola
 

Reported amounts released in pounds per yearb 

Total release 

On- and 

Statec RFd Aire Waterf UIg Landh Otheri On-sitej Off-sitek off-site 

SC 20 93,387 1,284 0 148,473 0 115,489 127,656 243,145 

TN 15 81,725 305 0 2,006 45 82,439 1,642 84,081 

TX 75 233,116 7,659 1,225,465 99,083 118 1,416,533 148,909 1,565,442 

UT 3 31,100 No data 0 7,600 0 38,700 0 38,700 

VA 12 56,625 299 0 31,225 750 87,264 1,635 88,899 

VI 1 78,848 612 0 1 0 79,460 1 79,461 

WA 19 127,933 5,382 0 427 181 133,355 568 133,923 

WI 23 305,630 55 0 27,762 30 305,685 27,792 333,477 

WV 6 20,279 188 0 69 44 20,475 105 20,580 

WY 2 750 No data 0 0 0 750 0 750 

Total 677 4,935,360 99,546 1,477,621 1,040,033 118,999 6,561,054 1,110,505 7,671,559 

a

The TRI data should be used with caution since only certain types of facilities are required to report. This is not an 

exhaustive list. Data are rounded to nearest whole number.
 b

Data in TRI are maximum amounts released by each facility.
 c

Post office state abbreviations are used.
 d

Number of reporting facilities.

e

The sum of fugitive and point source releases are included in releases to air by a given facility.
 f

Surface water discharges, waste water treatment-(metals only), and publicly owned treatment works (POTWs) (metal
 

and metal compounds).

g

Class I wells, Class II-V wells, and underground injection. h

Resource Conservation and Recovery Act (RCRA) subtitle C landfills; other on-site landfills, land treatment, surface 

impoundments, other land disposal, other landfills.

i

Storage only, solidification/stabilization (metals only), other off-site management, transfers to waste broker for
 

disposal, unknown

j

The sum of all releases of the chemical to air, land, water, and underground injection wells.

k

Total amount of chemical transferred off-site, including to POTWs.
 

RF = reporting facilities; UI = underground injection 

Source: TRI05 2007 (Data are from 2005) 
 

 

 

 

 

 

 

 

 

PHENOL 154 

6. POTENTIAL FOR HUMAN EXPOSURE 

found in cigarette smoke and in plastics (Graedel 1978), but no data are available to determine the extent 

of exposure to phenol from these sources. 

6.2.2 Water 

Estimated releases of 99,546 pounds (~45 metric tons) of phenol to surface water from 677 domestic 

manufacturing and processing facilities in 2005, accounted for about 0.1% of the estimated total 

environmental releases from facilities required to report to the TRI (TRI05 2007). These releases are 

summarized in Table 6-1. 

The most common anthropogenic sources of phenol in natural water include coal tar (Thurman 1982) and 

waste water from manufacturing industries such as resins, plastics, fibers, adhesives, iron, steel, 

aluminum, leather, rubber (EPA 1981b), and effluents from synthetic fuel manufacturing (Parkhurst et al. 

1979). Phenol is also released from paper pulp mills (Keith 1976) and wood treatment facilities (Goerlitz 

et al. 1985). Other releases of phenol result from commercial use of phenol and phenol-containing 

products, including slimicides, general disinfectants (Budavari et al. 1989; Hawley 1981), and medicinal 

preparations such as throat lozenges, mouthwashes, gargles, and antiseptic lotions (Darisimall 2006). 

Two natural sources of phenol in aquatic media are animal wastes and decomposition of organic wastes 

(EPA 1980). As a metabolite of benzene, phenol may be released from publicly owned treatment works 

(POTWs) and sewage overflow. For example, it has been estimated that 3.8 kg/day of phenol are released 

to Newark Bay, in New Jersey, from municipal treatment facilities (Crawford et al. 1995). Phenol was 

detected in 2% of the effluent samples from New York City sewage waste facilities collected during 1989 

to 1993 at concentrations of 6–310 g/L (Stubin et al. 1996). Because it is a metabolite, phenol is likely to 

be found in other sewage and POTWs facilities. No data are available to determine the extent of exposure 

from these sources. 

Estimated releases of 85,700 pounds (~39 metric tons) of phenol to surface water from 689 domestic 

manufacturing and processing facilities in 2004, accounted for about 0.1% of the estimated total 

environmental releases from facilities required to report to the TRI (TRI05 2007). These releases are 

summarized in Table 6-1. 

The most common anthropogenic sources of phenol in natural water include coal tar (Thurman 1982) and 

waste water from manufacturing industries such as resins, plastics, fibers, adhesives, iron, steel, 

aluminum, leather, rubber (EPA 1981b), and effluents from synthetic fuel manufacturing (Parkhurst et al. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

PHENOL 155 

6. POTENTIAL FOR HUMAN EXPOSURE 

1979). Phenol is also released from paper pulp mills (Keith 1976) and wood treatment facilities (Goerlitz 

et al. 1985). Other releases of phenol result from commercial use of phenol and phenol-containing 

products, including slimicides, general disinfectants (Budavari et al. 1989; Hawley 1981), and medicinal 

preparations such as throat lozenges, mouthwashes, gargles, and antiseptic lotions (Darisimall 2006). 

6.2.3 Soil 

Estimated releases of 1 million pounds (~472 metric tons) of phenol to soils from 689 domestic 

manufacturing and processing facilities in 2005, accounted for about 14% of the estimated total 

environmental releases from facilities required to report to the TRI (TRI05 2007). An additional 

1.5 million pounds (~670 metric tons), constituting about 19% of the total environmental emissions, were 

released via underground injection (TRI05 2007). These releases are summarized in Table 6-1. 

Phenol may be released to the soil during its manufacturing process, when spills occur during loading and 

transport, and when it leaches from hazardous waste sites and landfills (Xing et al. 1994). Generally, data 

on concentrations of phenol found in soil at sites other than hazardous waste sites are lacking. This may 

be due in part to a rapid rate of biodegradation and leaching (see Sections 6.3.1 and 6.3.2.3). Phenol can 

be expected to be found in soils that receive continuous or consistent releases from a point source. Phenol 

that leaches through soil to groundwater spends at least some time in that soil as it travels to the 

groundwater. Phenol has been found in groundwater, mainly at or near hazardous waste sites. 

6.3 ENVIRONMENTAL FATE 

6.3.1 Transport and Partitioning 

Phenol is released into the air and discharged into water from both manufacturing and use. Based on its 

high water solubility (see Table 4-2) and the fact that it has been detected in rainwater, some phenol may 

wash out of the atmosphere; however, it is probable that only limited amounts wash out because of the 

short atmospheric half-life of phenol. During the day, when photochemically produced hydroxyl radical 

concentrations are highest in the atmosphere, very little atmospheric transport of phenol is likely to occur. 

In water, neither volatilization nor sorption to sediments and suspended particulates are expected to be 

important transport mechanisms. Using the Henry's Law constant of 3x10-7 atm m3

/mol (Gaffney et al. 

1987), a volatilization half-life of 88 days was calculated for phenol evaporation from a model river 1 m 

deep with a current of 1 m/second, and wind velocity of 3 m/second (Lyman et al. 1982). The biological 
 

 

 

 

 

 

 

 

PHENOL 156 

6. POTENTIAL FOR HUMAN EXPOSURE 

treatment of waste water containing phenol has shown that <1% of phenol is removed by stripping 

(Kincannon et al. 1983; Petrasek et al. 1983). 

Phenol has been reported in sediments at levels as high as 608 ppm dry weight; however, it is not known 

whether the location of the site where this concentration was reported is at or near a point source of 

release, such as a hazardous waste dump. The concentrations of the overlying waters were not reported. 

The moderately low soil sorption partition coefficient (1.21–1.96) suggests that sorption to sediment is 

not an important transport process. There is very little sorption of phenol onto aquifer materials (Ehrlich 

et al. 1982), suggesting that phenol sorption to sediments may also be minimal. Based on the soil 

adsorption coefficient, phenol is expected to leach to groundwater; however, the rate of phenol 

biodegradation in the soil may be so rapid, except in cases of large releases such as spills or continuous 

releases such as leaching from landfill sites, that the probability of groundwater contamination may be 

low (Ehrlich et al. 1982). Phenol has been detected in groundwater as a result of leaching through soil 

from a spill of phenol (Delfino and Dube 1976), from landfill sites (Clark and Piskin 1977), and from 

hazardous waste sites (Plumb 1987). The sorption coefficient for phenol by soils increases with 

increasing soil organic matter which may indicate that soil organic matter may be the primary phenol 

sorbent in soil (Xing et al. 1994). 

Phenol is not expected to bioconcentrate significantly in aquatic organisms. Reported log bioconcentration factors (BCF) in fish for phenol include 0.28 for goldfish, (Kobayashi et al. 1979) and 1.3 for golden 

orfe (Freitag et al. 1984). The highest mean level of phenol detected in bottom fish from Commencement 

Bay in Tacoma, Washington, was 0.14 ppm (Nicola et al. 1987). The levels of phenol in the water or 

sediments were not stated. 

The pKa of phenol is 10 (O’Neil 2001), indicating that phenol will primarily exist as the protonated acid 

at environmental pH values. In alkaline soils and water, phenol will partially exist as an anion, which can 

affect its fate and transport processes. 

Although it has been shown that plants readily uptake phenol (DOE 1987), bioaccumulation does not take 

place due to a high rate of respiratory decomposition of phenol to CO2. 
 

 

 

 

 

 

 

 

 

 

 

PHENOL 157 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.3.2 Transformation and Degradation 

6.3.2.1 Air 

The gas-phase reaction of phenol with photochemically produced hydroxyl radicals is probably a major 

removal mechanism in the atmosphere. An estimated half-life for phenol for this reaction is 0.61 days 

(EPA 1979a). The reaction of phenol with nitrate radicals during the night may constitute a significant 

removal process. This is based on a rate constant of 3.8x10-12 cm3

/molecule second for this reaction, 

corresponding to a half-life of 15 minutes at an atmospheric concentration of 2x108 nitrate radicals per 

cm3 (Atkinson et al. 1987). The reaction of phenol with nitrate radicals present in the atmosphere during 

smog episodes may decrease the half-life of phenol in polluted atmospheres. The above data indicate that 

phenol has a short half-life in the atmosphere, probably <1 day. Phenol does not absorb light in the 

region of 290–330 nm (Lide and Milne 1994); therefore, it should not photodegrade directly in the 

atmosphere. 

6.3.2.2 Water 

Although phenol does not absorb light at wavelengths >290, phenols react rapidly to sunlit natural water 

via an indirect reaction with photochemically produced hydroxyl radicals and peroxyl radicals; typical 

half-lives for hydroxyl and peroxyl radical reactions are on the order of 100 and 19.2 hours of sunlight, 

respectively (Canonica et al. 1995; Mill and Mabey 1985). These reactions require dissolved natural 

organic materials that function as photosensitizers (Canonica et al. 1995). The estimated half-life for the 

reaction of phenol with photochemically produced singlet oxygen in sunlit surface waters contaminated 

by humic substances is 83 days (assuming Switzerland summer sunlight and a singlet oxygen 

concentration of 4x10-14 molar [M]) (Scully and Hoigne 1987). 

Phenol is readily biodegradable in natural water, provided the concentration is not high enough to cause 

significant inhibition through microbial toxicity. Complete degradation in <1 day has been reported in 

water from three lakes; the rates of degradation were affected by the concentration of organic and 

inorganic nutrients in the water (Rubin and Alexander 1983). Complete removal of phenol in river water 

has been reported after 2 days at 20 °C and after 4 days at 4 °C (Ludzack and Ettinger 1960). The 

degradation of phenol is somewhat slower in salt water, and a half-life of 9 days has been reported in an 

estuarine river (EPA 1979b). Rapid degradation of phenol also has been reported in various sewage and 

water treatment processes. Removal in aerobic activated sludge reactors is frequently >90% with a 

retention time of 8 hours (Stover and Kincannon 1983). In aerobic reactors using municipal seed 
 

 

 

 

 

 

 

PHENOL 158 

6. POTENTIAL FOR HUMAN EXPOSURE 

(conventional activated sludge organisms) and in reactors using an industrial seed (mixture of organisms), 

it was noted that concentrations as low as 50 mg/L inhibited organism respiration rates, but complete 

inhibition was not observed at concentrations as high as 200 mg/L (Davis et al. 1981). Utilization is also 

very high in anaerobic reactors, although acclimation periods are longer and degradation usually takes 

about 2 weeks (Boyd et al. 1983; Healy and Young 1978). One method of phenol breakdown is 

accomplished by the bacterium Pseudomonas sp. CF600, which uses a set of enzymes encoded by the 

plasmid dmp operon (Powlowski and Shingler 1994). The use of sequence batch reactors (SBR) in 

treating sludge contaminated with phenolic compounds has proven effective in breaking down the 

compounds biologically with no evidence of phenol volatility (Al-Harazin et al. 1991). Levels as high as 

a one-time treatment of 1,600 mg/L can be broken down by 75% with a 1-day retention time. Lower 

concentrations as high as 800 mg/L can be broken down to <0.5 mg/L with a 1-day retention time. The 

alga Ochromonas danica has also been shown to degrade phenol (Semple and Cain 1996). When grown 

in the dark with 0.1–1 mM phenol as the sole carbon source, phenol was removed within 3 days. Because 

of the rapid rate of biodegradation, groundwater is generally free of phenol even though it is highly 

mobile in soil. However, monitoring data in Section 6.4.2 contain groundwater concentrations in areas of 

large phenol releases. 

While the evidence presented in the literature cited above suggests that phenol can be rapidly and 

virtually completely degraded under both natural water and sewage treatment plant conditions, 

monitoring data presented in Section 6.4 below indicate that phenol, despite this apparent 

biodegradability, is still present in the environment. This suggests that the exact conditions under which 

phenol is rapidly degraded are not present in all instances. In some situations, the concentration of phenol 

may be too high or the populations of microorganisms may not be present in sufficient concentration for 

significant biodegradation to occur. 

6.3.2.3 Sediment and Soil 

Available data indicate that phenol biodegrades in soil under both aerobic and anaerobic soil conditions. 

The half-life of phenol in soil is generally <5 days (Baker and Mayfield 1980), but acidic soils and some 

surface soils may have half-lives of up to 23 days (Shiu et al. 1994). Mineralization in an alkaline, parabrown soil under aerobic conditions was 45.5, 48, and 65% after 3, 7, and 70 days, respectively (Haider et 

al. 1974). Half-lives for degradation of low concentrations of phenol in two silt loam soils were 2.70 and 

3.51 hours (Scott et al. 1983). Plants have been shown to be capable of metabolizing phenol readily 

(DOE 1987). 
 

