TOXICOLOGICAL PROFILE FOR
 

STYRENE
 


 


 


 


 

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
 

Public Health Service
 

Agency for Toxic Substances and Disease Registry
 

November 2010 
 

STYRENE 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. 
 


 


 


 


 


 


 

STYRENE iii 

UPDATE STATEMENT
 

A Toxicological Profile for Styrene, Draft for Public Comment was released in October 2007. 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-62
 

Atlanta, Georgia 30333
 
STYRENE iv 

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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 infonnation for these toxic substances described therein. Each peer-reviewed profile identifies and 

reviews the key literature that describes a 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 ofthe profiles is on health and toxicologic infonnation; 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 infonnation concerning levels 

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

to detennine 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. 

Each profile includes the following: 

(A) The examination, summary, and interpretation ofavailable toxicologic infonnation and 

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

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

(B) 	A determination ofwhether adequate infonnation on the health effects of each substance is 

available or in the process of development to detennine levels ofexposure that present a 

significant risk to human health ofacute, subacute, and chronic health effects; and 

(C) Where appropriate, identification oftoxicologic testing needed to identifY the types or levels 

ofexposure 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 ofthe public. 

This profile reflects ATSDR's assessment ofall relevant toxicologic testing and infonnation that 

has been peer-reviewed. Staffs ofthe Centers for Disease Control and Prevention and other Federal 

scientists have also reviewed the profile. In addition, this profile has been peer-reviewed by a 

nongovernmental panel and was made available for public review. Final responsibility for the contents 

and views expressed in this toxicological profile resides with ATSDR. 

// 7\\ /) ;/A~-'0/.L.-- /r:../C~--(Xj 

Thomas R. Frieden, M.D., M.P.H. 


Administrator 


Agency for Toxic Substances and 


Disease Registry 

"Legislative Background 

The toxicological profiles are developed under the Comprehensive Environmental Response, 

Compensation, and Liability Act of 1980, as amended (CERCLA or Superfund). CERCLA section 

104(i)(1) directs the Administrator of ATSDR to " ...effectuate and implement the health related 

authorities" ofthe statute. This includes the preparation oftoxicological 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. Section 

104(i)(3) ofCERCLA, as amended, directs the Administrator ofATSDR to prepare a toxicological profile 

for each substance on the list. In addition, A TSDR has the authority to prepare toxicological profiles for 

substances not found at sites on the National Priorities List, in an effort to " ...establish and maintain 

inventory of literature, research, and studies on the health effects oftoxic substances" under CERCLA 

Section 104(i)(IXB), to respond to requests for consultation under section 104(i)(4), and as otherwise 

necessary to support the site-specific response actions conducted by A TSDR. 
 

 

 

 


 


 


 


 

STYRENE 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. 
 

 

 

 

 

STYRENE 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. 

 


 


 


 


 


 


 


 


 


 

	 

	 

	 

	 

STYRENE ix 

CONTRIBUTORS 

CHEMICAL MANAGER(S)/AUTHOR(S): 

Zemoria Rosemond, B.A.
 

Selene Chou, Ph.D.
 

Jewell Wilson, Ph.D.
 

Michael Schwartz, M.D.
 

Francisco Tomei-Torres, Ph.D.
 

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

Lisa Ingerman, Ph.D., DABT
 

David B. Knaebel, Ph.D.
 

Mario Citra, Ph.D.
 

SRC, Inc., North Syracuse, NY
 

THE PROFILE HAS UNDERGONE THE FOLLOWING ATSDR INTERNAL REVIEWS: 

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

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

end points. 

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

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

profile, and makes recommendations for derivation of MRLs. 

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

consistency across profiles and adherence to instructions in the Guidance. 

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

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STYRENE xi 

PEER REVIEW 

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

Draft for Public Comment: 

1.	 George Cruzan, Ph.D., DABT, ToxWorks, Bridgeton, New Jersey; 

2.	 Teresa Leavens, Ph.D., Research Assistant Professor, Center for Chemical Toxicology Research 

and Pharmacokinetics, North Carolina State University, Raleigh, North Carolina; and 

3.	 Jean Rabovsky, Ph.D., Retired Toxicologist, El Cerrito, California. 

These experts collectively have knowledge of styrene’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. 
STYRENE xii 

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STYRENE 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 STYRENE? ................................................................................................................. 1
 

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

1.3 HOW MIGHT I BE EXPOSED TO STYRENE?......................................................................... 3
 

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

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

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

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

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

TO STYRENE? ............................................................................................................................ 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 STYRENE IN THE
 

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

2.2	 SUMMARY OF HEALTH EFFECTS ......................................................................................... 9
 

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

3. HEALTH EFFECTS.............................................................................................................................. 23
 

3.1 INTRODUCTION ...................................................................................................................... 23
 

3.2 DISCUSSION OF HEALTH EFFECTS BY ROUTE OF EXPOSURE.................................... 23
 

3.2.1 Inhalation Exposure ............................................................................................................ 24
 

3.2.1.1 Death ............................................................................................................................... 24
 

3.2.1.2 Systemic Effects.............................................................................................................. 25
 

3.2.1.3 Immunological and Lymphoreticular Effects ................................................................. 51
 

3.2.1.4 Neurological Effects ....................................................................................................... 52
 

3.2.1.5 Reproductive Effects....................................................................................................... 68
 

3.2.1.6 Developmental Effects.................................................................................................... 70
 

3.2.1.7 Cancer ............................................................................................................................. 72
 

3.2.2 Oral Exposure ..................................................................................................................... 77
 

3.2.2.1 Death ............................................................................................................................... 77
 

3.2.2.2 Systemic Effects.............................................................................................................. 78
 

3.2.2.3 Immunological and Lymphoreticular Effects ................................................................. 87
 

3.2.2.4 Neurological Effects ....................................................................................................... 88
 

3.2.2.5 Reproductive Effects....................................................................................................... 89
 

3.2.2.6 Developmental Effects.................................................................................................... 89
 

3.2.2.7 Cancer ............................................................................................................................. 90
 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 

3.2.3 Dermal Exposure................................................................................................................. 91
 

3.2.3.1 Death ............................................................................................................................... 91
 

3.2.3.2 Systemic Effects.............................................................................................................. 91
 

3.2.3.3 Immunological and Lymphoreticular Effects ................................................................. 92
 

3.2.3.4 Neurological Effects ....................................................................................................... 92
 

3.2.3.5 Reproductive Effects....................................................................................................... 92
 

3.2.3.6 Developmental Effects.................................................................................................... 92
 

3.2.3.7 Cancer ............................................................................................................................. 92
 

3.3 GENOTOXICITY....................................................................................................................... 92
 

3.4 TOXICOKINETICS ................................................................................................................... 96
 

3.4.1 Absorption........................................................................................................................... 96
 

3.4.1.1 Inhalation Exposure ........................................................................................................ 96
 

3.4.1.2 Oral Exposure ................................................................................................................. 98
 

3.4.1.3 Dermal Exposure............................................................................................................. 98
 

3.4.2 Distribution ......................................................................................................................... 99
 

3.4.2.1 Inhalation Exposure ........................................................................................................ 99
 

3.4.2.2 Oral Exposure ............................................................................................................... 100
 

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

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

3.4.4 Elimination and Excretion ................................................................................................ 104
 

3.4.4.1 Inhalation Exposure ...................................................................................................... 104
 

3.4.4.2 Oral Exposure ............................................................................................................... 105
 

3.4.4.3 Dermal Exposure........................................................................................................... 106
 

3.4.5 Physiologically Based Pharmacokinetic (PBPK)/Pharmacodynamic (PD) Models ......... 106
 

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

3.4.5.2 Discussion of Model .................................................................................................... 109
 

3.5 MECHANISMS OF ACTION.................................................................................................. 111
 

3.5.1 Pharmacokinetic Mechanisms........................................................................................... 111
 

3.5.2 Mechanisms of Toxicity.................................................................................................... 116
 

3.5.3 Animal-to-Human Extrapolations..................................................................................... 117
 

3.6 TOXICITIES MEDIATED THROUGH THE NEUROENDOCRINE AXIS.......................... 118
 

3.7 CHILDREN’S SUSCEPTIBILITY .......................................................................................... 120
 

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

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

3.8.2 Biomarkers Used to Characterize Effects Caused by Styrene .......................................... 124
 

3.9 INTERACTIONS WITH OTHER CHEMICALS.................................................................... 125
 

3.10 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE .............................................. 126
 

3.11 METHODS FOR REDUCING TOXIC EFFECTS .................................................................. 126
 

3.11.1 Reducing Peak Absorption Following Exposure .............................................................. 126
 

3.11.2 Reducing Body Burden..................................................................................................... 127
 

3.11.3 Interfering with the Mechanism of Action for Toxic Effects............................................ 127
 

3.12 ADEQUACY OF THE DATABASE ....................................................................................... 128
 

3.12.1 Existing Information on Health Effects of Styrene........................................................... 129
 

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

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

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

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

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

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

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

5.2 IMPORT/EXPORT................................................................................................................... 146
 

5.3 USE........................................................................................................................................... 146
 

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

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

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

6.2 RELEASES TO THE ENVIRONMENT.................................................................................. 149
 

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............................................................................................................................. 158
 

6.3.2.3 Sediment and Soil ......................................................................................................... 159
 

6.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT ................................ 160
 

6.4.1 Air ..................................................................................................................................... 160
 

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

6.4.3 Sediment and Soil ............................................................................................................. 162
 

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

6.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE....................................... 165
 

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

6.7 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES............................................. 169
 

6.8 ADEQUACY OF THE DATABASE ....................................................................................... 169
 

6.8.1 Identification of Data Needs ............................................................................................. 169
 

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

7. ANALYTICAL METHODS ............................................................................................................... 175
 

7.1 BIOLOGICAL MATERIALS .................................................................................................. 175
 

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

7.3 ADEQUACY OF THE DATABASE ....................................................................................... 179
 

7.3.1 Identification of Data Needs ............................................................................................. 179
 

7.3.2 Ongoing Studies................................................................................................................ 183
 

8. REGULATIONS, ADVISORIES, AND GUIDELINES..................................................................... 185
 

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

10. GLOSSARY ...................................................................................................................................... 231
 

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
 

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STYRENE xvii 

LIST OF FIGURES
 

3-1. Levels of Significant Exposure to Styrene - Inhalation...................................................................... 43
 

3-2. Levels of Significant Exposure to Styrene - Oral............................................................................... 83
 

3-3. Scheme for Styrene Metabolism in Humans and Animals ............................................................... 102
 

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

Hypothetical Chemical Substance .................................................................................................... 108
 

3-5. Styrene and Styrene Oxide Models used in the Sarangapani PBPK Model..................................... 110
 

3-6. Existing Information on Health Effects of Styrene .......................................................................... 130
 

6-1. Frequency of NPL Sites with Styrene Contamination...................................................................... 150
 
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STYRENE xix 

LIST OF TABLES
 

2-1. Results of Selected Human Neurotoxicity Studies............................................................................. 18
 

3-1. Levels of Significant Exposure to Styrene - Inhalation...................................................................... 26
 

3-2. Summary of Occupational Exposure Studies Examining Neurological End Points........................... 54
 

3-3. Levels of Significant Exposure to Styrene - Oral............................................................................... 79
 

3-4. Genotoxicity of Styrene In Vivo ......................................................................................................... 93
 

3-5. Genotoxicity of Styrene In Vitro ........................................................................................................ 97
 

3-6. Physiological and Flow Parameters Used in the Sarangapani PBPK Model.................................... 112
 

3-7. Respiratory Tract-Specific Physiological Parameters Used in the Sarangapani PBPK Model ........ 113
 

3-8. Kinetic Parameters Used in the Sarangapani PBPK Model ............................................................. 114
 

3-9. Stereospecific Kinetic Parameters for Styrene and Styrene Oxide Metabolism in Rodents
 

Used in the Sarangapani PBPK Model ............................................................................................. 115
 

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

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

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

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

6-2. Styrene Concentrations in Representative Air Samples ................................................................... 161
 

6-3. Styrene Levels in Food Items ........................................................................................................... 164
 

6-4. Concentrations of Styrene in the Surrounding Air, Blood, and Urine of Reinforced Plastics
 

Workers, Including Urinary Concentrations of the Styrene Metabolites, MA and PGA ................. 167
 

7-1. Analytical Methods for Determining Styrene in Biological Materials............................................. 177
 

7-2. Analytical Methods for Determining Styrene in Environmental Samples ....................................... 180
 

8-1. Regulations, Advisories, and Guidelines Applicable to Styrene ...................................................... 187
 
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STYRENE 1 

1. PUBLIC HEALTH STATEMENT 

This public health statement tells you about styrene 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. Styrene has been found in at least 251 of the 1,699 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 styrene 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 styrene, 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 STYRENE? 

Styrene is a colorless liquid that evaporates easily. 

In its pure form, styrene has a sweet smell. Manufactured styrene may 

contain aldehydes, which give it a sharp, unpleasant odor. 

Description 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

STYRENE 2 

1. PUBLIC HEALTH STATEMENT 

Uses 

• Manufacturing 

• Consumer 

products 

Large amounts of styrene are produced in the United States. Small amounts 

are produced naturally by plants, bacteria, and fungi. Styrene is also present 

in combustion products such as cigarette smoke and automobile exhaust. 

Styrene is widely used to make plastics and rubber. Consumer products 

containing styrene include: 

• packaging materials 

• insulation for electrical uses (i.e., wiring and appliances) 

• insulation for homes and other buildings 

• fiberglass, plastic pipes, automobile parts 

• drinking cups and other "food-use" items 

• carpet backing 

These products mainly contain styrene linked together in long chains 

(polystyrene). However, most of these products also contain a small amount 

of unlinked styrene. 

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

use, see Chapters 4 and 5. 

1.2 WHAT HAPPENS TO STYRENE WHEN IT ENTERS THE ENVIRONMENT? 

Sources Styrene can be found in air, soil, and water after release from the 

manufacture, use, and disposal of styrene-based products. 

Break down 

• Air 

• Water and soil 

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

Styrene evaporates from shallow soils and surface water. Styrene that 

remains in soil or water may be broken down by bacteria or other 

microorganisms. 

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

 

 

STYRENE 3 

1. PUBLIC HEALTH STATEMENT 

1.3 HOW MIGHT I BE EXPOSED TO STYRENE? 

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

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

 industries using or manufacturing styrene 

 automobile exhaust 

 cigarette smoke, and 

 use of photocopiers 

Rural or suburban air generally contains lower concentrations of styrene 

than urban air. Indoor air often contains higher levels of styrene than 

outdoor air. 

 0.06–4.6 parts per billion (ppb) in outdoor air 

 0.07–11.5 ppb in indoor air 

Water and soil Styrene is occasionally detected in groundwater, drinking water, or soil 

samples. Drinking water containing styrene or bathing in water containing 

styrene may expose you to low levels of this chemical. 

Workplace air A large number of workers are potentially exposed to styrene. The highest 

potential exposure occurs in the reinforced-plastics industry, where workers 

may be exposed to high air concentrations and also have dermal exposure 

to liquid styrene or resins. 

Workers involved in styrene polymerization, rubber manufacturing, and 

styrene-polyester resin facilities and workers at photocopy centers may also 

be exposed to styrene. 

Food Low levels of styrene occur naturally in a variety of foods, such as fruits, 

vegetables, nuts, beverages, and meats. Small amounts of styrene can be 

transferred to food from styrene-based packaging material. 

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

 

 

STYRENE 4 

1. PUBLIC HEALTH STATEMENT 

1.4 HOW CAN STYRENE ENTER AND LEAVE MY BODY? 

Enter your body

 • Inhalation 

 • Ingestion 

• Dermal contact 

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

enter your body through your lungs. 

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

digestive tract. 

A very small amount may enter through your skin when you come into 

contact with liquids containing styrene. 

Leave your body Once in your body, styrene is broken down into other chemicals. Most of 

these other chemicals leave your body in the urine within few days. 

For more information on how styrene enters and leaves the body, see Chapter 3. 

1.5 HOW CAN STYRENE AFFECT MY HEALTH? 

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

Health Effects 

Workers

 • Inhalation The most common health problems in workers exposed to styrene involve 

the nervous system. These health effects include changes in color vision, 

tiredness, feeling drunk, slowed reaction time, concentration problems, and 

balance problems. 

The styrene concentrations that cause these effects are more than 

1,000 times higher than the levels normally found in the environment. 

Laboratory 

animals 

• Inhalation Hearing loss has been observed in animals exposed to very high 

concentrations of styrene. 

Animal studies have shown that inhalation of styrene can result in changes 

in the lining of the nose and damage to the liver; however, animals may be 

more sensitive than humans to the nose and liver effects. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

STYRENE 5 

1. PUBLIC HEALTH STATEMENT 

Laboratory 

animals 

• Oral Impaired learning has been observed in rats exposed to high doses of 

styrene. 

Sperm damage has also been observed in rats exposed to high doses of 

styrene. 

Cancer The International Agency for Research on Cancer has determined that 

styrene is a possible carcinogen. 

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

Chapters 2 and 3. 

1.6 HOW CAN STYRENE 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 There are no studies evaluating the effect of styrene exposure on children 

or immature animals. It is likely that children would have the same health 

effects as adults. We do not know whether children would be more 

sensitive than adults to the effects of styrene. 

Birth defects Studies in workers have examined whether styrene can cause birth defects 

or low birth weight; however, the results are inconclusive. No birth defects 

were observed in animal studies. 

Breast milk Nursing infants can be exposed to styrene from breast milk. 

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

Tobacco smoke Styrene 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. 

Copier Styrene is released during the use of home copiers. Families should use a 

copier only when needed and turn it off when finished. It is also important to 

keep the room with the copier well ventilated. 
 

 

 

 

 

 

 

 

 

 

 

 

 

STYRENE	 6 

1. PUBLIC HEALTH STATEMENT 

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

STYRENE? 

Detecting 

exposure 

Styrene can be measured in blood, urine, and body tissues for a short time 

following exposure to moderate-to-high levels. 

Measuring 

exposure 

The presence of styrene breakdown products (metabolites) in urine might 

indicate that you were exposed to styrene; however, these metabolites can 

also form when you are exposed to other substances. 

Measuring styrene metabolites in urine within 1 day of exposure allows 

medical personnel to estimate actual exposure level. 

The detection of these 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 styrene 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. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

STYRENE 7 

1. PUBLIC HEALTH STATEMENT 

Some regulations and recommendations for styrene include the following: 

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

concentrations of 20 ppm for 1 day or 2 ppm for 10 days is not expected to 

cause any adverse effects in a child. 

The EPA has determined that lifetime exposure to 0.1 ppm styrene in 

drinking water is not expected to cause any adverse effects. 

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

water should not exceed 0.1 ppm. 

Workplace air OSHA set a legal limit of 100 ppm styrene 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-62
 

Atlanta, GA 30333
 

Fax: 1-770-488-4178
 
 

 

 

 

 

STYRENE 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/ 
STYRENE 9 

2. RELEVANCE TO PUBLIC HEALTH 

2.1 BACKGROUND AND ENVIRONMENTAL EXPOSURES TO STYRENE IN THE UNITED 

STATES 

Styrene is a high production chemical; the production capacity for styrene in the United States was over 

12 billion pounds in 2008. Small amounts of styrene are naturally present in foods such as legumes, beef, 

clams, eggs, nectarines, and spices. It can also be present in packaged foods by migration from 

polystyrene food containers and packaging materials. Styrene is a combustion product of cigarette smoke 

and automobile exhaust. Manufactured styrene is primarily used in the production of polystyrene plastics 

and resins used principally for insulation or in the fabrication of fiberglass boats; production of 

copolymers such as styrene-acrylonitrile and acrylonitrile-butadiene-styrene, which are used to 

manufacture piping, automotive components, and plastic drinking glasses; production of styrenebutadiene rubber used to manufacture car tires, hoses for industrial purposes, and shoes; or formulated 

with unsaturated polyester resins used as fiberglass reinforcement materials. Styrene copolymers are also 

frequently used in liquid toner for photocopiers and printers. 

Median styrene concentrations in urban and rural/suburban air samples are 0.07–4.6 ppb and 0.06– 

0.1 ppb. The median styrene concentration in indoor air samples ranged from 0.07 to 11.5 ppb; the 

primary sources of styrene in indoor air are cigarette smoke and photocopiers. Styrene is rarely detected 

in drinking water samples and is rarely detected in soil samples. 

General population exposure to styrene in air and food has been estimated to be 18–54 and 0.2– 

1.2 μg/person/day, respectively, with a total daily exposure of 18.2–55.2 μg/day or 0.0003– 

0.0008 mg/kg/day (assuming a 70-kg reference body weight). 

2.2 SUMMARY OF HEALTH EFFECTS 

Styrene-induced neurotoxicity has been reported in workers since the 1970s. Studies over the last 

15 years have firmly established the central nervous system as the critical target of toxicity. Both shortand long-term exposures to styrene can result in neurological effects. Acute exposure data are limited to 

the finding of impaired performance on tests of vestibular function in test subjects exposed to 87– 

376 ppm for 1–3 hours and studies finding no alterations in performance of neurobehavioral tests 

(reaction time, color discrimination, and tests of memory or attention) in subjects exposed to 20 or 

49 ppm. A variety of neurological effects have been observed in chronically exposed styrene workers; 
 

 

 

 

 

 

STYRENE 10 

2. RELEVANCE TO PUBLIC HEALTH 

these effects include decreased color discrimination, vestibular effects, hearing impairment, symptoms of 

neurotoxicity, particularly ”feeling drunk” and tiredness, delays in reaction time, impaired performance 

on tests measuring attention and memory, increased vibration perception thresholds, impaired nerve 

conduction velocity, and EEG alterations. The LOAELs for these effects range from about 10 ppm to 

93 ppm. In most of the occupational exposure studies, neurological function tests were conducted in the 

morning before work, suggesting that the deficits were not acute effects. Results of a meta-analysis 

suggest that the severity of the some of the neurological symptoms increases with exposure duration. For 

example, 8, 15, 25, and 35% increases in reaction time were observed in workers exposed to 100 ppm for 

2, 4, 6, and 8 work-years, respectively. However, this may also be reflective of higher exposure levels in 

the past rather than a duration-related increase in severity. The existing data are inadequate to determine 

whether chronic styrene exposure results in permanent damage. Mixed results have been found in studies 

examining workers before and after an extended period without styrene exposure. Neurotoxicity studies 

in animals have primarily focused on effects on hearing and damage to the organ of Corti. 

Other effects that have been observed in animal studies include damage to the nasal olfactory epithelium 

and liver necrosis; testicular damage and developmental effects have also been reported, but the weight of 

evidence does not support concluding that these are sensitive targets. Damage to the nasal olfactory 

epithelium was observed in mice after 3 days of exposure. The severity of the lesion progressed from 

single cell necrosis to atrophy and respiratory metaplasia with increasing exposure duration. The lowestobserved-adverse-effect levels (LOAELs) for these lesions are 80, 50, and 20 ppm for acute, intermediate, 

and chronic exposure, respectively. Rats do not appear to be as sensitive as mice to the nasal olfactory 

epithelial damage; an intermediate-duration study identified a no-observed-adverse-effect level (NOAEL) 

and LOAEL of 500 and 1,000 ppm for focal hyperplasia and a chronic study identified a LOAEL of 

50 ppm for atrophy and degeneration. The observed species differences may be due to differences in 

styrene metabolism in the nasal cavity. In particular, rats have a higher capacity to detoxify styrene oxide 

with epoxide hydrolases and glutathione S-transferase. Humans are not likely sensitive to the nasal 

toxicity of styrene because styrene oxide has not been detected and high levels of epoxide hydrolases 

have been found in in vitro assays of human nasal tissue. 

Unlike the nasal lesions, the severity of hepatic lesions decreases with increased exposure durations. 

Severe hepatocellular necrosis was observed in mice exposed to 250 ppm for 3 days; however, continued 

exposure at this concentration resulted in focal necrosis and an increase in pigmented macrophages. 

Centrilobular aggregates of siderophages were observed in mice exposed to 200 ppm for 13 weeks; no 

liver effects were observed at 160 ppm after 2 years of exposure. Rats are less sensitive than mice to liver 
 

 

 

 

 

 

 

STYRENE 11 

2. RELEVANCE TO PUBLIC HEALTH 

toxicity; no liver effects were observed in an intermediate-duration study in which rats were exposed to a 

styrene concentration 10-fold higher than the concentration eliciting hepatic effects in mice. No 

alterations in serum markers of liver damage were observed in styrene workers exposed to 40 ppm for 

approximately 5 years. Liver effects have not been observed in rats orally exposed to 35 mg/kg/day for 

105 weeks. Some hepatic alterations (increases in liver weight and small areas of focal necrosis) have 

been reported in rats exposed to 400 mg/kg for an intermediate duration; however, the studies are poorly 

reported and lack statistical comparisons with controls. No studies examined systemic end points 

following acute exposure. 

Occupational exposure studies have not found significant increases in the occurrence of stillbirth, infant 

death, malformations, or low birth weight. An increase in fetal deaths were observed in hamsters exposed 

to very high concentrations (1,000 ppm on gestation days 6–18) and in rats exposed to 300 ppm on 

gestation days 6–20. However, most single and multigeneration inhalation and oral exposure animal 

studies did not find significant alterations in fetus/pup survival, growth, or incidence of abnormalities in 

rats, mice, rabbits, and hamsters exposed to styrene. Two studies have examined neurodevelopmental 

effects in rats; one study found some minor effects (slight delays in some developmental landmarks). The 

other, higher-quality study did not find any significant alterations in a number of neurodevelopmental end 

points. The National Toxicology Program (NTP) Expert Panel examining the developmental potential of 

styrene concluded that the human data are not sufficient to evaluate the potential developmental toxicity 

of styrene in humans and that there was no convincing evidence of developmental toxicity in animals. 

Although several epidemiology studies have examined potential reproductive effects in male and female 

styrene workers, adequate analysis of the data is limited by the lack of exposure information and 

concomitant exposure to other compounds. Mixed results have been found for increased occurrence of 

spontaneous abortions and oligomenorrhea. In male workers, sperm abnormalities have been reported 

(Kolstad et al. 1999a), but not alterations in time-to-pregnancy or fertility rates. No adverse reproductive 

effects were observed in inhalation and oral multigeneration studies in rats. A series of studies found 

decreases in spermatozoa counts in rats exposed as adults, as neonates, and through lactation. However, 

as noted by the NTP Expert Panel, this finding is not consistent with the lack of reproductive effects 

found in the inhalation two-generation study. The NOAEL identified in the two-generation inhalation 

study was 500 ppm (6 hours/day), which is roughly equivalent to 230 mg/day using a reference inhalation 

rate of 0.42 m3

/day. The LOAEL for spermatozoa effects in adult rats was 400 mg/kg (6 days/week), 

which is roughly equivalent to 158 mg/day using a reference body weight of 0.462 kg. 
 

 

 

 

 

STYRENE 12 

2. RELEVANCE TO PUBLIC HEALTH 

There are several epidemiologic studies of workers at styrene manufacturing and polymerization facilities 

and reinforced plastics facilities that suggest an association between occupational exposure and an 

increased incidence of cancer of the lymphatic and hematopoietic tissues in styrene. However, the 

reported studies are inconclusive due to exposure to multiple chemicals (including benzene) and the small 

size of the cohorts. Other studies have reported negative results. More consistent results for increases in 

the risk of lymphatic and hematopoietic cancers have been observed among workers at styrene-butadiene 

manufacturing facilities. There is suggestive evidence that these increased risks may be due to exposure 

to 1,3-butadiene rather styrene exposure; however, it is difficult to separate the risks for styrene and 

1,3-butadiene because the exposure is highly correlated. There are no reports of cancer resulting from 

styrene exposure by the oral or dermal routes in humans. Species differences in styrene carcinogenicity 

have been detected in animal studies. Inhalation and oral exposure studies in rats have not found 

significant increases in neoplastic lesions. However, increases in lung tumors have been found in mice 

following inhalation and oral exposure. The increased production of styrene 7,8-oxide in lung Clara cells 

and the higher ratio of styrene oxide R- to S-enantiomers likely resulted in the increased sensitivity of 

mice. Overall, human and animal studies suggest that styrene may be a weak human carcinogen. The 

International Agency for Research on Cancer (IARC) has assigned styrene to Group 2B, possibly 

carcinogenic to humans. EPA and DHHS have not evaluated the carcinogenic potential of styrene. One 

study lists a cancer classification of A4, not classifiable as a human carcinogen based on a 1996 

evaluation of the available data. 