 

 

 

 

 

 

 

 

 

 

 

 

PHENOL 159 

6. POTENTIAL FOR HUMAN EXPOSURE 

While degradation is slower under anaerobic conditions, evidence presented in the literature suggests that 

phenol can be rapidly and virtually completely degraded in soil under both aerobic and anaerobic 

conditions (Baker and Mayfield 1980). 

6.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT 

Reliable evaluation of the potential for human exposure to phenol depends in part on the reliability of 

supporting analytical data from environmental samples and biological specimens. Concentrations of 

phenol in unpolluted atmospheres and in pristine surface waters are often so low as to be near the limits of 

current analytical methods. In reviewing data on phenol levels monitored or estimated in the 

environment, it should also be noted that the amount of chemical identified analytically is not necessarily 

equivalent to the amount that is bioavailable. The analytical methods available for monitoring phenol in a 

variety of environmental media are detailed in Chapter 7. 

6.4.1 Air 

There are very few monitoring data concerning the presence of phenol in ambient air. Phenol was found 

at a median concentration of 30 parts per trillion (ppt) in 7 samples from 1 U.S. urban/suburban site in 

1974 and at an overall median concentration of 5,000 ppt in 83 samples from 7 source-dominated sites 

between 1974 and 1978 (EPA 1982). The individual medians of the seven source sites ranged from 

520 to 44,000 ppt (EPA 1982). Phenol was detected, but not quantified, in air above the Niagara River in 

September of 1982 (Hoff and Chan 1987). Phenol concentrations in two urban areas ranged from 13 to 

91 ppt and from <5 to 75 ppb with 50% of all measurements <8 ppb (EPA 1981a). Phenol was found at 

approximately 1 ppb in the ambient air near a fishmeal factory in Japan (Hoshika et al. 1981). In a study 

to determine contaminants in the air of agricultural areas, phenol was found in 42 out of 53 air samples 

taken from 8 farms at an average concentration of 10 μg/m3 (Sunesson et al. 2001). Phenol was detected 

in indoor and outdoor air in the city of Ottawa, Canada at concentration ranges of 0.01–5.16 and 0.01– 

1.41 μg/m3

, respectively (Zhu et al. 2005). 

In a study of various air samples from Helsinki, Finland, 92% of outdoor air and 86% of indoor air did 

not have detectible quantities of phenol (Edwards et al. 2001). Workplace and personal exposure samples 

also had low relative percentages of phenol with only 12 and 11% of the samples above the limits of 

detection, respectively (Edwards et al. 2001). 
 

 

 

 

 

 

 

 

 

 

 

 

PHENOL 160 

6. POTENTIAL FOR HUMAN EXPOSURE 

Higher phenol concentrations may occur when there is smog or in highly contaminated air. During a 

smog episode in West Covina, California, in July of 1973, phenol concentrations ranged from 16 to 

91 ppt, with a mean concentration of 60 ppt (Cronn et al. 1977). During a haze episode in 1998 in Brunei, 

Syria, phenol was found in 8 out of 15 sites tested in concentrations ranging from 0.07 to 0.41 μg/m3

; of 

these sites, 4 were near a hospital (Muraleedharan et al. 2000). 

Phenol and other volatile organic compounds were measured in the air of 50 homes or apartments in 

Finland (Kostiainen 1995). The average concentration was 0.23 ppb, with a range of 0–0.77 ppb. Phenol 

levels were not significantly higher in houses in which people complained of symptoms that resembled 

those of a sick building syndrome. 

Phenol has been detected in the ash phase of burning pine, oak, and eucalyptus in concentrations of 524, 

300, and 434 mg/kg, respectively (Schauer et al. 2001). Phenol has also been identified in the combustion 

of soft fireplace wood, hard fireplace wood, stove wood, and synthetic wood at concentrations of 158, 

247, 142, and 8.58 mg/kg, respectively (McDonald et al. 2000). 

Phenol is released to the atmosphere from burning coal. In a study of three urban sites in Brazil near 

coal-fired power stations, phenol was detected in all three locations with concentrations ranging from 

0.98 to 1.60 μg/m3 (Moreira dos Santos et al. 2004). This indicates that families living near coal-fired 

power stations may be exposed to higher concentrations of phenol. 

6.4.2 Water 

Phenol has been detected in surface waters, rainwater, sediments, drinking water, groundwater, industrial 

effluents, urban runoff, and at hazardous waste sites. Background levels of phenol from relatively pristine 

sites can be as high as 1 ppb for unpolluted groundwater and have been reported to range from 0.01 to 

1 ppb in unpolluted rivers (Thurman 1985). Phenol has been detected in Lake Huron water at 3–24 ppb 

(Konasewich et al. 1978) and industrial rivers in the United States at 0–5 ppb (Sheldon and Hites 1978, 

1979). The annual mean concentration of phenol in water from the lower Mississippi River was 1.5 ppb 

(EPA 1980). River water in an unspecified location in the United States was reported to contain 10– 

100 ppb of phenol (Jungclaus et al. 1978). Phenol was detected, but not quantified, in a Niagara River 

watershed (Elder et al. 1981) and in 2 of 110 raw water samples analyzed during the National Organic 

Monitoring Survey (EPA 1980). 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PHENOL 161 

6. POTENTIAL FOR HUMAN EXPOSURE 

In a study of 95 organic waste components from 139 streams in 30 states from 1999 to 2000, phenol was 

detected in 85 samples with a median concentration of 0.7 μg/L (Kolpin et al. 2002). Phenol has been 

detected in China in water samples taken near the Huanchao River water factory, in the Tanking River, 

and near the Tanking River water factory at concentrations of 0.053, 0.044, and 0.033 μg/L, respectively

(Huang et al. 2003). 

Each year about 30 million m3 of mine water is pumped into the Samara River in the Ukraine. Phenol 

was detected in the surface water in the Samara River from 1987 to 1990 with concentrations ranging 

from 1.5 to 8.3 μg/L (Goncharuk and Milyukin 1999). In a study of organic contaminants in the

groundwater from creosote contaminated sites in Denmark, phenol was detected in all 11 sites tested with 

concentrations ranging from 11 to 249 μg/L (Johansen et al. 1997). 

In general, higher levels of phenol appear to be found in lakes and rivers that serve as water sources and 

discharge receivers for industrial and population centers, probably as a result of industrial activity and 

commercial use of phenol-containing products. For example, the presence of higher levels of phenol in 

the Delaware River near Philadelphia is the result of industrial effluents discharged into the sewer system 

(Sheldon and Hites 1979). Phenol was detected in 23% of samples of influent of waste water from New 

York City during 1989 to 1993 at concentrations ranging from 8 to 490 g/L; phenol was detected in 2% of 

effluent samples at concentrations ranging from 6 to 310 g/L during the same period (Stubin et al. 1996). 

The presence of phenol in drinking water probably results from using contaminated surface water or 

groundwater as a source. Its presence in groundwater is probably the result of release to soil, often 

industrial releases or leachate from waste dumps, and the subsequent leaching of phenol through the soil 

to the groundwater. Phenol has been detected, but not quantified, in drinking water from 5 of 14 drinking 

water treatment plants between July 1977 and June 1979 in one of three sites (groundwater source), in 

three out of ten (surface water source) as well as water source used after distribution (Fielding et al. 

1981). Phenol levels in tap water, spring water, and mineral water in Italy were 0.58, 0.051, and 

0.161 μg/L, respectively (Achilli et al. 1995). Phenol was detected at a maximum concentration of 

1,130 ppm in ninewells in Wisconsin after a spill, and was detected for at least 1.5 years after the spill 

(Delfino and Dube 1976). It was found at concentrations up to 10.4 ppm in groundwater from a sand 

aquifer adjacent to waste ponds at a wood-preserving facility in Florida (Goerlitz et al. 1985), and was 

detected at 6.510,000 ppb in two aquifers 15 months after the completion of a coal gasification project 

(Stuermer et al. 1982). Phenol was detected at a maximum concentration of 1.9 ppm in leachates from 

landfill sites in Illinois (Clark and Piskin 1977). Near a landfill in central Florida, phenol was found in 
 

 

 

 

 

 

 

 

 

 

 

 

PHENOL 162 

6. POTENTIAL FOR HUMAN EXPOSURE 

groundwater and surface water at about 17and 15 ppb, respectively (Chen and Zoltek 1995). Phenol was 

detected, but not quantified, in the groundwater at 13.6% of 178 CERCLA hazardous waste sites (Plumb 

1987). 

Phenol was detected during seven rain events in Portland, Oregon, between February and April of 1984. 

Concentrations in rain ranged from >75 to 1,200 ppt, and averaged above 280 ppt. Gas-phase 

concentrations ranged from 220 (56.1 ppt) to 410 ng/m3 (105 ppt) and averaged 320 ng/m3 (82 ppt) 

(Leuenberger et al. 1985). 

Phenol can also be transported in snow and rain. In Germany, phenol has also been detected in clouds at 

Mount Brocken in June 1994 and during April to May in Great Dun Fell with mean concentrations of 

3.0 μg/L and 5.4 μg/L, respectively (Lüttke 1999). Snow from Neulaniemi, Muonio, and Levi, Finland, 

contained phenol in concentrations of 0.16, 0.04, and 0.02 μg/kg, respectively (Poliakova et al. 2000). In 

Russia, phenol was detected in snow samples at concentrations of 0.02, 0.21, and 1.3 μg/kg in Butovo,

Moscow State University, and Shosse Entuzoastov (a heavily industrial district in Moscow), respectively 

(Poliakova et al. 2000). 

Phenol has been detected in the effluent discharges of a variety of industries. It was found in petroleum 

refinery waste water at concentrations of 33.5 ppm (Pfeffer 1979) and 100 ppb (Paterson et al. 1996), in 

the treated and untreated effluent from a coal conversion plant at 4 and 4,780 ppm, respectively 

(Parkhurst et al. 1979), and in shale oil waste water at a maximum of 4.5 ppm (Hawthorne and Sievers 

1984). It has also been detected in the effluent from a chemical specialties manufacturing plant at 0.01– 

0.30 ppm (Jungclaus et al. 1978), in effluent from paper mills at 5–8 ppb (Keith 1976; Paterson et al. 

1996), and at 0.3 ppm in a 24-hour composite sample from a plant on the Delaware River, 2 and 4 miles 

downriver from a sewage treatment plant (Sheldon and Hites 1979). 

A study of the seasonal effects on the concentration of pesticides as well as other contaminants in Gulf of 

Gdansk in the Baltic Sea from autumn 2001 to spring 2003 showed only 1 out of 14 samples taken in 

autumn to have a detectable level of phenol with a concentration of 2.3 μg/L (Kot-Wasik et al. 2004). In 

the spring, phenol was detected in 11 of the 14 samples at concentrations ranging from 0.3 to 0.8 μg/L

(Kot-Wasik et al. 2004). 

Phenol has also been found in the primary and secondary effluent from the Los Angeles City Treatment 

Plant at concentrations of 32 and <10 ppb, respectively (Young et al. 1983). It was found in 3 of 
 

 

 

 

 

 

 

 

PHENOL 163 

6. POTENTIAL FOR HUMAN EXPOSURE 

86 samples of runoff from 2 of 15 cities at 3–10 ppb by the U.S. Nationwide Urban Runoff Program as of 

July of 1982 (Cole et al. 1984). 

6.4.3 Sediment and Soil 

Very few data concerning the presence of phenol in soils were found. Phenol generally does not adsorb 

very strongly to soils and tends to leach rapidly through soil, which may account for the lack of 

monitoring data, since any phenol released to soils is likely to leach to groundwater. Moreover, phenol is 

readily degraded in the environment, which is expected to attenuate its levels in soil. 

Sediment collected 6 km northwest of the Los Angeles County waste-water treatment plant discharge 

zone at Palos Verdes, California, contained 10 ppb (dry weight) phenol (Gossett et al. 1983). 

In a study of contaminants in stream bed sediments across the United States, phenol was detected at 

536 sites at a maximum concentration of 210 μg/kg (Lopes and Furlong 2001). 

6.4.4 Other Environmental Media 

Phenol has been reported at concentrations of 7 and 28.6 ppm in smoked summer sausage and smoked 

pork belly, respectively (EPA 1980), and was identified but not quantified in mountain cheese (Dumont 

and Adda 1978), fried bacon (Ho et al. 1983), fried chicken (Tang et al. 1983), and black fermented tea 

(Kaiser 1967). Phenol has also been found in honey at concentrations ranging from 0 (detection limit 

0.1 ppm) to 19 ppm (Sporns 1981). It was present each time the honey was collected with phenol-treated 

boards. Phenol has been reported in three different types of fermented soybean curds at concentrations 

ranging from 450 to 6,000 μg/kg (Chung 1999).

Phenol has been found in bottomfish from five sites in Commencement Bay in Tacoma, Washington, at a 

highest maximum average and overall maximum concentration of 0.14 and 0.22 ppm, respectively 

(Nicola et al. 1987). Phenol has been reported to be a natural component of animal matter; it has been 

found at 0–1.6 ppm in rabbit muscle tissue (EPA 1980). 

Phenol has been detected in the eggs of birds in the Lake Baikal Region of Italy in concentrations ranging 

from 840 to <20 μg/kg dry weight (Lebedev et al. 1998).
 

 

 

 

 

 

PHENOL 164 

6. POTENTIAL FOR HUMAN EXPOSURE 

Phenol is also found in medicinal preparations including throat lozenges, mouthwashes, gargles, and 

antiseptic lotions (Darisimall 2006). Commercial antiseptic lotions may contain up to 1.4% phenol 

(Darisimall 2006). Package labeling information indicates that commercial throat lozenges contain up to 

29 mg of phenol per lozenge (Darisimall 2006). Other consumer products such as disinfectants and 

cleaners may contain phenol (O’Neil 2001).. It has been found that the smoke of 1 nonfilter cigarette 

contains 60–140 μg of phenol, 19–35 μg for a filter-tipped cigarette, and 24–107 μg in cigars (IARC

1986; NCI 1998). Using a testing method developed by the U.S. Federal Trade Commission (FTC), 

analysis of the smoke from several different brands and types of cigarettes found phenol in concentrations 

ranging from 0.3 to 68 μg/cigarette (Roemer et al. 2004). The lowest concentration came from an 

electrically heated prototype cigarette, while most of the commercial brands were within a range of 2.6– 

23.4 μg/cigarette (Roemer et al. 2004).

While not detected in topsoil from Holy Cross Mountain Park, Poland, and surrounding area, phenol was 

detected in 4 out of the 12 pine needle samples taken from the same area (Migaszewski 1999). 

Phenol was detected in 303 of 389 samples of settled dust from indoor residences in Sweden; the mean 

concentration of phenol was 4 μg/g dust (Nilsson et al. 2005).

6.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE 

Data concerning concentrations of phenol in ambient air are insufficient to estimate the potential for 

exposure by inhalation. However, smoke from a single nonfilter cigarette was observed to contain 60– 

140 μg phenol, while levels of phenol range from 19 to 35 μg in the smoke of filter-tipped cigarettes, and 

from 24 to 107 μg in the smoke of cigars (IARC 1986; NCI 1998). Therefore, indoor environments

polluted with tobacco smoke are likely to contain measurable amounts of phenol (Guerin et al. 1992). 

Nonsmokers who live with smokers are thought to be exposed to as much as 1.1 μg/m3

. This would 

account for a daily inhalation of 6–14 μg/day (Nazaroff and Singer 2004).

Phenol concentrations in surface and drinking waters are expected to vary with location and proximity to 

varying industrial and municipal discharges. Considering the lack of quantitative, current monitoring data 

and the probable seasonal, spatial, and temporal variations in the concentrations of phenol at these 

sources, it is not possible to estimate accurately a potential daily dose of phenol from drinking 

contaminated water or from dermal exposure to contaminated water. Nonetheless, it is probable that only 

those systems that receive their water from contaminated surface water and groundwater contain phenol. 
 

 

 

 

 

 

 

 

 

 

 

PHENOL 165 

6. POTENTIAL FOR HUMAN EXPOSURE 

Although phenol has been identified in various food products, a quantitative estimate regarding the intake 

of phenol from the ingestion of food has not been estimated. 

Few data concerning occupational exposures to phenol were located. The average airborne 

concentrations of phenol to which workers were exposed at three locations within two wood creosote 

impregnation plants ranged from 0.03 to 0.5 ppm (Heikkila et al. 1987). A phenol concentration of 

approximately 0.5 ppm was measured in the workroom air at a casting factory in Osaka City, Japan 

(Kuwata et al. 1980), and concentrations as high as 3.2 ppm were measured in Japanese Bakelite factories 

(Ohtsuji and Ikeda 1972). Considering the lack of quantitative monitoring data for phenol in occupational 

atmospheres, it is not possible to estimate the potential for occupational exposure to phenol. The data, 

however, do show that exposure to phenol through breathing and dermal contact with contaminated 

workroom atmospheres is possible. The National Occupational Exposure Survey (NOES) conducted by 

NIOSH estimated that 584,372 workers were exposed to phenol in the United States (NIOSH 1990). The 

NOES database does not contain information on the frequency, concentration, or duration of exposures. 

The survey provides only estimates of workers potentially exposed to chemicals in the workplace. 

Other occupations that may have increased exposure risk include laboratory workers, morticians, and 

house cleaners. Phenol is a common solvent used in laboratory research as well as a component of 

embalming fluid. The general population may be exposed to phenol found in consumer products such as 

general disinfectants used to clean toilets, floors, drains, and other areas (Lewis 2001; O’Neil 2001). 

House cleaners and people who work with these products daily are likely to have increased exposure. 

Exposure to phenol also occurs through the use and subsequent ingestion of phenol-containing products, 

including mouthwashes, gargles, and throat sprays (Darisimall 2006). The concentration of phenol in 

throat sprays ranged from 0.5 to 1.4% phenol. Determining actual dosage from these sprays would be 

difficult as the delivery method is not precise. Cepastat® lozenges, a readily available remedy for sore 

throats, contains 14.5–29 mg phenol/lozenge (Darisimall 2006). If a patient (adults and children over 6) 

takes the maximum recommended daily number of 18 lozenges, this would result in approximate doses of 

270–520 mg phenol/day. There is no control over the intake of non-prescription drugs and therefore, 

some individuals may consume considerably higher doses of phenol. 

The estimated relative contributions of the various exposure routes and sources of total phenol exposure 

cannot be estimated using the available data. Nonetheless, for persons not exposed to phenol in the 

workplace, exposure will most likely result from: inhalation of contaminated ambient air, primarily in the 
 

 

 

 

 

 

 

 

PHENOL 166 

6. POTENTIAL FOR HUMAN EXPOSURE 

vicinity of industries and municipalities that release significant amounts of phenol into the atmosphere; 

ingestion of drinking water from contaminated surface waters or groundwaters; ingestion of phenolcontaining products; and dermal exposure to contaminated water and to phenol-containing products. 

Dermal contact with phenol or ingestion of phenol-containing products probably constitutes the largest 

consumer exposure, although this exposure may occur on an acute basis. Inhalation and dermal 

exposures appear to be most significant in occupational settings. Total phenol exposure for workers 

exposed to phenol in the workplace is probably substantially higher than for those not exposed in the 

workplace. 

Exposure to benzene is likely to increase phenol exposure because phenol is a metabolite of benzene and 

is often used to detect benzene exposure. Major releases of benzene include cigarette smoke, auto 

exhaust, and gasoline fumes. 

6.6 EXPOSURES OF CHILDREN 

This section focuses on exposures from conception to maturity at 18 years in humans. Differences from 

adults in susceptibility to hazardous substances are discussed in Section 3.7, Children’s Susceptibility. 

Children are not small adults. A child’s exposure may differ from an adult’s exposure in many ways. 

Children drink more fluids, eat more food, breathe more air per kilogram of body weight, and have a 

larger skin surface in proportion to their body volume. A child’s diet often differs from that of adults. 

The developing human’s source of nutrition changes with age: from placental nourishment to breast milk 

or formula to the diet of older children who eat more of certain types of foods than adults. A child’s 

behavior and lifestyle also influence exposure. Children crawl on the floor, put things in their mouths, 

sometimes eat inappropriate things (such as dirt or paint chips), and spend more time outdoors. Children 

also are closer to the ground, and they do not use the judgment of adults to avoid hazards (NRC 1993). 

Oral, dermal, and combined oral-dermal exposures are the most likely routes by which children will be 

exposed to phenol. Oral exposure to low levels of phenol among children is likely because many 

consumer products contain phenol, particularly in medicines such as gargles, throat lozenges, and others 

(Darisimall 2006). Products other than medicines that contain phenols include general disinfectants, 

cleaners, and epoxies. 
 

 

 

PHENOL 167 

6. POTENTIAL FOR HUMAN EXPOSURE 

Some foods containing phenol have been identified (see Section 6.4.4) and ingestion of these could result 

in low levels of phenol exposure in children. In addition, phenol is produced endogenously as a 

breakdown product of protein metabolism; normal concentrations in urine generally do not exceed 

20 mg/L (ACGIH 2001). 

Since phenol can be readily absorbed through the skin (ACGIH 2001), children may be more susceptible 

to low levels of phenol exposure since they have a higher skin-surface-area to weight ratio. Since young 

children are more likely to come in contact with the floor and other low-lying areas, they may be exposed 

to phenol found in consumer products such as general disinfectants used to clean toilets, floors, drains, 

and other areas (Lewis 2001; O’Neil 2001). 

Exposure to phenol through inhalation is a less probable route than oral and dermal. It is known that both 

cigarettes and cigars contain small amounts (19–140 μg) of phenol (IARC 1986; NCI 1998), and smoking

these products indoors produces a measurable amount of phenol (Guerin et al. 1992). If children are 

present in indoor environments polluted with tobacco smoke, they may be exposed to low levels of 

phenol. 

6.7 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES 

Populations with potentially high exposure to phenol generally include those who are exposed to 

relatively highly contaminated environments over long periods of time. These include populations 

exposed to both identified and unidentified phenol-containing waste disposal sites and landfills. 

Populations residing in the vicinity of industries that manufacture or use phenol and large population 

centers may be exposed to potentially high levels of phenol. Persons who work at establishments that 

manufacture or use phenol have a risk for high exposure to phenol. Populations that regularly ingest food 

contaminated with phenol or that regularly ingest or come in contact with phenol-containing products are 

at risk for high exposure to phenol. Populations that live near a phenol spill site, especially those whose 

water supply sources are near the spill sites, have a risk for high exposure to phenol. Relatively high 

exposure may also result from exposure to emissions from municipal waste incinerators and cigarette 

smoke, although no quantitative data concerning phenol emission from these sources were located. Low 

income communities and minority populations are more likely to live adjacent to waste disposal sites and 

landfills where phenol is present. 
 

 

 

 

 

 

 

 

PHENOL 168 

6. POTENTIAL FOR HUMAN EXPOSURE 

THE NOES conducted by NIOSH estimated that 584,372 workers were exposed to phenol in the United 

States (CDC Website). Workers in the petroleum industry, as well as workers in industries that 

manufacture of caprolactam (nylon manufacture), bisphenol A (epoxy resin and polycarbonate 

manufacture), herbicides, wood preservatives, hydraulic fluids, heavy-duty surfactants, lube-oil additives, 

tank linings and coatings, and intermediates for plasticizers and other specialty chemicals, may be 

exposed to phenol. Phenol is also used in throat lozenges, disinfectants, and ointments. It is also used for 

facial skin peels and to cause nerve block (Gingell et al. 2001). A list of estimated work induced 

exposure events for 19 different industries is presented in Table 6-2 (Brandorff et al. 1995). 

People who are exposed to large amounts of benzene are also likely to be exposed to large amounts of 

phenol, a metabolite of benzene. Elevated levels of phenol have been detected in workers occupationally 

exposed to benzene. Workers exposed to 0.8–25.1 or 33.1–331.7 ppm for 2.5–3 hours during an 8-hour 

workday had median urinary phenol levels of 55.6 and 351 ng/g creatine, respectively (Rothman et al. 

1998). Control workers who were not exposed to benzene at the workplace had urinary phenol levels of 

17.3 ng/g creatine (Rothman et al. 1998). 

6.8 ADEQUACY OF THE DATABASE 

Section 104(i)(5) of CERCLA, as amended, directs the Administrator of ATSDR (in consultation with the 

Administrator of EPA and agencies and programs of the Public Health Service) to assess whether 

adequate information on the health effects of phenol 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 phenol. 

6.8.1 Identification of Data Needs 

Physical and Chemical Properties. Knowledge of physical and chemical properties is essential for 

estimating the partitioning of a chemical in the environment. Information about the physical and 

chemical properties of phenol is available (Hawley 1981; HSDB 2008; IARC 1989), and the database is 

adequate for the input requirements of environmental models that predict the behavior of a chemical 

under specific conditions. 

Production, Import/Export, Use, Release, and Disposal. According to the Emergency 

Planning and Community Right-to-Know Act of 1986, 42 U.S.C. Section 11023, industries are required 
 

 

PHENOL 169 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-2. Estimated Exposure To Phenol At Various Industry Sites 

Estimated number of Estimated weight used in 

Industry exposure events tonnes of substance 

Manufacture of basic metals 180 1.7 

Manufacture of fabricated metal products 8,200 27 

Electrical machinery and apparatus 1,400 0.0012 

Manufacture of transport equipment 700 40 

Painters and carpenters 440 0.021 

Construction 4,300 11 

Wholesale trade 840 16 

Manufacture of textiles and leather 2,600 1 

Manufacture of wood and furniture 670 1.2 

Manufacture of chemicals 580 0.85 

Manufacture of non-metallic mineral 1,300 4,100 

products 

Manufacture of precision and optical 1,300 0.0023 

instruments 

Manufacture of plastic and boat building 840 <0.0001 

repair 

Personal services, cleaning, and hair 260 0.0002 

dressing 

Sewage and refuse disposal 210 0.0009 

Agricultural, hunting, and forestry 550 0.65 

Health sciences and pharmacies 1,200 0.25 

Source: Brandorff et al. 1995 
 

 

 

 

 

 

 

 

 

 

 

 

PHENOL 170 

6. POTENTIAL FOR HUMAN EXPOSURE 

to submit substance release and off-site transfer information to the EPA. The TRI, which contains this 

information for 2005, became available in May of 2007. This database is updated yearly and should 

provide a list of industrial production facilities and emissions. 

Additional production data are available from the Chemical Marketing Reporter (CMR 2005), and 

import/export data for phenol are available on the U.S. International Trade Commission website (USITC 

2008). Additional data are not needed at this time. 

Environmental Fate. Based on the physical properties of phenol, volatilization and sorption of 

phenol to sediments are not expected to be important transport mechanisms (Lyman et al. 1982). The 

adsorption of phenol to soils has been shown to increase with increasing organic matter (Xing et al. 

1994). Photochemical degradation of phenol is thought to be an important process both in air (EPA 

1979a) and water (Scully and Hoigne 1987). Phenol is also readily biodegradable (Ludzack and Ettinger 

1960; Rubin and Alexander 1983; Scott et al. 1983; Stover and Kincannon 1983). Soil sorption data are 

available (Artiola-Fortuny and Fuller 1982; Boyd 1982; Briggs 1981; Sacan and Balcioglu 1996; Scott et 

al. 1983). Additional data are not needed at this time. 

Bioavailability from Environmental Media. Data from monitoring studies indicate that phenol is 

present in the environment (EPA 1981a, 1982; Gossett et al. 1983; Hoff and Chan 1987; Konasewich et 

al. 1978; Sheldon and Hites 1978, 1979; Thurman 1985) as well as in environmental organisms (Nicola et 

al. 1987). Exposure to phenol is most likely to be highest in areas at or near industrial centers and 

population centers where drinking and bathing water, ambient air, and certain foods, such as fish, are 

obtained from sources contaminated with phenol. Reliable data on the bioavailability of phenol from 

inhaled air and from skin exposed to phenol vapor have been reported for humans (Piotrowski 1971). 

Studies of bioavailability of phenol from ingested soil and foods and dermal contact with contaminated 

water are needed for evaluating the hazards posed by ingesting materials that have been contaminated 

with phenol. 

Food Chain Bioaccumulation. No studies were located regarding the food chain bioaccumulation 

of phenol from environmental media. Data from monitoring studies indicate that phenol is present in the 

environment as well as in environmental organisms (Nicola et al. 1987). The available bioaccumulation 

studies are concerned only with exposure of fish to aqueous concentrations of phenol. Although the 

results of these studies indicate a low potential for bioaccumulation (see Section 6.3.1), the detection of 

phenol in fish (see Section 6.4.4) indicates that phenol can be found in aquatic organisms; it is possible 
 

 

 

 

 

 

 

 

 

PHENOL 171 

6. POTENTIAL FOR HUMAN EXPOSURE 

that food chain bioaccumulation may occur. A clearer understanding of the potential for bioaccumulation 

would aid in determining how levels in the environment affect the food chain and potentially impact 

human exposure levels. A study examining phenol levels in organisms from several trophic levels is 

needed. 

Exposure Levels in Environmental Media. Reliable monitoring data for the levels of phenol in 

contaminated media at hazardous waste sites are needed so that the information obtained on levels of 

phenol in the environment can be used in combination with the known body burden of phenol to assess 

the potential risk of adverse health effects in populations living in the vicinity of hazardous waste sites. 