2.3 MINIMAL RISK LEVELS (MRLs) 

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

 

 

 

 

 

 

STYRENE 13 

2. RELEVANCE TO PUBLIC HEALTH 

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

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

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

significant human exposure improve, these MRLs will be revised. 

Inhalation MRLs 

Acute-Duration Inhalation MRL 

An MRL of 5 ppm has been derived for acute-duration inhalation exposure (14 days or less) to 

styrene. 

The acute-duration inhalation toxicity database for styrene consists of several human experimental studies 

primarily examining neurotoxicity (Ödkvist et al. 1982; Seeber et al. 2004; Ska et al. 2003; Stewart et al. 

1968), systemic toxicity studies in mice (Cruzan et al. 1997, 2001; Morgan et al. 1993a, 1993b, 1993c), 

neurotoxicity studies in rats (Campo et al. 2001; Crofton et al. 1994; Lataye et al. 2003), mice (Cruzan et 

al. 1997; DeCeaurriz et al. 1983), and guinea pigs (Lataye et al. 2003), a reproductive toxicity study in 

mice (Salomaa et al. 1985), and developmental toxicity studies in rats (Murray et al. 1978), mice 

(Kankaanpää et al. 1980), hamsters (Kankaanpää et al. 1980), and rabbits (Murray et al. 1978). Eye 

irritation was reported in humans exposed to 99 ppm for 7 hours or 376 ppm for 1 hour (Stewart et al. 

1968); nasal irritation was also reported at 376 ppm. A significant inhibition of the vestibular-oculomotor 

system was observed in subjects exposed to 87 ppm for 1 hour (Ödkvist et al. 1982). Studies by (Stewart 

et al. 1968) found alterations in tests of balance or coordination in subjects exposed to 376 ppm for 

1 hour, but not after exposure to 99 ppm for 7 hours or 216 ppm for 1 hour; the test used in the Stewart et 

al. (1968) studies is probably less sensitive than those used by Ödkvist et al. (1982). No significant 

alterations in performance on tests of reaction time were observed in subjects exposed to 20 ppm for 

3 hours (Seeber et al. 2004) or 49 ppm for 6 hours with or without four 15-minute peak exposures to 

98 ppm) (Ska et al. 2003). Additionally, no significant alterations in color discrimination, olfactory 

threshold, or performance on neurobehavioral tests of memory or attention were observed in subjects 

exposed to 49 ppm for 6 hours with or without four 15-minute peak exposures to 98 ppm (Ska et al. 

2003). 

In mice, the most sensitive target of styrene toxicity appears to be the nasal olfactory epithelium; single 

cell necrosis was observed following exposure to 80 ppm 6 hours/day for 3 days (Cruzan et al. 2001). At 

250 ppm, hepatocellular necrosis and degeneration have been observed (Cruzan et al. 1997; Morgan et al. 

1993a, 1993b, 1993c). The severity of this lesion appears to be inversely related to the duration of 

exposure, with more severe damage observed in mice killed within 3 days of exposure (Morgan et al. 
 

 

 

 

 

 

 

 

 

 

STYRENE 14 

2. RELEVANCE TO PUBLIC HEALTH 

1993a, 1993b, 1993c) compared to animals killed after 2 weeks of exposure (Cruzan et al. 1997; Morgan 

et al. 1993a). Exposure to 250 ppm 6 hours/day, 5 days/week for 2 weeks also resulted in lethargy and 

unsteady gait in mice (Cruzan et al. 1997). Impaired performance on a swimming test was observed in 

mice exposed to 610 ppm for 4 hours, but not in animals exposed to 413 ppm (DeCeaurriz et al. 1983). 

Exposure of rats to high concentrations (1,000 or 1,600 ppm) 6–8 hours/day for 5–14 days resulted in 

auditory threshold shifts (indicative of hearing loss) and loss of outer hair cells (OHC) in the organ of 

Corti (Campo et al. 2001; Crofton et al. 1994; Lataye et al. 2003). No alterations in sperm morphology 

were observed in mice exposed to 300 ppm styrene 5 hours/day for 5 days (Salomaa et al. 1985) and no 

developmental effects were observed in rats or rabbits exposed to 600 ppm 7 hours/day on gestational 

days 6–15 or 6–18, respectively, (Murray et al. 1978) or mice exposed to 250 ppm 6 hours/day on 

gestational days 6–16 (Kankaanpää et al. 1980). An increase in fetal deaths or resorptions was observed 

in hamsters exposed to 1,000 ppm 6 hours/day on gestational days 6–18 (Kankaanpää et al. 1980). 

These data suggest that the nervous system is the most sensitive target of styrene toxicity in humans 

following acute-duration inhalation exposure. The lowest LOAEL for a relevant end point in humans is 

87 ppm for vestibular impairment in subjects exposed to styrene for 1 hour (Ödkvist et al. 1982). A 

similar LOAEL (80 ppm) was identified for nasal effects in mice exposed to styrene for 3 days (Cruzan et 

al. 2001). Although nasal irritation has been observed in humans exposed to 376 ppm for 1 hour (Stewart 

et al. 1968) and focal hyperplasia in the nasal olfactory epithelium was observed in rats exposed to 

1,000 ppm (NOAEL of 500 ppm) for 13 weeks (Cruzan et al. 1997), mice appears to be unusually 

susceptible to this effect. As discussed in Section 2.2, mice appear to have a greater capacity than 

humans to generate the reactive metabolite, styrene oxide, in the nasal cavity and a lower capacity to 

detoxify styrene oxide (Green et al. 2001a). Thus, nasal lesions in mice were not considered suitable as 

the basis of an MRL. The identification of the nervous system as the critical target of toxicity for styrene 

is supported by a large number of occupational exposure studies. Delays in reaction time have been 

observed in workers exposed to 21.9–92 ppm (Cherry et al. 1980; Fallas et al. 1992; Gamberale et al. 

1976; Jegaden et al. 1993; Mutti et al. 1984a; Tsai and Chen 1996) and vestibular effects have been 

observed at 18–36 ppm (Calabrese et al. 1996; Möller et al. 1990; Toppila et al. 2006). 

The Ödkvist et al. (1982) study did not identify a NOAEL for vestibular effects; however, a NOAEL of 

49 ppm for performance on several tests of reaction time, memory, attention, color discrimination, and 

olfactory threshold was identified by Ska et al. (2003) in subjects exposed to styrene for 6 hours. 

Although there is some uncertainty whether deriving an MRL based on a 6-hour exposure study would be 
 

 

 

 

 

 

 

 

 

 

 

 

STYRENE 15 

2. RELEVANCE TO PUBLIC HEALTH 

protective of continuous exposure to styrene for 2 weeks, the Ska et al. (2003) study was selected as the 

basis of an acute duration inhalation MRL for styrene. 

In this study (Ska et al. 2003), groups of 24 healthy men (aged 20–50 years) were exposed to 1 ppm 

(control exposure), 24 ppm, and 24 ppm with four 15-minute exposures to peak concentrations of 49 ppm, 

49 ppm, or 49 ppm with four 15-minute exposures to peak concentrations of 98 ppm for 6 hours. The 

subjects were exposed to each concentration with a 2-week period between each session. The subjects 

did not have a history of styrene exposure. At the end of the exposure session the subjects were tested for 

color discrimination (using the Lanthony D-15 desaturated panel), vision contrast, olfactory threshold, 

simple reaction time, color word stress (response time), symbol digit matching, digit span memory, and 

continuous tracking. The subjects were also given a questionnaire to assess mood and symptoms. No 

significant styrene-related alterations in performance on color discrimination, olfactory threshold, 

neurobehavioral tests, mood, or subjective symptoms were found. 

The NOAEL of 49 ppm was selected as the point of departure for the MRL; it was not adjusted for 

intermittent exposure because the study involved a single exposure for 6 hours. The NOAEL of 49 ppm 

from the Ska et al. (2003) study was divided by an uncertainty factor of 10 to account for human 

variability resulting in an acute-duration inhalation MRL of 5 ppm. 

Intermediate-Duration Inhalation MRL 

No human intermediate-duration studies were identified. Animal studies examining systemic, 

neurological, reproductive, and developmental toxicity have identified the respiratory tract as the most 

sensitive target of toxicity. Atrophy of the olfactory epithelium, hypertrophy/hyperplasia of Bowman’s 

gland has been observed in mice exposed to 50 ppm 6 hours/day, 5 days/week for 13 weeks (Cruzan et al. 

1997), decreased nasal cilia activity has been observed in rats exposed to 150 ppm 4 hours/day, 

5 days/week for 21 days (Ohashi et al. 1986), and focal hyperplasia has been observed in rats exposed to 

1,000 ppm 6 hours/day, 5 days/week for 13 weeks (Cruzan et al. 1997). As discussed previously, the 

mouse does not appear to be a good model for nasal effects in humans due to metabolic differences. 

Other systemic effects that have been observed include eye irritation in rats exposed to 200 ppm 

6 hours/day, 5 days/week for 13 weeks (Cruzan et al. 1997) and centrilobular aggregates of siderophages 

in the livers of mice exposed to 200 ppm 6 hours/day, 5 days/week for 13 weeks (Cruzan et al. 1997). 

A number of studies in rats have reported outer hair cell loss in the organ of Corti in rats exposed to 600– 

650 ppm for 4 weeks (Loquet et al. 2000; Makitie et al. 2002; Pouyatos et al. 2002) and hearing loss at 
 

 

 

 

 

 

 

 

 

STYRENE 16 

2. RELEVANCE TO PUBLIC HEALTH 

750–1,000 ppm for 3–4 weeks (Campo et al. 2001; Lataye et al. 2000, 2001; Loquet et al. 1999, 2000;
 

Pouyatos et al. 2002). A NOAEL of hearing effects of 300 ppm was identified in rats exposed for
 

12 hours/day, 5 days/week for 4 weeks (Makitie et al. 2002). Other neurological effects include 

alterations in astroglial cells in rats continuously exposed to 320 ppm for 3 months (Rosengren and 

Haglid 1989) and decreased sensory nerve conduction velocity in rats exposed to 2,000 ppm 8 hours/day,
 

5 days/week for 32 weeks (Yamamoto et al. 1997). No reproductive, developmental, or neurodevelopmental effects were observed in a two-generation study (Cruzan et al. 2005a, 2005b); the NOAEL was 

500 ppm. In contrast, an increase in neonatal deaths, developmental landmark delays, and alterations in
 

neurochemical levels were observed in the offspring of rats exposed to 300 ppm 6 hours/day on 

gestational days 6–20 (Katakura et al. 1999, 2001).
 

Chronic-duration studies suggest that the most sensitive target of styrene toxicity is the nervous system.
 

It is likely that this would also be the most sensitive effect following intermediate-duration exposure. In 

the absence of human neurotoxicity data, an intermediate-duration inhalation MRL is not recommended at
 

this time.
 

Chronic-Duration Inhalation MRL 

An MRL of 0.2 ppm has been derived for chronic-duration inhalation exposure (greater than 

365 days) to styrene.
 

A large number of occupational exposure studies have examined the toxicity of styrene; however, most of 

these studies have focused on the potential neurotoxicity of styrene, which appears to be the most 

sensitive effect. Two common limitations of the occupational exposure studies are: (1) the range of 

current styrene levels for the workers is typically large and it is difficult to ascribe the observed effects to 

the mean or median exposure level and (2) historical exposure to higher styrene levels are not adequately 

taken into consideration. The use of urinary levels of mandelic acid, phenylglyoxylic acid, or mandelic 

acid plus phenylglyoxylic acid levels as biomarkers for styrene exposure eliminates another common 

limitation of styrene occupational exposure studies, which is poor characterization of styrene exposure 

levels due to the lack of personal air samples and the workers’ use of respirators with or without canisters. 

A variety of neurological effects have been reported in workers at reinforced plastic manufacturing 

facilities, including decreased color discrimination, slowed reaction time, impaired performance on other 

neurobehavioral tests, permanent hearing threshold shifts, vestibular effects, altered nerve conduction 

velocity, and increases in subjective symptoms. A summary of the results of studies for some of these 

neurological effects is presented in Table 2-1. An alteration in color discrimination is one of the more 
 

 

 

 

 

STYRENE 17 

2. RELEVANCE TO PUBLIC HEALTH 

consistently found neurological effects; it may also be one of the more sensitive effects. Color 

discrimination was typically measured using the Lanthony desaturated panel D-15 test in which the 

subjects were asked to arrange 15 painted caps in a line with definite chromatic sequence; the total color 

distance score (TCDS) and color confusion index (CCI) are used to quantitatively analyze the results. 

LOAEL values of 6 to 93 ppm have been identified; however, these LOAELs often reflect the mean 

exposure level or the lower end of the range of exposure levels. Other neurological effects that have been 

frequently found include alterations in performance on neurobehavioral tests, particularly reaction time, in 

workers exposed to ≥21 ppm; vestibular alterations at ≥18 ppm; and increased frequency of clinical 

symptoms (e.g., tiredness and headaches in workers exposed to ≥6 ppm). Hearing loss and alterations in 

nerve conduction velocity have also been reported in some studies, but the finding is not consistent across 

studies. 

Non-neurological effects observed in styrene workers include obstructive lung effects (Chmielewski and 

Renke 1975), mild hematological alterations (Checkoway and Williams 1982; Stengel et al. 1990; Thiess 

and Friedheim 1978), and impaired immune response to concanavalin (Somorowská et al. 1999; Tulinska 

et al. 2000). Although exposure levels were not reported in all of these studies, effects were typically 

observed at styrene concentrations of >20 ppm. Clinical chemistry studies did not find alterations 

indicative of impaired liver (Härkönen et al. 1984; Hotz et al. 1980; Lorimer et al. 1978; Thiess and 

Friedheim 1978) or kidney (Verplanke and Herber 1998; Viau et al. 1987; Vyskocil et al. 1989) function 

in workers exposed to ≥24 ppm. 

Chronic-duration studies in laboratory animals identify the nasal olfactory epithelium as the most 

sensitive end point. Atrophic and/or degenerative changes were observed in rats exposed to 50 ppm 

styrene 6 hours/day, 5 days/week for 104 weeks (Cruzan et al. 1998) and respiratory metaplasia in the 

nasal olfactory epithelium were observed in mice exposed to 20 ppm 6 hours/day, 5 days/week for 98– 

104 weeks (Cruzan et al. 2001). As noted previously, mice do not appear to be a good model for potential 

respiratory effects in humans. 

Alterations in color discrimination and reaction time are two neurological effects consistently found in 

styrene workers. Benignus et al. (2005) conducted a meta-analysis using color discrimination impairment 

data from the Campagna et al. (1996), Eguchi et al. (1995), Gobba et al. (1991), Gong et al. (2002), and 

Kishi et al. (2001) studies and choice reaction time data from the Jegaden et al. (1993), Mutti et al. 

(1984a), Triebig et al. (1989), and Tsai and Chen (1996) studies. Average styrene exposure 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

STYRENE 18 

2. RELEVANCE TO PUBLIC HEALTH 

Table 2-1. Results of Selected Human Neurotoxicity Studies 

Result	 Reference NOAEL ppm LOAEL ppm 

Decreased color discrimination	 Chia et al. 1994 6 

Kishi et al. 2001 4 10 

Gong et al. 2002 10 

Gobba et al. 1991 16 

Triebig et al. 2001 20 

Iregren et al. 2005 22 

Fallas et al. 1992 24.3 

Campagna et al. 1996 26 

Eguchi et al. 1995 8 93 

Neurological symptoms	 Flodin et al. 1989 6 

Edling et al. 1993 8.6 

Checkoway et al. 1992 10.8 18.9 

Cherry et al. 1980 92 

Vestibular effects	 Möller et al. 1990 18 

Toppila et al. 2006 24.8 

Calabrese et al. 1996 36 

Reaction time	 Edling et al. 1993 8.6 

Tsai and Chen 1996 21.9 

Jegaden et al. 1993 22.68 

Fallas et al. 1992 24.3 

Mutti et al. 1984a 25 

Gamberale et al. 1976 47 

Cherry et al. 1980 92 

Hearing	 Morata et al. 2002 3.68 

Śliwińska-Kowalska et al. 2003 15.6 

Morioka et al. 1999 16 

Möller et al. 1990 18 

Calabrese et al. 1996 36 

Triebig et al. 2009 40 50 

Nerve conduction velocity	 Seppäläinen and Härkönen 1976 30 

Štĕtkářová et al. 1993 50 

Triebig et al. 1985 100 
 

 

STYRENE 19 

2. RELEVANCE TO PUBLIC HEALTH 

concentrations were estimated from individual data reported in the papers; for studies reporting individual 

data as urinary mandelic acid levels, standardized methods for converting to styrene exposure levels were 

used. Cumulative styrene exposure was estimated by multiplying exposure level by length of 

employment. A common metric of effect magnitude (percentage of baseline) was calculated for the 

different neurological effects. The analysis found a significant linear relationship between choice reaction 

time and cumulative styrene exposure; cumulative exposure accounted for 91% of the variance in reaction 

time. Similarly, a significant relationship between CCI and cumulative styrene exposure was found, with 

cumulative exposure accounting for 35% of the variance in CCI. Using the regression equations for these 

two effects, Benignus et al. (2005) estimated that exposure to 150 ppm for 8 work-years would result in a 

50% increase in choice reaction time and a 17% increase in CCI score; exposure to 20 ppm for 8 workyears would result in a 6.5% increase in choice reaction time and a 2.23% increase in CCI score. As 

discussed in Benignus et al. (2005), a 7% decrease in reaction time would prevent 58,000–70,000 injuries 

per year from automobile accidents. The investigators also noted that CCI increases with age, and the 

rate of increase is about 10% per 13 years of age; thus, a 2.23% decrease in color perception would be 

roughly equivalent to 2.9 additional years of age. Based on this analysis, 20 ppm is considered a LOAEL 

for neurological effects. 

In addition to the studies included in the Benignus et al. (2005) meta-analysis, a LOAEL of 20 ppm is 

supported by a color discrimination study conducted by Triebig et al. (2001). In this study, significant 

increases in CCI values were observed in styrene workers with urinary mandelic acid plus 

phenylglyoxylic acid levels of ≥472 mg/g creatinine (approximately 20 ppm air styrene concentration), 

when compared to >95th percentile age-dependent reference CCI values. An advantage of the Triebig et 

al. (2001) study is that individual exposure and CCI data were reported, which diminishes the problem of 

ascribing an observed effect to the mean or median concentration and the study addresses the issue of 

biological relevance because the CCI scores were compared to the 95th percentile of age-dependent 

reference values rather than values in the control group. 

In comparisons between styrene workers and a control group employed at the same facility without 

styrene exposure, Triebig et al. (2001) found no significant differences in CCI scores between workers 

and controls when the tests were conducted on a Monday morning, but CCI scores were significantly 

different when measured on a Thursday afternoon. Within the styrene-exposed workers, CCI scores on 

Monday morning and Thursday afternoon were not significantly different. After a 4-week nonexposure 

period, the CCI scores were significantly reduced in the styrene workers. After styrene exposure levels 

were lowered, no difference between workers and controls was observed on Monday morning or 
 

 

 

 

 

STYRENE 20 

2. RELEVANCE TO PUBLIC HEALTH 

Thursday afternoon. However, among styrene workers, there were significant differences between 

Monday morning and Thursday afternoon measurements and between Monday morning and postvacation levels. These findings provide suggestive evidence that the alterations in color discrimination 

were reversible. 

The LOAEL of 20 ppm identified in the Benignus et al. (2005) meta-analysis was selected as the point of 

departure for the chronic-duration inhalation MRL. The LOAEL was adjusted for intermittent exposure 

(8 hours/day, 5 days/week) and divided by an uncertainty factor of 30 (3 for use of a minimal LOAEL and 

10 for human variability), resulting in a chronic-duration inhalation MRL of 0.2 ppm. The LOAEL was 

classified as a minimal LOAEL based on the findings of Triebig et al. (2001) that alterations in color 

vision were reversible and the workers were not aware of any changes in color vision. 

Oral MRLs 

Acute-Duration Oral MRL 

An MRL of 0.1 mg/kg/day has been derived for acute-duration oral exposure (14 days or less) to 

styrene. 

A limited number of studies have examined the acute toxicity of orally administered styrene; these studies 

have examined potential neurotoxicity and developmental toxicity. No developmental effects were 

observed in rats administered a single dose of 300 mg/kg on gestational day 11 (Daston et al. 1991) or 

administered 300 mg/kg/day (administered as two daily doses of 150 mg/kg) on gestational days 6– 

15 (Murray et al. 1978). Impaired learning was observed in rats administered via gavage 100 or 

200 mg/kg/day for 14 days; increases in serotonin levels were observed in the hypothalamus, 

hippocampus, and midbrain (Husain et al. 1985). In another study, increases in dopamine receptor 

binding was observed in rats administered a single gavage dose of 200 mg/kg (Agrawal et al. 1982). 

Although a limited number of toxicity end points have been examined following acute-duration oral 

exposure, longer-term oral studies examining systemic and reproductive end points have identified 

LOAELs that were higher than the 100 mg/kg/day LOAEL identified for neurotoxicity in the Husain et al. 

(1985) study. The lowest LOAEL identified for a systemic effect is 400 mg/kg/day for Heinz body 

formation in dogs administered styrene by gavage for 561 days (Quast et al. 1979); the NOAEL was 

200 mg/kg/day. Decreased spermatozoa counts were observed in adult rats administered 400 mg/kg 

6 days/week for 60 days (Srivastava et al. 1989), young rats exposed via lactation on postnatal days 1– 
 

 

 

 

 

 

 

 

STYRENE 21 

2. RELEVANCE TO PUBLIC HEALTH 

21 (maternal dose of 400 mg/kg/day) (Srivastava et al. 1992a), and young rats administered 200 mg/kg 

6 days/week on postnatal days 1–61 (Srivastava et al. 1992b); the NOAELs identified in these three 

studies were 200, 200, and 100 mg/kg, respectively. Marked degeneration of the seminiferous tubules 

was also observed in the adult rats administered 400 mg/kg (Srivastava et al. 1989). Impaired learning 

observed in rats administered 500 mg/kg 5 days/week for 8 weeks (no NOAEL identified) (Bushnell 

1994) also supports the identification of neurotoxicity as a sensitive end point following oral exposure. 

Additionally, the extensive inhalation toxicity database for styrene supports the selection of neurotoxicity 

as the most sensitive target of toxicity; both the acute- and chronic-duration inhalation MRLs are based on 

neurological effects in humans. Neurological effects observed in chronically exposed styrene workers 

include decreased color discrimination, slowed reaction time, increased prevalence of neurological 

symptoms, and ototoxicity (hearing and vestibular effects). 

The Husain et al. (1985) study was selected as the basis of the acute-duration oral MRL. In this study, 

groups of 15 male Wistar rats were administered by gavage 0, 100, or 200 mg/kg/day styrene in ground 

nut oil for 14 consecutive days. Spontaneous motor activity with or without amphetamine induction was 

observed 1 day after the last dose. Two days after exposure termination, the rats underwent acquisition 

training for 4 days. Learning was assessed by measuring the number of times the rat climbed the pole 

after the conditioned stimulus to avoid the foot-shock unconditioned stimulus. Noradrenaline, dopamine, 

and serotonin levels were measured in seven regions of the brain in six rats/group sacrificed after the 

acquisition training. No overt signs of toxicity were observed. No significant alterations in locomotor 

activity were observed with or without amphetamine induction. Significantly greater increases in percent 

avoidance response in the conditioned avoidance response test (indicative of impaired learning) were 

observed at 100 and 200 mg/kg/day; no difference was found between the two styrene groups. The 

effects were observed on test day 3 and 4. Significant increases in the level of serotonin in the 

hypothalamus (70%), hippocampus (51%), and midbrain (29%) were observed at 200 mg/kg/day. 

Styrene exposure did not affect brain noradrenaline and dopamine levels. 

The LOAEL of 100 mg/kg/day was divided by an uncertainty factor of 1,000 (10 for use of a LOAEL, 

10 for extrapolation from animals to humans, and 10 for human variability). 

Intermediate-Duration Oral MRL 

The systemic toxicity of styrene has not been investigated in intermediate-duration oral exposure studies. 

Neurotoxicity studies have identified a LOAEL of 200 mg/kg/day for increased dopamine receptor 
 

 

 

 

 

 

STYRENE 22 

2. RELEVANCE TO PUBLIC HEALTH 

binding in rats (Agrawal et al. 1982), a LOAEL of 500 mg/kg (5 days/week) for impaired learning in rats 

(Bushnell 1994), and a LOAEL of 906 mg/kg/day for alterations in serotonin and noradrenaline levels in 

rats (Husain et al. 1980); none of these studies identified a NOAEL for neurological effects. An increase 

in dopamine receptor binding was also observed in the offspring of rats administered 200 mg/kg/day 

during gestation, lactation, or both (Zaidi et al. 1985). Reproductive and immunological effects were 

reported in the other intermediate-duration oral studies. Decreases in spermatozoa counts were observed 

in rats exposed as 400 mg/kg (6 days/week) as adults, 200 mg/kg (6 days/week) as neonates, or during 

lactation (maternal dose of 400 mg/kg/day) (Srivastava et al. 1989, 1992a, 1992b). Impaired immune 

function was observed in mice exposed to 30 mg/kg/day and in rats exposed to 294 mg/kg/day (Dogra et 

al. 1992); the NOAELs were 23 and 196 mg/kg/day. 

Dogra et al. (1992) identified the lowest LOAEL following intermediate-duration oral exposure to 

styrene; however, there are limited data to support the identification of the immune system as a sensitive, 

relevant target for humans. Although, the sensitivity of the nervous system has been firmly established 

following inhalation and oral exposure, the LOAELs identified in the intermediate-duration studies are 

higher than the lowest LOAEL for neurotoxicity identified in an acute-duration study (Husain et al. 

1985). An MRL based on the Dogra et al. (1992) study would be higher than the acute-duration oral 

MRL; thus, an intermediate-duration MRL is not recommended at this time. 

Chronic-Duration Oral MRL 

The available data on the chronic toxicity of styrene comes from three systemic toxicity studies. No 

adverse effects were observed in rats exposed to 35 mg/kg/day styrene in drinking water for 2 years 

(Beliles et al. 1985) and no liver or kidney alterations were observed in rats administered 500 mg/kg 

1 day/week for 120 weeks (Ponomarkov and Tomatis 1978). Increase in Heinz body formation was 

observed in dogs administered 400 mg/kg/day for 561 days (Quast et al. 1979); the NOAEL for this effect 

is 200 mg/kg/day. 

The chronic-duration inhalation database provides strong evidence that neurotoxicity is the most sensitive 

target of styrene toxicity. It is not known if this would also be true for chronic-duration oral exposure; the 

acute-toxicity oral database provides suggestive evidence that it would be a sensitive target. In the 

absence of a long-term oral study examining neurological end points, a chronic-duration oral MRL is not 

recommended. 
 

 

 

STYRENE 23 

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 styrene. It 

contains descriptions and evaluations of toxicological studies and epidemiological investigations and 

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

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

3.2 DISCUSSION OF HEALTH EFFECTS BY ROUTE OF EXPOSURE 

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

 

 

 

 

 

 

STYRENE 24 

3. HEALTH EFFECTS 

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

effects to human health. 

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

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

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

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

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

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

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

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

3.2.1 Inhalation Exposure 

Most information on the effects of inhalation exposure to styrene in humans comes from studies of 

workers exposed to styrene vapors in the production and use of plastics and resins, especially polyester 

resins dissolved in styrene. In most cases, the studies involve workplace exposures such as fiberglass 

boat building factories where the actual levels of styrene are reported as a range of styrene air 

concentrations. However, there are a few human clinical studies in which exposures are better quantified. 

A common limitation of many of the occupational exposure studies is the phenomenon of the healthy 

worker effect. The selection of healthy individuals for employment and the likelihood that more 

susceptible workers are more likely to leave the workforce can result in workers who are healthier than 

the general population. This type of bias typically affects comparisons with the general population and is 

less likely to influence comparisons with other groups of workers. Provided below are descriptions of the 

known effects of inhalation exposure of humans and animals to styrene. 

3.2.1.1 Death 

There have been no reports of deaths in humans directly associated with exposure to styrene in the 

workplace (EPA 1985a; Gosselin et al. 1984; NIOSH 1983). 