Phenol has been measured in air (Cronn et al. 1977; EPA 1981a, 1982), water (EPA 1980; Sheldon and 

Hites 1978, 1979; Thurman 1985), and sediments (Gossett et al. 1983). Additional more recent 

monitoring data would help to estimate human exposure to phenol. 

Exposure Levels in Humans. Data concerning exposure levels in humans are incomplete and not 

current (Heikkila et al. 1987; Kuwata et al. 1980; Ohtsuji and Ikeda 1972). A detailed recent database of 

exposure would be helpful in determining the current exposure levels, thereby allowing the estimation of 

the average daily dose associated with various scenarios such as living near a hazardous waste site or 

landfill, or with drinking water containing phenol. An environmental media monitoring program would 

provide the necessary information for estimating environmental exposures, while a detailed examination 

of the uses of phenol and the kinds of potential exposure in addition to workplace monitoring would 

probably provide adequate workplace information. The environmental media that would provide the most 

useful information are air, groundwater, and surface and drinking water in urban and industrial locations, 

and air, groundwater, and surface water at hazardous waste sites. Performing the monitoring over a 

1-year period would allow estimation of seasonal variations. 

This information is necessary for assessing the need to conduct health studies on these populations. 

Exposures of Children. Children are likely to be exposed to low levels of phenol from the use of 

many consumer products including medicines and cleaning agents (Budavari et al. 1989; Douglas 1972; 

EPA 1980; Hawley 1981). There are no known data that quantify the level of exposure to phenol in 

children. It is likely that young children may be exposed to low levels of phenol because they come into 

contact with the floor and other areas where disinfectants containing phenol might be used. More studies 

are needed to assess whether children differ in their weight-adjusted intake of phenol, as little or no 
 

 

 

 

 

 

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6. POTENTIAL FOR HUMAN EXPOSURE 

information is known. Studies are needed to measure the baseline phenol level in children’s urine in 

order to use phenol levels in urine as a biomarker of exposure. 

Child health data needs relating to susceptibility are discussed in Section 3.12.2, Identification of Data 

Needs: Children’s Susceptibility. 

Exposure Registries. No exposure registries for phenol were located. This substance is not 

currently one of the compounds for which a sub-registry has been established in the National Exposure 

Registry. The substance will be considered in the future when chemical selection is made for subregistries to be established. The information that is amassed in the National Exposure Registry facilitates 

the epidemiological research needed to assess adverse health outcomes that may be related to exposure to 

this substance. 

6.8.2 Ongoing Studies 

The Federal Research in Progress (FEDRIP 2006) database provides additional information obtainable 

from a few ongoing studies that may fill in some of the data needs identified in Section 6.8.1. The only 

study pertaining to the potential for human exposure found in this database was an exposure assessment 

study done at Mount Sinai School of Medicine at New York University and supported by National 

Institute of Environmental Health Sciences. Part of this research is to design new approaches to assess 

and quantify the levels of exposures to known toxicants in children and infants. 
 

 

 

 

 

 

PHENOL 173 

7. ANALYTICAL METHODS 

The purpose of this chapter is to describe the analytical methods that are available for detecting, 

measuring, and/or monitoring phenol, its metabolites, and other biomarkers of exposure and effect to 

phenol. The intent is not to provide an exhaustive list of analytical methods. Rather, the intention is to 

identify well-established methods that are used as the standard methods of analysis. Many of the 

analytical methods used for environmental samples are the methods approved by federal agencies and 

organizations such as EPA and the National Institute for Occupational Safety and Health (NIOSH). Other 

methods presented in this chapter are those that are approved by groups such as the Association of 

Official Analytical Chemists (AOAC) and the American Public Health Association (APHA). 

Additionally, analytical methods are included that modify previously used methods to obtain lower 

detection limits and/or to improve accuracy and precision. 

7.1 BIOLOGICAL MATERIALS 

Analytical methods for the detection of phenol in biological materials are summarized in Table 7-1. 

Phenol is expected to be present in blood and urine in its free acid and conjugated forms (glucuronide and 

sulfate). The average urinary phenol concentration in unexposed individuals is 9.5±3.6 mg/L when 

corrected to a standard specific gravity of 1.024 (Piotrowski 1971). In exposed individuals, the urinary 

phenol level may vary from 10 to 200 mg/L (Tesarova and Packova 1983). The two common methods 

for quantifying conjugated phenol are chemical and enzymatic hydrolysis of the conjugate to the free 

phenol form. The chemical method uses acidic hydrolysis (Baldwin et al. 1981; Needham et al. 1984). 

Both the nature of the acid (sulfuric versus perchloric) and the temperature should be controlled carefully 

to obtain a quantitative yield and to avoid thermal decomposition of other phenolic or related compounds 

that may interfere with phenol quantification (Baldwin et al. 1981; Rick et al. 1982). The best available 

method appears to be specific enzyme hydrolysis or hydrolysis at ambient temperature with sulfuric acid. 

Enzymatic hydrolysis with an extract of Helix pomatia has also been used to liberate phenol from its 

conjugates (Ahmed and Hale 1994). 

High-performance liquid chromatographic separation with electrochemical detection may provide the best 

sensitivity for phenol quantification in biological samples (Tesarova and Packova 1983). The use of gas 

chromatography with a flame ionization detector may be a more versatile method, if other non-ionic 

pollutants must be quantified. The advantages and disadvantages of different methods available for the 

quantification of phenol and metabolites in biological and environmental samples have been discussed by 

Tesarova and Packova (1983). 
 

 

 

 

PHENOL	 174 

7. ANALYTICAL METHODS 

Table 7-1. Analytical Methods for Determining Phenol in Biological Samples 

Sample 

Analytical detection Percent 

Sample matrix Preparation method method limit recovery Reference 

Whole blood	 Sample extracted with ethyl 

acetate, extract concentrated 

and analyzed (for free phenol), 

packed blood cells previously 

extracted for free phenol 

incubated with β-glucuronidase 

containing sulfatase at 37 °C, 

extracted with ethyl acetate 

after addition of normal saline 

solution, and extract 

concentrated and analyzed (for 

conjugated phenol) 

Whole blood	 Sample with spiked internal 

standard extracted with ethyl 

acetate and extract 

concentrated and analyzed 

Urine	 Sample mixed with phosphoric 

acid, passed through a precolumn at 165 °C for hydrolysis 

of conjugates (for free and 

conjugated phenol), and 

analyzed 

Urine	 Sample heated under reflux 

with HClO4, solvent extracted, 

concentrated, and separated 

by TLC; spot developed by 

p-nitro-benzenediazonium 

fluoroborate, removed 

quantitatively and solvent 

extracted (for free and 

conjugated phenol), and 

analyzed 

Urine	 Acidified sample stream 

distilled, reacted with ammonia, 

N-chloro-succinimide, and 

sodium nitroprusside at basic 

pH (method probably for free 

phenol), and analyzed 

Urine	 Sample incubated with 

glucuronidase and sulfatase at 

pH 5 and 3.7 °C, H2SO4 added 

and steam distilled (total 

phenol) and analyzed 

Urine	 Sample hydrolyzed at room 

temperature and extracted with 

methyl tert-butyl ether (total 

phenol) and analyzed 

GC-FID <1 mg/mL 

GC-FID 0.1 mg/L 

GC-FID NG 

Spectro- NG 

photometry 

Spectro- 0.3 mg/L 

photometry 

HPLC- 2 ng/ 

electro- inection 

chemical 

detector 

GC-FID NG 

97% (free O’Grodnick et 

phenol); 103% al. 1983 

(conjugated 

phenol) 

>90% at Handson and 

concentrations Hanrahan 1983 

above 0.5 mg/L 

89% (for Baldwin et al. 

conjugates) 1981 

NG	 Bienick and 

Wilczok 1986 

>95%	 Amlathe et al. 

1987 

95–107%	 Schaltenbrand 

and Coburn 

1985 

NG	 Rick et al. 1982 
 

 

 

 

 

 

PHENOL 175 

7. ANALYTICAL METHODS 

Table 7-1. Analytical Methods for Determining Phenol in Biological Samples 

Sample 

Analytical detection Percent 

Sample matrix Preparation method method limit recovery Reference 

Urine Sample spiked with internal GC-FID NG 93–97% at 20– Needham et al. 

standard, hydrolyzed with 70 mg/L 1984 

H2SO4, and extracted with ethyl 

acetate (free and conjugated) 

and analyzed 

Urine Sample spiked with internal GC-FID 0.1 mg/L 99% at Van 

standard, distilled with H2SO4 5.9 mg/L Roosmalen et 

in a special apparatus, distillate al. 1981 

directly injected into GC (free 

and conjugated) 

Urine Two spot urine samples GC-FID 0.5 μg/mL 94–95% NIOSH 1994a 

(before and after exposure), (Method 

hydrolyzed with HCl or 8305) 

perchloric acid, extracted with 

diethyl ether, and directly 

injected into GC 

FID = flame ionization detector; GC = gas chromatography; H2SO4 = sulfuric acid; HCl = hydrochloric acid; 

HClO4 = perchloric acid; HPLC = high performance liquid chromatography; NG = not given; TLC = thin layer 

chromatography 
 

 

 

 

 

 

 

 

 

PHENOL 176 

7. ANALYTICAL METHODS 

The level of phenol detected in blood or urine may not accurately reflect actual phenol exposure because 

phenol may also appear as a metabolite of benzene or other drugs. It has been shown that under certain 

acidic conditions used for the hydrolysis of conjugated phenols, acetyl salicylic acid (aspirin) may 

produce phenol (Baldwin et al. 1981) and yield spuriously higher values for phenol in blood and urine. 

For occupational exposure, it is recommended that urine samples be collected at the end of an 8-hour 

work shift (ACGIH 2001). Small amounts of thymol can be used as a preservative, and the urine can be 

stored for 4 days if refrigerated, or at least 3 months if frozen. 

7.2 ENVIRONMENTAL SAMPLES 

Analytical methods for detecting phenol in environmental samples are summarized in Table 7-2. The 

accuracy and sensitivity of phenol determination in environmental samples depends on sample preconcentration and pretreatment and the analytical method employed. The recovery of phenol from air and 

water by the various preconcentration methods is usually low for samples containing low levels of phenol. 

The two preconcentration methods commonly used for phenols in water are adsorption on XAD resin and 

adsorption on carbon. Both can give low recoveries, as shown by Van Rossum and Webb (1978). 

Solvent extraction at acidic pH with subsequent solvent concentration also gives unsatisfactory recovery 

for phenol. Even during carefully controlled conditions, phenol losses of up to 60% may occur during 

solvent evaporation (Handson and Hanrahan 1983). The in situ acetylation with subsequent solvent 

extraction as developed by Sithole et al. (1986) is probably one of the most promising methods. 

Capillary columns may provide the best method for the separation of phenols prior to their quantification 

(Eichelberger et al. 1983; Shafer et al. 1981; Sithole et al. 1986). Of the various methods available for 

detection, the two commonly used methods that are most sensitive are mass spectrometry and flame 

ionization detection. Although electron capture detectors provide good sensitivities for higher chlorinesubstituted phenols, they are poor for phenol itself (Sithole et al. 1986). The best method for the 

quantification of phenol may be mass spectrometric detection in the selected ion mode, but the loss of 

qualitative information may be significant (Eichelberger et al. 1983). 

7.3 ADEQUACY OF THE DATABASE 

Section 104(i)(5) of CERCLA, as amended, directs the Administrator of ATSDR (in consultation with the 

Administrator of EPA and agencies and programs of the Public Health Service) to assess whether 

adequate information on the health effects of phenol is available. Where adequate information is not 
 

 

 

 

 

PHENOL 177 

7. ANALYTICAL METHODS 

Table 7-2. Analytical Methods for Determining Phenol in Environmental Samples 

Sample Analytical Sample Percent 

matrix Preparation method method detection limit recovery Reference 

Urban air 

Air 

Occupational 

air 

Occupational 

air 

Occupational 

air 

Total 

particulate 

matter in 

cigarette 

smoke 

Industrial 

emission, 

auto exhaust, 

and tobacco 

smoke 

Drinking 

water, waste 

water, and 

natural water 

Waste water 

and natural 

water 

Water 

Sample collected in bubbler 

containing NaOH, derivatized 

as nitrobenzeneazo compound 

Sample collected on a solid 

sorbent tube, desorbed using 

methanol 

Sorption on activated carbon, 

desorption by solvent and 

derivatized to trimethylsilyl 

product 

Sorption on XAD-2, desorption 

by acetonitrile and 

concentrated if necessary 

Sample collected with a 

thermal desorption tube using a 

sorbent capable of capturing a 

C6 organic compound 

Extract particulate matter with 

NaOH, buffer to pH 4.6 

Sample collected in NaOH 

bubbler and derivatized to 

p-nitrobenzene-diazonium 

tetrafluoroborate 

Direct distillation of solventcleaned sample (if necessary) 

at acidic pH, react with 

4-amino-antipyrine and 

potassium ferricyanide at pH 8, 

extract in chloroform 

None 

1-L sample acidified and 

extracted with methylene 

chloride 

HPLC-UV 

GC-FID 

(Method 

2546) 

GC-FID 

HPLCelectrochemical 

detector and 

HPLC-UV 

GC-MS 

(Method 

2549) 

HPLCfluorescence 

spectrophotometer 

HPLC-UV 

Spectrophotometric 

(Method 

5530c) 

GC-FID 

(Method 

6420b) 

GC-FID 

(Method 604) 

Kuwata et al. 

1980 

NIOSH 1994b 

Yrjanheikki 

1987 

Nieminen and 

Heikkila 1986 

NIOSH 1996 

Tomkins et al. 

1984 

Kuwata et al. 

1980 

APHA 1998a 

APHA 1998b 

EPA 2001a 

0.05 ppb for 

150-L sample; 

58–60% at 

0.33–0.5 μg 

phenol 

1–3 μg/sample ND 

72.3% at 

10–50 μg 

phenol 

0.5 mg/m3 

(0.13 ppm) 

8 μg/m3 

(2.04 ppb) with 

12 L air 

(electrochemical); 

0.16 mg/m3 

(0.04 ppm) with 

12 L air (UV) 

100 ng/tube or 

less 

0.3 mg/L 

0.05 ppb for 

150-L sample 

1 μg/L for 

500-mL sample 

<1 mg/L 

0.14 μg/L 

96–102% 

at 2.5– 

100 mg/m3 

ND 

NA 

91% at 20– 

30 μg 

ND 

ND 

ND 

44% 
 

 

 

 

 

 

PHENOL 178 

7. ANALYTICAL METHODS 

Table 7-2. Analytical Methods for Determining Phenol in Environmental Samples 

Sample Analytical Sample Percent 

matrix Preparation method method detection limit recovery Reference 

Water 

Water, waste 

water 

Water, waste 

water 

Water 

Water 

Waste water 

Potable water 

and raw 

source water 

Drinking 

water 

1-L sample is adjusted to pH 

>11 and extracted with 

methylene chloride 

Acidified sample extract with 

solvent, concentrated or 

derivatized to pentafluorobenzylbromide product 

Sample extracted in acidic pH, 

extract concentrated 

Sample passed through 

graphitized carbon black, 

eluted with methylene chloride 

Sample passed through a 

mixed XAD-4/8 column, solvent 

eluted and concentrated 

Distillation of acidified solution, 

reacted with ammonia, 

N-chloro-succinimide, and 

sodium nitro-prusside at basic 

pH 

Sample acetylated in situ by 

addition of acetic anhydride, 

solvent extracted and 

concentrated; alternatively, 

extracted acidic sample 

derivatized by 

pentafluorobenzyl bromide and 

cleaned up by column 

chromatography 

1-L sample is extracted using a 

solid phase extraction cartridge 

GC-MS 

(Method 635) 

GC-FID; GCECD (for 

derivatized 

EPA Method 

604) 

GC-MS (EPA 

Method 625); 

HRGC-MS 

(EPA Method 

625.1) 

Ionsuppression; 

reversed 

phase LC 

with UV 

detection 

GC-MS 

Spectrophotometric 

HRGC-ECD 

(for 

pentafluorobenzyl 

derivative); 

HRGC-MS 

(for acetyl 

derivative) 

GC-MS 

(Method 528) 

1.5 μg/L 

0.14 μg/L 

(FID); 2.2 μg/L 

(ECD) 

1.5 μg/L (GCMS); 1–10 μg/L 

(HRGC-MS) 

50–100 ng/L 

ND 

<0.3 mg/L 

<50 ng/L 

(pentafluorobenzyl); 

<50 ng/L 

(acetyl 

derivative) 

0.026 μg/L 

56% 

41% (FID); 

ND (ECD) 

36% (GCMS) at 10– 

1,500 μg/L; 

25% (GCMS) at 

8.3 μg/L; 

42% 

(HRGCMS) at 

20 μg/L 

91–97% 

46-70% 

(distilled 

water); 9% 

(tap water) 

96.7% at 

3 mg/L 

10–64% 

(pentafluorobenzyl 

derivative); 

70–132% 

(acetyl 

derivative) 

85 

EPA 2001c 

EPA 1982 

Eichelberger 

et al. 1983; 

EPA 1982 

Di Corcia et 

al. 1996 

Van Rossum 

and Webb 

1978 

Amlathe et al. 

1987 

Sithole et al. 

1986 

EPA 2000a 
 

 

 

 

 

PHENOL	 179 

7. ANALYTICAL METHODS 

Table 7-2. Analytical Methods for Determining Phenol in Environmental Samples 

Sample Analytical Sample Percent 

matrix Preparation method method detection limit recovery Reference 

Water The sample is extracted at pH 

12–13, then at pH <2 with 

methylene chloride using 

continuous extraction 

techniques; the extract is dried 

over sodium sulfate and 

concentrated to a volume of 

1 mL 

Drinking 

water 

Water samples collected and 

analyzed via GC-MS 

Aqueous 

samples 

Samples extracted and cleaned 

up (according to sample matrix) 

and the solvent appropriately 

exchanged; the phenols are 

then determined with or without 

derivatization 

Sediment Homogenized sample solvent 

extracted at acidic pH, 

fractionated by GPC and 

fractions concentrated 

Groundwater Solvent extraction in acidic pH, 

extract concentrated 

Soil, sediment Sample mixed with anhydrous 

powdered Na2SO4, solvent 

extracted ultrasonically, extract 

subjected to GPC if necessary, 

extract concentrated 

Water and Phenols separated on a Novawaste water	 Pak Phenyl column eluted with 

ammonium acetate:acetonitrile 

Groundwater	 Solvent extraction, column 

chromatographic cleanup, 

concentration of extract 

Bottom	 Wet sediment samples dried 

sediment	 and compounds extracted 

using dichloromethane 

Water	 Water samples filtered using 

glass fiber filters; samples 

extracted using SPE cartridges 

Soil, sludge,	 Extracted by soxhlet or 

or solid waste	 sonication, extract subjected to 

column chromatographic 

cleanup and concentrated 

GC-MS 

(Method 

1625) 

GC-MS 

(Method 

OM100R 

GC-MS 

(Method 

8041A 

HRGC-MS 

GC-MS (EPACLP Method) 

GC-MS (EPACLP Method 

LC-ED 

GC-MS (EPA 

Method 

8250A) 

GC-MS 

(Method 0­

5130-95) 

GC-MS 

(Method 0­

1433-01) 

GC-MS (EPA 

Method 

8250A) 

Not applicable 

Not applicable
 

Not applicable
 

ND 

10 μg/L 

330 μg/kg 

0.5 mg/L 

1.5 mg/L 

23.5 μg/kg 

0.11 μg/L 

1.5 mg/kg 

Not 

applicable 

Not 

applicable 

93% 

112–128% 

at 400 ng/g 

ND 

ND 

91–100% 

0.43c+ 

1.26)/cx 

100 where 

c is the 

actual 

concentration 

84 

93 

ND 

EPA 2001b 

DOE 1997
 

EPA 2000b 

Lopez-Avila 

et al. 1983 

EPA 1987 

EPA 1987 

Paterson et 

al. 1996 

EPA 1994b 

USGS 1995 

USGS 2002 

EPA 1994b 
 

 

 

 

PHENOL 180 

7. ANALYTICAL METHODS 

Table 7-2. Analytical Methods for Determining Phenol in Environmental Samples 

Sample 

matrix Preparation method 

Analytical 

method 

Sample 

detection limit 

Percent 

recovery Reference 

Aqueous and 

nonaqueous 

samples 

Samples are extracted; extracts 

are cleaned up, as necessary, 

and the solvent exchanged to 

one that is compatible with the 

GC detector to be used 

EPA Method 

8041A 

ND 93% EPA 2007 

Soil, air, 

water, 

Soxhlet extraction with 

acetone/hexane 

GC-MS 

(Method 

8270D) 

10 μg/L 46% EPA 1998 

Honey Sample dissolved in water, 

steam distilled; distillate 

cleaned up by column 

chromatography 

HPLC-UP 0.1 ppm (for 

10-g sample 

98% at 

111 μg 

added 

phenol 

Sporns 1981 

C6 = 6 carbon; ECD = electron capture detector; ED = electrochemical detection; FID = flame ionization detector; 

GC = gas chromatography; GPC = gel permeation chromatography; HPLC = high performance liquid 

chromatography; HRGC = high resolution gas chromatography; LC = liquid chromatography; MS = mass 

spectrometry; Na2SO4 = sodium sulfate; NaOH = sodium hydroxide; ND = no data; SPE = solid-phase extraction; 

UV = ultraviolet detection 
 

 

 

 

 

 

 

PHENOL 181 

7. ANALYTICAL METHODS 

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 phenol. 

The following categories of possible data needs have been identified by a joint team of scientists from 

ATSDR, NTP, and EPA. They are defined as substance-specific informational needs that if met would 

reduce the uncertainties of human health assessment. This definition should not be interpreted to mean 

that all data needs discussed in this section must be filled. In the future, the identified data needs will be 

evaluated and prioritized, and a substance-specific research agenda will be proposed. 

7.3.1 Identification of Data Needs 

Methods for Determining Biomarkers of Exposure and Effect. 

Exposure. Measurement of total phenol in urine serves as a biomarker of exposure for persons 

occupationally exposed to phenol (ACGIH 2001). 

Effect. Specific biomarkers used to characterize effects caused by phenol have not been identified. Dark 

urine has been reported in persons occupationally exposed to phenol (inhalation, dermal) (ACGIH 2001; 

Merliss 1972) and following oral exposure (Baker et al. 1978; Kim et al. 1994). The dark urine may be a 

result of an oxidation product of phenol, or hemoglobin and hemoglobin breakdown products. Further 

research is required to identify the cause of the dark urine and relate it to exposure concentration. 

Methods for Determining Parent Compounds and Degradation Products in Environmental 

Media. The analytical methods available (Amlathe et al. 1987; Baldwin et al. 1981; Bieniek and 

Wilczok 1986; Handson and Hanrahan 1983; Needham et al. 1984; O'Grodnick et al. 1983; Rick et al. 

1982; Schaltenbrand and Coburn 1985; Van Roosmalen et al. 1981) are adequate for the quantification of 

phenol and its conjugates in biological samples. The study of the levels of parent compound in human 

blood, urine, or other biological matrices can be useful in deriving a correlation between the levels of this 

compound found in the environment and those found in human tissue or body fluid. 

The changes in metabolite concentrations in human blood, urine, or other appropriate biological media 

over time may be useful in estimating phenol's rate of metabolism in humans. In some instances, the 

quantification of metabolites may be useful in correlating the exposure doses to the human body burden. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PHENOL 182 

7. ANALYTICAL METHODS 

Studies that correlate phenol exposure with levels of metabolites in human biological matrices are not 

available for this compound, although analytical methods for the quantification of the metabolites are 

available. 

Methods for Determining Parent Compounds and Degradation Products in Environmental 

Media. The analytical methods available (Eichelberger et al. 1983; EPA 1982, 1986b, 1986c, 1987; 

Kuwata et al. 1980; Nieminen and Heikkila 1986; NIOSH 1994a, 1994b, 1996; Sithole et al. 1986; 

Tomkins et al. 1984; Van Rossum and Webb 1978; Yrjanheikki 1978) are adequate for the quantification 

of phenol in environmental materials. Knowledge of the levels of this compound in environmental media, 

such as air, water, and food, can be used to indicate exposure of humans to this compound through the 

inhalation of air and ingestion of drinking water and foods containing phenol. 

Although the products of environmental biotic and abiotic degradation of phenol have been identified 

adequately, no systematic study measuring the concentrations of the degradation products in the 

environment was found. Analytical methods are available for determining the levels of the degradation 

products such as hydroxylated phenol. Knowledge of the levels of degradation products would allow the 

development of a monitoring program designed to assess the ambient concentrations of phenol 

degradation products in the environment. Such a program could provide information concerning both 

human and environmental exposure to phenol since it might allow an estimation of the concentration of 

phenol in the environment prior to degradation. 

7.3.2 Ongoing Studies 

The Federal Research in Progress (FEDRIP 2006) database provides additional information obtainable 

from a few ongoing studies that may fill in some of the data needs identified in Section 7.3.1. Two 

studies pertaining to analytical procedures for phenol detection were found in this database. Research 

being done at Mount Sinai School of Medicine at New York University and supported by National 

Institute of Environmental Health Sciences is looking into more accurate methods for quantitative 

detection to toxicants in children and infants. A study from A.D. Grosso sponsored by the Center for 

Biologics and Evaluation—Quality Control is looking at chromatographic determination of phenol used 

as an antimicrobial preservative in vaccines and allergenic extracts. 

The Environmental Health Laboratory Sciences Division of the National Center for Environmental 

Health, Centers for Disease Control and Prevention, is developing methods for the analysis of phenol and 
 

 

 

PHENOL 183 

7. ANALYTICAL METHODS 

other volatile organic compounds in blood. These methods use purge and trap methodology, highresolution gas chromatography, and magnetic sector mass spectrometry, which give detection limits in the 

low parts per trillion (ppt) range. 

The Environmental Health Laboratory Sciences Division of the National Center for Environmental 

Health, Centers for Disease Control and Prevention, is developing methods for the analysis of phenol and 

other phenolic compounds in urine. These methods use high-resolution gas chromatography and 

magnetic sector mass spectrometry, which give detection limits in the low parts per trillion (ppt) range. 
 

PHENOL 184
 

7. ANALYTICAL METHODS 

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PHENOL 185 

8. REGULATIONS AND ADVISORIES
 

International and national regulations and guidelines pertinent to human exposure to phenol are 

summarized in Table 8-1. 

ATSDR has derived an acute-duration oral MRL of 1.0 mg/kg/day based on a BMDL of 125 mg/kg/day 

for changes in body weight gain in pregnant rats exposed to phenol by gavage using divided dosing 

during GDs 6–15 (York 1997). An uncertainty factor of 100 was used (10 for animal to human 

extrapolation and 10 for human variability). 

EPA (IRIS 2006) derived an oral reference dose (RfD) of 0.3 mg/kg/day for phenol based on a BMDL of 

93 mg/kg/day for decreased maternal weight gain observed in Sprague-Dawley rats dosed with phenol 

during gestation (York 1997). 

The IARC classification for phenol is Group 3, not classifiable with regard to its carcinogenicity to 

humans (IARC 2004). The EPA cancer classification for phenol is D, not classifiable as to human 

carcinogenicity (IRIS 2006). The National Toxicology Program has not classified phenol for human 

carcinogenicity (NTP 2005). The American Conference of Governmental Industrial Hygienists (ACGIH) 

has classified phenol as an A4 carcinogen (not classifiable as a human carcinogen) (ACGIH 2005). 

OSHA has required employers of workers who are occupationally exposed to phenol to institute 

engineering controls and work practices to reduce and maintain employee exposure at or below 

permissible exposure limits (PELs) (OSHA 2005a). The employer must use engineering and work 

practice controls to reduce exposures to or below an 8-hour time-weighted average (TWA) of 5 ppm for 

phenol (OSHA 2005a). ACGIH (2005) and NIOSH (2005) also recommend a TWA exposure limit of 

5 ppm for occupational exposure. 

Phenol is regulated by the Clean Water Effluent Guidelines for the following industrial point sources: 

electroplating, organic chemicals, steam electric, asbestos, timber products processing, metal finishing, 

paving and roofing, paint formulating, ink formulating, gum and wood, carbon black, metal molding and 

casting, aluminum forming, and electrical and electronic components; see the electronic Code of Federal 

Regulations for a complete listing (NARA 2006). 
 

 

 

 

PHENOL 186 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Phenol 

Agency Description Information Reference 

INTERNATIONAL 

Guidelines: 

IARC Carcinogenicity classification Group 3a IARC 2004 

WHO Air quality guidelines No data WHO 2000 

Drinking water quality guidelines No data WHO 2004 

NATIONAL 

Regulations and 

Guidelines: 

a. Air 

ACGIH TLV (8-hour TWA)b 5 ppm ACGIH 2005 

EPA AEGL-1c,d EPA 2006a 

10 minutes 19 ppm 

30 minutes 19 ppm 

60 minutes 15 ppm 

4 hours 9.5 ppm 

8 hours 6.3 ppm 

AEGL-2c,d 

10 minutes 29 ppm 

30 minutes 29 ppm 

60 minutes 23 ppm 

4 hours 15 ppm 

8 hours 12 ppm 

AEGL-3c,d Not recommended due 

to insufficient data 

Hazardous air pollutant Yes EPA 2006d 

42 USC 7412 

NIOSH REL (10-hour TWA)e 5 ppm NIOSH 2005 

Ceiling limit (15-minute TWA) 15.6 ppm 

IDLH 250 ppm 

OSHA PEL (8-hour TWA) for general industryf 5 ppm OSHA 2005c 

29 CFR 1910.1000 

PEL (8-hour TWA) for construction 

industryf 

5 ppm OSHA 2005b 

29 CFR 1926.55, 

Appendix A 

PEL (8-hour TWA) for shipyard 

industryf 

5 ppm OSHA 2005a 

29 CFR 1915.1000 

b. Water 

EPA Designated as a hazardous substances Yes EPA 2006b 

in accordance with Section 311(b)(2)(A) 40 CFR 116.4 

of the Clean Water Act 

Designated as a toxic pollutant in Yes EPA 2006c 

accordance with Section 307(a)(1) of 40 CFR 401.15 

the Federal Water Pollution Control Act 
 

 

 

 

 

PHENOL	 187 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Phenol 

Agency Description	 Information Reference 

NATIONAL (cont.) 