In animals, inhalation studies indicate that the acute toxicity of styrene is low to moderate. An LC50 of 

2,770 ppm after 2 hours of exposure was reported in rats, and the LC50 for mice after exposure for 4 hours 

was 4,940 ppm (Shugaev 1969). All rats and guinea pigs survived after exposure to 1,300 ppm styrene 
 

 

 

 

 

 

 

 

 

STYRENE 25 

3. HEALTH EFFECTS 

for 30 hours and 16 hours, respectively (Spencer et al. 1942). However, all animals died after 40 hours of 

exposure. Gender differences in mortality were observed in repeated-exposure studies (6 hours/day, 

5 days/week for 2 weeks) (Cruzan et al. 1997). Increases in mortality were observed in female CD-1 and 

B6C3F1 female mice exposed to 250 ppm; no deaths were observed at 500 ppm. In the CD-1 and 

B6C3F1 males, very few deaths were observed at 250 ppm, but increases in deaths were observed at 

500 ppm. A similar finding was reported by Morgan et al. (1993a): increases in mortality were observed 

in female B6C3F1 mice exposed to 250 ppm and no deaths were observed at 500 ppm; in males, deaths 

were observed at 250 and 500 ppm. In contrast to these findings, no deaths were observed in Sprague 

Dawley rats exposed to concentrations as high as 1,500 ppm 6 hours/day, 5 days/week for 13 weeks 

(Cruzan et al. 1997). 

All reliable LOAEL values and LC50 values for lethality in each species and duration category are 

recorded in Table 3-1 and plotted in Figure 3-1. 

3.2.1.2 Systemic Effects 

No studies were located regarding dermal or metabolic effects in humans or animals after inhalation 

exposure to styrene. 

For the following systemic effects resulting from inhalation exposure to styrene, the highest NOAEL 

values and all reliable LOAEL values in each species and duration category are recorded in Table 3-1 and 

plotted in Figure 3-1. 

Respiratory Effects. Several human studies have examined the respiratory effects caused by 

inhalation exposure to styrene. The most commonly reported general symptom is mucous membrane 

irritation. Irritation of the upper respiratory tract (i.e., nose and throat) has been reported by volunteers 

(Carpenter et al. 1944; Stewart et al. 1968) and workers (NIOSH 1983). Throat irritation and increased 

nasal secretion occurred following exposure of two male subjects to 800 ppm for 4 hours (Carpenter et al. 

1944). Nasal irritation was observed in all volunteers after exposure to 376 ppm styrene for 60 minutes 

(Stewart et al. 1968). Obstructive lung changes were observed in 4 of 21 workers exposed to styrene for 

about 10 years (Chmielewski and Renke 1975). However, exposure levels were not defined. No 

histological alterations were observed in nasal biopsies from styrene workers exposed to 50–60 ppm 

styrene for 7 years (Ödkvist et al. 1985). 
160

1300

165

250

175

250

161

1300

159

99

20

216 376216 376

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

a 

Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) 

ACUTE EXPOSURE Death 

1 Rat 3-40 hr 

System 

NOAEL 

(ppm) 

Less Serious 

(ppm) 

LOAEL 

Serious 

(ppm) 

Reference Chemical Form 

Spencer et al. 1942 Styrene 

1300 (100% mortality after >40 

hours exposure) 

2 Mouse 

(CD-1 and B6C3F1) 

6 hr/d 5 d/wk 2 wk 

250 (increased mortality) Cruzan et al. 1997 

Styrene 

3 Mouse 

(B6C3F1) 

6 hr/d 14 d 250 M (44% mortality) Morgan et al. 1993a 

Styrene 

4 Gn Pig 3-40 hr 1300 (100% mortality after 40 

hours exposure) 

Spencer et al. 1942 Styrene 

Systemic 

5 Human 7 hr Ocular 99 M (mild, transient eye 

irritation) 

Stewart et al. 1968 Styrene 

6 Human 1 or 2 hr Resp 216 M 376 M (nasal irritation) Stewart et al. 1968 

Styrene 

Ocular 216 M 376 M (eye irritation) 
164

250

60

250

173

80

207

40

160

174

125

250

500500

176

250

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

a 

Key to Species 

Figure (Strain) 

7 Mouse 

(CD-1 and B6C3F1) 

8 Mouse 

(CD-1) 

9 Mouse 

(CD-1) 

10 Mouse 

(B6C3F1) 

11 Mouse 

(B6C3F1) 

Exposure/ 

Duration/ 

Frequency 

(Route) 

6 hr/d 5 d/wk 2 wk 6 hr/d 3 d 6 hr/d 3 d 6 hr/d 14 d 6 hr/d 1-3 d 

LOAEL 

System 

NOAEL 

(ppm) 

Less Serious 

(ppm) 

Serious 

(ppm) 

Reference Chemical Form 

Resp 250 (shallow breathing) Cruzan et al. 1997 

Styrene 

Hepatic 60 250 (increased liver weight 

and centrilobular hepatocyte necrosis) 

Resp 80 M (single cell necrosis in 

nasal olfactory epithelium) 

Cruzan et al. 2001 Styrene 

Resp 40 M 160 M (moderate to marked 

degenerative changes in olfactory epithelium) 

Green et al. 2001a Styrene 

Hepatic 125 250 M (pigmented macrophages 

and focal necrosis) 

Morgan et al. 1993a Styrene 

Renal Bd Wt 

500 

500 

Hepatic Morgan et al. 1993a 

Styrene 

250 M (mild to marked necrosis) 
171

125

250

177

125

250

195

100

27

87

154

20

208

49

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

a 

Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

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

LOAEL 

Serious 

(ppm) 

Reference Chemical Form 

12 Mouse 

(B6C3F1) 

6 hr/d 3 d Hepatic 125 250 (severe hepatocellular degeneration/necrosis) Morgan et al. 1993b Styrene 

13 Mouse 6 hr/d 

4 d Hepatic 125 250 (marked degeneration and/or coagulative 

necrosis of centrilobular hepatocytes) 

Morgan et al. 1993c Styrene 

Immuno/ Lymphoret 

14 Mouse 

(BALB/c) 

6 hr/d 4 d 100 F (exacerbated inflammatory reaction 

after ovalbumin challenge) 

Ban et al. 2006 Styrene 

Neurological 

15 Human 1 hr 87 (inhibition of 

vestibular-oculomotor system) 

Odkvist et al. 1982 Styrene 

16 Human 3 or 4 hr 20 Seeber et al. 2004 

Styrene 

17 Human 6 h b 49 M Ska et al. 2003 

Styrene 
112

216

376

113

99

134

1000

121

1600

128

1000

166

60

250

29

413

610

Table 3-1 Levels of Significant Exposure to Styrene - Inhalation (continued) Exposure/ LOAEL 

Duration/ 

a 

Key to 

Figure 

18 19 20 21 22 23 24 

Species 

(Strain) 

Frequency 

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

Human 1 or 2 hr 216 M 376 M (impaired performance 

on balance and coordination tests) 

Human 7 hr 99 M 

Rat (Long- Evans) 

6 hr/d 5 d/wk 1 or 2 wk 

1000 M (hearing loss and loss of 

OHC) 

Rat (Long- Evans) 

8 hr/d 5 d 1600 M (hearing loss at 8 and 16 kHz) 

Rat (Long- Evans) 

6 hr/d 5 d 1000 M (hearing loss, loss of OHC) 

Mouse (CD-1 and B6C3F1) 

6 hr/d 5 d/wk 2 wk 

60 250 (lethargy and unsteady 

gait) 

Mouse (Swiss OF1) 

4 hr 413 M 610 M (impaired performance 

on a swimming test) 

Reference Chemical Form 

Stewart et al. 1968 Styrene Stewart et al. 1968 Styrene Campo et al. 2001 Styrene Crofton et al. 1994 Styrene Lataye et al. 2003 Styrene Cruzan et al. 1997 Styrene De Ceaurriz et al. 1983 Styrene 
129

1000

36

300

30

600

34

250

35

750

1000

31

600

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

a 

Key to Species 

Figure (Strain) 

25 Gn Pig 

(NS) 

Reproductive 

26 Mouse 

Developmental 

27 Rat 

(SpragueDawley) 

28 Mouse 

(BMR/T6T6) 

29 Hamster 

(Chinese) 

30 Rabbit 

(New Zealand) 

Exposure/ 

Duration/ 

Frequency 

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

LOAEL 

Serious 

(ppm) 

Reference Chemical Form 

6 hr/d 5 d 1000 M Lataye et al. 2003 

Styrene 

5 d 5 hr/d 300 M Salomaa et al. 1985 

Styrene 

7 hr/d Gd 6-15 600 F Murray et al. 1978 

Styrene 

6 hr/d Gd 6-16 250 F Kankaanpaa et al. 1980 

Styrene 

6 hr/d Gd 6-18 750 F 1000 F (fetal deaths or resorptions) Kankaanpaa et al. 1980 Styrene 

7 hr/d Gd 6-18 600 F Murray et al. 1978 

Styrene 
162

500

1000

150015001500

200

1000

1500

127

750750

37

150 1000

42

133

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

Duration/ 

a 

Key to Species Frequency 

Figure (Strain) (Route) System 

Resp Hemato Hepatic Renal Ocular Bd Wt Hepatic 

Renal Resp Renal 

NOAEL 

(ppm) 

500 

1500 1500 1500 1000 M 

750 M 

750 M 

133 

LOAEL 

Less Serious 

(ppm) 

1000 (focal hyperplasia in 

nasal olfactory epithelium) 

200 (eye irritation) 

1500 M (10% decrease in body 

weight gain) 

150 M (decreased nasal cilia 

activity) 

Serious

(ppm)

1000 M (disabled nasal cilia 

activity) 

Reference Chemical Form 

Cruzan et al. 1997 Styrene Loquet et al. 2000 Styrene Ohashi et al. 1986 Styrene Viau et al. 1987 Styrene 

INTERMEDIATE EXPOSURESystemic 

31 32 33 34 

Rat(SpragueDawley)Rat(Long- Evans)RatRat(SpragueDawley)

6 hr/d 5 d/wk 13 wk 6 hr/d 5 d/wk 4 wk 21 d 5 d/wk 4 hr/d 13 wk 5 d/wk 7 hr/d 
157

200

2000

122

800

163

50

200100

150

150

200

45

360

132

1000

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

a 

Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) System NOAEL (ppm) 

LOAEL 

Less Serious 

(ppm) 

Serious 

(ppm) 

Reference Chemical Form 

35 Rat 

(Wistar) 

8 hr/d 5 d/wk 32 wk 

Bd Wt 200 M 2000 M (>15% decrease in body 

weight gain) 

Yamamoto et al. 1997 Styrene 

36 Rat 

(Fischer- 344) 

14 hr/d 5 d/wk 3 wk 

Bd Wt 800 M (10-13.5% decrease in 

body weight) 

Yano et al. 1992 Styrene 

37 Mouse 

(CD-1) 

6 hr/d 5 d/wk 13 wk 

Resp 50 (atrophy of olfactory 

epithelium, dilatation, hypertrophy, hyperplasia of Bowman's gland; decreased eosinophilia of 

bronchiolar epithelial cells) 

Cruzan et al. 1997 Styrene 

Hemato Hepatic 

200 100 F 150 F (centrilobular aggregates 

of siderphages) 

Bd Wt 150 M 200 M (decreased body weight 

gain) 

38 Pig 3 wk 

5 d/wk 6 hr/d 

Neurological 

39 Rat 

(Long- Evans) 

6 hr/d 5 d/wk 3 or 4 wk 

Hemato 360 

1000 M (hearing loss, loss of 

OHC in organ of Corti) 

Johnston et al. 1983 Styrene Campo et al. 2001 Styrene 
133

750

131

1000

130

650

850

126

750

124

300

600

125

650

750

46

800

Table 3-1 Levels of Significant Exposure to Styrene - Inhalation (continued) Exposure/ LOAEL 

Duration/ 

a 

Key to 

Figure 

Species 

(Strain) 

Frequency 

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

40 Rat 

(Long- Evans) 

6 hr/d 5 d/wk 4 wk 

750 M (hearing loss and loss of 

OHC) 

41 Rat 

(Long- Evans) 

6 hr/d 5 d/wk 4 wk 

1000 M (loss of OHC and spiral 

ganglion cell density in organ of Corti) 

42 Rat 

(Long- Evans) 

6 hr/d 5 d/wk 4 wk 

650 M (OHC loss) 850 M (hearing loss and loss of 

OHC) 

43 Rat 

(Long- Evans) 

6 hr/d 5 d/wk 4 wk 

750 M (hearing loss and loss of 

OHC) 

44 Rat 

(Wistar) 

12 hr/d 5 d/wk 4 wk 

300 M 600 M (hearing impairment and 

loss of OHC) 

45 Rat 

(Long- Evans) 

6 hr/d 5 d/wk 4 wk 

650 M (OHC loss) 750 M (hearing loss and OHC 

loss) 

46 Rat 

(Fischer- 344) 

3 wk 14 hr/d 800 M (hearing loss) 

Reference Chemical Form 

Lataye et al. 2000 Styrene Lataye et al. 2001 Styrene Loquet et al. 1999 Styrene Loquet et al. 2000 Styrene Makitie et al. 2002 Styrene Pouyatos et al. 2002 Styrene Pryor et al. 1987 Styrene 
47

90 320

156

200

2000

123

800

167

50

100

200

181

500

182

500

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

a 

Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

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

LOAEL 

Serious 

(ppm) 

Reference Chemical Form 

47 Rat 

(SpragueDawley) 

3 mo continuous 90 M 320 M (astroglial alterations) Rosengren and Haglid 1

Styrene 

48 Rat 

(Wistar) 

8 hr/d 5 d/wk 32 wk 

200 M 2000 M (decreased sensory 

nerve conduction velocity) 

Yamamoto et al. 1997 Styrene 

49 Rat 

(Fischer- 344) 

14 hr/d 5 d/wk 3 wk 

800 M (hearing loss and loss of 

OHC in organ of Corti) 

Yano et al. 1992 Styrene 

50 Mouse 

(CD-1) 

6 hr/d 5 d/wk 13 wk 

50 100 (atrophy of olfactory 

nerve fibers) 

200 F (transient lethargy, cold 

to touch, and slow respiration) 

Cruzan et al. 1997 Styrene 

Reproductive 

51 Rat 

(CD) 

Developmental 

52 Rat 

(CD) 

6 hr/d 70 pmd 14 d mating Gd 0-21 Ld 5-21 6 hr/d 70 pmd 14 d mating Gd 0-21 Ld 5-21 

500 500 

Cruzan et al. 2005a, 20Styrene Cruzan et al. 2005a, 20Styrene 
186

300

53

40

206

46

179

26

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

a 

Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

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

LOAEL 

Serious 

(ppm) 

Reference Chemical Form 

53 Rat 

(Wistar) 

6 hr/d Gd 6-20 Katakura et al. 1999, 20

Styrene 

300 (increased neonatal 

deaths, delays in righting reflex and incisor eruption, alterations in neurochemical levels) 

CHRONIC EXPOSURE Systemic 

54 Human 5.1 yr 

(Occup) Hepatic 40 F Harkonen et al. 1984 Styrene 

55 Human 7 yr 

(Occup) Resp 46 M Odkvist et al. 1985 Styrene 

56 Human 12.6 yr 

(Occup) Renal 26 Verplanke et al. 1998 Styrene 
168

50

100010001000100010001000200

500

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

a 

Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

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

LOAEL 

Serious 

(ppm) 

Reference Chemical Form 

57 Rat 

(SpragueDawley) 

6 hr/d 5 d/wk 104 wk 

Resp 50 (atrophic and/or 

degenerative changes in nasal olfactory epithelium) 

Cruzan et al. 1998 Styrene 

Cardio 1000 Gastro 1000 Hemato 1000 Hepatic Renal 

1000 1000 

Ocular 1000 Bd Wt 200 F 500 F (decreased body weight 

gain) 
169

20

16016016016016016080

160

196

30

197

26

205

20

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

Duration/ 

a 

Key to Species Frequency 

Figure (Strain) (Route) 

58 Mouse 6 hr/d 

5 d/wk (CD-1) 98-104 wk 

Immuno/ Lymphoret 

59 Human 7 yr 

(Occup) 

60 Human 13 yr 

(Occup) 

Neurological

61 Human (Occup)

LOAEL 

System 

NOAEL 

(ppm) 

Less Serious 

(ppm) 

Serious 

(ppm) 

Reference Chemical Form 

Resp 20 (respiratory metaplasia in 

nasal olfactory epithelium, bronchiolar epithelial hyperplasia) 

Cruzan et al. 2001 Styrene 

Cardio Gastro Hemato Hepatic Renal Ocular Bd Wt 

160 

160 160 

160 160 

160 

80 M 160 M (11% decrease in body 

weight gain) 

30 (alterations in lymphocyte 

subsets) 

Bergamaschi et al. 1995Styrene 

26 (impaired immune 

response to concanavalin 

A) 

Tulinska et al. 2000 Styrene 

c

20 (decreased color 

discrimination and reaction time) 

Benignus et al. 2005 Styrene 
155

36

141

26

148

10.8

18.9

28

92

142

6

153

24.6

145

8.6

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

a 

Key to Species 

Figure (Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) 

7.6 yr (Occup) 

System 

NOAEL 

(ppm) 

Less Serious 

(ppm) 

36 (altered performance 

vestibular tests) 

LOAEL 

Serious 

(ppm) 

Reference Chemical Form 

Calabrese et al. 1996 Styrene 

62.5 or 79.3 mo (Occup) 26 (decreased color discrimination) Campagna et al. 1996 Styrene 

4-6.4 yr (Occup) 10.8 18.9 (increased prevalence of neurological symptoms) Checkoway et al. 1992 Styrene 

(Occup) 92 M (tiredness, slow reaction 

times, mood changes) 

Cherry et al. 1980 Styrene 

18.8 yr (Occup) 6 M (decreased color discrimination and 

performance on neurobehavioral tests) 

Chia et al. 1994 Styrene 

12.5 yr (Occup) 9 yr (Occup) 

24.6 

8.6 M (increased symptoms of 

neurotoxicity) 

Dalton et al. 2003 Styrene Edling et al. 1993 Styrene 

62 Human 63 Human 64 Human 65 Human 66 Human 67 Human 68 Human 
140

8

93

139

24.3

23

47

137

16

136

10

194

22

143

22.68

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

a 

Key to Species 

Figure (Strain) 

Exposure/ 

Duration/ 

Frequency 

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

LOAEL 

Serious 

(ppm) 

Reference Chemical Form 

7.0 yr (Occup) 8 M 93 M (decreased color discrimination) Eguchi et al. 1995 Styrene 

6.5 yr (Occup) 24.3 M (decreased color discrimination) Fallas et al. 1992 Styrene 

2.7 yr (Occup) (Occup) 

47 M (slowed reaction time) 

16 (decreased color 

discrimination) 

Gamberale et al. 1976 Styrene Gobba et al. 1991 Styrene 

76.6 mo (Occup) 10 M (decreased color discrimination) Gong et al. 2002 Styrene 

12.9-17.8 yr (Occup) 22 M (decreased color discrimination) Iregren et al. 2005 Styrene 

5 yr (Occup) 22.68 (impaired performance on neurobehavioral tests 

of visual reaction and memory) 

Jegaden et al. 1993 Styrene 

69 Human 70 Human 71 Human 72 Human 73 Human 74 Human 75 Human 
135

4

10

65

75

178

18

151

3.68

149

16

152

22

66

25

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

a 

Key to Species 

Figure (Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) 

6.2 yr (Occup) 

System 

NOAEL 

(ppm) 

4 

Less Serious 

(ppm) 

10 (decreased color 

discrimination) 

LOAEL 

Serious 

(ppm) 

Reference Chemical Form 

Kishi et al. 2001 Styrene 

4.9 yr (Occup) 75 M (impaired performance on visuomotor accuracy 

and psychomotor performance tests) 

Lindstrom et al. 1976 Styrene 

10.8 yr (Occup) 18 M (impaired vestibular function) Moller et al. 1990 Styrene 

17 yr (Occup) 9.4 yr (Occup) 

3.68 

16 M (reduction in upper limit 

of hearing) 

Morata et al. 2002 Styrene Morioka et al. 1999 Styrene 

5 yr (Occup) 22 M (slowed distribution of nerve conduction 

velocities and ECG R-R interval) 

Murata et al. 1991 Styrene 

8.6 yr (Occup) 25 (decreased verbal learning skills) Mutti et al. 1984a Styrene 

76 Human 77 Human 78 Human 79 Human 80 Human 81 Human 82 Human 
212

15.9

67

30

150

15.6

192

50

147

24.8

193

100

200

20

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

a 

Key to Species 

Figure (Strain) 

Exposure/ 

Duration/ 

Frequency 

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

LOAEL 

Serious 

(ppm) 

Reference Chemical Form 

6.4 years (mean) 15.9 M (increased vibration perception threshold) Sato et al. 2009 Styrene 

5 yr (Occup) (Occup) 11 yr (Occup) 

30 M (EEG abnormalities) 

15.6 (hearing loss) 

50 F (decreased peripheral 

nerve conduction velocity and prolonged latency of somatosensory evoked potentials) 

Seppalainen and Harko1976 Styrene Sliwinska-Kowalska et aStyrene Stetkarova et al. 1993 Styrene 

(Occup) 24.8 M (impaired postural 

stability) 

Toppila et al. 2006 Styrene 

4 yr 4.5 years (Occup) 

100 M 

20 M (impaired color vision) 

Triebig et al. 1985 Styrene Triebig et al. 2001 Styrene 

83 Human 84 Human 85 Human 86 Human 87 Human 88 Human 89 Human 
209

50

144

21.9

73

82

170

160

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

a 

Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

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

LOAEL 

Serious 

(ppm) 

Reference Chemical Form 

90 Human mean of 5.7-6.3 

years (Occup) 

50 M (increased hearing 

threshold in workers exposed to high concentrations for long durations) 

Triebig et al. 2009 Styrene 

91 Human 8.3 yr 

(Occup) 21.9 (impaired performance on neurobehavioral tests) Tsai and Chen 1996 Styrene 

Developmental 

92 Human 

Cancer 

93 Mouse 

(CD-1) 

>1 yr 7 d/wk 8 hr/d 6 hr/d 5 d/wk 98-104 wk 

82 F 

160 F (CEL: bronchioloalveolar 

carcinoma) 

Lemasters et al. 1989 Styrene Cruzan et al. 2001 Styrene 

a The number corresponds to entries in Figure 3-1. b The acute-duration inhalation MRL of 5 ppm was calculated based on NOAEL of 49 ppm and divided by an uncertainty factor of 10 to account for human variabilitc The chronic-duration inhalation MRL of 0.2 ppm was calculated from a minimal LOAEL of 20 ppm identified in a meta-analysis of occupational exposure studies ralterations in color discrimination and choice reaction time; the LOAEL was adjusted for intermittent exposure (8 hours/day, 5 days/week) and divided by an uncertafor use of a minimal LOAEL and 10 for human variability. Bd Wt = body weight; Cardio = cardiovascular; CEL = cancer effect level; d = day(s); ECG = electrocardiographic; F = Female; Gastro = gastrointestinal; Gd = gesta= guinea pig; Hemato = hematological; hr = hour(s); kHz = kilohertz; LOAEL = lowest-observed-adverse-effect level; M = male; min = minute(s); mo = month(s); NOno-observed-adverse-effect level; NS = not specified; occup = occupational; OHC = outer hair cell(s); pmd = pre-mating day; ppm = parts per million; Resp = respirawk = week(s); yr = year(s) 
Figure 3-1 Levels of Significant Exposure to Styrene - Inhalation
	

Acute (≥14 days)
	

Systemic
	

Death 

Respiratory 

Hepatic 

Renal 

Ocular 

ppm 

Body Weight 

Immuno/Lymphor 

Neurological 

Reproductive 

Developmental 

10000 

21r 

4g 1r 

1000 25g 20r 22r 29s 

29s 

24m 27r 30h 

10m 10m 

24m 6 6 18 

26m 

2m 3m 7m 7m 10m 11m 12m 13m 23m 28m 6 6 18 

9m 

10m 12m 13m 

100 5 14m 19 15 8m 

7m 23m 

17 

9m 

16 

10 

1 

c-Cat -Humans f-Ferret n-Mink Cancer Effect Level-Animals Cancer Effect Level-Humans LD50/LC50

d-Dog k-Monkey j-Pigeon o-Other LOAEL, More Serious-Animals LOAEL, More Serious-Humans Minimal Risk Level

r-Rat m-Mouse e-Gerbil LOAEL, Less Serious-Animals LOAEL, Less Serious-Humans for effects

p-Pig h-Rabbit s-Hamster NOAEL - Animals NOAEL - Humans other than

q-Cow a-Sheep g-Guinea Pig Cancer 

STYRENE

3. HEALTH EFFECTS

43
Figure 3-1 Levels of Significant Exposure to Styrene - Inhalation (Continued)
 

Intermediate (15-364 days)
	

Systemic 

Respiratory 

Hematological 

Hepatic 

Renal 

Ocular 

ppm 

Body Weight 

Neurological 

Reproductive 

Developmental 

10000 

35r 48r 

31r 31r 31r 31r 

1000 31r 33r 31r 39r 41r 

42r 36r 46r 49r 32r 32r 40r 43r 45r 

42r 45r 44r 

31r 51r 52r 

38p 47r 44r 53r 

37m 31r 37m 35r 50m 48r 

33r 37m 37m

34r
	

100
	 37m 50m 47r 

37m 50m 

10 

c-Cat -Humans f-Ferret n-Mink Cancer Effect Level-Animals Cancer Effect Level-Humans LD50/LC50

d-Dog k-Monkey j-Pigeon o-Other LOAEL, More Serious-Animals LOAEL, More Serious-Humans Minimal Risk Level

r-Rat m-Mouse e-Gerbil LOAEL, Less Serious-Animals LOAEL, Less Serious-Humans for effects

p-Pig h-Rabbit s-Hamster NOAEL - Animals NOAEL - Humans other than

q-Cow a-Sheep g-Guinea Pig Cancer 

STYRENE

3. HEALTH EFFECTS

44
Figure 3-1 Levels of Significant Exposure to Styrene - Inhalation (Continued)
 

Chronic (≥365 days)
	

Systemic
	

Respiratory 

Cardiovascular 

Gastrointestinal 

Hematological 

Hepatic 

Renal 

Ocular 


	

Body Weight 

Immuno/Lymphor 

Neurological 

Developmental 

Cancer * 

ppm

10000
	

1000
	 57r 57r 57r 57r 57r 57r 

57r 

57r 

58m 58m 58m 58m 58m 58m 58m 93m
	

100
	 65 69 88 
	 58m 92 77
	

55
	 57r 71 86
	 90

54
	 62 59
	 84 56
	 60 63
	 67
	 70
	 82
	 87 74 58m 61 
	 75 81
	 91 
	 64
	 78 72

89 
	 80
	 83
	 85
	

10
	 64 73
	 76 68
	 69
	

66
	

76
	 79
	

1
	

*Doses represent the lowest dose tested per study that produced a tumorigenic 0.1 response and do not imply the existence of a threshold for the cancer endpoint. 

c-Cat -Humans f-Ferret n-Mink Cancer Effect Level-Animals Cancer Effect Level-Humans LD50/LC50

d-Dog k-Monkey j-Pigeon o-Other LOAEL, More Serious-Animals LOAEL, More Serious-Humans Minimal Risk Level

r-Rat m-Mouse e-Gerbil LOAEL, Less Serious-Animals LOAEL, Less Serious-Humans for effects

p-Pig h-Rabbit s-Hamster NOAEL - Animals NOAEL - Humans other than

q-Cow a-Sheep g-Guinea Pig Cancer 

STYRENE

3. HEALTH EFFECTS

45
 

 

 

 

 

 

 

 

 

 

STYRENE 46 

3. HEALTH EFFECTS 

In rats exposed to 150 ppm styrene 4 hours/day, 5 days/week for 3 weeks a decrease in nasal ciliary 

activity was observed; at 1,000 ppm, the nasal cilia activity was considered disabled (Ohashi et al. 1986). 