EPA Drinking water standards and health EPA 2004 

advisories 

1-day health advisory for a 10-kg 6 mg/L 

child 

10-day health advisory for a 10-kg 6 mg/L 

child 

DWEL 11 mg/L 

Lifetime 2 mg/L 

National primary drinking water No data EPA 2003 

standards 

Reportable quantities of hazardous 1,000 pounds EPA 2006g 

substances designated pursuant to 40 CFR 117.3 

Section 311 of the Clean Water Act 

Toxics criteria for those states not EPA 2006m 

complying with Clean Water Act 40 CFR 131.36 

Section 303(c)(2)(B) for human health 

(10-6 risk for carcinogens) for 

consumption of: 

Water + organism	 21 mg/L 

Organism only 4,600 mg/L 

Water quality criteria for human health EPA 2006f 

consumption of: 

Water + organism 21 mg/L 

Organism only 1,700 mg/L 

c. Food 

EPA	 Exemptions from the requirement of a Yes EPA 2006k 

tolerance as an inert ingredient (as a 40 CFR 180.920 

solvent) when used pre-harvest 

Exemptions from the requirement of a Yes EPA 2006l 

tolerance as an inert ingredients (as a 40 CFR 180.930 

solvent) when applied to animals 

FDA	 Bottled drinking water 0.001 mg/L FDA 2005
 

Included on the “Everything Added to Yes FDA 2006
 

Foods in the United States” List
 

d. Other 

ACGIH	 Carcinogenicity classification A4g ACGIH 2005 

Biological exposure indices (end of 250 mg/g creatinine 

shift) for total phenol in urine 

CPSC	 Substance named in the Federal ≤5% CPSC 2005 

Caustic Poison Act; phenol and any 

preparation containing phenol in a 

concentration 

EPA	 Carcinogenicity classification Group Dh IRIS 2006
 

Oral slope factor Not applicable
 

Inhalation unit risk Not applicable
 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PHENOL 188 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Phenol 

Agency Description Information Reference 

NATIONAL (cont.) 

RfC Not applicablei IRIS 2006 

RfD 0.3 mg/kg/day 

Identification and listing of hazardous U188 EPA 2006e 

waste; hazardous waste number 40 CFR 261, 

Appendix VIII 

Superfund, emergency planning, and 

community right-to-know 

Designated CERCLA hazardous Yes EPA 2006h 

substance 40 CFR 302.4 

Reportable quantity 1,000 pounds 

Effective date of toxic chemical 01/01/87 EPA 2006j 

release reporting 40 CFR 372.65 

Extremely hazardous substances 500/10,000 pounds EPA 2006i 

and their threshold planning 40 CFR 355, 

quantities Appendix A 

NTP Carcinogenicity classification No data NTP 2005 

a

Group 3: not classifiable as to carcinogenicity to humans

b

Skin notation: refers to the potential significant contribution to the overall exposure by the cutaneous route,
 

including mucous membranes and the eyes, either by contact with vapors, liquids, or solids. c

AEGL-1 is the airborne concentration of a substance above which it is predicted that the general population,
 

including susceptible individuals, could experience notable discomfort, irritation, or certain asymptomatic nonsensory
 

effects. AEGL-2 is the airborne concentration of a substance above which it is predicted that the general population,
 

including susceptible individuals, could experience irreversible or other serious, long-lasting adverse health effects or
 

an impaired ability to escape. AEGL-3 is the airborne concentration of a substance above which it is predicted that
 

the general population, including susceptible individuals, could experience life-threatening health effects or death. d

Level of distinct odor awareness = 0.25 ppm e

Skin designation: indicates the potential for dermal absorption; skin exposure should be prevented as necessary
 

through the use of good work practices, gloves, coveralls, goggles, and other appropriate equipment. f

Skin designation

g

A4: not classifiable as a human carcinogen
 h

Group D: not classifiable as to human carcinogenicity
 i

Not applicable: no adequate inhalation exposure studies exist from which an inhalation RfC may be derived. A
 

route-to-route extrapolation is not appropriate, because phenol can be a direct contact irritant, and so portal-of-entry
 

effects are a potential concern.
 

ACGIH = American Conference of Governmental Industrial Hygienists; AEGL = Acute Exposure Guideline Level;
 

CERCLA = Comprehensive Environmetnal Response, Compensation, and Liability Act; CFR = Code of Federal
 

Regulations; CPSC = Consumer Product Safety Commission; DWEL = drinking water equivalent level;
 

EPA = Environmental Protection Agency; FDA = Food and Drug Administration; IARC = International Agency for
 

Research on Cancer; IDLH = immediately dangerous to life or health; IRIS = Integrated Risk Information System;
 

NIOSH = National Institute for Occupational Safety and Health; NTP = National Toxicology Program;
 

OSHA = Occupational Safety and Health Administration; PEL = permissible exposure limit; REL = recommended 

exposure limit; RfC = inhalation reference concentration; RfD = oral reference dose; TLV = threshold limit values;
 

TWA = time-weighted average; USC = United States Code; WHO = World Health Organization
 
 

 

 

 

 

PHENOL 189 

8. REGULATIONS AND ADVISORIES 

EPA regulates phenol under the Clean Water Act (CWA) and the Clean Air Act (CAA) and has 

designated it as a hazardous substance and a hazardous air pollutant (HAP) (EPA 2006b, 2006c). Phenol 

is on the list of chemicals appearing in “Toxic Chemicals Subject to Section 313 of the Emergency 

Planning and Community Right-to-Know Act of 1986" (EPA 2006j) and has been assigned a reportable 

quantity (RQ) limit of 1,000 pounds (EPA 2006h). The RQ represents the amount of a designated 

hazardous substance which, when released to the environment, must be reported to the appropriate 

authority. Phenol is also considered to be an extremely hazardous substance (EPA 2006i). 
PHENOL 190
 

8. REGULATIONS AND ADVISORIES 

This page is intentionally blank. 
 

 

 

 

_______________________ 

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* Not cited in text 
 

 

 

 

 

 

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Van Duuren BL, Katz C, Goldschmidt BM. 1973. Cocarcinogenic agents in tobacco carcinogenesis. J 

Natl Cancer Inst 51:703-705. 
 

 

 

 

 

 

 

 

 

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PHENOL 221 

10. GLOSSARY 

Absorption—The taking up of liquids by solids, or of gases by solids or liquids. 

Acute Exposure—Exposure to a chemical for a duration of 14 days or less, as specified in the 

Toxicological Profiles. 

Adsorption—The adhesion in an extremely thin layer of molecules (as of gases, solutes, or liquids) to the 

surfaces of solid bodies or liquids with which they are in contact. 

Adsorption Coefficient (Koc)—The ratio of the amount of a chemical adsorbed per unit weight of 

organic carbon in the soil or sediment to the concentration of the chemical in solution at equilibrium. 

Adsorption Ratio (Kd)—The amount of a chemical adsorbed by sediment or soil (i.e., the solid phase) 

divided by the amount of chemical in the solution phase, which is in equilibrium with the solid phase, at a 

fixed solid/solution ratio. It is generally expressed in micrograms of chemical sorbed per gram of soil or 

sediment. 

Benchmark Dose (BMD)—Usually defined as the lower confidence limit on the dose that produces a 

specified magnitude of changes in a specified adverse response. For example, a BMD10 would be the 

dose at the 95% lower confidence limit on a 10% response, and the benchmark response (BMR) would be 

10%. The BMD is determined by modeling the dose response curve in the region of the dose response 

relationship where biologically observable data are feasible. 

Benchmark Dose Model—A statistical dose-response model applied to either experimental toxicological 

or epidemiological data to calculate a BMD. 

Bioconcentration Factor (BCF)—The quotient of the concentration of a chemical in aquatic organisms 

at a specific time or during a discrete time period of exposure divided by the concentration in the 

surrounding water at the same time or during the same period. 

Biomarkers—Broadly defined as indicators signaling events in biologic systems or samples. They have 

been classified as markers of exposure, markers of effect, and markers of susceptibility. 

Cancer Effect Level (CEL)—The lowest dose of chemical in a study, or group of studies, that produces 

significant increases in the incidence of cancer (or tumors) between the exposed population and its 

appropriate control. 

Carcinogen—A chemical capable of inducing cancer. 

Case-Control Study—A type of epidemiological study that examines the relationship between a 

particular outcome (disease or condition) and a variety of potential causative agents (such as toxic 

chemicals). In a case-controlled study, a group of people with a specified and well-defined outcome is 

identified and compared to a similar group of people without outcome. 

Case Report—Describes a single individual with a particular disease or exposure. These may suggest 

some potential topics for scientific research, but are not actual research studies. 

Case Series—Describes the experience of a small number of individuals with the same disease or 

exposure. These may suggest potential topics for scientific research, but are not actual research studies. 
 

 

 

 

 

 

 

 

 

 

 

 

PHENOL 222 

10. GLOSSARY 

Ceiling Value—A concentration of a substance that should not be exceeded, even instantaneously. 

Chronic Exposure—Exposure to a chemical for 365 days or more, as specified in the Toxicological 

Profiles. 

Cohort Study—A type of epidemiological study of a specific group or groups of people who have had a 

common insult (e.g., exposure to an agent suspected of causing disease or a common disease) and are 

followed forward from exposure to outcome. At least one exposed group is compared to one unexposed 

group. 

Cross-sectional Study—A type of epidemiological study of a group or groups of people that examines 

the relationship between exposure and outcome to a chemical or to chemicals at one point in time. 

Data Needs—Substance-specific informational needs that if met would reduce the uncertainties of human 

health assessment. 

Developmental Toxicity—The occurrence of adverse effects on the developing organism that may result 

from exposure to a chemical prior to conception (either parent), during prenatal development, or 

postnatally to the time of sexual maturation. Adverse developmental effects may be detected at any point 

in the life span of the organism. 

Dose-Response Relationship—The quantitative relationship between the amount of exposure to a 

toxicant and the incidence of the adverse effects. 

Embryotoxicity and Fetotoxicity—Any toxic effect on the conceptus as a result of prenatal exposure to 

a chemical; the distinguishing feature between the two terms is the stage of development during which the 

insult occurs. The terms, as used here, include malformations and variations, altered growth, and in utero 

death. 

Environmental Protection Agency (EPA) Health Advisory—An estimate of acceptable drinking water 

levels for a chemical substance based on health effects information. A health advisory is not a legally 

enforceable federal standard, but serves as technical guidance to assist federal, state, and local officials. 

Epidemiology—Refers to the investigation of factors that determine the frequency and distribution of 

disease or other health-related conditions within a defined human population during a specified period. 

Genotoxicity—A specific adverse effect on the genome of living cells that, upon the duplication of 

affected cells, can be expressed as a mutagenic, clastogenic, or carcinogenic event because of specific 

alteration of the molecular structure of the genome. 

Half-life—A measure of rate for the time required to eliminate one half of a quantity of a chemical from 

the body or environmental media. 

Immediately Dangerous to Life or Health (IDLH)—The maximum environmental concentration of a 

contaminant from which one could escape within 30 minutes without any escape-impairing symptoms or 

irreversible health effects. 

Immunologic Toxicity—The occurrence of adverse effects on the immune system that may result from 

exposure to environmental agents such as chemicals. 
 

 

 

 

 

 

 

PHENOL 223 

10. 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. 
 

 

 

 

 

 

 

 

PHENOL 224 

10. GLOSSARY 

Mutagen—A substance that causes mutations. A mutation is a change in the DNA sequence of a cell’s 

DNA. Mutations can lead to birth defects, miscarriages, or cancer. 

Necropsy—The gross examination of the organs and tissues of a dead body to determine the cause of 

death or pathological conditions. 

Neurotoxicity—The occurrence of adverse effects on the nervous system following exposure to a 

chemical. 

No-Observed-Adverse-Effect Level (NOAEL)—The dose of a chemical at which there were no 

statistically or biologically significant increases in frequency or severity of adverse effects seen between 

the exposed population and its appropriate control. Effects may be produced at this dose, but they are not 

considered to be adverse. 

Octanol-Water Partition Coefficient (Kow)—The equilibrium ratio of the concentrations of a chemical 

in n-octanol and water, in dilute solution. 

Odds Ratio (OR)—A means of measuring the association between an exposure (such as toxic substances 

and a disease or condition) that represents the best estimate of relative risk (risk as a ratio of the incidence 

among subjects exposed to a particular risk factor divided by the incidence among subjects who were not 

exposed to the risk factor). An OR of greater than 1 is considered to indicate greater risk of disease in the 

exposed group compared to the unexposed group. 

Organophosphate or Organophosphorus Compound—A phosphorus-containing organic compound 

and especially a pesticide that acts by inhibiting cholinesterase. 

Permissible Exposure Limit (PEL)—An Occupational Safety and Health Administration (OSHA) 

allowable exposure level in workplace air averaged over an 8-hour shift of a 40-hour workweek. 

Pesticide—General classification of chemicals specifically developed and produced for use in the control 

of agricultural and public health pests. 

Pharmacokinetics—The dynamic behavior of a material in the body, used to predict the fate 

(disposition) of an exogenous substance in an organism. Utilizing computational techniques, it provides 

the means of studying the absorption, distribution, metabolism, and excretion of chemicals by the body. 

Pharmacokinetic Model—A set of equations that can be used to describe the time course of a parent 

chemical or metabolite in an animal system. There are two types of pharmacokinetic models: data-based 

and physiologically-based. A data-based model divides the animal system into a series of compartments, 

which, in general, do not represent real, identifiable anatomic regions of the body, whereas the 

physiologically-based model compartments represent real anatomic regions of the body. 

Physiologically Based Pharmacodynamic (PBPD) Model—A type of physiologically based doseresponse model that quantitatively describes the relationship between target tissue dose and toxic end 

points. These models advance the importance of physiologically based models in that they clearly 

describe the biological effect (response) produced by the system following exposure to an exogenous 

substance. 