Electron microscopic examination of the nasal cavity of rats exposed to 1,000 ppm revealed very few 

ciliated cells and severe degeneration with marked vacuolization. Decreases in cilia activity were also 

observed in the trachea at 150 and 1,000 ppm. After a 12-week recovery period, nasal and tracheal cilia 

activity in the 150 ppm group was similar to controls; nasal cilia activity in the 1,000 ppm group was still 

lower than controls but was increased compared to rats killed at the end of the exposure period (Ohashi et 

al. 1986). In a longer-term study, focal hyperplasia was observed in the nasal olfactory epithelium of rats 

exposed to 1,000 ppm for 13 weeks (Cruzan et al. 1997); at 500 ppm, no histological alterations were 

observed in the respiratory tract. Chronic exposure to 50 ppm resulted in atrophic and/or degenerative 

changes in the nasal olfactory epithelium (Cruzan et al. 1998). 

Mice appear to be more sensitive than rats to the respiratory toxicity of styrene. Exposure to 50 ppm 

styrene for 13 weeks resulted in atrophy of the nasal olfactory epithelium and dilatation, hypertrophy and 

hyperplasia of Bowman’s gland (Cruzan et al. 1997). At 100 ppm, atrophy of the nasal olfactory nerve 

fibers was observed; focal crowding of nonciliated epithelial cells in the bronchioles were observed at 

150 ppm. Chronic exposure resulted in respiratory metaplasia of the nasal olfactory epithelium and 

dilatation, respiratory metaplasia, epithelial hyperplasia of the Bowman’s gland in mice exposed to 

≥20 ppm for 2 years (Cruzan et al. 2001). Decreased eosinophilia of epithelial cells and bronchiolar 

epithelial hyperplasia were observed in the lungs of mice exposed to ≥20 ppm. 

A study by Spencer et al. (1942) also provides some information on species differences. Rats and guinea 

pigs exposed 1,300 ppm for 7–8 hours/day, 5 days/week for 6 months showed nasal irritation, but rabbits 

and monkeys did not (Spencer et al. 1942). Histopathological examinations revealed no changes between 

test and control rats, but pronounced lung irritation was seen in guinea pigs that died after a few 

exposures. The irritation, which included congestion, hemorrhages, edema, exudation, and a general 

acute inflammatory reaction, was not seen in the guinea pigs, rabbits, and monkeys that survived the 

6-month exposure period (Spencer et al. 1942). 

Green et al. (2001a) suggest that the observed species differences between mice and rats are due to 

differences in styrene metabolism in the nasal epithelium. The rates of metabolism of styrene by 

cytochromes P-450 CYP2E1 and CYP2F2 to styrene oxide was similar for the two species. However, 

styrene oxide is more efficiently metabolized by epoxide hydrolases and glutathione S-transferases in rats 

than in mice. Thus, the higher levels of the reactive epoxide styrene oxide in mice is the likely cause of 
 

 

 

 

 

 

 

STYRENE 47 

3. HEALTH EFFECTS 

the increased sensitivity in this species. In in vitro assays in fresh human nasal tissues, styrene oxide was 

not detected and high levels of epoxide hydrolases were detected, suggesting that humans have limited 

capacity to metabolize styrene in the nasal cavity and a high potential to detoxify styrene oxide. These 

data suggest that rodents may not be a good model for nasal toxicity in humans. 

These well-conducted human and animal studies demonstrate the characteristic irritant properties of 

styrene on the upper respiratory tract. 

Cardiovascular Effects. No studies were located regarding cardiovascular effects in humans after 

inhalation exposure to styrene. 

No cardiovascular effects were observed in rats or mice exposed to concentrations as high as 1,000 ppm 

or 160 ppm, respectively, for 2 years (Cruzan et al. 1998, 2001). 

Gastrointestinal Effects. Nausea was observed in humans exposed to 376 ppm styrene after 1 hour 

of exposure (Stewart et al. 1968). This effect is probably secondary to effects on the central nervous 

system, although mucociliary transport of styrene aerosol droplets from the upper respiratory tract to the 

gastrointestinal tract might also contribute to gastrointestinal irritation. A Russian study (Basirov 1975) 

reviewed by the World Health Organization (WHO 1983) investigated the effects of styrene on digestive 

function by testing the secretory, excretory, motor, and pepsinogen-generating functions of the stomach in 

20 unexposed and 80 exposed workers. The authors reported that some workers in the styrene-butadiene 

synthetic rubber manufacture exposed to 60–130 mg/m3 (14–31 ppm) styrene had decreased digestive 

function and decreased stomach acidity. 

No histological alterations were observed in the stomach or intestines of rats exposed to 1,000 ppm 

(Cruzan et al. 1998) or mice exposed to 160 ppm (Cruzan et al. 2001) styrene for 2 years. 

Hematological Effects. Several studies indicate that inhalation exposure of humans to styrene cause 

mild or no effects on the blood. In one study, the incidence of abnormal values for hematological 

parameters including erythrocyte, leukocyte, and platelet counts, and hemoglobin levels for 84 styrene 

workers generally exposed to <1 ppm styrene for 1–36 years was investigated. However, these workers 

were also exposed to intermittent high levels of styrene as well as to other chemicals. The percentages of 

the exposed group with abnormally low hemoglobin and erythrocyte values or abnormally high leukocyte 

values were less than those percentages in the 62-person control group. There were no abnormal 
 

 

 

 

 

 

 

 

STYRENE 48 

3. HEALTH EFFECTS 

thrombocyte values reported in either the exposed or control groups (Thiess and Friedheim 1978). 

Findings from a group of 93 workers engaged in the manufacture of styrene polymers and exposed to 

generally <1 ppm styrene for 1–38 years were also presented in this study; only the incidence of 

abnormally low erythrocyte counts (in the group exposed to styrene) was found to be statistically 

significant (p≤0.05). However, because exposures could not be determined accurately and because there 

were concomitant exposures to other chemicals, the results of these studies are difficult to interpret. 

Lowered erythrocyte counts, hemoglobin, platelets, and neutrophils and slightly higher mean corpuscular 

red cell volumes and neutrophil band counts were observed in workers in a styrene-butadiene rubber 

manufacturing plant (Checkoway and Williams 1982). The highest mean styrene level was 13.67 ppm. 

However, interpretation of this study is limited because multiple-chemical exposures were involved and 

exposure and clinical signs were measured at the same time and only once. An earlier study of styrene 

workers showed no definite pattern of hematological changes (Lorimer et al. 1978). In these studies, 

exposure levels were uncertain and multiple chemicals were involved. 

In rats exposed to 49 ppm styrene, erythrocyte-aminolevulinate dehydratase (ALA-D) was depressed 

markedly. The decrease in enzyme activity was accompanied by a decrease in the enzyme content in 

bone marrow cells (Fujita et al. 1987). The investigators suggested that the changes may have been a 

result of styrene oxide reducing the enzyme protein is based on in vitro data. No hematological 

alterations were observed in 2-year studies in rats (Cruzan et al. 1998) and mice (Cruzan et al. 2001) 

exposed to concentrations as high as 1,000 or 160 ppm, respectively. 

The well-conducted Thiess and Friedheim (1978) study as well as the more limited studies indicate that 

few adverse hematological effects occurred in styrene-exposed workers. However, the full meaning of 

the findings is not clear because of poor characterization of the exposure level and concurrent exposures 

to other chemicals. 

Musculoskeletal Effects. No studies were located regarding musculoskeletal effects in humans after 

inhalation exposure to styrene. 

No histological alterations were observed in skeletal muscle or bone of rats exposed to 1,000 ppm 

(Cruzan et al. 1998) or mice exposed to 160 ppm (Cruzan et al. 2001) for 2 years. 
 

 

 

 

 

 

 

 

 

 

 

 

STYRENE 49 

3. HEALTH EFFECTS 

Hepatic Effects. Human studies on the hepatic effects of styrene inhalation frequently used serum 

levels of enzymes as indicators of liver dysfunction. In general, human studies have resulted in negative 

or equivocal results (Härkönen et al. 1984; Hotz et al. 1980; Lorimer et al. 1978; Thiess and Friedheim 

1978). No significant alterations in alanine aminotransferase, aspartate aminotransferase, or γ-glutamyl 

transferase levels were observed in workers exposed to generally <1 ppm for 1–36 years (Thiess and 

Friedheim 1978) or 50–120 ppm for 5.1 years (Härkönen et al. 1984). A significant increase in 

γ-glutamyl transferase levels was observed in workers exposed to 5–20 ppm for up to 20 years; however, 

no alterations in alanine aminotransferase, aspartate aminotransferase, or alkaline phosphatase levels were 

observed (Lorimer et al. 1978). Another study of workers (Hotz et al. 1980) found significant 

correlations between the exposure level (as measured by styrene metabolite concentrations in morning 

urine) and ornithine carbamoyl transferase, alanine aminotransferase, and γ-glutamyl transferase levels. 

Among workers exposed to 50–100 ppm, the increases in these enzymes were modest, 67.8, 55, and 

64.9% of reference levels. 

Animal studies provide evidence that the liver is a target tissue for styrene; however, the hepatotoxicity of 

styrene in mice is inversely related to the duration of exposure. Hepatic effects have been observed 

following acute- and intermediate-duration exposure, but not after chronic exposure and the severity of 

the effects decreases with continuing exposure. Exposure to 250 or 500 ppm for 1–4 days resulted in 

marked to severe hepatocellular necrosis and degeneration in mice (Morgan et al. 1993a, 1993b, 1993c). 

The necrosis was characterized as centrilobular coagulative necrosis and was accompanied by pooling of 

erythrocytes in dilated sinusoids (Morgan et al. 1993a). The necrosis was often observed after a single 

exposure to 500 ppm or a 2-day exposure to 250 ppm and the severity did not increase with increasing 

duration (Morgan et al. 1993a). However, continued exposure resulted in regeneration and repair of the 

initial hepatic damage. After 14 days of exposure, minimal to mild focal necrosis was observed in female 

mice exposed to 250 ppm and no hepatic effects were observed in male mice exposed to 250 ppm or male 

and female mice exposed to 500 ppm (Morgan et al. 1993a). Similarly, a 13-week exposure to 200 ppm 

resulted in focal loss of hepatocytes with siderosis and centrilobular aggregates of siderophages in female 

mice (Cruzan et al. 1997). No histological alterations were observed in the livers of mice exposed to 

160 ppm for 2 years (Cruzan et al. 2001). Strain differences have also been detected in mice. Morgan et 

al. (1993c) found that B6C3F1 and C57BL/6 mice were more sensitive than DBA/2 mice, which were 

more sensitive than Swiss mice. The severity scores for hepatocellular degeneration/necrosis following a 

4-day exposure to 250 ppm were 3.2–3.5 in B6C3F1 mice, 3.6 in C57BL/6 mice, 2.4–2.9 in DBA/2 mice, 

and 2.0 in Swiss mice. 
 

 

 

 

 

 

 

 

STYRENE 50 

3. HEALTH EFFECTS 

Rats appear to be less sensitive than mice to styrene-induced hepatotoxicity. No histological alterations 

were observed in the livers of Sprague Dawley rats exposed to 1,000 ppm styrene for 13 weeks (Cruzan et 

al. 1997) or 2 years (Cruzan et al. 1998; Jersey et al. 1978). Parenchymal hydropic degeneration, 

steatosis, and congestion were observed in rats exposed to 300 ppm for 2 weeks (Vainio et al. 1979); the 

lack of incidence data limits the interpretation of these results. 

Renal Effects. Based on the results of occupational exposure studies and animal toxicity studies, the 

kidney does not appear to be a sensitive target of styrene toxicity. Occupational exposure studies of 

workers exposed to 24 ppm (Viau et al. 1987), 53 ppm (Vyskocil et al. 1989), or 26 ppm styrene 

(Verplanke and Herber 1998) did not find significant alterations in urinary levels of β-microglobulin (not 

examined in Verplanke and Herber 1998 study), retinol-binding protein, or albumin. The Vyskocil et al. 

(1989) study also found no significant alterations in total protein, glucose, lysozyme, lactate 

dehydrogenase, or β-N-acetyl-D-glucosaminidase levels and Verplanke and Herber (1998) did not find 

alterations in β-galactosidase, N-acetyl-β-D-glucosaminidase, or alanine aminopeptidase. No histological 

alterations were observed in the kidneys following acute exposure of rats to 300 ppm (Vainio et al. 1979) 

or mice to 500 ppm (Morgan et al. 1993a), intermediate exposure of rats to 133–1,500 ppm (Cruzan et al. 

1997; Spencer et al. 1942; Viau et al. 1987), or chronic exposure of rats to 1,000 ppm (Cruzan et al. 1998) 

or mice to 160 ppm (Cruzan et al. 2001). Additionally, no alterations in urinary levels of N-acetylD-glucosaminidase, γ-glutamyl transpeptidase, protein, or urea were observed in rats exposed to 500 ppm 

for 4 weeks (Loquet et al. 2000). 

Endocrine Effects. Several occupational studies have examined potential endocrine effects in 

reinforced plastics industry workers exposed to styrene. Significant increases in serum prolactin levels 

were observed in male and female workers (Bergamaschi et al. 1996, 1997; Luderer et al. 2004; Mutti et 

al. 1984b). The serum prolactin levels significantly correlated with urinary metabolite (mandelic acid 

plus phenylglyoxylic acid) levels (Mutti et al. 1984b) and blood styrene levels (Luderer et al. 2004). 

Based on a logistic regression model, Luderer et al. (2004) estimated that workers exposed to styrene 

exposures >20 ppm would be more likely to have elevated serum prolactin levels than workers exposed to 

lower levels; a 10-fold increase in blood styrene concentrations would result in a 2.06-fold increase in 

serum prolactin levels. Similarly, Arfini et al. (1987) found that female styrene workers had an abnormal 

response to an intravenous dose of thyrotropin-releasing hormone; the levels of serum prolactin were 

significantly higher following exposure to thyrotropin-releasing hormone, as compared to referents. Two 

of these workers were re-examined after a 3-month period without styrene exposure; the serum prolactin 

response following thyrotrophin-releasing hormone exposure was similar to that in the referent group. No 
 

 

 

 

 

 

 

 

 

 

STYRENE 51 

3. HEALTH EFFECTS 

significant alterations in the levels of thyroid stimulating hormone, follicle stimulating hormone, or 

luteinizing hormone were found in this study (Arfini et al. 1987). However, thyroid stimulating hormone 

levels were significantly correlated with urinary metabolite (mandelic acid plus phenylglyoxylic acid) 

levels. As noted in an editorial comment to this paper, the baseline levels of prolactin in the styrene 

workers were within the normal range and a supraphysiological dose of thyrotropin-releasing hormone 

level was used. 

Significant increases in serum prolactin levels have also been observed in female rats exposed to 

150 ppm, 8 hours/day for 10 days (Umemura et al. 2005). No significant alterations in serum prolactin 

levels were observed in similarly exposed male rats (Umemura et al. 2005) or in male rats exposed to 

approximately 150, 500, or 1,500 ppm 6 hours/day for 5 days (Jarry et al. 2002). Acute exposure to 

styrene did not result in significant alterations in thyroid stimulating hormone levels in male or female 

rats (Umemura et al. 2005). 

Ocular Effects. Eye irritation in humans has been reported at high styrene concentrations (Carpenter 

et al. 1944; Stewart et al. 1968). Immediate eye irritation was reported in two human subjects exposed to 

800 ppm styrene for 4 hours (Carpenter et al. 1944). Eye irritation was also noted by Stewart et al. (1968) 

in two of five volunteers exposed to 376 ppm styrene for 1 hour. Also, 345 styrene-exposed workers 98% 

male) were evaluated for ocular toxicity due to exposure to styrene (5–200 ppm) for 7–20 years. No 

evidence of optic neuritis, central retinal vein occlusion, or retrobulbar neuritis was found. Conjunctival 

irritation was a complaint of 22% of the 345 workers exposed to styrene levels above 50 ppm (Kohn 

1978). 

Eye and nasal irritation was observed in rats and guinea pigs exposed to 1,300 or 2,000 ppm styrene, 7– 

8 hours/day, 5 days/week for durations ranging from 21 to 30 weeks (Wolf et al. 1956). Rabbits and 

monkeys were exposed for up to 360 days with no effects. 

3.2.1.3 Immunological and Lymphoreticular Effects 

Two occupational studies have found significant alterations in lymphocyte subsets in styrene workers. 

Increase in percentage of CD4+/CD3CD4 T-lymphocytes and decrease in CD35+CD+ peripheral 

lymphocytes were observed in oil industry workers exposed to styrene, as compared to unexposed 

controls (Biró et al. 2002). However, these results should be interpreted cautiously because there were 

marked differences in smoking habits between the styrene workers and controls (80% styrene workers 
 

 

 

 

 

 

 

 

 

STYRENE 52 

3. HEALTH EFFECTS 

smoked compared to 20% of controls) and the two groups were not matched for gender. Bergamaschi et 

al. (1995b) found an altered distribution of lymphocyte subsets in styrene workers exposed to an 8-hour 

time-weighted average (TWA) of 10–50 ppm. Some of these alterations, particularly the reduction in 

total T-lymphocytes (CD3+) and T-helper cells (CD4+), may be indicative of reduced cell-mediated 

immunity. This is supported by the finding of an impaired response to concanavalin in styrene workers 

exposed to a median styrene concentration of 26 ppm (Tulinska et al. 2000), 187–256 ppm (Somorovská 

et al. 1999) or 54–56 ppm (Somorovská et al. 1999). No alterations in the response to pokeweed mitogen 

were observed (Somorovská et al. 1999; Tulinska et al. 2000). 

In patch-testing studies of cross-reactors to styrene, styrene 7,8-oxide was more sensitizing than styrene 

itself (Sjöborg et al. 1984). The authors interpreted this as evidence that styrene requires metabolism by 

skin aryl hydrocarbon hydroxylase to styrene epoxide for its sensitizing activity. 

In animals, styrene exacerbated the inflammatory reaction in mice challenged with ovalbumin (Ban et al. 

2006). Styrene-only exposure resulted in slight increases in Th2 cytokine (IL-4, IL-5, IL-13) and 

Th1 cytokine (interferon-γ) levels; however, the statistical significance of these alterations were not 

reported. 

3.2.1.4 Neurological Effects 

The available human data suggest that the nervous system is the most sensitive target following chronicduration inhalation exposure. It is likely the most sensitive target following shorter-term durations, but 

this has not been as extensively investigated. In studies examining the acute neurotoxicity of styrene, 

impairment of the vestibular-oculomotor system was observed in experimental subjects exposed to 

87 ppm for 1 hour (Ödkvist et al. 1982) or 376 ppm for 1 hour (Stewart et al. 1968). No alterations in the 

performance of balance tests were observed at 216 ppm for 1 hour (Stewart et al. 1968), 117 ppm for 

2 hours (Stewart et al. 1968), or 99 ppm for 7 hours (Stewart et al. 1968). Although these NOAELs are 

higher than the LOAEL identified in the Ödkvist et al. (1982) study, the studies are not comparable. The 

Ödkvist et al. (1982) study used sensitive tests of vestibular-oculomotor function compared to the 

modified Romberg test (subjects stand on one foot with eyes closed, walk heel to toe, touch finger to 

nose) used in the Stewart et al. (1968) studies. An increase in the reporting of “feeling inebriated” was 

found in subjects exposed to 376 ppm for 1 hour (Stewart et al. 1968); no increases in subjective 

symptoms were observed in subjects exposed to 20 ppm for 3–4 hours (Seeber et al. 2004), 49 ppm for 

6 hours with or without four 15-minute peak exposures to 98 ppm (Ska et al. 2003), or 216 ppm for 

1 hour (Stewart et al. 1968). No alterations in reaction time were observed in subjects exposed to 20 ppm 
 

 

 

 

 

 

 

 

 

 

 

 

 

STYRENE 53 

3. HEALTH EFFECTS 

for 3 or 4 hours (Seeber et al. 2004), 49 ppm for 6 hours with or without four 15-minute peak exposures 

to 98 ppm (Ska et al. 2003). Additionally, no alterations in color vision, olfactory threshold, or tests of 

memory or attention were observed in subjects exposed to 49 ppm for 6 hours with or without four 15-

minute peak exposures to 98 ppm (Ska et al. 2003). No human studies examined neurotoxicity following 

intermediate-duration exposure. 

In an international cohort of styrene workers, a significant association between mortality from central 

nervous system disease and cumulative styrene exposure was found (Welp et al. 1996c). The rate ratio 

was 3.29 (95% confidence interval [CI] of 0.48–22.65) for workers exposed to 25–49 ppm-years and 

16.32 (95% CI 3.47–76.73) for those exposed for 200–349 ppm-years. A similar relationship was found 

for shorter durations of styrene exposure. The rate ratio was 2.33 (95% CI 0.40–13.56) for workers 

exposed for 6–11 months and 8.80 (95% CI 1.87–41.33) for workers exposed for 7–9 months. A 

significant association between mortality from epilepsy and duration of styrene exposure was found; the 

rate ratio in workers exposed for ≥10 years was 28.4 (95% CI 2.11–381.5). Time since first exposure was 

also significantly associated with mortality from epilepsy. Significant associations between mental 

disorders and duration of exposure and between suicide and duration of exposure were also found; 

however, for both of these causes of death, the rate ratio decreased with increasing duration of exposure 

and the investigators noted that lifestyle factors, rather than a direct effect of styrene, appear to be the 

most likely cause of the higher mortality. 

A variety of neurological effects have been reported in workers chronically exposed to styrene including 

altered vestibular function, impaired hearing, decreased color discrimination, altered performance on 

neurobehavioral tests, and increased clinical symptoms. In general, these occupational exposure studies 

have several limitations. In most cases, the exposure levels reflect current exposure conditions and do not 

take into consideration past exposure to higher styrene levels that may have resulted in permanent 

damage. Some workers, particularly laminators, wore respiratory masks with or without canisters; many 

investigators estimated exposure based on biomarker levels, particularly urinary mandelic acid levels, 

while others did not. As discussed in greater detail in Sections 3.4.3, 3.4.3.1, and 3.8.1, urinary levels of 

styrene metabolites mandelic acid and phenylglyoxylic acid have been shown to correlate with timeweighted average styrene exposure levels and may be a more reliable biological indicator of styrene 

exposure in workplaces with highly variable styrene exposure levels. Significant differences between 

workers and referents were reported as LOAELs; however, the magnitude of the alteration may have been 

subclinical. A summary of the neurological effects observed in styrene workers is presented in Table 3-2. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

STYRENE 54 

3. HEALTH EFFECTS 

Table 3-2. Summary of Occupational Exposure Studies Examining Neurological
 

End Points 

Mean 

Number duration of 

of exposure NOAEL LOAEL 

Reference workers (years) (ppm) (ppm) Comments 

Decreased color discrimination 

Chia et al. 21 18.8 6 Styrene exposure was estimated from 

1994 (range: 5–23) mean urinary levels of MA (84.0 mg/g 

creatinine; range of 1.3–504.1 mg/g 

creatinine). 

Significant decreases in color 

discrimination, as expressed as total color 

difference score; no concentrationresponse relationship was found. 

Kishi et al. 21–42 6.2 4 10 Workers divided into three groups based on 

2001 urinary MA levels. Significant differences in 

CCI, compared to age-matched controls, 

were found in the two highest groups. 

Mean CCI in 4, 10, and 46 ppm groups 

(CCI levels in age-paired controls): 

1.21 (1.17), 1.23 (1.12), and 1.27 (1.13). 

Significant difference in CCI also found in 

analysis using 87 age-matched workers/ 

controls. 

Gong et al. 43 6.4 10 Workers divided into two groups based on 

2002 combined urinary MA and PGA level 

dividing line of 0.24 g/g creatinine 

(approximately 10 ppm); both groups were 

significantly different from controls. Mean 

CCI (mean of right and left eyes) in 

controls, low exposure, and high exposure 

groups: 1.02, 1.09, and 1.14. 

Gobba et al. 41 16 Significant differences found when 

1991 compared to age-matched controls 

(41 workers/controls) and in older workers 

(≥40 years of age). 

CCI was significantly different in workers 

exposed to ≥50 ppm compared to workers 

exposed to <50 ppm. 

Triebig et al. 19 4.5 20 Significant increase in CCI in workers 

2001 (range: 1–21) (mean of 1.29), compared to controls (mean 

of 1.10), when test conducted after work on 

a Thursday; no difference when measured 

before work on a Monday. Abnormal CCI 

values (>95th percentile age-dependent 

reference value) associated with urinary MA 

plus PGA levels of approximately 500 mg/g 

creatinine and higher. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

STYRENE 55 

3. HEALTH EFFECTS 

Table 3-2. Summary of Occupational Exposure Studies Examining Neurological
 

End Points 

Mean 

Number duration of 

of exposure NOAEL LOAEL 

Reference workers (years) (ppm) (ppm) Comments 

Iregren et al. 53–55 12.9–17.9 22	 Lifetime weighted average exposure 

2005 (range: 2–39)	 calculated for each worker using historical 

exposure data. 

Total error score was significantly different 

from workers in the low exposure group 

(9 ppm). 

Fallas et al. 60 6.5 24.3	 Significant difference in the number of 

1992 (range: >1–29)	 subjects with error axis in the red-green or 

blue-yellow ranges; no significant difference 

in calculated error scores. 

Campagna et 118 5.2 or 6.6 26 Mathematical threshold of impaired CCI 

al. 1996 was 4 ppm; the upper limit of the CI was 

25.7 ppm. 

Eguchi et al. 57 7.0 8 93 Significant difference in CCI between age1995 (range: 0.2– matched workers and controls. Workers 

26.8) divided into two groups—significant 

difference in CCI between highconcentration workers (urinary MA level of 

1.06 g/L [range: 0.46–3.98 g/L] equivalent 

to 93 ppm) and age-matched controls. No 

difference in low concentration workers 

(urinary MA levels—mean of 0.02 g/L; 

range of 0.04–0.41 g/L; equivalent to 

8 ppm). CCI scores in low and high 

exposure groups (CCI in age-matched 

controls) of 1.173 (1.118) and 1.332 

(1.125). 

Seeber et al. 242 Mean 5–8-6.4	 Workers divided into three groups (low, 

2009b	 medium, high) based on urinary MA and 

PGA levels. No significant differences in 

CCI score or visual contrast sensitivity were 

observed between groups. No associations 

were found when workers were divided into 

groups with long-duration-high exposure 

(air concentration of 27 ppm for over 

15 years) and short duration-low exposure. 

Interpretation of these results is limited by 

the lack of a control group. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

STYRENE 56 

3. HEALTH EFFECTS 

Table 3-2. Summary of Occupational Exposure Studies Examining Neurological
 

End Points 

Mean 

Number duration of 

Reference 

of 

workers 

exposure 

(years) 

NOAEL 

(ppm) 

LOAEL 

(ppm) Comments 

Reaction time 

Edling et al. 

1993 

20 9 

(range: 1–25) 

8.6 Simple and choice reaction time (measured 

before and after work). 

Tsai and 

Chen 1996 

45 8.3 21.9 Directly exposed workers compared to 

workers without direct styrene exposure 

(range of styrene levels was 0–6.4 ppm). 

Complex reaction time (continuous 

performance test): 532.8 and 495.6 ms in 

directly and indirectly exposed groups. 

Jegaden et 

al. 1993 

30 5 22.68 Reaction times (measured in morning 

before work) in workers and controls were 

0.29 and 0.27 seconds for simple reaction 

time and 0.37 and 0.32 seconds for 

complex reaction time. 

Fallas et al. 

1992 

60 6.5 

(range: >1–29) 

24.3 No significant difference in simple reaction 

time (23.7 seconds versus 22.7 seconds in 

controls). 

Mutti et al. 

1984a 

50 25 Workers divided into four groups based on 

combined levels of urinary MA and PGA of 

<150, 150–299, 300–350, and 

>450 mmole/mole creatinine; 

150 mmole/mole creatinine equivalent to 

25 ppm. 

Complex reaction time in all workers and 

controls: 623.6 and 488.3 ms; the percent 

variations from matched controls were 

120 and 165% in the 25 and 50 ppm 

groups. 

Gamberale 

et al. 1976 

106 2.7 

(range: 0.1– 

11) 

47 Mean styrene levels in each location were 

16.6, 59.3, 41.6, and 101.4 ppm for resin 

appliers and 13.6 and 49.3 ppm for 

assemblers. The average styrene level for 

the six sites was 47 ppm. 

Simple reaction times (measured in 

morning before work) were 274 ms in 

workers and 260 ms in controls. 

Cherry et al. 