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 
 

 

 

 

 

 

 

 

 

 

PHENOL 225 

10. 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. 
 

 

 

 

PHENOL 226 

10. 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. 
 

 

 

 

 

PHENOL A-1 

APPENDIX A. ATSDR MINIMAL RISK LEVELS AND WORKSHEETS 

The Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) [42 U.S.C. 

9601 et seq.], as amended by the Superfund Amendments and Reauthorization Act (SARA) [Pub. L. 99– 

499], requires that the Agency for Toxic Substances and Disease Registry (ATSDR) develop jointly with 

the U.S. Environmental Protection Agency (EPA), in order of priority, a list of hazardous substances most 

commonly found at facilities on the CERCLA National Priorities List (NPL); prepare toxicological 

profiles for each substance included on the priority list of hazardous substances; and assure the initiation 

of a research program to fill identified data needs associated with the substances. 

The toxicological profiles include an examination, summary, and interpretation of available toxicological 

information and epidemiologic evaluations of a hazardous substance. During the development of 

toxicological profiles, Minimal Risk Levels (MRLs) are derived when reliable and sufficient data exist to 

identify the target organ(s) of effect or the most sensitive health effect(s) for a specific duration for a 

given route of exposure. An MRL is an estimate of the daily human exposure to a hazardous substance 

that is likely to be without appreciable risk of adverse noncancer health effects over a specified duration 

of exposure. MRLs are based on noncancer health effects only and are not based on a consideration of 

cancer effects. These substance-specific estimates, which are intended to serve as screening levels, are 

used by ATSDR health assessors to identify contaminants and potential health effects that may be of 

concern at hazardous waste sites. It is important to note that MRLs are not intended to define clean-up or 

action levels. 

MRLs are derived for hazardous substances using the no-observed-adverse-effect level/uncertainty factor 

approach. They are below levels that might cause adverse health effects in the people most sensitive to 

such chemical-induced effects. MRLs are derived for acute (1–14 days), intermediate (15–364 days), and 

chronic (365 days and longer) durations and for the oral and inhalation routes of exposure. Currently, 

MRLs for the dermal route of exposure are not derived because ATSDR has not yet identified a method 

suitable for this route of exposure. MRLs are generally based on the most sensitive chemical-induced end 

point considered to be of relevance to humans. Serious health effects (such as irreparable damage to the 

liver or kidneys, or birth defects) are not used as a basis for establishing MRLs. Exposure to a level 

above the MRL does not mean that adverse health effects will occur. 

MRLs are intended only to serve as a screening tool to help public health professionals decide where to 

look more closely. They may also be viewed as a mechanism to identify those hazardous waste sites that 
 

 

 

PHENOL A-2 

APPENDIX A 

are not expected to cause adverse health effects. Most MRLs contain a degree of uncertainty because of 

the lack of precise toxicological information on the people who might be most sensitive (e.g., infants, 

elderly, nutritionally or immunologically compromised) to the effects of hazardous substances. ATSDR 

uses a conservative (i.e., protective) approach to address this uncertainty consistent with the public health 

principle of prevention. Although human data are preferred, MRLs often must be based on animal studies 

because relevant human studies are lacking. In the absence of evidence to the contrary, ATSDR assumes 

that humans are more sensitive to the effects of hazardous substance than animals and that certain persons 

may be particularly sensitive. Thus, the resulting MRL may be as much as 100-fold below levels that 

have been shown to be nontoxic in laboratory animals. 

Proposed MRLs undergo a rigorous review process: Health Effects/MRL Workgroup reviews within the 

Division of Toxicology and Environmental Medicine, expert panel peer reviews, and agency-wide MRL 

Workgroup reviews, with participation from other federal agencies and comments from the public. They 

are subject to change as new information becomes available concomitant with updating the toxicological 

profiles. Thus, MRLs in the most recent toxicological profiles supersede previously published levels. 

For additional information regarding MRLs, please contact the Division of Toxicology and 

Environmental Medicine, Agency for Toxic Substances and Disease Registry, 1600 Clifton Road NE, 

Mailstop F-32, Atlanta, Georgia 30333. 
 

 

 

 

 

 

 

 

 

 

 

 

 

PHENOL A-3 

APPENDIX A 

MINIMAL RISK LEVEL (MRL) WORKSHEET 

Chemical Name: Phenol 

CAS Numbers: 108-95-2 

Date: July 2008 

Profile Status: Draft 3 Post-Public 

Route: [ ] Inhalation [x] Oral 

Duration: [x] Acute [ ] Intermediate [ ] Chronic 

Graph Key: 13 

Species: Rat 

Minimal Risk Level: 1 [x] mg/kg/day [ ] ppm 

Reference: York. 1997. Oral (gavage) developmental toxicity study of phenol in rats. Procter & 

Gamble Co. Submitted to the U.S. Environmental Protection Agency under TSCA Section 8D. 

OTS0573686. 

Experimental design: Groups of pregnant Sprague-Dawley rats (25/dose group) were dosed 3 times daily 

with 0, 20, 40, or 120 mg phenol/kg (total daily doses of 0, 60, 120, and 360 mg/kg) by gavage in water 

on gestation days (GDs) 6–15; the dosing volume was 10 mL/kg. Maternal end points evaluated included 

clinical signs, body weight, and food consumption. Dams were also observed for abortions and premature 

deliveries. Dams were sacrificed on GD 20 and a gross necropsy was conducted. The uterus was 

examined for pregnancy, number and distribution of implantations, live and dead fetuses, and early and 

late resorptions. Fetuses were weighed and examined for sex and gross external alterations. Half of the 

fetuses were examined for soft tissue alterations and the remaining fetuses were examined for skeletal 

alterations. 

Effect noted in study and corresponding doses: One dam in the 360 mg/kg/day group died on GD 11 and 

the death was attributed to phenol treatment. Clinical signs considered treatment-related included excess 

salivation and tachypnea in rats exposed to 360 mg/kg/day. Gross necropsy of the dams did not reveal 

any treatment-related alterations. In the 120 mg/kg/day group, maternal body weight gain was 

significantly reduced for GDs 6–16 (11%) and for GDs 12–16 (19%), whereas in the 360 mg/kg/day 

group, body weight gain was reduced 38% for gestation days 6–16. Maternal final body weight in the 

360 mg/kg/day group was reduced, but <10% relative to controls. Food consumption was reduced in the 

360 mg/kg/day group by 16% for GDs 6–20 and by 15% for GDs 0–20; in the 120 mg/kg/day group, food 

consumption for GDs 6–16 was reduced 11%. Fetal body weight at the 360 mg/kg/day level was reduced 

5–7% relative to controls. There was a significant decrease in ossification sites on the hindlimb 

metatarsals in the 360 mg/kg/day group. At the 120 and 360 mg/kg/day dose levels, there were increases 

in litters with fetuses with "any alteration" and with "any variation", but neither reached statistical 

significance and there were no clear dose-response relationships. There were no significant effects on 

corpora lutea, implantations, litter sizes, live fetuses, early and late resorptions, and percent resorbed 

conceptuses. Based on decreased fetal body weight and delayed ossification, the dose of 360 mg/kg/day 

is a LOAEL for developmental effects; the NOAEL is 120 mg/kg/day. Based on decreased weight gain 

during gestation, the dose of 120 mg/kg/day is a LOAEL for decreased maternal body weight gain; the 

NOAEL is 60 mg/kg/day. 

Data from York (1997) were analyzed using the BMD approach for MRL derivation. BMD models in the 

EPA Benchmark Dose Software (BMDS version 2.0) (linear, polynomial, power, and Hill models) were 

fit to the maternal body weight gain data to determine potential points of departure for the MRL. The 

linear model with homogeneous variance, which is the simplest model and the model that provided the 

best fit for the data, was selected. In the absence of a clear criteria as to what level of change in weight 
 

 

 

 

 

 

 

 

 

 

 

 

PHENOL A-4 

APPENDIX A 

gain during pregnancy should be considered adverse, the benchmark response (BMR) was defined as a 

change in mean body weight gain equal to one standard deviation from the control mean (EPA 2000c). 

The corresponding BMD was 152 mg/kg/day; the corresponding benchmark dose limit (BMDL) was 

125 mg/kg/day. Applying an uncertainty factor of 100 (10 for animal to human extrapolation and 10 for 

human variability) to the BMDL results in an acute-duration oral MRL of 1 mg/kg/day. 

Dose and end point used for MRL derivation: BMDL of 125 mg/kg/day for decreased maternal weight 

gain. 

[ ] NOAEL [ ] LOAEL [x] BMDL 

Uncertainty Factors used in MRL derivation: 

[x] 10 for extrapolation from animals to humans 

[x] 10 for human variability 

Was a conversion factor used from ppm in food or water to a mg/body weight dose? Not applicable. 

If an inhalation study in animals, list conversion factors used in determining human equivalent dose: Not 

applicable. 

Was a conversion used from intermittent to continuous exposure? Not applicable. 

Other additional studies or pertinent information that lend support to this MRL: In another developmental 

study, rats were gavaged with phenol in doses of 0, 30, 60, and 120 mg/kg/day in a dosing volume of 

5 mL/kg during GDs 6–15 (NTP 1983a). There was no maternal toxicity, but mean fetal body weight at 

this dose level was approximately 7% lower than controls. However, since historical control data showed 

that the concurrent control fetal weight for the CD rat was much higher (22%) than the historical control 

weight and a larger litter size in the high-dose group may have contributed to the smaller fetal weight in 

the high-dose group, the dose of 120 mg/kg/day can be considered an equivocal LOAEL for 

developmental effects; the NOAEL was 60 mg/kg/day and supports the NOAEL of 60 mg/kg/day 

identified in the York (1997) study. 

As discussed in Section 2.3, effects of phenol administered to animals by oral gavage are different than 

those observed in drinking water studies. Phenol administered by gavage is much more toxic than 

administered in the drinking water and this is related to the pharmacokinetics of phenol. Furthermore, it 

has been shown that the volume of administration is important; the smaller the volume, the greater the 

toxicity of a given amount of phenol (NTP 1983a). Studies have shown that the toxicity of phenol is 

correlated with peak blood concentration rather than with total dose, such as the area under the phenol 

blood concentration curve (AUC) (Hiser et al. 1994). In general, NOAELs in oral gavage studies were 5– 

10 times lower than in drinking water studies. The York (1997) study was considered an appropriate 

study for MRL derivation because it used a divided dosing protocol that resembles more closely a 

potential environmental exposure scenario to phenol. 

Agency Contacts (Chemical Managers): Jewel Crawford; Obaid Faroon; Jewell Wilson 
 

 

 

 

 

PHENOL A-5 

APPENDIX A 

BENCHMARK MODELING OF MATERNAL WEIGHT GAIN IN RATS 

Benchmark dose models in the EPA Benchmark Dose Software (BMDS version 2.0) (linear, polynomial, 

power, and Hill models) were fit to the maternal body weight gain data (see Tables A-1, and A-2, and 

Figure A-1) to determine potential points of departure for the MRL. The linear model with homogeneous 

variance (which was identical to the power model), was selected because it was the simplest model and 

provided the best fit. In the absence of a clear criteria as to what level of change in weight gain during 

pregnancy should be considered adverse, the BMR was defined as a change in mean body weight gain 

equal to one standard deviation from the control mean (EPA 2000c). 

Table A-1. Data for the Change in Body Weight Gain in Pregnant Rats Exposed 

to Phenol on Gestation Days 6–15 

Dose (mg/kg/day) Number of animals tested Body weight gain (g) Standard deviation 

0 23 64 10.7 

60 25 58 9.4 

120 23 56.8 10.8 

360 25 39.8 9.5 

Source: York 1997 

The corresponding BMD was 152.1 mg/kg/day; the corresponding BMDL was 124.6 mg/kg/day. 

Applying an uncertainty factor of 100 (10 for animal to human extrapolation and 10 for human 

variability) to the BMDL results in an acute-duration oral MRL of 1 mg/kg/day. 

Table A-2. Model Predictions for Changes in Body Weight Gain in Pregnant Rats 

Exposed to Phenol on Gestation Days 6–15 

Model BMD1stddev (mg/kg/day) BMDL1stddev (mg/kg/day) p-valuea AIC-fitted 

Linearb,c 152.1 124.6 0.6055 542.79 

2-degree polynomial c 157.0 124.6 0.3191 544.78 

Powerb 152.1 124.6 0.6055 542.79 

Hill 151.2 123.7 0.3156 544.79 

a

Values <0.05 fail to meet conventional goodness-of-fit criteria. b

Best-fitting models
 c

The polynomial coefficients are restricted to be negative.
 

AIC = Akaike’s Information Criteria; BMD = benchmark dose; BMDL = lower confidence limit (95%) on the 

benchmark dose; NA = not applicable; p = p value from the Chi-squared test
 

Source: York 1997
 
 

 

PHENOL A-6 

APPENDIX A 

Figure A-1. Changes in Body Weight Gain in Pregnant Rats Exposed to Phenol 

on Gestation Days 6–15*

Linear Model with 0.95 Confidence Level 

Linear 70

Mean Response 

65

 60

 55

 50

 45

 40

 35

BMDL BMD 

0 50 100 150 200 250 300 350 

dose 09:09 07/18 2008 

*BMDs and BMDLs indicated are for a change of 1 standard deviation and are in units of mg/kg/day. 

Source: York 1997 

The homogeneous variance linear model form of the response function for the change in maternal body 

weight gain is: 

Y[dose] = beta_0 + beta_1*dose + beta_2*dose^2 + ... 

Linear Model Parameter Estimates for the Change in Maternal Body Weight Gain: 

Variable Estimate Standard Error 

alpha 98.6 14.2 

beta_0 63.4 1.4 

beta_1 -0.07 0.007 
 

 

 

 

 

 

 

PHENOL	 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. 
 

 

 

 

 

 

 

 

 

 

PHENOL 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. 
 

 

 

 

 

 

PHENOL	 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"). 
 

 

 

 

 

 

 

 

 

 

 

 

 

PHENOL	 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. 
 

 

PHENOL	 B-5 

APPENDIX B 

(18)	 Estimated Upper-Bound Human Cancer Risk Levels. This is the range associated with the upperbound for lifetime cancer risk of 1 in 10,000 to 1 in 10,000,000. These risk levels are derived 

from the EPA's Human Health Assessment Group's upper-bound estimates of the slope of the 

cancer dose response curve at low dose levels (q1*). 