1980 

27 NR 92 Simple reaction times (measured in 

morning before work) were 252 and 230 ms 

in workers and controls. A slower reaction 

time was also observed during the 

workshift. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

STYRENE 57 

3. HEALTH EFFECTS 

Table 3-2. Summary of Occupational Exposure Studies Examining Neurological
 

End Points 

Mean 

Number duration of 

Reference 

of 

workers 

exposure 

(years) 

NOAEL 

(ppm) 

LOAEL 

(ppm) Comments 

Seeber et al. 

2009a 

213 Mean: 5–8-6.4 Workers divided into three groups (low, 

medium, high) based on urinary MA and 

PGA levels. No significant differences in 

choice reaction time were observed 

between groups. No association were 

found when workers were divided into 

groups with long-duration-high exposure 

(air concentration of 27 ppm for over 

15 years) and short duration-low exposure. 

Interpretation of these results is limited by 

the lack of a control group. 

Other neurobehavioral tests 

Chia et al. 

1994 

21 18.8 

(range: 5–23) 

6 Styrene exposure was estimated from 

mean urinary levels of MA (84.0 mg/g 

creatinine; range of 1.3–504.1 mg/g 

creatinine). 

Several tests of memory—Benton Visual 

Retention test (score 6.0 in workers vs. 

7.7 in controls), digit symbol test (26.3 in 

workers vs. 38.0 in controls), and digit span 

(11.7 in workers vs. 15.6 in controls) were 

significantly affected. No significant 

relations between test score and urinary MA 

or PGA levels. No alteration in Santa Ana 

dexterity test or pursuit aiming. 

Edling et al. 

1993 

20 9 

(range: 1–25) 

8.6 No effect on performance of symbol digit 

test. 

Sato et al. 

2009 

67 Mean: 6.4 

(range:0.08– 

10.3) 

15.9 Significant increase in vibration perception 

threshold in upper and lower limbs in 

workers (mean urinary MA plus PGA level 

of 0.42 g/g creatinine equivalent to 

16.9 ppm styrene in air). Increased 

vibration perception threshold in lower limbs 

in workers with mean past maximum urinary 

MA level of 0.30 g/g creatinine (equivalent 

to 15.9 ppm) 

Jegaden et 

al. 1993 

30 5 22.68 Significant impairment in performance on 

digit span test. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

STYRENE 58 

3. HEALTH EFFECTS 

Table 3-2. Summary of Occupational Exposure Studies Examining Neurological
 

End Points 

Mean 

Number duration of 

Reference 

of 

workers 

exposure 

(years) 

NOAEL 

(ppm) 

LOAEL 

(ppm) Comments 

Fallas et al. 

1992 

60 6.5 

(range: >1–29) 

24.3 Significant alteration in aiming test. No 

significant alteration in Santa Ana test of 

dexterity, digit span, digit symbol, or Benton 

visual retention tests. However, there were 

significantly more workers with digit span 

test scores differing by more than one 

standard deviation from the mean, 

particularly in workers exposed to styrene 

for >10 years. 

Mutti et al. 

1984a 

50 25 Workers divided into four groups based on 

combined levels of urinary MA and PGA of 

<150, 150–299, 300–350, and 

>450 mmole/mole creatinine; 

150 mmole/mole creatinine equivalent to 

25 ppm. 

Impaired performance on verbal learning 

test; no significant relationship with test 

scores in duration of exposure or exposure 

level. 

Clinical symptoms 

Flodin et al. 

1989 

8 or 9 11.6 

(range: 6–21) 

6 High prevalence of clinical symptoms— 

abnormal tiredness (7/8 subjects) and short 

memory (8/8 subjects) in workers exposed 

to 6 ppm styrene; high prevalences of 

problems concentrating (7/9 subjects) and 

irritation (8/9 subjects) were also observed 

in workers exposed to 12 ppm. Prevalence 

was not compared to a referent group. 

Edling et al. 

1993 

20 9 

(range: 1–25) 

8.6 Reported more acute symptoms than 

controls (mean of 2.9 in workers versus 

1.8 in controls). More frequently responded 

positively to the following questions: are 

you abnormally tired, do you often have 

painful tingling in some parts of your body, 

do you have a headache at least once a 

week. 

Checkoway 16–27 3.4–4.1 10.8 18.9 Higher prevalence of headache, dizziness, 

et al. 1992 light headedness, fatigue, irritability, feeling 

"drunk" at work, and memory loss. 

Cherry et al. 27 NR 92 At the end of the workshift, changes in self1980 reported physical and mental tiredness and 

general health scores were correlated with 

blood styrene concentrations. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

STYRENE 59 

3. HEALTH EFFECTS 

Table 3-2. Summary of Occupational Exposure Studies Examining Neurological
 

End Points 

Mean 

Number duration of 

Reference 

of 

workers 

exposure 

(years) 

NOAEL 

(ppm) 

LOAEL 

(ppm) Comments 

Hearing 

Triebig et al. 

2009 

17 14.6 

(range: 10–26) 

50 Average exposure was 30–50 ppm; in the 

past, workers were exposed to 80– 

100 ppm. Workers exposed to >85 dBA 

noise were excluded from analysis. Lower 

hearing thresholds were observed at 

1,000–1,500 and 8,000–12,500 Hz. 

Significant improvement in hearing 

following an exposure-free period. 

Triebig et al. 

2009 

31 6.3 

(range: 1–26) 

40 No significant alterations in hearing 

threshold among workers with urinary MA 

plus PGA levels of 970 mg/g creatinine 

(approximately 40 ppm). 

Morata et al. 65 17 3.68 Noise level 82 dBA. 

2002 (range: 1–39) A higher prevalence of high frequency 

hearing loss (47%) compared to controls 

(33%), but difference was not statistically 

significant. Significantly poorer thresholds 

were observed at 2, 3, 4, 6, and 8 kHz in 

the styrene group. The OR of 1.19 (95% 

CI, 1.11–1.28) times greater for each 1 year 

of age was calculated and 2.44 times 

greater (95% CI, 1.01–5.89) for each 

increment of 1 mmol MA/g creatinine in 

urine. 

Śliwińska­ 194 NR 15.6 Current styrene concentrations ranged from 

Kowalska et 0.05 to 46 ppm; average worklife mean 

al. 2003 styrene concentration was 15.6 ppm. 

Average noise level was 80.3 dBA. 

Abnormal audiograms were found in 63.3% 

of styrene workers, compared to 33.8% in 

the unexposed controls. The OR of hearing 

loss was 5.2 (95% CI, 2.9–8.9). A positive 

linear relationship between styrene working 

life exposure levels and hearing thresholds. 

Morioka et al. 93 9.4 16 Sound levels in the workplace ranged from 

1999 53 to 95 dBA. 

Significant correlation between individual 

percentiles of the upper limit of hearing and 

styrene concentrations in workers exposed 

for ≥5 years; the prevalence rates below the 

75th percentile were significantly higher 

than 25% in workers exposed to >16 ppm. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

STYRENE 60 

3. HEALTH EFFECTS 

Table 3-2. Summary of Occupational Exposure Studies Examining Neurological
 

End Points 

Mean 

Number duration of 

Reference 

of 

workers 

exposure 

(years) 

NOAEL 

(ppm) 

LOAEL 

(ppm) Comments 

Möller et al. 

1990 

18 10.8 

(range: 6–15) 

18 No styrene-related alterations in the puretone audiometry and speech discrimination 

tests were found. Seven workers displayed 

abnormal results in distorted speech and/or 

cortical response audiometry tests. 

Calabrese et 

al. 1996 

20 7.6 

(range: 2–23) 

36 All workers had normal hearing thresholds 

and no abnormalities of stapedial reflex 

were found. No significant effect on ABRs 

(as compared to 10 control subjects) were 

observed; additionally, when nine subjects 

were re-tested after 3 weeks without 

exposure, no significant difference between 

pre- and postrecovery values were found. 

Vestibular 

Möller et al. 

1990 

18 10.8 

(range: 6–15) 

18 Significantly higher sway with eyes open or 

closed in the static posturography test, 

increased latency in saccade test, a phase 

lag and depressed gain in unpredictable 

and predictable stimulation in the smooth 

eye pursuit test, and impaired ability to 

suppress vestibulo-ocular reflex in 

sinusoidal and pseudorandomized tests. 

Toppila et al. 

2006 

88 NR 24.8 Nonlaminators used as the comparison 

group; 88 pairs of age-matched workers 

were used for postural stability tests; the 

mean styrene and MA PGA concentrations 

for these pairs were 24.8 ppm and 

1.4 mmol/L for the laminators and 4.8 ppm 

and 0.3 mmol/L for the nonlaminators. 

Poorer performance in dynamic tests on the 

static platform. In the tilting platform and 

virtual reality tests, sway velocity was 

greater and workers became unstable and 

displayed large correctional movements. 

Calabrese et 20 7.6 36 Abnormal results in the vestibulo-ocular 

al. 1996 (range: 2–23) tests, these alterations persisted after the 

3-week recovery period. No alterations in 

visual suppression test or postural 

performance were found. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

STYRENE 61 

3. HEALTH EFFECTS 

Table 3-2. Summary of Occupational Exposure Studies Examining Neurological
 

End Points 

Mean 

Number duration of 

Reference 

of 

workers 

exposure 

(years) 

NOAEL 

(ppm) 

LOAEL 

(ppm) Comments 

Nerve conduction velocity 

Seppäläinen 

and 

Härkönen 

96 5 30 Styrene exposure was estimated using endof-shift urinary MA levels collected weekly 

for 5 consecutive weeks. 

1976 No significant differences in median, ulnar, 

deep peroneal, or posterior tibial nerve 

motor or sensory conduction velocities were 

observed, as compared to a referent group 

with a similar age distribution. 

Štĕtkářová et 

al. 1993 

15 11 50 Decreased peripheral conduction velocities 

in median and tibial nerves were observed 

in female styrene workers; prolonged 

latencies of peripheral and cortical 

somatosensory evoked potentials were also 

observed in the female workers exposed to 

styrene. 

Triebig et al. 

1985 

11 4 100 No significant alterations in maximum 

conduction velocity in the ulnar nerve or 

distal conduction velocity of the sensory 

fibers of the ulnar and median nerves. 

ABR = auditory brainstem response; CCI = color confusion index; CI = confidence interval; LOAEL = lowest-observedadverse-effect level; MA = mandelic acid; MS = millisecond; NOAEL = no-observed-adverse-effect level; NR = not 

reported; OR = odds ratio; PGA = phenylglyoxylic acid 
 

 

STYRENE 62 

3. HEALTH EFFECTS 

Color vision appears to be one of the more sensitive targets of styrene toxicity, with many studies 

reporting alterations. Color vision was typically measured using the Lanthony desaturated panel 

D-15 test in which the subjects were asked to arrange 15 painted caps in a line with definite chromatic 

sequence; the color confusion index (CCI) quantifies the number of types of mistake. A significant 

correlation between CCI and urinary mandelic acid concentration (after correction for age) was observed 

in workers at fiberglass reinforced plastic facilities (Kishi et al. 2001). When workers were divided into 

three groups based on end-of-shift urinary mandelic acid levels, there were significant differences 

between CCI in workers with a mean a mandelic acid level of 0.14 or 0.65 g/L and age-matched referents; 

no difference was found for the third group with a mean mandelic acid level of 0.05 g/L. The 

investigators estimated that these urinary mandelic acid levels were equivalent to styrene exposure levels 

of 4, 10, and 46 ppm. Thus, this study identifies a NOAEL of 4 ppm and a LOAEL of 10 ppm for 

decreased color discrimination. Similarly, Gong et al. (2002) found significantly higher CCI values in 

workers at a fiberglass reinforced plastic boat facility with end-of-shift urinary mandelic acid and 

phenylglyoxylic acid levels of ≥0.24 g/g creatinine or <0.24 g/g creatinine; a mandelic acid plus 

phenylglyoxylic acid urine level of 0.24 g/g creatinine is equivalent to a styrene exposure level of 

10 ppm. A significant increase in CCI was also observed in workers at fiberglass reinforced plastic 

facilities as compared to age-matched controls (Gobba et al. 1991); although the mean styrene 

concentration was 16 ppm for all workers (n=73), the mean for the subset of workers used for agematched analysis was not reported. When workers were stratified based on styrene air levels, workers 

exposed to 49 ppm styrene had significantly higher CCI scores than workers exposed to lower levels. In 

contrast to other studies, Gobba et al. (1991) did not find a significant relationship between end-of-shift 

urinary mandelic acid levels and CCI; however, urinary styrene levels correlated with CCI values. CCI 

values were significantly higher in laminators at a boat manufacturing facility with a median urinary 

mandelic acid plus phenylglyoxylic acid levels of 472 mg/g creatinine compared to control subjects when 

the test was administered on a Thursday after work (Triebig et al. 2001). Although CCI values were also 

elevated on a Monday before work, the values were not significantly different from controls. Classifying 

CCI values for the workers as normal or abnormal (exceeding the 95th percentile of the age reference 

values) demonstrated that abnormal CCI values were typically associated with urinary mandelic acid plus 

phenylglyoxylic acid levels of approximately 500 mg/g creatinine and higher (approximately 20 ppm 

styrene in air for 8 hours). Significantly higher CCI values were observed in fiberglass reinforced 

workers with a mean urinary mandelic acid levels of 1.06 g/L, which is roughly equivalent to a styrene 

exposure level of 93 ppm (Eguchi et al. 1995). This study did not find significant alteration in workers 

with a mean urinary mandelic acid level of 0.02 g/L, equivalent to 8 ppm. Another study of fiberglass 

reinforced plastic workers (some of this cohort was examined by Gobba et al. 1991 and Campagna et al. 
 

 

 

 

 

STYRENE 63 

3. HEALTH EFFECTS 

1995) found a significant association between CCI and styrene exposure levels (Campagna et al. 1996). 

The investigators concluded that color vision impairment could be detected at styrene levels of 4 ppm 

with a 95% upper confidence limit of 26 ppm. Two other occupational exposure studies using different 

measures of color vision impairment also found significant alterations. Chia et al. (1994) found 

significantly poorer color discrimination, after adjusting for age, education, and alcohol consumption, in 

21 workers at a fiber-reinforced plastic boat manufacturing facility; the styrene exposure level of 6 ppm 

was estimated from a mean end-of-shift urinary mandelic acid level of 84.0 mg/g creatinine. No 

relationship between the total color difference score and the urinary mandelic acid level was found. In 

60 workers in the shipbuilding industry with a mean styrene exposure level of 24.3 ppm, a significantly 

higher incidence of workers with errors in the blue-yellow or red-green ranges, compared to a referent 

group, was found (Fallas et al. 1992). Total error score was significantly different in workers, with a 

lifetime weighted average exposure level of 22 ppm styrene, as compared to workers in a low exposure 

group (9 ppm) (Iregren et al. 2005). In contrast to these results, Seeber et al. (2009b) found no significant 

association between CCI scores or visual contrast sensitivity among styrene workers with long-term 

exposure to average styrene concentrations up to 27 ppm; identification of a NOAEL from this study is 

limited by the lack of a control group. 

Several studies found improvements in color vision following an extended period of no styrene exposure 

or lower exposure. Triebig et al. (2001) reported a significant improvement in CCI scores following a 

4-week period with no styrene exposure; in contrast, no improvement in CCI scores was found in another 

group of styrene workers following a 1-month period without styrene exposure (Gobba et al. 1991). Two 

studies found significant improvements in color vision (age-adjusted color confusion score or CCI score) 

were observed in styrene workers following a decrease in styrene air level (Castillo et al. 2001; Triebig et 

al. 2001). However, one study found no change in age-adjusted near visual contrast sensitivity following 

a decrease in styrene exposure levels (Castillo et al. 2001). 

A number of studies have found significant alterations in performance on a variety of neurobehavioral 

tests; among these studies, reaction time appears to be the most frequently examined end point. 

Significant increases in simple reaction time have been observed in styrene workers exposed to 

concentrations of 21.9, 22.68, 47, or 92 ppm (Cherry et al. 1980; Gamberale et al. 1976; Jegaden et al. 

1993; Tsai and Chen 1996); tests for reaction time were measured in the morning before the work shift, 

suggesting that the effect was not due to acute exposure to styrene. The reaction times were 4–10% 

slower in the styrene workers as compared to the referent groups. No significant alterations in simple 

reaction time were observed in workers exposed to 8.6 ppm (Edling et al. 1993) or 24.3 ppm (Fallas et al. 
 

 

 

 

 

 

STYRENE 64 

3. HEALTH EFFECTS 

1992). Similarly, complex reaction time was significantly increased among styrene workers exposed to 

21.9, 22.68, or 25 ppm (Fallas et al. 1992; Jegaden et al. 1993; Mutti et al. 1984a); the variance from 

controls ranged from 7.5 to 20%. No alterations in complex reaction time were observed in workers 

exposed to 8.6 ppm (Edling et al. 1993). No alterations in choice reaction time were observed in styrene 

workers exposed up to 27 ppm averaged over 15 years (Seeber et al. 2009a); this value was not identified 

as a NOAEL because the study did not include a control group. Impaired performance on the digit span 

test, which measures attention/concentration, was observed in workers exposed to 6 ppm (Chia et al. 

1994), 22.68 ppm (Jegaden et al. 1993), or 24.3 ppm (Fallas et al. 1992). Other neurobehavioral 

performance tests that may be altered by chronic exposure to styrene included digit symbol or symbol 

digit tests at 6 ppm (Chia et al. 1994), vibration perception threshold at 15.9 ppm (Sato et al. 2009), 

memory at 25 ppm (Mutti et al. 1984a), and visuomotor at 50 ppm (Mutti et al. 1984a) or 75 ppm 

(Lindstrom et al. 1976). However, other studies have not found significant alterations in digit symbol at 

8.6 ppm (Edling et al. 1993), 24.3 ppm (Fallas et al. 1992), or 25 ppm (Mutti et al. 1984a), or memory at 

75 ppm (Lindstrom et al. 1976). By pooling response data for several tests of neurobehavioral 

performance, Mutti et al. (1984a) were able to analyze exposure-response relationships. When workers 

were divided into four groups based on morning urinary mandelic acid and phenylglyoxylic acid levels, 

the number of subjects with abnormal scores on greater than one, two, or three tests increased with 

increasing exposure concentration. Additional analyses demonstrated that the exposure intensity and 

duration of exposure affected a worker’s performance on neurobehavioral tests and the duration of 

exposure appeared to affect performance more than exposure intensity. 

Clinical symptoms of neurotoxicity have been reported by styrene workers; commonly reported 

symptoms included headaches, dizziness, impaired memory, and feeling “drunk”. At 6 or 12 ppm, 

abnormal tiredness and short memory were reported by most of the styrene workers examined by Flodin 

et al. (1989); problems concentrating and irritation were also reported by most workers exposed to 

12 ppm. After a 7-month period without styrene exposure, there was a marked improvement in 

symptoms and the mean number of symptoms reported was 1.9, compared to 5.3 reported 7 months 

earlier. Fiberglass reinforced plastic industry workers exposed to 18.9 or 50.0 ppm reported a higher 

prevalence of headaches, dizziness, light headedness, fatigue, irritability, feeling “drunk”, and memory 

loss (Checkoway et al. 1992); the prevalence of clinical signs was not significantly increased in workers 

exposed to 10.8 ppm. Increases in the incidence of headache, memory disturbances, forgetfulness, 

dizziness, and sensory symptoms in the upper and lower extremities were observed in workers with high 

exposure to styrene compared to those with low styrene exposure (Matikainen et al. 1993a); exposure 

levels were not reported. A significantly higher incidence of subjective symptoms (nausea, feeling of 
 

 

 

 

 

STYRENE 65 

3. HEALTH EFFECTS 

drunkenness, dizziness, and disturbance) was observed in styrene workers exposed to 4–164 ppm, as 

compared to controls (Geuskens et al. 1992). No significant difference in the incidence of symptoms 

related to cognitive motor disturbances (lack of concentration, understanding, trouble with movements) 

was found. Fiberglass boat manufacturing workers exposed to 92 ppm reported a higher prevalence of 

physical and mental tiredness at the end of the work shift than controls (Cherry et al. 1980). No 

alterations in the reporting of clinical symptoms were observed in plastic industry workers exposed to a 

mean concentration of 8.6 ppm (Edling et al. 1993). 

Styrene-induced damage to hearing and the vestibular system have been examined in a number of studies 

of chronically exposed workers. Several studies have reported significant associations between styrene 

exposure and hearing impairment; however, interpretation of the findings of most of these studies is 

limited by confounding exposure to noise or other solvents. Noise studies have found that exposure to 

>85 dB for over 10 years can result in a 10% hearing loss (Prince et al. 1997). Triebig et al. (2009) did 

not find an association between hearing loss and current styrene exposure among workers at a boat 

building plant (workers exposed to noise levels >85 dBA were excluded from the analysis); the high 

exposure group had a mean urinary mandelic acid plus phenylglyoxylic acid level of 970 mg/g creatinine 

(approximately 40 ppm). However, among long-term workers (exposed to styrene for >10 years) exposed 

to high levels of styrene, several effects were observed including hearing losses at 1,000–1,500 and 

8,000–12,500 Hz and an improvement in hearing function following a non-exposure period; the average 

exposure level was 30–50 ppm with >50 ppm exposure (80–100 ppm) in the past. Morioka et al. (1999) 

found an increased prevalence of workers with a urinary mandelic acid level of >0.3 g/L (approximately 

16 ppm) with an upper frequency of hearing below the 75th percentile for normal. However, 

interpretation of the results is limited by confounding exposure to noise and exposure to other solvents, 

particularly toluene, which has been shown to be ototoxic. The noise levels ranged from 53.0 to 

95.0 dBA with 14% of the measurements exceeding 85 dBA. Another study (Muijser et al. 1988) of 

styrene workers found a significant difference in hearing threshold at 8 kHz between indirectly exposed 

workers (mean styrene level of 14 ppm) and directly exposed workers (mean styrene level of 32 ppm); 

however, no differences were found in comparisons of indirectly and directly exposed workers with 

referent workers. The noise level for both groups of styrene workers was 80–85 dBA for most of the day. 

Śliwińska-Kowalska et al. (2003) found a significantly elevated risks of hearing loss among styrene 

workers exposed to a mean styrene concentration of 15.6 ppm (average noise level of 80.3 dBA). The 

odds ratio (adjusted for noise and gender) in workers only exposed to styrene was 5.2 (95% CI 2.9–8.9). 

The hearing losses were found within the range of 2–8 kHz. Morata et al. (2002) found significant 

decreases in hearing thresholds at 2, 3, 4, and 6 kHz in workers exposed to 0.05–22 ppm (mean of 
 

 

 

 

 

 

 

 

 

STYRENE 66 

3. HEALTH EFFECTS 

4 ppm); no difference in the prevalence of high frequency hearing loss, as compared to referent workers, 

was found. The fairly wide range of exposure levels adds a great deal of uncertainty to estimating the 

LOAEL from this study; although the mean exposure is reported as the LOAEL in Figure 3-1, this value 

may be an overly conservative estimate of the true LOAEL. Other studies have not found significant 

alterations in hearing. Möller et al. (1990) found no indications of hearing loss in workers exposed to 

18 ppm styrene. Sass-Korstak et al. (1995) did not find significant relationships between lifetime styrene 

exposure and hearing loss in workers at fiber-reinforced plastics manufacturing facilities. The cumulative 

styrene exposure level was calculated using data for current exposure (25 ppm for directly exposed 

workers and 8 ppm for indirectly exposed workers), length of time in each job category, and a downward 

adjustment for self-reported respirator use. The average noise levels (Leq) were 88.1 and 89.2 dBA for the 

directly and indirectly exposed workers, for nonexposed workers, a sound level of 80 dBA was assumed. 

In another study of fiberglass workers (Calabrese et al. 1996), no significant alterations in audiometric 

tests or auditory brainstem response were observed in workers exposed to a mean styrene level of 36 ppm. 

Additionally, a 3-week recovery period did not result in any significant changes in auditory brainstem 

responses (pre- and post-recovery) in nine of the workers. 

Other studies have examined workers for styrene-induced vestibular effects. Significant alteration in tests 

of central vestibulo-ocular and opto-ocular motor movements (i.e., static posturography, smooth eye 

pursuit, saccade, and vestibulo-ocular reflex tests) were observed in workers at a plastic boat 

manufacturing facility exposed to a TWA styrene concentration of 18 ppm (Möller et al. 1990). No 

indications of labyrinthine or peripheral vestibular lesions were observed. Toppila et al. (2006) also 

found significant alterations in postural stability in workers at fiberglass-reinforced plastic boat 

manufacturing facilities exposed to 25 ppm styrene. In contrast, Calabrese et al. (1996) did not find 

significant alterations in visual suppression tests or postural stability in fiberglass plant workers exposed 

to 36 ppm styrene. Significant alterations in vestibulo-ocular reflex were found. A 3-week recovery 

period did not result in significant changes in the test results. 

Styrene’s potential to impair odor threshold and vibration potential threshold have also been examined in 

styrene workers. Two studies examined styrene’s potential to affect olfactory function. No alterations in 

three clinical tests of olfactory function were observed in styrene workers exposed to 24.6 ppm styrene 

for minimum of 4 years (Dalton et al. 2003). Another study by these investigators (Dalton et al. 2007) 

found a significant impairment in performance on an odor identification test between styrene workers 

(current exposure levels ranging from 11 to 22 ppm as assessed via urinary mandelic acid plus 

phenylglyoxylic acid levels) compared to non-exposed workers (current styrene levels of 0.6–7.1 ppm). 
 

 

 

 

 

STYRENE 67 

3. HEALTH EFFECTS 

However, no significant relationships between current (on the day of olfactory testing or on the preceding 

day) or historical styrene exposure levels were found, suggesting that the difference was not related to 

styrene exposure. Sato et al. (2009) reported significant differences in vibration potential threshold in 

upper and lower limbs in workers at fiberglass-reinforced plastic boat facilities with a mean urinary 

mandelic acid plus phenylglyoxylic acid level of 0.42 g/g creatinine (approximately 17 ppm styrene in 

air), as compared to age-matched controls; however, the relationship between current urinary metabolites 

level and vibration threshold potential was not statistically significant. A past maximum urinary mandelic 

acid level of ≥50 ppm were significantly associated with impaired vibration threshold potential. 

Workers exposed to styrene in several industries at mean concentrations of 5–125 ppm had mild sensory 

neuropathy characterized by decreased sensory conduction amplitude and increased duration, but there 

were too few people to define a NOAEL (Rosen et al. 1978). Peripheral neuropathy and reduced nerve 

conduction velocity was also reported in an individual following a 2-day exposure to an unknown amount 

of styrene (and other chemicals) (Fung and Clark 1999). Leg weakness, leg muscle cramps, and 

paresthesia were also reported in two styrene workers (Gobba et al. 1995). Moderate sensorimotor 

neuropathy of the demyelinating type was diagnosed in both cases based on the clinical symptoms and the 

decreased motor nerve conduction velocity in the peroneal nerve and decreased sensory nerve conduction 

velocity in the sural and median nerves. Alterations in nerve conduction velocity have also been observed 

in styrene workers. Decreased peripheral conduction velocities in the median and tibial nerves and 

prolonged latencies of peripheral and cortical somatosensory evoked potentials were observed in female 

styrene workers exposed to 30–130 ppm (midpoint of the range is 50 ppm) (Štĕtkářová et al. 1993). 

Significant decreases in ulnar and peroneal maximum conduction velocities and increased peroneal motor 

distal latencies were observed in fiber reinforced workers exposed with urinary mandelic acid levels (end 

of shift) of ≥250 mg/L, as compared to referent workers. Motor distal latencies in the workers with 

urinary mandelic acid levels ≥250 mg/L were also significantly lower than in workers with urinary 

mandelic acid levels <250 mg/L (Yuasa et al. 1996). In contrast, no alterations in motor or sensory nerve 

conduction velocity in the ulnar, median, deep peroneal, or posterior tibial nerve were observed in 

workers exposed a to TWA styrene concentration of 30 ppm (based on urinary mandelic acid excretion) 

(Seppäläinen and Härkönen 1976), and no alteration in motor or sensory nerve conduction velocity was 

observed in workers exposed to approximately 100 ppm for a median of 4 years (Triebig et al. 1985). 

Although Seppäläinen and Härkönen (1976) did not find alterations in nerve conduction velocity, they 

found abnormal EEGs in 24% of the styrene workers, as compared to reported values for the normal 

population. The mean urinary mandelic acid level (975 mg/dm3

) was higher in workers with abnormal 

EEGs compared to those with normal readings (750 mg/dm3

). Similarly, a significantly higher absolute 
 

 

 

 

 

 

STYRENE 68 

3. HEALTH EFFECTS 

EEG power in alpha band in the fronto-temporal region of the brain was found in workers with high 

styrene exposures, as compared to workers with low-level exposure (Matikainen et al. 1993a). 