(19)	 Key to LSE Figure. The Key explains the abbreviations and symbols used in the figure. 
SAMPLE

1 → Table 3-1. Levels of Significant Exposure to [Chemical x] – Inhalation 

LOAEL (effect) Exposure 

Key to frequency/ NOAEL Less serious Serious (ppm) figurea Species duration System (ppm) (ppm) Re

2 3 4 

→ INTERMEDIATE EXPOSURE 

5 6 7 8 9 10 

→ Systemic ↓ ↓ ↓ ↓ ↓ ↓

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 

12 → a The number corresponds to entries in Figure 3-1. b Used to derive an intermediate inhalation Minimal Risk Level (MRL) of 5x10-3 ppm; dose adjusted for intermittent ex

by an uncertainty factor of 100 (10 for extrapolation from animal to humans, 10 for human variability). 

PHENOL B-8
 

APPENDIX B 

This page is intentionally blank. 
 

 

 

PHENOL C-1 

APPENDIX C. ACRONYMS, ABBREVIATIONS, AND SYMBOLS
 

ACGIH American Conference of Governmental Industrial Hygienists 

ACOEM American College of Occupational and Environmental Medicine 

ADI acceptable daily intake 

ADME absorption, distribution, metabolism, and excretion 

AED atomic emission detection 

AFID alkali flame ionization detector 

AFOSH Air Force Office of Safety and Health 

ALT alanine aminotransferase 

AML acute myeloid leukemia 

AOAC Association of Official Analytical Chemists 

AOEC Association of Occupational and Environmental Clinics 

AP alkaline phosphatase 

APHA American Public Health Association 

AST aspartate aminotransferase 

atm atmosphere 

ATSDR Agency for Toxic Substances and Disease Registry 

AWQC Ambient Water Quality Criteria 

BAT best available technology 

BCF bioconcentration factor 

BEI Biological Exposure Index 

BMD benchmark dose 

BMR benchmark response 

BSC Board of Scientific Counselors 

C centigrade 

CAA Clean Air Act 

CAG Cancer Assessment Group of the U.S. Environmental Protection Agency 

CAS Chemical Abstract Services 

CDC Centers for Disease Control and Prevention 

CEL cancer effect level 

CELDS Computer-Environmental Legislative Data System 

CERCLA Comprehensive Environmental Response, Compensation, and Liability Act 

CFR Code of Federal Regulations 

Ci curie 

CI confidence interval 

CL ceiling limit value 

CLP Contract Laboratory Program 

cm centimeter 

CML chronic myeloid leukemia 

CPSC Consumer Products Safety Commission 

CWA Clean Water Act 

DHEW Department of Health, Education, and Welfare 

DHHS Department of Health and Human Services 

DNA deoxyribonucleic acid 

DOD Department of Defense 

DOE Department of Energy 

DOL Department of Labor 

DOT Department of Transportation 

DOT/UN/ Department of Transportation/United Nations/ 

NA/IMCO North America/Intergovernmental Maritime Dangerous Goods Code 
 

 

PHENOL C-2 

APPENDIX C 

DWEL drinking water exposure level 

ECD electron capture detection 

ECG/EKG electrocardiogram 

EEG electroencephalogram 

EEGL Emergency Exposure Guidance Level 

EPA Environmental Protection Agency 

F Fahrenheit F1 first-filial generation 

FAO Food and Agricultural Organization of the United Nations 

FDA Food and Drug Administration 

FEMA Federal Emergency Management Agency 

FIFRA Federal Insecticide, Fungicide, and Rodenticide Act 

FPD flame photometric detection 

fpm feet per minute 

FR Federal Register 

FSH follicle stimulating hormone 

g gram 

GC gas chromatography 

gd gestational day 

GLC gas liquid chromatography 

GPC gel permeation chromatography 

HPLC high-performance liquid chromatography 

HRGC high resolution gas chromatography 

HSDB Hazardous Substance Data Bank 

IARC International Agency for Research on Cancer 

IDLH immediately dangerous to life and health 

ILO International Labor Organization 

IRIS Integrated Risk Information System 

Kd adsorption ratio 

kg kilogram 

kkg metric ton Koc organic carbon partition coefficient Kow octanol-water partition coefficient 

L liter 

LC liquid chromatography 

LC50 lethal concentration, 50% kill 

LCLo lethal concentration, low 

LD50 lethal dose, 50% kill 

LDLo lethal dose, low 

LDH lactic dehydrogenase 

LH luteinizing hormone 

LOAEL lowest-observed-adverse-effect level 

LSE Levels of Significant Exposure 

LT50 lethal time, 50% kill 

m meter 

MA trans,trans-muconic acid 

MAL maximum allowable level 

mCi millicurie 

MCL maximum contaminant level 

MCLG maximum contaminant level goal 

MF modifying factor 
 

PHENOL C-3 

APPENDIX C 

MFO mixed function oxidase 

mg milligram 

mL milliliter 

mm millimeter 

mmHg millimeters of mercury 

mmol millimole 

mppcf millions of particles per cubic foot 

MRL Minimal Risk Level 

MS mass spectrometry 

NAAQS National Ambient Air Quality Standard 

NAS National Academy of Science 

NATICH National Air Toxics Information Clearinghouse 

NATO North Atlantic Treaty Organization 

NCE normochromatic erythrocytes 

NCEH National Center for Environmental Health 

NCI National Cancer Institute 

ND not detected 

NFPA National Fire Protection Association 

ng nanogram 

NHANES National Health and Nutrition Examination Survey 

NIEHS National Institute of Environmental Health Sciences 

NIOSH National Institute for Occupational Safety and Health 

NIOSHTIC NIOSH's Computerized Information Retrieval System 

NLM National Library of Medicine 

nm nanometer 

nmol nanomole 

NOAEL no-observed-adverse-effect level 

NOES National Occupational Exposure Survey 

NOHS National Occupational Hazard Survey 

NPD nitrogen phosphorus detection 

NPDES National Pollutant Discharge Elimination System 

NPL National Priorities List 

NR not reported 

NRC National Research Council 

NS not specified 

NSPS New Source Performance Standards 

NTIS National Technical Information Service 

NTP National Toxicology Program 

ODW Office of Drinking Water, EPA 

OERR Office of Emergency and Remedial Response, EPA 

OHM/TADS Oil and Hazardous Materials/Technical Assistance Data System 

OPP Office of Pesticide Programs, EPA 

OPPT Office of Pollution Prevention and Toxics, EPA 

OPPTS Office of Prevention, Pesticides and Toxic Substances, EPA 

OR odds ratio 

OSHA Occupational Safety and Health Administration 

OSW Office of Solid Waste, EPA 

OTS Office of Toxic Substances 

OW Office of Water 

OWRS Office of Water Regulations and Standards, EPA 

PAH polycyclic aromatic hydrocarbon 
 

 

PHENOL C-4 

APPENDIX C 

PBPD physiologically based pharmacodynamic 

PBPK physiologically based pharmacokinetic 

PCE polychromatic erythrocytes 

PEL permissible exposure limit 

pg picogram 

PHS Public Health Service 

PID photo ionization detector 

pmol picomole 

PMR proportionate mortality ratio 

ppb parts per billion 

ppm parts per million 

ppt parts per trillion 

PSNS pretreatment standards for new sources 

RBC red blood cell 

REL recommended exposure level/limit 

RfC reference concentration 

RfD reference dose 

RNA ribonucleic acid 

RQ reportable quantity 

RTECS Registry of Toxic Effects of Chemical Substances 

SARA Superfund Amendments and Reauthorization Act 

SCE sister chromatid exchange 

SGOT serum glutamic oxaloacetic transaminase 

SGPT serum glutamic pyruvic transaminase 

SIC standard industrial classification 

SIM selected ion monitoring 

SMCL secondary maximum contaminant level 

SMR standardized mortality ratio 

SNARL suggested no adverse response level 

SPEGL Short-Term Public Emergency Guidance Level 

STEL short term exposure limit 

STORET Storage and Retrieval 

TD50 toxic dose, 50% specific toxic effect 

TLV threshold limit value 

TOC total organic carbon 

TPQ threshold planning quantity 

TRI Toxics Release Inventory 

TSCA Toxic Substances Control Act 

TWA time-weighted average 

UF uncertainty factor 

U.S. United States 

USDA United States Department of Agriculture 

USGS United States Geological Survey 

VOC volatile organic compound 

WBC white blood cell 

WHO World Health Organization 
 

PHENOL 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 
PHENOL C-6
 

APPENDIX C 

This page is intentionally blank. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PHENOL D-1 

APPENDIX D. INDEX
 

absorbed dose............................................................................................................................................122
 

acetylcholine .............................................................................................................................................124
 

adrenal gland........................................................................................................................... 14, 67, 75, 131
 

adsorption.................................................................................................................................. 156, 170, 176
 

aerobic................................................................................................................................... 9, 157, 158, 159
 

alanine aminotransferase (see ALT) ..................................................................................................... 10, 36
 

ALT (see alanine aminotransferase) ........................................................................... 10, 36, 37, 65, 82, 131
 

ambient air ................................................................................................................ 149, 159, 164, 165, 170
 

anaerobic....................................................................................................................................... 9, 158, 159
 

aspartate aminotransferase (see AST)................................................................................................... 35, 36
 

AST (see aspartate aminotransferase)......................................................................... 10, 36, 37, 65, 82, 131
 

bioaccumulation................................................................................................................................ 156, 170
 

bioavailability ...........................................................................................................................................170
 

bioconcentration factor .............................................................................................................................156
 

biodegradation............................................................................................................. 10, 149, 155, 156, 158
 

biomarker .................................................................. 106, 111, 121, 122, 123, 124, 134, 135, 172, 173, 181
 

blood cell count............................................................................................................................... 12, 36, 64
 

body weight effects......................................................................................................................... 39, 68, 85
 

breast milk............................................................................................................................... 5, 10, 137, 166
 

cancer...................................................................................................... 4, 22, 44, 75, 86, 87, 118, 121, 185
 

carcinogen................................................................................................................................... 86, 185, 188
 

carcinogenic ...................................................................................................................... 14, 21, 75, 86, 111
 

carcinogenicity............................................................................ 4, 14, 75, 87, 112, 129, 131, 136, 185, 188
 

carcinoma.............................................................................................................................................. 86, 87
 

cardiac arrhythmia ........................................................................................ 12, 77, 118, 119, 120, 126, 129
 

cardiovascular ............................................................................... 4, 10, 23, 34, 62, 127, 129, 131, 134, 136
 

cardiovascular effects...................................................................................................................... 34, 62, 77
 

catechol ............................................................................................................................... 93, 101, 112, 115
 

chromosomal aberrations................................................................................................................ 87, 91, 92
 

clearance ............................................................................................................................................. 95, 100
 

consumer products ............................................................................................ 1, 9, 164, 165, 166, 167, 171
 

death.......................................... 4, 11, 18, 21, 22, 23, 35, 43, 44, 61, 70, 75, 76, 77, 85, 120, 125, 127, 188
 

deoxyribonucleic acid (see DNA)................................................................................................... 87, 88, 90
 

dermal effects............................................................................................................................ 38, 39, 67, 83
 

disinfectant.................................................................................................................... 1, 5, 67, 70, 119, 143
 

DNA (see deoxyribonucleic acid)..................................................... 87, 88, 89, 90, 91, 92, 93, 99, 114, 122
 

dopamine............................................................................................................................................... 20, 71
 

elimination half-time...................................................................................................................................99
 

endocrine..................................................................................................................................... 67, 115, 116
 

endocrine effects .........................................................................................................................................67
 

erythema............................................................................................................................ 11, 63, 77, 83, 125
 

estrogen receptor.......................................................................................................................................117
 

estrogenic ..................................................................................................................................................117
 

fetal tissue ...................................................................................................................................................98
 

fetus...........................................................................................................................................................117
 

gastrointestinal effects .............................................................................................................. 34, 35, 63, 81
 

general population..................................................................................... 10, 22, 35, 44, 122, 134, 165, 188
 

genotoxic............................................................................................................................... 21, 91, 112, 132
 

genotoxicity................................................................................................................................. 87, 129, 132
 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PHENOL D-2 

APPENDIX D 

germinal cell................................................................................................................................................72
 

glucuronide ............................................................................... 100, 101, 103, 104, 114, 121, 136, 137, 173
 

groundwater ...................................................................... 2, 9, 149, 155, 156, 158, 160, 161, 163, 164, 171
 

growth retardation.......................................................................................................................................73
 

half-life.............................................................................................. 9, 94, 95, 107, 122, 149, 155, 157, 158
 

hematological effects ...................................................................................................................... 35, 64, 81
 

hematopoietic..............................................................................................................................................35
 

hepatic effects ......................................................................................................................... 36, 65, 82, 124
 

hydrolysis.......................................................................................................................... 143, 173, 174, 176
 

hydroquinone ...................................................................................... 93, 101, 103, 104, 111, 112, 115, 124
 

hydroxyl radical ........................................................................................................................ 149, 155, 157
 

immune system ...........................................................................................................................................40
 

immunological .............................................................. 12, 13, 19, 21, 35, 40, 41, 69, 70, 85, 129, 130, 131
 

immunological effects................................................................................................................... 19, 69, 130
 

Kow ............................................................................................................................................................141
 

LD50..................................................................................................................................... 45, 61, 76, 77, 99
 

leukemia........................................................................................................................................ 14, 75, 131
 

lymphoreticular............................................................................................................. 13, 20, 41, 69, 70, 85
 

metabolic effects .........................................................................................................................................40
 

micronuclei .................................................................................................................................................91
 

milk ............................................................................................................................................... 5, 121, 137
 

musculoskeletal effects ............................................................................................................. 36, 65, 81, 82
 

neurobehavioral.........................................................................................................................................116
 

neurochemical............................................................................................................................... 12, 19, 130
 

norepinephrine ...................................................................................................................................... 20, 71
 

nuclear................................................................................................................................................. 82, 114
 

ocular effects................................................................................................................................. 68, 84, 130
 

odds ratio.....................................................................................................................................................44
 

pharmacodynamic.....................................................................................................................................108
 

pharmacokinetic........................................................................................................ 108, 109, 110, 118, 121
 

placenta ............................................................................................................................................. 121, 137
 

placental barrier ..........................................................................................................................................98
 

rate constant ........................................................................................................................................ 94, 157
 

renal effects..................................................................................................................................... 38, 66, 82
 

retention .................................................................................................................................. 93, 94, 95, 157
 

salivation............................................................................................................................................... 18, 85
 

solubility ...................................................................................................................................................155
 

spermatogonia.............................................................................................................................................91
 

sulfate.................................... 93, 97, 101, 103, 104, 113, 115, 120, 121, 124, 135, 136, 137, 173, 179, 180
 

thyroid................................................................................................................................................... 67, 99
 

toxicokinetic.................................................................................................................... 12, 16, 21, 127, 135
 

tremors .............................................................................. 4, 11, 12, 14, 15, 16, 40, 42, 70, 73, 85, 115, 124
 

tumors ..................................................................................................................................... 77, 86, 87, 124
 

volatility....................................................................................................................................................158
 

volatilization ..................................................................................................................................... 155, 170