The majority of the available animal neurotoxicity studies have focused on hearing impairment. Hearing 

loss and a loss of outer hair cells (OHC) in the organ of Corti were observed in rats acutely exposed to 

1,000 ppm (Campo et al. 2001; Lataye et al. 2003) or 1,600 ppm (Crofton et al. 1994). In contrast, acute 

exposure of guinea pigs to 1,000 ppm did not result in hearing loss or OHC damage (Lataye et al. 2003). 

Intermediate-duration exposure studies have consistently found hearing loss and loss of OHC in rats 

exposed to ≥750 ppm styrene (Campo et al. 2001; Lataye et al. 2000, 2001; Loquet et al. 2000; Pouyatos 

et al. 2002; Pryor et al. 1987; Yano et al. 1992). Exposure to 600–650 ppm resulted in OHC losses but no 

alterations in hearing threshold (Loquet et al. 1999; Makitie et al. 2002; Pouyatos et al. 2002). A NOAEL 

of 300 ppm was identified by Makitie et al. (2002). 

Other neurological effects that have been observed in animal studies include lethargy and unsteady gait in 

mice exposed to 250 ppm for 2 weeks (Cruzan et al. 1997), an increase in astroglial alterations at 

320 ppm (Rosengren and Haglid 1989), a decrease in nerve conduction velocity in rats exposed to 

2,000 ppm, but not 200 ppm, for 32 weeks (Yamamoto et al. 1997), and concentration-related alterations 

in nystagmus elicited by optokinetic, vestibular, simultaneous optokinetic-vestibular, and saccadic 

stimulation in rats exposed to 830–4,000 ppm styrene for at least 60 minutes (actual duration of exposure 

was not reported) (Niklasson et al. 1993). 

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

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

3.2.1.5 Reproductive Effects 

Information on the reproductive effects of styrene in humans is available from epidemiological studies of 

the reproductive outcomes of females employed in the various industrial operations in which styrene is 

used. However, exposures to styrene were not adequately quantified in any of the studies cited. In one 

study, spontaneous abortions among 9,000 Finnish chemical workers from 1973 to 1976 were analyzed 

(Hemminki et al. 1980). The risk of spontaneous abortion expressed as number of abortions per 

100 pregnancies) was significantly higher in women employed in styrene production compared to all 

women in Finland 15.0 vs. 5.5). However, this increase was not detected in a follow-up study of the same 

workers (Hemminki et al. 1984). An increase in the occurrence of spontaneous abortions was also 
 

 

 

STYRENE 69 

3. HEALTH EFFECTS 

observed in a study of 76 women involved in processing polystyrene plastics (McDonald et al. 1988); the 

ratio of observed to expected abortions was 1.58 (95% CI 1.02–2.35). The possible embryotoxic effects 

of styrene on 67 female lamination workers compared to 67 age-matched controls were evaluated in a 

second study (Härkönen and Holmberg 1982). The number of births was significantly lower among the 

workers exposed to styrene. This result was explained in part by a greater number of induced abortions in 

the styrene-exposed group. The number of spontaneous abortions was not elevated in the exposed 

women. No increased risk of spontaneous abortions among workers processing polymerized plastics or 

heated plastics made of vinyl chloride or styrene was reported (Lindbohm et al. 1985). The authors 

reported that the statistical power of the study was low due to the small study population. These studies 

are not conclusive since the workers were exposed to chemicals other than styrene in the workplace and 

the concentrations of styrene were not adequately reported. Two studies have examined the potential of 

styrene to induce menstrual disturbances. A significant increase in the incidence of oligomenorrhea was 

observed in petrochemical industry workers; the adjusted odds ratio was 1.65 (95% CI 1.05–2.55) (Cho et 

al. 2001). Although the odds ratio includes an adjustment for exposure to other aromatic chemicals, there 

was potential for exposure to other chemicals; only three workers were exposed to styrene only and none 

of these women reported oligomenorrhea. In contrast, no significant alterations were observed in women 

working at reinforced plastics facilities with a mean styrene exposure level of 52 ppm for women directly 

exposed to styrene and 13 ppm for those indirectly exposed (Lemasters et al. 1985). Several studies have 

examined levels of prolactin, follicle stimulating hormone, and luteinizing hormone levels in female 

styrene workers; the results of these studies are discussed in Section 3.2.1.2, Endocrine Effects. 

Several studies have also examined styrene’s potential to induce male reproductive effects. A significant 

decrease in sperm concentration, total sperm count, percentage of normal sperm, and percentage of 

nonvital sperm and an increase in sperm velocity were observed in 23 workers employed at a styrene 

manufacturing facility for approximately 6 months, as compared to levels during the first week of 

employment (Kolstad et al. 1999a; results are also presented in Kolstad et al. 1999b). No significant 

relationships between urinary mandelic acid level and sperm density, total sperm count, or proportion of 

sperm with normal morphology were observed. A positive correlation between mandelic acid levels and 

the percentage of nonvital sperm was found, but the trend test was not statistically significant. In a large 

multinational study of male styrene workers, no significant alterations in time-to-pregnancy were found; 

the odds ratio, adjusted for maternal age, use of oral contraceptives, maternal and paternal smoking 

habits, time-to-pregnancy starting year, length of employment, and country, was 0.79 (95% CI 0.59–1.05) 

(Kolstad et al. 2000). Additionally, no significant alterations in fertility rates were found when workers 

were divided into groups based on length of exposure, period of attempting pregnancy, or exposure group 
 

 

 

 

 

 

 

 

 

STYRENE 70 

3. HEALTH EFFECTS 

(monitoring data from a subset of facilities were used to divide workers into different exposure groups)
 

(preliminary data from this study was reported by Kolstad et al. 1999c). Similarly, no significant 

alterations in time to pregnancy among styrene workers exposed to high or intermediate/low exposure
 

levels (based on urinary mandelic acid levels) (Sallmén et al. 1998).
 

Two animal studies have examined the reproductive toxicity of styrene following inhalation exposure.
 

No statistically significant alterations in the frequency of abnormal sperm heads were observed in mice 3–
 

5 weeks after exposure to 300 ppm for 5 days (Salomaa et al. 1985). In a two-generation study in rats 

(Cruzan et al. 2005b), no significant alterations in reproductive performance, estrous cycle length,
 

spermatogenic parameters, or histological alterations in reproductive tissues were observed at
 

concentrations up to 500 ppm.
 

3.2.1.6 Developmental Effects 

Limited information concerning developmental effects of styrene in humans is available from studies of 

delivery outcome of women employed in the plastics industry (processing styrene or polyurethane 

plastics). Case-control studies performed in Sweden and Norway did not detect an increase in the odds 

ratio for developmental effects (stillbirth, infant death, malformations, low birth weight) in women who 

worked in the plastic industry (Ahlborg et al. 1987). However, actual levels of styrene exposure were not 

known for either group of workers. Another study did not find significant increases in the occurrence of 

congenital malformations in children of men or women working at reinforced plastics facilities (Härkönen 

et al. 1984). A <4% lower birthweight were observed in the children of women who worked in the 

reinforced plastics industry in areas with elevated levels of styrene (mean concentration of approximately 

82 ppm) during pregnancy (Lemasters et al. 1989). However, this decrease was not statistically 

significant (p=0.08). These studies suggest that developmental effects in exposed workers are not of 

major concern, but the data are not adequate to exclude this effect. Moreover, interpretation of the results 

is complicated due to exposure of the workers to other chemicals in the workplace such as toluene, 

xylene, acetone, methylene chloride, and methyl ketone (Lemasters et al. 1989), as well as thermal 

degradation products of styrene polymers (Ahlborg et al. 1987). Workers may also be exposed to 

aerosols containing aldehydes, ketones, alcohols, esters, acids, and anhydrides. An expert panel convened 

by the National Toxicology Program (NTP 2006) concluded that the human data are not sufficient to 

evaluate the potential developmental toxicity of styrene in humans. 
 

 

 

 

STYRENE 71 

3. HEALTH EFFECTS 

The developmental toxicity of styrene has been examined in several animal studies. The average fetal 

crown-rump length was significantly reduced in rats exposed to 300 ppm on gestational days 6–15, but 

was not affected in rats exposed to 600 ppm (Murray et al. 1978); the investigators concluded that this 

effect was not treatment-related. A few skeletal variants such as lumbar spurs and delayed ossification of 

sternebrae occurred in the styrene-exposed litters at a higher incidence than the control litters; however, 

the occurrence of this effect was similar to historical controls. No developmental effects were observed 

in rabbits exposed to 600 ppm styrene on days 6–18 of gestation (Murray et al. 1978). Although there 

was a significant increase in the incidence of unossified sternebrae in the 600 ppm group, it did not 

exceed that found in historical control data. No significant alterations in the number of live fetuses, 

dead/resorbed fetuses, or malformed fetuses were observed in the offspring of mice exposed to 250 ppm 

styrene on days 6–16 of gestation (Kankaanpää et al. 1980). In the same study, exposure of hamsters to 

1,000 ppm of styrene on days 6–18 of gestation resulted in a significant increase in the number of dead or 

resorbed fetuses; no other alterations were observed (Kankaanpää et al. 1980). No effects were observed 

at 750 ppm. Similarly, no developmental effects were observed in a two-generation study in which rats 

were exposed to 500 ppm prior to mating, during mating, and during gestation and lactation (Cruzan et al. 

2005b). In contrast, Katakura et al. (1999, 2001) reported a significant increase in neonatal deaths in the 

offspring of rats exposed to 300 ppm on gestational days 6–20. 

Two studies have examined potential neurodevelopmental effects. Some minor alterations in tests of 

developmental milestones (incisor eruption), functional observational battery tests (forelimb grip 

strength), and swimming maze test were observed in the F2 offspring of rats exposed to 500 ppm in a 

two-generation study; these alterations were attributed to a lower body weight rather than a 

neurodevelopmental effect of styrene (Cruzan et al. 2005a). No alterations in locomotor activity, acoustic 

startle response, or brain morphology and weights were observed in this study. Another study found 

delays in righting reflex and incisor eruption in the offspring of rats exposed to 300 ppm on gestational 

days 6–20 (Katakura et al. 2001). This study (Katakura et al. 1999, 2001) also found alterations in 

homovanillic acid levels in the cerebrum and 5-hydroxyindoleacetic acid levels in the hippocampus of the 

offspring in the 300 ppm group. 

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

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

 

 

 

 

 

STYRENE 72 

3. HEALTH EFFECTS 

3.2.1.7 Cancer 

A number of studies have examined the carcinogenic potential of styrene in workers at styrene 

manufacturing and polymerization facilities, reinforced plastics facilities, and styrene-butadiene 

manufacturing facilities and among community members exposed to elevated styrene workers. Although 

there are several epidemiologic studies which suggest there may be an association between styrene 

exposure and an increased risk of leukemia and lymphoma, the evidence is generally inconclusive due to 

multiple chemical exposures and inadequate documentation of the levels and durations of exposure to 

styrene. 

Of the industries examined, workers employed at glass-reinforced plastics manufacturing facilities are 

likely to be exposed to higher levels of styrene and have lower potential for exposure to other 

carcinogenic agents. Some studies of glass-reinforced plastic workers have found suggestive evidence of 

increased cancer risks, particularly in workers with longer exposures to higher levels of styrene. No 

alterations in the number of deaths from cancer were observed in workers with high styrene exposure 

(mean levels at two facilities were 42.5 and 71.5 ppm) (Okun et al. 1985). In a follow-up study of these 

workers (Ruder et al. 2004), a significant increase in the number of deaths from urinary tract cancer 

(standardized mortality ratio [SMR] 3.44; 95% CI 1.26–7.50) was observed among workers with high 

styrene exposure; a trend for increasing SMRs for urinary tract cancer with increasing duration of 

exposure was also observed. The SMRs were not significantly elevated for other cancer types. In a very 

large epidemiological study of nearly 16,000 workers in the styrene plastic industry, the death rate from 

leukemia was twice as high in areas of high exposure as in areas of low exposure (Wong 1990); however, 

there were no statistically significant differences. In a follow-up study conducted 12 years later (Wong et 

al. 1994), significant increases in deaths from all cancers (SMR 115.5, 95% CI 104.8–127.1), cancer of 

the esophagus (SMR 191.7; 95% CI 104.8–321.7), bronchus, trachea, or lung (SMR 140.6; 95% CI 

119.3–164.0), cervix or uteri (SMR 283.5; 95% CI 135.9–521.3), and female genital organs (SMR 201.6; 

95% CI 107.4–344.8) were observed. However, no relationships between styrene exposure (exposure 

level or duration of exposure) and deaths from these cancer types were found. No significant increases in 

the incidence of non-Hodgkin’s lymphoma, Hodgkin’s disease, multiple myeloma, leukemia, or all 

lymphohematopoietic malignancies were observed in workers at Danish reinforced plastics facilities in 

which 50–100% of the workers were involved in reinforced plastics production (Kolstad et al. 1993, 

1994). However, when workers were divided by first year of employment, there was a significant 

increase in leukemia (standard incidence ratio [SIR] 1.69, 95% CI 1.09–2.49) among workers with a 

latency of ≥10 years and first year of employment of 1964–1970; when the data were analyzed by the 
 

 

 

 

 

 

 

STYRENE 73 

3. HEALTH EFFECTS 

length of employment, the incidence of leukemia was only significantly elevated among workers 

employed for <1 year. Significant increases in incidence were also observed for pancreatic cancer in 

workers with a high probability of styrene exposure (incidence rate ratio of 2.2; 95% CI 1.1–4.5) and 

urinary bladder cancer in workers with the highest probability of exposure and employed for >1 year 

(incidence rate ratio of 2.1; 95% CI 1.1–4.1) (Kolstad et al. 1995). No significant alterations in the 

incidence of leukemia, lymphoma, or other cancers were observed in styrene workers at eight British 

reinforced plastic manufacturing facilities (Coggon et al. 1987). In a large international cohort of workers 

employed in the reinforced plastics industry (this cohort included the British cohort examined by Coggon 

et al. 1987 and the Danish cohort examined by Kolstad et al. 1993, 1994, 1995), no significant alterations 

in no excess in mortality from all cancer or cancer of the lymphatic and hematopoietic tissues were 

observed (Kogevinas et al. 1993, 1994). However, significant increases in the incidence of lymphatic and 

hematopoietic neoplasms were observed in workers with a latency of at least 10 years (relative risk [RR] 

2.90; 95% CI 1.29–6.48 in workers with a latency of 10–19 years and RR 3.97; 95% CI 1.30–12.13 for 

workers with a latency of ≥20 years) and in workers exposed to ≥100 ppm styrene (RR 3.11; 95% CI 

1.07–9.06 for workers exposed to 100–119 ppm; RR 3.08; 95% CI 1.04–9.08 for workers exposed to 

120–199 ppm; RR 3.59; 95% CI 0.98–13.14 for workers exposed to ≥200 ppm), as compared to 

unexposed workers. An increase in the number deaths from malignant lymphomas was also observed in 

workers exposed to 120–199 ppm styrene (RR 7.15; 95% CI 1.21–42.11). 

An increase in lymphatic leukemia (4 observed deaths versus 0.5 expected) in workers exposed to 

polymer extrusion fumes, solvents, and colorants, but was not found to be related to duration or level of 

exposure (Ott et al. 1980). In a follow-up to this study, which followed the workers for another 11 years 

(Bond et al. 1992), a nonsignificant increase in the number of deaths from lymphatic and hematopoietic 

tissue cancers (SMR 144; 95% CI 95–208) was observed. Statistically significant increases in the number 

of deaths from lymphatic and hematopoietic cancer were observed in workers exposed to 1–4 ppm 

styrene and a 15-year minimum latency (SMR 160; 95% CI 102–238); however, significant alterations 

were not found in workers exposed to ≥5 ppm or with longer latency periods. In another study of workers 

involved in the styrene production, polymerization, or processing, a statistically significant excess of 

lymphoma deaths (3 deaths observed versus 0.56 expected) was reported; 2 of the 3 deaths occurred in 

men <40 years of age who had been exposed for at least a year (Hodgson and Jones 1985). However, the 

lack of association with actual exposure levels or specific durations and the small number of observed 

deaths requires cautious interpretation. No significant alterations in the number of deaths from cancer 

were observed in workers (1960 subjects) exposed to styrene in a production and polymerization facility 

(Frentzel-Beyme et al. 1978). In a study of workers at a styrene-polystyrene manufacturing facility who 
 

 

 

 

 

STYRENE 74 

3. HEALTH EFFECTS 

had at least 5 years of exposure, there were no significant increases in cause-specific mortality (Nicholson 

et al. 1978). However, when workers employed for <5 years were included in the analysis, there was an 

apparent increase in the number of deaths from lymphoma or leukemia (statistical analysis not 

conducted). 

A number of older studies provide suggestive evidence of increased risk of lymphatic and hematopoietic 

cancers in workers at styrene-butadiene rubber manufacturing facilities (Matanoski and Schwartz 1987; 

Matanoski et al. 1990; McMichael et al. 1976; Meinhardt et al. 1982); however, these studies provided 

limited exposure data and did not adjust for contribution of 1,3-butadiene to the overall cancer risk. A 

case-control study (Matanoski et al. 1993, 1997; Santos-Burgoa et al. 1992) provides suggestive evidence 

that the increase in leukemia was due to exposure to 1,3-butadiene rather than to styrene exposure. 

However, increases in the risk of lymphosarcoma and myeloma were associated with styrene exposure 

(Matanoski et al. 1997). More recent studies of styrene-butadiene workers include adjustments for 

1,3-butadiene exposure. A cohort mortality study conducted by Delzell and associates (Delzell et al. 

1996; Macaluso et al. 1996) examined workers at many of the same styrene-butadiene rubber 

manufacturing facilities examined by Matanoski and associates and Meinhardt and associates. In this 

examination of 15,649 male synthetic rubber workers employed for at least 1 year at one of eight styrenebutadiene rubber manufacturing facilities in the United States or Canada, significant increases in deaths 

from leukemia were observed among hourly employees (SMR 143; 95% CI 104–191), particularly among 

workers employed for ≥10 and ≥20 years since hire (SMR 224; 95% CI 149–323) (Delzell et al. 1996). 

When workers were divided by year of hire and age at death, leukemia deaths were elevated in workers 

who were hired between 1950 and 1959 (SMR 200; 95% CI 122–310) and who were <55 years of age at 

the time of death (SMR 179; 95% CI 104–287). Using calculated estimates of exposure levels to 

1,3-butadiene, styrene, and benzene, Macaluso et al. (1996) found that 75% of the cohort was exposed to 

1,3-butadiene with a median cumulative exposure of 11.2 ppm-years, 83% of the cohort was exposed to 

styrene with a median cumulative exposure of 7.4 ppm-years, and 25% of the cohort was exposed to 

benzene with a cumulative exposure of 2.9 ppm-years. Among workers with leukemia, 86% had 

1,3-butadiene exposure and 90% had styrene exposure; median cumulative exposure levels of 

1,3-butadiene and styrene were about 3 times higher than the rest of the cohort. Workers with a 

cumulative exposure of 20–79 ppm 1,3-butadiene had a relative risk of leukemia mortality (after 

adjustment by race, age, and cumulative styrene exposure) that was 50% higher than workers with a 

cumulative exposure of 0.1–19 ppm and workers with a cumulative exposure of >80 ppm had a 70% 

higher relative risk than the low exposure group; the progressive of relative risk with increasing 

cumulative exposure was statistically significant. Although a similar progression was observed for 
 

 

 

 

 

 

 

 

STYRENE 75 

3. HEALTH EFFECTS 

cumulative styrene exposure, the trend was not statistically significant. A follow-up to the Delzell et al. 

(1996) study, which tracked deaths for an additional 7 years (Sathiakumar et al. 2005), found similar 

results. A significant increase in deaths from leukemia was observed among hourly workers employed 

for >10 years and hired 20–29 years earlier (SMR 258; 95% CI 156–403). Increases in deaths for 

colorectal cancer among workers employed for >10 years and hired 20–29 years earlier (SMR 147; 95% 

CI 103–205) and deaths from prostate cancer among workers employed for <10 years and hired >30 years 

earlier (SMR 155; 95% CI 113–206). Significant increases deaths from leukemia were observed in 

workers involved in polymerization, coagulation, and finishing processes, maintenance workers, and 

laboratory workers; these workers had the highest potential exposure to 1,3-butadiene, styrene, and 

possibly dimethyldithiocarbamate. Subsequent analysis of these data using updated exposure assessments 

(Cheng et al. 2007; Delzell et al. 2001; Graff et al. 2005) found that the increased risk of leukemia was 

positively associated with 1,3-butadiene exposure. Positive associations between cumulative 

1,3-butadiene exposure (ppm-years) and leukemia and between cumulative styrene exposure and 

leukemia were observed; the associations were only statistically significant at the highest cumulative 

exposure levels for 1,3-butadiene (≥362.2 ppm-years) or styrene (≥60.4 ppm) (Delzell et al. 2001). 

However, when the relative risks were adjusted for 1,3-butadiene and dimethyldithiocarbamate 

cumulative exposure, cumulative styrene exposure was no longer significantly associated with leukemia 

(Delzell et al. 2001; Graff et al. 2005). Because styrene, 1,3-butadiene, and dimethyldithiocarbamate 

exposure were correlated, it is difficult to separate the risks for each individual compound. 

Several population-based studies have examined the possible carcinogenicity of styrene. A case-control 

study found a significant increase in prostate cancer (odds ratio of 5.5; 95% CI 1.4–21.8) and rectal 

cancer (odds ratio of 5.1; 95% CI 1.4–19.4) among workers with medium to high exposure to styrene 

(Gerin et al. 1998). Workers in the following professions were considered to have medium to high 

styrene exposure: motor vehicle painters, motor vehicle repairers, firemen, and plastic mould makers. 

Another study found a significant increase in the incidence of rectal cancer (SIR 3.11; 95% CI 1.14–6.77) 

among individuals with occupational exposure to styrene (Antilla et al. 1998). A limitation of both of 

these studies is the lack of exposure information, including levels of styrene and confounding exposure to 

other chemicals; thus, it is difficult to ascribe the increased cancer risks to styrene exposure. Loughlin et 

al. (1999) examined former students who attended a high school adjacent to synthetic styrene-butadiene 

rubber production facilities between 1963 and 1993 and found no significant alterations in deaths from 

lymphatic and hematopoietic cancer. Two studies have examined the possible association between 

styrene exposure and breast cancer. A case-control study by Cantor et al. (1995) found significant 

elevations in the risk of breast cancer among women possibly exposed to styrene in the workplace. Coyle 
 

 

 

 

 

 

 

 

 

 

 

STYRENE 76 

3. HEALTH EFFECTS 

et al. (2005) found a significant higher incidence of age-adjusted breast cancer rate in men and women, 

women, and women ≥50 years of age and living in counties with EPA toxics release inventory (TRI) 

facilities with on-site releases of styrene. As with the other population-based studies, these studies did 

not monitor styrene levels or exposure to other potentially carcinogenic chemicals and thus provided 

limited information on the carcinogenic potential of styrene. 

The carcinogenicity of styrene has been examined in three studies in rats (Conti et al. 1988; Cruzan et al. 

1998; Jersey et al. 1978; Maltoni et al. 1982) and one study in mice (Cruzan et al. 2001). No significant 

increases in the incidence neoplastic lesions were observed in rats exposed to styrene concentrations as 

high as 1,000 ppm 6 hours/day, 5 days/week for 2 years (Cruzan et al. 1998). Similarly, exposure of 

female rats to 600 or 1,000 ppm styrene 6 hours/day, 5 days/week for 21 months did not result in styrenerelated increases in the incidence neoplastic tumors (Jersey et al. 1978); a high incidence of chronic 

murine pneumonia in the control and 1,000 ppm male rats precludes the use of the male data for assessing 

the carcinogenic potential of styrene. There was a significant trend (Cochran-Armitage test conducted by 

ATSDR) for increased incidence of malignant mammary tumors in female rats exposed to styrene 

4 hours/day, 5 days/week for 52 weeks (Conti et al. 1988); the incidences were 6/60, 6/30, 4/30, 9/30, 

12/30, and 9/30 in the 0, 25, 50, 100, 200, and 300 ppm groups, respectively. No other significant 

increases in specific tumors were observed in this study (Conti et al. 1988; Maltoni et al. 1982). The 

findings of the Conti et al. (1988) study conflict with those of Cruzan et al. (1998), who found a 

concentration-related decrease in mammary tumors in female rats exposed to similar or higher styrene 

concentrations for a longer duration (20/60, 13/44, 9/43, 5/38, and 2/59 in female rats exposed to 0, 50, 

200, 500, or 1,000 ppm, respectively). The decrease in body weight observed in the female rats exposed 

to ≥200 ppm may have influenced the occurrence of mammary tumors. In contrast to the results in rat 

studies, significant increases in the incidence of bronchioloalveolar carcinoma were observed in female 

mice exposed to 160 ppm 6 hours/day, 5 days/week for approximately 2 years (Cruzan et al. 2001). The 

incidences of bronchioloalveolar carcinoma were 0/50, 0/50, 2/50, 0/50, and 7/50 in the 0, 20, 40, 80, and 

160 ppm female mice, respectively). Significant trends for increasing incidences of bronchioloalveolar 

adenoma were also observed for the male and female mice; the respective incidence of adenomas was 

15/50, 21/50, 35/50, 30/50, and 33/50 in males and 6/50, 16/50, 16/50, 11/50, and 24/50 in females. The 

incidence of adenoma was significantly higher than controls in males exposed to 40, 80, or 160 ppm and 

in females exposed to 20, 40, or 160 ppm. 

As discussed by IARC (2002) and Cruzan et al. (2002), the lung tumors observed in the mice are likely 

due to the in situ formation of styrene 7,8-oxide and 4-vinylphenol resulting in cytotoxicity and increased 
 

 

 

 

 

 

STYRENE 77 

3. HEALTH EFFECTS 

cell proliferation. The relevance of these tumors to humans has been questioned due to species 

differences in the metabolism of styrene in the lungs. In rats and mice, Clara cells have the ability to 

metabolize styrene to styrene 7,8-oxide and 4-vinylphenol in the lung, whereas humans have limited 

ability to metabolize styrene to these metabolites in the lung. A physiologically based pharmacokinetic 

(PBPK) model predicted that the total amount of styrene oxide in the terminal bronchioles in mice is 

10 times higher than in rats and 100-fold higher than in humans. In addition to these quantitative 

differences in the generation of styrene 7,8-oxide between rats and mice, there are qualitative differences 

in styrene metabolism. Mice produce higher levels of the R-enantiomer of styrene oxide, as compared to 

rats; the R-enantiomer has been shown to be more potent pneumotoxic than the S-enantiomer. The ratio 

of R- to S-enantiomers ranges from 2.2 to 2.87 in mice exposed to 20–160 ppm styrene and from 0.7 to 

0.73 in rats exposed to 50–1,000 ppm. Thus, mice appear to be very sensitive to the induction of lung 

tumors and the mechanism of inducing lung tumors is not likely to be relevant to humans. Although the 

mechanism involved in the development of lung tumors in mice may not be applicable to humans, other 

mechanisms of styrene carcinogenicity may be relevant for humans. 

3.2.2 Oral Exposure 

No studies were located regarding health effects in humans after oral ingestion of styrene. Based on the 

animal data that follow, the oral toxicity of styrene in humans would be expected to be low to moderate. 

3.2.2.1 Death 

No deaths in humans from ingesting styrene have been reported in the evaluations of case studies (EPA 

1989c; Gosselin et al. 1984; NIOSH 1983). 

The approximate reported oral LD50 for male and female rats was 5,000 mg/kg (Wolf et al. 1956). A 

100% survival rate and 100% mortality rate were reported in rats exposed to single oral doses of styrene 

(observation period 2 weeks) at 1,600 and 8,000 mg/kg, respectively (Spencer et al. 1942). Death in this 

study was mainly due to pronounced irritation of the esophagus and stomach. In another study, female 

mice were given a single oral dose of 1,350 mg/kg styrene on the 17th day of pregnancy (Ponomarkov 

and Tomatis 1978). After weaning, the progeny received the same dose once per week. The treatment 

was suspended after 16 weeks due to high mortality among the progeny (including both males and 

females). Fifty percent of the males and 20% of the females had died after 20 weeks, despite the 

suspension of treatment at week 16. The cause of death was liver necrosis and lung congestion. A high 

mortality rate was reported in 40 female rats exposed to 250 mg/kg/day styrene for 52 weeks (Conti et al. 
 

 

 

 

 

 

 

 

STYRENE 78 

3. HEALTH EFFECTS 

1988). Mortality was significantly elevated in male and female rats administered styrene by gavage at a 

dosage level of 2,000 mg/kg/day for 78 weeks (NCI 1979b). In this study, mortality was unaffected at 

dosage levels of 500 and 1,000 mg/kg/day in male and female rats. Male mice administered styrene at 

doses of 150 or 300 mg/kg/day for 78 weeks showed increased mortality; however, the female mice did 

not. 

The highest reliable LOAEL values and LD50s values in each species and duration category are recorded 

in Table 3-3 and plotted in Figure 3-2. 

3.2.2.2 Systemic Effects 

No studies were located regarding endocrine, metabolic, musculoskeletal, or dermal/ocular effects in 

humans or animals after oral exposure to styrene. 

For the following systemic effects resulting from oral exposure to styrene, the highest NOAEL values and 

all reliable LOAEL values for each species and duration category are recorded in Table 3-3 and plotted in 

Figure 3-2. 

Respiratory Effects. No studies were located regarding respiratory effects in humans after oral 

exposure to styrene. 

Severe lung congestion was observed in mice that were the offspring of dams given a single oral dose of 

styrene at 1,350 mg/kg on the 17th day of gestation and that continued to receive the same dose once per 

week after weaning (Ponomarkov and Tomatis 1978). The lung congestion was noted following 

16 weeks of styrene administration. No respiratory effects were observed in rats exposed to 

35 mg/kg/day styrene in drinking water for 105 weeks (Beliles et al. 1985). 

Cardiovascular Effects. No studies were located regarding cardiovascular effects in humans 

following oral exposure to styrene. 

No cardiovascular effects were observed in rats chronically exposed to 35 mg/kg/day in drinking water 

(Beliles et al. 1985). 
88

5000

189

200

92

100

185

300

32

300

199

196

294

198

23

30

Table 3-3 Levels of Significant Exposure to Styrene - Oral 

a 

Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) 

ACUTE EXPOSURE Death 

1 Rat 1 d 

(GO) 

Neurological 

2 Rat once 

(GO) 

System 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

200 M (increased dopamine 

receptor binding) 

LOAEL 

Serious 

(mg/kg/day) 

5000 (LD50) 

Reference Chemical Form 

Wolf et al. 1956 Styrene 

Agrawal et al. 1982 Styrene 

3 Rat 

(Wistar) 

Developmental 

4 Rat 

(SpragueDawley) 

14 d 1 x/d (GO) Gd 11 (GO) 300 

b

100 M (impaired learning) Husain et al. 1985 

Styrene Daston et al. 1991 Styrene 

5 Rat 

(SpragueDawley) 

2 x/d Gd 6-15 (GW) 

INTERMEDIATE EXPOSURE Immuno/ Lymphoret 

6 Rat 

(UF) 

5 d/wk 4 wk (GO) 

300 F 196 M 294 M (impaired immune 

response) 

Murray et al. 1978 Styrene Dogra et al. 1992 Styrene 

7 Mouse 

(Swiss) 

5 d/wk 4 wk (GO) 

23 M 30 M (impaired immune 

response) 

Dogra et al. 1992 Styrene 
102

200

158

500

101

906

202

250

103

35

99

200

400

Table 3-3 Levels of Significant Exposure to Styrene - 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 

8 Rat 90 d 

1 x/d (GO) 

Agrawal et al. 1982 Styrene 

200 M (increased dopamine 

receptor binding) 

9 Rat 

(Long- Evans) 

5 d/wk 8 wk (GO) 

Bushnell 1994 Styrene 

500 M (impaired learning) 

10 Rat 15 d 

1 x/d (G) 

Husain et al. 1980 Styrene 

906 M (increased serotonin and 

noradrenaline and decreased monoamine oxidase levels) 

11 Rat 

(Wistar) 

15 days (GO) 

Reproductive 

12 Rat 90 d 

(continuous) (W) 

Khanna et al. 1994 Styrene 

250 F 

Beliles et al. 1985 Styrene 

35 

13 Rat 60 d 

6 d/wk 1 x/d (GO) 

Srivastava et al. 1989 Styrene 

200 M 400 M (marked degeneration of 

seminiferous tubules, decreased spermatozoa) 
187

200

400

191

100

200

190

200

95

1350

105

2000

Table 3-3 Levels of Significant Exposure to Styrene - Oral (continued) 

a 

Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) System NOAEL (mg/kg/day) Less Serious (mg/kg/day) 

LOAEL 

Serious 

(mg/kg/day) 

Reference Chemical Form 

Developmental 

14 Rat Ld 1-21 

(GO) 200 M 400 M (altered testicular enzyme levels and 

decreased spermatozoa counts) 

Srivastava et al. 1992a Styrene 

15 Rat 

(Wistar) 

6 d/wk pnd 1-61 (GO) 

100 M 200 M (decreased testes weight 

and spermatozoa counts) 

Srivastava et al. 1992b Styrene 

16 Rat 

(NS) 

Gd 1-21, Gd 1- Ld 14-21, or Ld 1- Ld 14-21 (GO) 

Cancer 

17 Mouse 16 wk 

1 d/wk (GO) 

CHRONIC EXPOSURE Death 

18 Rat 78 wk 

5 d/wk 1 x/d (GO) 

200 (increased dopamine 

receptor binding) 

1350 2000 

(CEL: lung tumors) (decreased survival in 

males and females) 

Zaidi et al. 1985 Styrene Ponomarkov and TomaStyrene NCI 1979b Styrene 
104

353535353535353535

96

500500

107

200 400

108

300

Table 3-3 Levels of Significant Exposure to Styrene - 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 

Systemic 

19 Rat 105 wk 

7 d/wk (W) 

Resp 35 Beliles et al. 1985 

Styrene 

Cardio 35 Gastro 35 Hemato 35 Musc/skel Hepatic Renal 

35 35 35 

Dermal 35 Other 35 

20 Rat 120 wk 

1 d/wk 1 x/d (GO) 

Hepatic 500 Ponomarkov and Toma

Styrene 

Renal 500 

21 Dog 

Cancer 

22 Mouse 

561 d 1 x/d (GO) 78-103 wk 5 d/wk 1 x/d (GO) 

Hemato 200 400 (Heinz body formation) 

300 (CEL: lung tumors) 

Quast et al. 1979 Styrene NCI 1979b Styrene 

a The number corresponds to entries in Figure 3-2. b The acute-duration oral MRL of 0.1 mg/kg/day; dose divided by an uncertainty factor of 1,000 (10 for use of a LOAEL, 10 for extrapolation from animals to humanhuman variability). Cardio = cardiovascular; CEL = cancer effect level; d = day(s); F = Female; (G) = gavage; Gastro = gastrointestinal; Gd = gestational day; (GO) = gavage in oil; (GWwater; Hemato = hematological; LD50 = lethal dose, 50% kill; LOAEL = lowest-observed-adverse-effect level; M = male; min = minute(s); mo = month(s); Musc/skemusculoskeletal; NOAEL = no-observed-adverse-effect level; NS = not specified; pnd = post-natal day; Resp = respiratory; x = time(s); (W) = drinking water; wk = w
Figure 3-2 Levels of Significant Exposure to Styrene - Oral
	

Acute (≤14 days)
	

Death 

mg/kg/day Neurological 

Developmental 

10000 

1r 

1000 

4r 5r 

2r 

100 3r 

10 

1 

0.1 

c-Cat -Humans f-Ferret n-Mink Cancer Effect Level-Animals Cancer Effect Level-Humans LD50/LC50

d-Dog k-Monkey j-Pigeon o-Other LOAEL, More Serious-Animals LOAEL, More Serious-Humans Minimal Risk Level

r-Rat m-Mouse e-Gerbil LOAEL, Less Serious-Animals LOAEL, Less Serious-Humans for effects

p-Pig h-Rabbit s-Hamster NOAEL - Animals NOAEL - Humans other than

q-Cow a-Sheep g-Guinea Pig Cancer 

STYRENE

3. HEALTH EFFECTS

83
Figure 3-2 Levels of Significant Exposure to Styrene - Oral (Continued)
 

Intermediate (15-364 days)
	

mg/kg/day Immuno/Lymphor 

Neurological 

Reproductive 

Developmental 

Cancer * 

10000 

17m 

1000 10r 

9r 

13r 14r 

6r 

11r 

6r 8r 13r 14r 15r 16r 

100 15r 

12r 

7m 

7m 

*Doses represent the lowest dose tested per study that produced a tumorigenic 

10 response and do not imply the existence of a threshold for the cancer endpoint. 

c-Cat -Humans f-Ferret n-Mink Cancer Effect Level-Animals Cancer Effect Level-Humans LD50/LC50

d-Dog k-Monkey j-Pigeon o-Other LOAEL, More Serious-Animals LOAEL, More Serious-Humans Minimal Risk Level

r-Rat m-Mouse e-Gerbil LOAEL, Less Serious-Animals LOAEL, Less Serious-Humans for effects

p-Pig h-Rabbit s-Hamster NOAEL - Animals NOAEL - Humans other than

q-Cow a-Sheep g-Guinea Pig Cancer 

STYRENE

3. HEALTH EFFECTS

84
Figure 3-2 Levels of Significant Exposure to Styrene - Oral (Continued)
 

Chronic (≥365 days)
	

Systemic 

mg/kg/day Death 

Respiratory 

Cardiovascular 

Gastrointestinal 

Hematological 

Musculoskeletal 

Hepatic 

Renal 

Dermal 

Other 

Cancer * 

10000 

18r 

1000 

20r 20r 

21d 

22m 

21d 

100 

19r 19r 19r 19r 19r 19r 19r 19r 19r 

*Doses represent the lowest dose tested per study that produced a tumorigenic 

10 response and do not imply the existence of a threshold for the cancer endpoint. 

c-Cat -Humans f-Ferret n-Mink Cancer Effect Level-Animals Cancer Effect Level-Humans LD50/LC50

d-Dog k-Monkey j-Pigeon o-Other LOAEL, More Serious-Animals LOAEL, More Serious-Humans Minimal Risk Level

r-Rat m-Mouse e-Gerbil LOAEL, Less Serious-Animals LOAEL, Less Serious-Humans for effects

p-Pig h-Rabbit s-Hamster NOAEL - Animals NOAEL - Humans other than

q-Cow a-Sheep g-Guinea Pig Cancer 

STYRENE

3. HEALTH EFFECTS

85
 

 

 

 

 

 

 

 

 

 

STYRENE 86 

3. HEALTH EFFECTS 

Gastrointestinal Effects. Abdominal pain was reported by 11% of the residents of two apartment 

buildings exposed to elevated levels of styrene in drinking water for 3 days (Arnedo-Pena et al. 2003). 

The concentration of styrene in the water was 900 μg/L and the dose was estimated to be 

0.026 mg/kg/day. Based on other symptoms and the higher prevalence of symptoms among residents 

living near the contaminated water tank, it is likely that some of the observed effects were due to 

inhalation exposure of styrene vapors from the repair of a firewater tank adjacent to the drinking water 

tank. 

No gastrointestinal effects were observed in rats chronically exposed to 35 mg/kg/day styrene in drinking 

water (Beliles et al. 1985). 

Hematological Effects. No studies were located regarding hematological effects in humans after oral 

exposure to styrene. 

Intra-erythrocytic Heinz bodies were regularly detected in a dose-related manner in male and female dogs 

chronically exposed to 400 or 600 mg/kg/day groups and sporadically in females in the 200 mg/kg/day 

group (Quast et al. 1979). There were occasional decreased red blood cell counts, hemoglobin levels, and 

erythrocyte sedimentation rates in males and females in the 600 mg/kg/day groups. Increased 

hemosiderin deposits and intranuclear inclusions in liver were noted in animals dosed with 

600 mg/kg/day. This was probably secondary to the effects on the red blood cells. The formation of 

intra-erythrocytic Heinz bodies was readily reversible upon discontinuing the administration of styrene in 

the 600 mg/kg/day group after 470 days of exposure. No hematological effects were observed in rats 

chronically exposed to 35 mg/kg/day (Beliles et al. 1985). 

Hepatic Effects. No studies were located regarding hepatic effects in humans after oral exposure to 

styrene. 

Some animal studies have reported hepatic effects; however, the inconsistency of the findings and poor 

reporting of the data preclude drawing conclusion on the hepatotoxicity of orally administered styrene. 

Small areas of focal necrosis was observed in the livers of rats administered 400 mg/kg styrene in 

groundnut oil 6 days/week for 100 days (Srivastava et al. 1982). Because the incidence or statistical 

analysis data were not reported, it is not possible to determine whether 400 mg/kg is an adverse effect 

level. This study also found alteration in mitochondrial and microsomal enzymes at 200 and 400 mg/kg; 
 

 

 

 

 

 

 

 

STYRENE 87 

3. HEALTH EFFECTS 

the significance of these alterations in the absence of histological damage is not known. An increase in 

liver weights was observed in rats administered 400 or 677 mg/kg via gavage 5 days/week for 6 months 

(Wolf et al. 1956); no histological alterations were observed. Although the alterations in the liver weight 

were considered slight at 400 mg/kg and moderate at 677 mg/kg, the magnitude of the change and 

statistical significance is not known; slight and moderate alterations in body weight were also observed at 

these dose levels. Hepatic glutathione content was reduced in rats orally administered 900 mg/kg styrene 

for 7 consecutive days (Das et al. 1981); the toxicological significance of this effect is not known. As 

noted above, increased numbers of hemosiderin deposits and intranuclear crystalline inclusions were 

reported in the hepatocytes of dogs orally administered 600 mg/kg/day of styrene by gavage for 316 days 

(Quast et al. 1979). This was presumably secondary to Heinz body formation, and no other hepatic 

histological effects were in this study. No hepatic effects were observed in rats exposed to 35 mg/kg/day 

styrene in drinking water for 105 weeks (Beliles et al. 1985) or in rats administered 500 mg/kg styrene 

1 day/week for 120 weeks (Ponomarkov and Tomatis 1978). 

Renal Effects. No studies were located regarding renal effects in humans after oral exposure to 

styrene. 

A decrease in renal glutathione content and decreased glutathione-S-transferase activity was noted in rats 

orally administered 900 mg/kg styrene for 7 days (Das et al. 1983). Growth depression and slightly 

increased kidney weight were reported in female rats administered 400 and 667 mg/kg, 5 days/week for 

6 months (Wolf et al. 1956); the magnitude and statistical significance of the effect were not reported. 

Histopathological examination of kidney tissue showed no abnormalities; thus, the changes in organ 

weight were not considered adverse. In another study, female rats and mice were exposed to 

1,350 mg/kg/day of styrene on the 17th day of gestation; the offspring were also administered styrene, by 

gavage, 1 day/week for 120 weeks. No statistically significant increases in the incidence of kidney 

lesions were observed in rats exposed to 500 mg/kg (Ponomarkov and Tomatis 1978). No histological 

alterations were observed in the kidneys of rats chronically exposed to 35 mg/kg/day styrene in drinking 

water (Beliles et al. 1985). 

3.2.2.3 Immunological and Lymphoreticular Effects 

No studies were located regarding immunological effects in humans after oral exposure to styrene. 
 

 

 

 

 

STYRENE 88 

3. HEALTH EFFECTS 

The World Health Organization (WHO 1983) reviewed a Russian study conducted by Sinitskij in which 

styrene was fed to 36 rabbits at doses of 250 mg/kg for 58 days, 5 mg/kg for 216 days, and 0.5 mg/kg for 

202 days. Impairment of the immunological defense system was indicated by a nearly total suppression 

of leukocyte phagocytic activity. Although no statistical analysis was provided, the data showed a doseresponse relationship for both the severity of the effect and the time of onset. Similarly, impaired host 

resistance was observed in mice exposed to 30 mg/kg/day and infected with encephalomyocarditis or a 

rodent strain of malaria and rats exposed to 294 mg/kg/day and infected with a rodent hookworm parasite 

(Dogra et al. 1992). 

3.2.2.4 Neurological Effects 

No studies were located regarding neurological effects in humans following oral exposure to styrene. 

Neurobehavioral effects and alterations in neurochemicals have been observed in animal studies. 

Significant learning impairment was observed in an operant behavioral test in rats administered 

500 mg/kg styrene in corn oil, 5 days/week for 8 weeks (Bushnell 1994). A reversal of the effect was not 

observed 1 year after exposure termination. Another study found significantly increased mean percent 

avoidance response, indicative of impaired learning, in rats administered 100 or 200 mg/kg/day styrene 

for 14 days (Husain et al. 1985). No alterations in foot shock-induced aggressive behavior or 

amphetamine-induced motor activity were observed in young rats administered via gavage 250 mg/kg/day 

styrene for 15 days (Khanna et al. 1994). However, significant alterations were observed in similarly 

exposed rats maintained on a low protein diet (8% casein versus 20% in normal diet). 

Significant increases in serotonin levels in the hypothalamus, hippocampus, and midbrain were observed 

in rats administered 200 mg/kg/day for 14 days (Husain et al. 1985); no alterations in dopamine or 

noradrenaline levels were observed. Exposure to a higher dose (906 mg/kg/day) for 15 days resulted in 

increases in serotonin and noradrenalin in brain tissue (Husain et al. 1980). Neither study found 

significant alterations in brain dopamine levels. Another study found a significant increase in dopamine 

receptor binding, as assessed using labeled spiroperidol binding, in rats administered 200 or 

400 mg/kg/day for 1 day or 90 days (Agrawal et al. 1982). 

A series of studies by Chen and associates (Chen et al. 2007, 2008; Yang et al. 2008) examined the 

ototoxicity of styrene following gavage administration to rats. A dose-related increase in loss of outer 

hair cells was observed in rats exposed to 200–800 mg/kg/day styrene 5 days/week for 3 weeks (Chen et 
 

 

 

 

 

 

 

 

STYRENE 89 

3. HEALTH EFFECTS 

al. 2007). At 400 mg/kg/day styrene 5 days/week for 3 weeks, 51.4% of the outer hair cells in the middle 

cochlear region were damaged (Yang et al. 2008). In rats exposed to 800 mg/kg/day for various 

durations, damage to the outer hair cells was not observed at durations shorter than 5 days; however, 

damage to Deiters cells, which support the outer hair cells, was evident after 3 days of exposure (Chen et 

al. 2007). As with the loss of outer hair cells, a dose-related increase in hearing threshold shifts, as 

measured by auditory brainstem response, was observed at 200–800 mg/kg/day. At frequencies of 10 and 

20 kHz, a 100 mg/kg/day increase in styrene dose resulted in an additional 5 dB threshold shift. Because 

this study did not use a control group, a LOAEL value cannot be identified; however, Chen et al. (2008) 

noted that no losses of cochlear hair cells or hearing were observed in rats administered 100 mg/kg/day 

styrene 5 days/week for 24 weeks. 

The highest NOAEL and LOAEL values for neurological effects in each species and duration category 

are recorded in Table 3-3 and plotted in Figure 3-2. 

3.2.2.5 Reproductive Effects 

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

Marked degeneration in the seminiferous tubules and decreased spermatozoa were observed in rats 

administered 400 mg/kg styrene via gavage 6 days/week for 60 days (Srivastava et al. 1989). No adverse 

reproductive effects were observed in a three-generation reproduction study in which rats were exposed to 

35 mg/kg/day in drinking water (Beliles et al. 1985). In another study, marked degeneration of 

seminiferous tubules and decreased spermatozoa counts were observed in adult rats administered 

400 mg/kg styrene via gavage 6 days/week for 60 days (Srivastava et al. 1989). Significant decreases in 

sorbitol dehydrogenase and acid phosphatase levels and increases in lactate dehydrogenase, glucose6-phosphate dehydrogenase, β-glucuronidase, and γ-glutamyl transpeptidase levels were also observed at 

this dose level; the investigators considered these enzymes to be markers for testicular function. 

The highest NOAEL values and all reliable LOAEL values for reproductive effects in rats in the acute 

and intermediate duration categories are recorded in Table 3-3 and plotted in Figure 3-2. 

3.2.2.6 Developmental Effects 

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

 

 

 

 

 

 

 

STYRENE 90 

3. HEALTH EFFECTS 

No developmental effects were observed in the offspring of rats receiving a single gavage dose of 

300 mg/kg on gestational day 11 (Daston et al. 1991) or in rats administered 300 mg/kg/day (150 mg/kg 

administered twice daily) on gestational days 6–15 (Murray et al. 1978). 

Other developmental studies have focused on the impaired development of the reproductive system or 

neurodevelopmental effects. Decreases in spermatozoa counts (measured on postnatal days 61 and 91) 

were observed in offspring of rats administered to 400 mg/kg styrene on lactation days 0–21; no effects 

were observed at 200 mg/kg/day (Srivastava et al. 1992a). However, decreases in spermatozoa counts 

were observed in rats exposed to 200 mg/kg 6 days/week on postnatal days 1–61 (Srivastava et al. 

1992b). Both studies found significant alterations in testicular enzyme levels at the same dose level as 

spermatozoa effects; these enzymes were considered markers of testicular function. A decrease in 

dopamine receptor binding, as assessed using labeled spiroperidol, was observed in the offspring of rats 

administered to 200 mg/kg/day styrene throughout gestation and lactation or only during lactation, but 

was not observed in rat pups only observed during gestation (Zaidi et al. 1985). This decrease in receptor 

binding was attributed to an increase in the number of dopamine receptors rather than an alteration in 

binding affinity. Impaired amphetamine-induced locomotor activity and apomorphine-induced stereotypy 

were also observed in the pups exposed during gestation and lactation. 

The highest NOAEL value for developmental effects is recorded in Table 3-3 and plotted in Figure 3-2. 

3.2.2.7 Cancer 

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

Investigations of the carcinogenic potential of styrene in animals after oral exposure have yielded variable 

results. No significant alterations in the incidence of neoplastic tumors were observed in rats exposed to 

gavage doses as high as 250 mg/kg 4–5 days/week for 52 weeks (Conti et al. 1988; Maltoni et al. 1982) or 

2,000 mg/kg 5 days/week for 78–103 weeks (NCI 1979b) or in rats exposed to 35 mg/kg/day styrene in 

drinking water for 2 years (Beliles et al. 1985). In contrast, significant increases in the incidence of lung 

tumors were observed in mice receiving gavage doses of 300 mg/kg 5 days/week for 78–103 weeks (NCI 

1979b). The incidences of bronchioloalveolar carcinoma in male mice were 0/20, 3/44, and 5/43 in mice 

exposed to 0, 150, or 300 mg/kg, respectively, and the respective combined incidences of bronchioloalveolar carcinoma and adenoma in male mice were 0/20, 6/44, and 9/43. The incidence of bronchioloalveolar carcinoma in the 300 mg/kg group was similar to the incidence in untreated historical controls 
 

 

 

 

 

 

 

 

STYRENE 91 

3. HEALTH EFFECTS 

(12%), but lower than the incidence in historical vehicle controls 0/40; however, the National Cancer 

Institute (NCI 1979b) noted that the incidence in historical vehicle controls is based on too small a 

number of animals for meaningful use of historical control data. Two studies conducted by Ponomarkov 

and Tomatis (1978) examined the carcinogenicity of styrene following gestation and postnatal exposure. 

In the offspring of mice administered 1,350 mg/kg on gestation day 17 with continued exposure of the 

weanling mice to this dose level (1 day/week) for 16 weeks, a significant increase in lung tumors was 

observed during the 100-week observation period; this dose was also associated with treatment-related 

toxicity and mortality. In the second study, the mice were exposed to 300 mg/kg on gestation day 17 

followed by exposure to 300 mg/kg for 120 weeks (1 day/week) beginning at weaning. No significant 

alterations in tumor incidence were observed. 

3.2.3 Dermal Exposure 

No studies were located regarding health effects in humans after dermal exposure to styrene. 

3.2.3.1 Death 

No studies were located regarding lethality in humans or animals after dermal exposure to styrene. 

3.2.3.2 Systemic Effects 

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

musculoskeletal, hepatic, endocrine, or renal effects in humans or animals after dermal exposure to 

styrene. 

Dermal Effects. Marked irritation with denaturation of the skin was noted when styrene was applied 

in small amounts over a 4-week period to the shaved abdomen of rabbits at 20,000 mg/kg total dose) 

(Spencer et al. 1942). 

Ocular Effects. Moderate conjunctival irritation and transient corneal injury of the eyes were 

observed when undiluted styrene was tested in rabbit eyes (Wolf et al. 1956). The effects were produced 

immediately (within 3 minutes) by a single administration of two drops (about 0.1 mL) and persisted 

throughout the 7-day observation period. 
 

 

 

 

 

 

 

 

STYRENE 92 

3. HEALTH EFFECTS 

No studies were located regarding the following health effects in humans or animals after dermal 

exposure to styrene: 

3.2.3.3 Immunological and Lymphoreticular Effects 

3.2.3.4 Neurological Effects 

3.2.3.5 Reproductive Effects 

3.2.3.6 Developmental Effects 

3.2.3.7 Cancer 

3.3 GENOTOXICITY 

The genotoxicity of styrene has been examined in numerous in vivo studies of workers and laboratory 

animals; these data are summarized in Table 3-4. Chromosomal damage, DNA strand breaks, and 

mutagenic effects have frequently been studied in workers exposed to styrene in the production of 

reinforced plastic products and styrene/polystyrene production. In general, these studies are limited by 

the fact that workers in these industries are often exposed to chemicals other than styrene, such as 

methylene chloride and epoxide resins, and many studies did not control for potential confounding factors 

such as age, sex, and smoking status. Chromosomal aberrations have been reported in numerous studies 

of workers exposed to styrene for 1–25 years in reinforced plastic operations (Anwar and Shamy 1995; 

Artuso et al. 1995; Hogstedt et al. 1979; Mäki-Paakkanen et al. 1991; Meretoja et al. 1977, 1978; 

Somorovská et al. 1999; Tomanin et al. 1992); however, other studies have not found significant increases 

in chromosomal aberrations (Andersson et al. 1980; Hansteen et al. 1984; Jablonicka et al. 1988; MäkiPaakkanen 1987; Nordenson and Beckman 1984; Thiess et al. 1980; Vodicka et al. 2004; Watanabe et al. 

1981). The results of the Artuso et al. (1995) and Tomanin et al. (1992) studies provide suggestive 

evidence that the occurrence of chromosomal aberrations is concentrated-related. Significant increases in 

chromosomal aberrations alterations were observed in high exposure groups (20–326 or 27–104 ppm), 

but not in workers exposed to lower exposure levels (0.5–24 ppm). As with the occurrence of 

chromosomal aberrations, mixed results have been observed in studies of sister chromatid exchange 

(Andersson et al. 1980; Artuso et al. 1995; Hallier et al. 1994; Hansteen et al. 1984; Karakaya et al. 1997; 

Laffon et al. 2002; Mäki-Paakkanen 1987; Mäki-Paakkanen et al. 1991; Watanabe et al. 1981; Yager et 

al. 1993) and micronuclei formation (Anwar and Shamy 1995; Hogstedt et al. 1983; Karakaya et al. 1997; 

Laffon et al. 2002; Mäki-Paakkanen et al. 1991; Nordenson and Beckman 1984; Tomanin et al. 1993; 

Vodicka et al. 2004) in styrene workers. Other genotoxicity studies in styrene workers have found 

significant increases in glycophorin A mutations (Bigbee et al. 1996; Compton-Quintana et al. 1993), 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

STYRENE 93 

3. HEALTH EFFECTS 

Table 3-4. Genotoxicity of Styrene In Vivo 

Species (test system) End point Results Reference 

Human studies 

Human lymphocytes Chromosomal aberrations + Meretoja et al. 1977 

Human lymphocytes Chromosomal aberrations + Meretoja et al. 1978 

Human lymphocytes Chromosomal aberrations + Hogstedt et al. 1979 

Human lymphocytes Chromosomal aberrations + Anwar and Shamy 1995 

Human lymphocytes Chromosomal aberrations + Artuso et al. 1995 

Human lymphocytes Chromosomal aberrations + Mäki-Paakkanen et al. 1991 

Human lymphocytes Chromosomal aberrations + Tomanin et al. 1992 

Human mononuclear Chromosomal aberrations + Somorovská et al. 1999 

leukocytes 

Human lymphocytes Chromosomal aberrations – Thiess et al. 1980 

Human lymphocytes Chromosomal aberrations – Andersson et al. 1980 

Human lymphocytes Chromosomal aberrations – Watanabe et al. 1981 

Human lymphocytes Chromosomal aberrations – Nordenson and Beckman 1984 

Human lymphocytes Chromosomal aberrations – Hansteen et al. 1984 

Human lymphocytes Chromosomal aberrations – Maki-Paakkanen 1987 

Human lymphocytes Chromosomal aberrations – Jablonicka et al. 1988 

Human lymphocytes Chromosomal aberrations – Vodicka et al. 2004 

Human lymphocytes Sister chromatid + Yager et al. 1993 

exchange 

Human lymphocytes Sister chromatid + Laffon et al. 2002 

exchange 

Human lymphocytes Sister chromatid + Karakaya et al. 1997 

exchange 

Human lymphocytes Sister chromatid + Artuso et al. 1995 

exchange 

Human lymphocytes Sister chromatid + Hallier et al. 1994 

exchange 

Human lymphocytes Sister chromatid + Andersson et al. 1980 

exchange 

Human lymphocytes Sister chromatid – Mäki-Paakkanen et al. 1991 

exchange 

Human lymphocytes Sister chromatid – Hansteen et al. 1984 

exchange 

Human lymphocytes Sister chromatid – Watanabe et al. 1981 

exchange 

Human lymphocytes Sister chromatid – Maki-Paakkanen 1987 

exchange 

Human lymphocytes Micronuclei + Nordenson and Beckman 1984 

Human lymphocytes Micronuclei + Hogstedt et al. 1983 

Human lymphocytes Micronuclei + Laffon et al. 2002 

Human lymphocytes Micronuclei – Karakaya et al. 1997 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

STYRENE 94 

3. HEALTH EFFECTS 

Table 3-4. Genotoxicity of Styrene In Vivo 

Species (test system) End point Results Reference 

Human lymphocytes Micronuclei – Anwar and Shamy 1995 

Human lymphocytes Micronuclei – Mäki-Paakkanen et al. 1991 

Human lymphocytes Micronuclei – Tomanin et al. 1992 

Human lymphocytes Micronuclei – Vodicka et al. 2004 

Human erythrocytes Mutations in glycophorin A + Bigbee et al. 1996 

Human erythrocytes Mutations in glycophorin A + Compton-Quintana et al. 1993 

Human lymphocytes HPRT mutations ± Vodicka et al. 1995 

Human mononuclear DNA Single strand breaks + Somorovská et al. 1999 

leukocytes 

Human lymphocytes DNA Single strand breaks + Shamy et al. 2002 

Human lymphocytes DNA Single strand breaks + Mäki-Paakkanen et al. 1991 

Human leukocytes DNA Single strand breaks + Walles et al. 1993 

Human lymphocytes DNA Single strand breaks + Vodicka et al. 1995 

Human lymphocytes DNA Single strand breaks – Vodicka et al. 2004 

Human lymphocytes Unscheduled DNA + Pero et al. 1982 

synthesis 

Laboratory animal studies 

Mouse bone marrow Chromosomal aberrations – Sbrana et al. 1983 

Rat bone marrow Chromosomal aberrations – Sinha et al. 1983 

Mouse bone marrow Sister chromatid ± Simula and Priestly 1992 

exchange 

Mouse spleen, lung, Sister chromatid + Kligerman et al. 1992, 1993 

erythrocytes exchange 

Mouse bone marrow, Sister chromatid + Conner et al. 1980 

liver cells, and exchange 

alveolar macrophages 

Mouse bone marrow Sister chromatid ± Simula and Priestly 1992 

exchange 

Rat lymphocyte Sister chromatid + Kligerman et al. 1992, 1993 

exchange 

Mouse bone marrow Micronuclei ± Norppa 1981 

and polychromatic 

erythrocytes 

Mouse bone marrow Micronuclei ± Simula and Priestly 1992 

Mouse bone marrow Micronuclei – Engelhardt et al. 2003 

Mouse spleen, lung, Micronuclei – Kligerman et al. 1992, 1993 

erythrocytes 

Mouse bone marrow Micronuclei – Simula and Priestly 1992 

Rat lymphocyte Micronuclei – Kligerman et al. 1992, 1993 

Mouse bone marrow DNA single strand breaks – Vodicka et al. 2001a 

and lymphocytes 

Mouse kidney, liver, DNA + Walles and Orsen 1983 

lung, testes, and brain 
 

STYRENE 

3. HEALTH EFFECTS 

95 

Table 3-4. Genotoxicity of Styrene In Vivo 

Species (test system) 

Mouse liver 

End point 

Unscheduled DNA 

synthesis 

Results 

– 

Reference 

Clay 2004 

– = negative result; + = positive result; ± = weakly positive result; DNA = deoxyribonucleic acid 
 

 

 

 

 

 

 

 

STYRENE 96 

3. HEALTH EFFECTS 

DNA single strand breaks (Mäki-Paakkanen et al. 1991; Shamy et al. 2002; Somorovská et al. 1999; 

Walles et al. 1993; Vodicka et al. 1995), and increases in unscheduled DNA synthesis (Pero et al. 1982). 

Studies in laboratory animals have found significant increases in the occurrence of sister chromatid 

exchange (Conner et al. 1980; Kligerman et al. 1992, 1993; Simula and Priestly 1992). However, the 

results for chromosomal aberrations (Sbrana et al. 1983; Sinha et al. 1983), micronuclei formation 

(Engelhardt et al. 2003; Kligerman et al. 1992, 1993; Norppa 1981; Simula and Priestly 1992), DNA 

single strand breaks (Vodicka et al. 2001a), and unscheduled DNA synthesis (Clay 2004) have been 

weakly positive or negative. 

Styrene has been tested for genotoxic potential in a variety of in vitro systems, as summarized in 

Table 3-5. In the absence of metabolic activation, styrene has not produced gene mutations in Salmonella 

typhimurium (DeMeester et al. 1981; Dunkel et al. 1985; Vainio et al. 1976) or Escherichia coli (Dunkel 

et al. 1985); mixed results have been found in the presence of metabolic activation. Increases in 

chromosomal aberrations (Jantunen et al. 1986) and sister chromatid exchange (Norppa et al. 1983) have 

been found in human lymphocytes in the absence of metabolic activation. 

3.4 TOXICOKINETICS 

3.4.1 Absorption 

3.4.1.1 Inhalation Exposure 

The uptake of styrene following inhalation exposure in humans and animals is rapid (Ramsey and 

Andersen 1984; Ramsey and Young 1978; Ramsey et al. 1980; Withey and Collins 1979; Withey and 

Karpinski 1985). Pulmonary retention of inhaled styrene in humans is approximately 2/3 of the 

administered concentrations (Engstrom et al. 1978a, 1978b). For example, male human subjects were 

exposed to styrene in inspired air during 30-minute rest and three 30-minute work periods on a bicycle 

ergometer. The mean uptake was approximately 63% (range was 59–70%) of the amount of inspired 

styrene. In exercising volunteers exposed to 50 ppm styrene for 2 hours, an average of 66.5% of the 

inhaled styrene was absorbed (Johanson et al. 2000). Another study in volunteers exposed to 50 ppm 

styrene for 2 hours during exercise calculated that 64% of the styrene was absorbed (Norstöm et al. 1992). 

Exposures of rats to styrene concentrations of 50–2,000 ppm for 5 hours yielded blood uptakes that 

showed a continued and increasing rapid absorption, proportional to the styrene air level (Withey and 
 

 

 

 

 

 

 

 

STYRENE 97 

3. HEALTH EFFECTS 

Table 3-5. Genotoxicity of Styrene In Vitro 

Results 

With Without 

Species (test system) End point activation activation Reference 

Prokaryotic organisms: 

Salmonella typhimurium (two Gene mutation + – Vainio et al. 1976 

strains, plate incorporation 

method) 

S. typhimurium (three strains, Gene mutation – – Vainio et al. 1976 

plate incorporation method) 

S. typhimurium (three strains, Gene mutation + – DeMeester et al. 1981 

vapor exposure – disiccator test) 

S. typhimurium (four strains, Gene mutation – – DeMeester et al. 1981 

vapor exposure – disiccator test) 

S. typhimurium (five strains, Gene mutation – – Dunkel et al. 1985 

preincubation method) 

Escherichia coli (one strain, Gene mutation – – Dunkel et al. 1985 

preincubation method) 

Mammalian cells: 

Human lymphocytes Sister chromatid No data + Norppa et al. 1983 

exchange 

Human lymphocytes Chromosomal No data + Jantunen et al. 1986 

aberrations 

C = negative result; + = positive result 
 

 

 

 

 

 

 

STYRENE 98 

3. HEALTH EFFECTS 

Collins 1979). Plateau levels of styrene in rats' blood were reached within 6–8 hours during exposures 

ranging from 80 to 1,200 ppm styrene for up to 24 hours (Ramsey and Young 1978). 

3.4.1.2 Oral Exposure 

No studies were located regarding absorption in humans after oral exposure to styrene. 

The absorption of styrene from the gastrointestinal tract was rapid and complete in rats deprived of food 

overnight and administered, via gavage, 9.3 mg/kg styrene in aqueous solution. A peak blood level of 

6 μg/mL was reached in a few minutes. There was a much slower uptake of the styrene administered in 

vegetable oil (Withey 1976). Styrene administered in vegetable oil at a total dose of 32.61 mg produced a 

peak level of 12 μg/mL. This was reached at about 100 minutes (Withey 1976). 

3.4.1.3 Dermal Exposure 

Limited data indicate that absorption of styrene via the dermal route is probably low compared to 

absorption via other routes. When liquid styrene was applied to the forearms of male subjects, the 

absorption rate was estimated to be 9–15 mg/cm2

/hour (Dutkiewicz and Tyras 1968). By contrast, the 

rate of absorption through human skin was very low (10.5 μg/cm2

/minute) in subjects who dipped one 

hand into liquid styrene (Berode et al. 1985). The higher absorption rate reported by Dutkiewicz and 

Tyras (1968) likely included the disappearance rate of the solvent from the surface of the skin (Guillemin 

and Berode 1988). Riihimaki and Pfaffli (1978) demonstrated that in humans, dermal exposure to 

moderate concentrations of styrene vapor (300 and 600 ppm) resulted in percutaneous penetration 

corresponding to approximately 0.1–2% of the amount estimated to be absorbed from the respiratory 

tract. Similarly, Limasset et al. (1999) did not find significant differences in the levels of urinary 

metabolites in workers wearing total protective equipment (insulating suit and respiratory mask) and 

those wearing a respiratory mask only. 

Although absorption of styrene applied to the abdomen of rabbits was reported, there was no information 

on absorption rates (Spencer et al. 1942). Dermal exposure of rats to a neat solution of styrene resulted in 

peak blood levels of 5.3 μg/mL within 1 hour of exposure (Morgan et al. 1991). 
 

 

 

 

 

 

 

 

 

STYRENE 99 

3. HEALTH EFFECTS 

3.4.2 Distribution 

A blood:air partition coefficient of 40.2 and fat:air partition coefficient of 3,476 were calculated for rats 

(Gargas et al. 1989). Fisher et al. (1997) calculated a human blood:air partition coefficient of 69.74 and a 

breast milk:blood partition coefficient of 2.17. 

In a study of 81 adults without occupational exposure to styrene, average blood styrene levels were 

0.221 μg/L; in comparison, blood styrene levels in reinforced plastics industry workers were 1,068– 

1,590 μg/L at the end of workshift and 60–119 μg/L in the morning after exposure (Brugnone et al. 1993). 

3.4.2.1 Inhalation Exposure 

Inhalation studies in both humans and animals resulted in the widespread distribution of styrene with the 

highest concentration in adipose tissue. 

Three humans were exposed to 8–20 ppm styrene which resulted in a mean daily uptake of 193–558 mg 

styrene (Engstrom et al. 1978b). The concentration of styrene in adipose tissue was 2.8–8.1 mg/kg at the 

beginning of the week and 4.7–11.6 mg/kg at the end of the week. The authors estimated the half-life of 

styrene in the subcutaneous fat of humans to be about 72 hours. Subsequent studies by this author 

confirmed this estimate and reported the half-life of styrene in adipose tissue to be 2–5 days (Engstrom et 

al. 1978a). 

Fiberglass factory workers exposed to >50 ppm of styrene for 8-hour work shifts had blood styrene levels 

which ranged from 120 to 684 μg/L at the end of the shift (Apostoli et al. 1983). The concentrations of 

urinary MA and phenylglyoxylic acid (PGA) were 133–2,100 and 107–685 mg/L, respectively. These 

levels were also determined at the end of the work-shift. Distribution of styrene was also studied in adult 

men exposed to about 70 ppm of styrene for 2 hours during light physical exercise (Wigaeus et al. 1983). 

Blood styrene reached a level of approximately 2,000 μg/L after 75 minutes. The concentration of 

styrene in adipose tissue was about 5,000 μg/kg after 30–90 minutes of exposure. 

Rats were exposed for 5 hours to styrene at concentrations ranging from 50 to 2,000 ppm (Withey and 

Collins 1979). Tissue concentrations of styrene in the heart, liver, lung, kidney, spleen, brain, and 

perirenal fat demonstrated different patterns of distribution as the dose increased. The styrene 

concentration in perirenal fat was 10 times greater than in other organs. The largest amounts of styrene 

were found in the subcutaneous fat of male rats exposed to about 45 ppm of radioactively labeled styrene 
 

 

 

 

 

 

 

STYRENE 100 

3. HEALTH EFFECTS 

in the inspired air for 1–8 hours (Carlsson 1981). The concentration increased steadily during the first 

4 hours of exposure. Styrene concentrations in brain tissue and muscles were about 70% of the arterial 

blood value. Other investigators (Ramsey and Andersen 1984; Ramsey and Young 1978; Savolainen and 

Pfaffli 1978; Withey 1976) demonstrated that higher levels of styrene in adipose tissue increase with 

higher exposures to styrene. Styrene was found to distribute to the fetuses of pregnant rats after 

inhalation exposure, but at concentrations much lower than those measured in maternal organs and tissues 

(Withey and Karpinski 1985). 

3.4.2.2 Oral Exposure 

No studies were located regarding distribution in humans after oral exposure to styrene. 

An oral dose of 20 mg/kg of 14C styrene was administered to male and female rats (Plotnick and Weigel 

1979). Tissue levels peaked at 4 hours or earlier after dosing. Less than 10% of the administered dose 

was found in the stomach, small intestine, and large intestine 8 hours after dosing. The kidney had the 

highest concentration of radioactivity at all time intervals, with decreasing amounts in the liver and 

pancreas. Fat tissue showed increased levels after 2 hours. All tissue levels were below 1 μg/g at 

24 hours and at 48 and 72 hours were below the limit of detection. In rats receiving a gavage dose of 

800 mg/kg styrene, blood styrene levels peaked during the first 30 minutes of exposure and remained 

fairly steady for the first 6 hours. A similar pattern was observed when the rats were dosed with 

800 mg/kg/day for 6 days; 24 hours after administration of the sixth dose, styrene was not detected in the 

blood (Chen et al. 2007). A linear relationship between styrene dose and blood styrene levels was 

observed following single doses of 100–800 mg/kg (Chen et al. 2007). 

3.4.2.3 Dermal Exposure 

No studies were located regarding distribution in humans after dermal exposure to styrene. 

Immersion of rats' tails in pure liquid styrene for 1 hour resulted in styrene levels in the liver and brain 

that were estimated to be between 50 and 70% of the concentrations found in the same organs after 4-hour 

inhalation exposure to a vapor concentration of 11.8 g/m3 (Shugaev 1969). A skin:air partition coefficient 

of 91.9 was calculated for rat skin (Mattie et al. 1994). 
 

 

 

 

 

STYRENE 101 

3. HEALTH EFFECTS 

3.4.3 Metabolism 

There have been numerous in vivo studies, conducted primarily via inhalation, and in vitro studies that 

address the metabolism of styrene in humans and animals. There are several metabolic pathways for 

styrene (Cruzan et al. 2002; IARC 2002; Sumner and Fennel 1994), as illustrated in Figure 3-3. The 

primary pathway is oxidation of the side chain by cytochrome P450 to form styrene 7,8-oxide. Styrene 

oxide is predominantly metabolized by epoxide hydrolase to form styrene glycol; the styrene glycol is 

subsequently converted to mandelic acid, phenylglyoxylic acid, and hippuric acid. Styrene 7,8-oxide can 

also be conjugated with glutathione to ultimately form phenylhydroxylethylmercapturic acids. A minor 

pathway of styrene metabolism involves the formation of phenylacetaldehyde from styrene 7,8-oxide or 

cytochrome P450 conversion of styrene to pheylethanol and subsequent metabolism to phenylacetic acid. 

An alternative minor pathway involves ring oxidation resulting in the production of styrene 3,4-oxide, 

which is further metabolized to 4-vinylphenol. 

As summarized by Cruzan et al. (2002), over 95% of the styrene urinary metabolites excreted by humans 

are derived from styrene glycol (mandelic acid, phenylglyoxylic acid, hippuric acid) compared to 49–59% 

in mice and 68–72% in rats. In mice and rats, 25–35% of the metabolites are derived from glutathione 

conjugation (mercapturic acids). The remaining metabolites derive from phenylacetic acid production 

(12–22% in mice and 3–5% in rats) and ring oxidation (4–8% in mice and <1% in rats). Trace amounts 

of mercapturic acids (DePalma et al. 2001) and 4-vinylphenol (Manini et al. 2002, 2003) have also been 

detected in humans; both metabolites each account for <1% of the total styrene metabolites. 

The liver is the primary site of styrene metabolism and the source of styrene oxide in the blood (Cruzan et 

al. 2005). However, styrene is metabolized in other tissues, particularly the lung and nasal cavity 

following inhalation exposure, and it is this localized metabolism that results in the observed toxicity 

and/or carcinogenicity in these tissues. Studies in humans, mice, and rats indicate that styrene 

metabolism is concentration-dependent. At air concentrations of <200–300 ppm, most of the inhaled 

styrene is metabolized, only small amounts are exhaled unchanged, and there is little accumulation (Filser 

et al. 1993; Ramsey and Andersen 1984). At concentrations >300 ppm, metabolism was pregressively 

limited by metabolic capacity and was saturated (Vmax) at 700 ppm in rats and at 800 ppm in mice (Filser 

et al. 1993). Löf and Johanson (1993) estimated that metabolic saturation occurs at 100–200 ppm in 

humans; however, a subsequent analysis by this group (Jonsson and Johanson 2002) found that the Vmax 

was 40% higher. 
Figure 3-3. Scheme for Styrene Metabolism in Humans and Animals 

H Conjugates 

C CH2 

OH 

C CH Styrene H 3 

H H C CH2 C CH2 H 1-Phenyl 2O ethanol 

O 

H H 2 H C CH OH O 2

H 

cytochrome P450 2-Phenylethanol 

Styrene 1,2-oxide Styrene 3,4-oxide 

alcohol dehydrogenase 

H H 

H H H

C CH 2 

2 C CH2 C CH2 C C 

O O 

OH HO

2-Vinylphenol 4-Vinylphenol Styrene 7,8-oxide Phenylacetaldehyde 

glutathione aldehyde oxidase s-transferase epoxide hydrolase ? aldehyde dehydrogenase 

xanthine oxidase 

GS OH 

H H 2 2 H

C C 2 

C C C COOH H H OH H 

OH + SH 

C CH2 

OH GSH conjugate 1 GSH conjugate 2 Phenylacetic acid 

Phenylethylene glycol 

(styrene glycol) Glucuronide 

acetate 

1-Phenyl­ 2-Phenyl- O alcohol dehydrogenase H 2-hydroxy- 2-hydroxy- aldehyde dehydrogenase 2 

C C N C COOH ethylmercapturic ethylmercapturic H

acid acid 2 

H H 

C COOH 

OH Phenylaceturic acid 

alcohol 

dehydrogenase Mandelic acid 

O alcohol dehydrogenase O 

C COOH 

CHO COOH C N C COOH 

H2 

H 

Phenylglyoxylic acid 

Benzaldehyde Benzoic acid Hippuric acid 

GSH = glutathione 

Source: Adapted from IARC 2002; Manini et al. 2002; Sumner and Fennel 1994 

STYRENE 102 

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STYRENE 103 

3. HEALTH EFFECTS 

Comparisons of cytochrome P450, epoxide hydrolase, and glutathione S-transferase activity in the liver 

and lungs of rats and mice demonstrated 2–15-fold higher activities in the liver (Mendrala et al. 1993). In 

both tissues, previous exposure to styrene did not result in a dose-related increase in enzyme activity. In 

contrast, cytochrome P450 from human lung has a very limited ability to metabolize styrene to styrene 

oxide (Carlson et al. 2000; Nakajima et al. 1994); the capacity was 100-fold lower than in rat lung 

microsomes (Cruzan et al. 2002). 

A number of cytochrome P450 isozymes have the capacity to catalyze styrene to styrene oxide. In human 

livers, CYP2B6 was the most active isoform; the activities of CYP1A2 and CYP2E1 were about half that 

of CYP2B6 (Nakajima et al. 1993). Kim et al. (1997) found that CYP2E1 was the main isoform at low 

styrene concentrations and CYP2B6 at high styrene concentrations. In mice and rats, the CYP1A1 and 

CYP2B1, respectively, were the most active isoforms in the liver (Nakajima et al. 1993). In the lungs, 

CYP2F1 was the most active isoform in human (Nakajima et al. 1994) lung microsomes. In mice and rat 

lung and nasal cavity microsomes, CYP2F2 and CYP2E1 are the predominant isoforms (Hynes et al. 

1999). 

Studies by Mendrala et al. (1993) compared the kinetic constants of cytochrome P450 from the livers of 

humans, mice, and rats. The affinity of cytochrome P450 for styrene (based on Km valves) was similar 

for the three species. However, the mouse had the greatest capacity to form styrene 7,8-oxide from 

styrene based on the Vmax values and relative liver and body size, and humans had the lowest capacity. In 

contrast, marked differences in the Km values for epoxide hydrolase were found between species; the Km 

values were 0.01, 0.74, and 0.13-0.23 mmol for humans, mice, and rats, respectively. These results 

suggest that humans have a greater affinity to metabolize styrene 7,8-oxide and is more efficient at low 

levels of styrene oxide, as compared to rodent species. 

Styrene oxide exists as two enantiomeric forms (R) and (S). As with other aspects of styrene metabolism, 

species differences in the ratio of R enantiomer and S enantiomer have been detected. In human liver 

samples, the R:S ratio was 0.15 at low styrene concentrations (0.016 mM) and 1.4 at high styrene 

concentrations (1.1 mM) (Wenker et al. 2001). In mouse and rat liver microsomes (incubated with 2 mM 

styrene), the R:S ratio was 0.57 and 1.18, respectively (Hynes et al. 1999). In the lungs, the R:S ratio was 

2.4 and 0.52 for mice and rats, respectively. 
 

 

 

 

 

 

 

 

 

STYRENE 104 

3. HEALTH EFFECTS 

3.4.4 Elimination and Excretion 

3.4.4.1 Inhalation Exposure 

Several studies have demonstrated that styrene is almost totally excreted as urinary metabolites in 

humans, and at higher doses, the elimination profile indicates saturation of metabolic excretion or 

processes (Ramsey and Young 1978; Ramsey et al. 1980). Most of the inhaled styrene is excreted in 

urine as MA and PGA. In a study of the excretion of styrene and its metabolites resulting from a 

100-ppm/8-hour inhalation exposure, 2.6% of the total uptake was excreted as unchanged styrene in 

exhaled air (Guillemin and Berode 1988). The metabolites MA, PGA, and hippuric acid were excreted in 

the urine at 56.9, 33, and 7.5% of the absorbed dose, respectively. In exercising volunteers exposed to 

50 ppm styrene for 2 hours, 0.7–2.2% of the retained dose was exhaled as unchanged styrene (Johanson et 

al. 2000). Peak levels of styrene in the urine were measured immediately after exposure termination, 

whereas urinary excretion of MA and PGA peaked at 2 hours after exposure termination. MA excretion 

accounted for 6–29% of the estimated retained dose and PGA excretion accounted for 4–6%; the halftime 

excretion rates of MA and PGA were 2.2–4.2 and 3.5–13.9 hours, respectively. Phenylaceturic acid and 

hippuric acid was also detected in the urine samples collected 2 hours after exposure termination. At this 

time point, MA account for 73% of the total excreted metabolites, PGA 18%, phenylaceturic acid 4.5%, 

and hippuric acid 5.7%. In styrene workers exposed to 29–42 ppm styrene, both R-mandelic acid and 

S-mandelic acid were detected in the urine (Hallier et al. 1995). The ratio of R- to S-mandelic acid 

ranged from 0.7 to 1.2 in 19 of the 20 workers; in the last worker, the ratio was 2.2. 

An alternative pathway for the metabolism of styrene 7,8-oxide is conjugation with glutathione, resulting 

in the excretion of mercapturic acids. Low levels of mercapturic acids have been detected in workers 

exposed to an unspecified amount of styrene (Maestri et al. 1997a). The mean concentrations of styrene 

metabolites were 580 mg/g creatinine mandelic acid, 174 mg/g creatinine phenylglyoxylic acid, 

1.517 mg/g N-acetyl-S-(1-phenyl-2-hydroxyethyl)-cysteine S-enantiomer, 0.0637 mg/g N-acetylS-(1-phenyl-2-hydroxyethyl)-cysteine R- enantiomer, and 1.519 mg/g N-acetyl-S-(2-phenyl-2-hydroxyethyl)-cysteine. Another study of styrene workers (exposure level of 29–41 ppm) only detected 

styrene-specific mercapturic acid in 1 of 20 workers (Hallier et al. 1995). Similarly, in volunteers 

exposed to 50 ppm for 2 hours during exercise, N-acetyl-S-(2-phenyl-2-hydroxyethyl)-cysteine was not 

detected in urine samples collected up to 5 hours after exposure termination (Norström et al. 1992). 

In volunteers exposed to 80 ppm styrene, styrene is cleared from the blood in a biphasic manner, 

indicating a two-compartment pharmacokinetic model. The half-lives for the rapid and slow clearance 
 

 

 

 

 

 

 

 

 

STYRENE 105 

3. HEALTH EFFECTS 

phases are 0.58 and 13.0 hours, respectively. The half-life of styrene in subcutaneous adipose tissue of 

humans is 2–5 days (Engstrom et al. 1978a). The quantities of the major metabolites of styrene in urine 

compared with the quantity of styrene eliminated unchanged in expired air indicated that approximately 

97% is cleared by the metabolic route (Ramsey et al. 1980). 

Another human inhalation study determined that between 59 and 66% of inhaled styrene (50–200 ppm) 

was retained after a 4–8-hour exposure (Guillemin and Bauer 1979). Urinary elimination of MA was 

biphasic with a half-life for the first phase of 4 hours and for the second phase, 25 hours. These findings 

were comparable to those reported by Engstrom et al. (1976). The half-life of urinary elimination of PGA 

was determined to be 11 hours. This was regarded by the authors as being the first phase of elimination 

since MA is a precursor of PGA. 

A lactational transfer pharmacokinetic model developed by Fisher et al. (1997) predicted that exposure to 

50 ppm styrene would result in 0.650 mg styrene being ingested by a nursing infant over a 24-hour 

period. 

Styrene is almost totally excreted as urinary metabolites in animals. The blood elimination curve for rats 

is biphasic exponential at 80 and 200 ppm styrene over 6 hours. For exposures >600 ppm exposure levels 

for 6 hours duration), a nonlinear blood elimination curve following Michaelis-Menten kinetics was 

observed. In going from 80 to 1,200 ppm (a 15-fold increase) the area under the blood concentration 

curves increases by 112-fold (Ramsey and Young 1978; Young et al. 1979). Rats exposed to 50– 

2,000 ppm styrene by inhalation for 5 hours exhibited a dose dependent biphasic pattern of elimination 

(Withey and Collins 1979). 

3.4.4.2 Oral Exposure 

No studies were located regarding excretion in humans after oral exposure to styrene. 

Styrene was rapidly excreted in the urine of male and female rats administered 20 mg/kg of 14C styrene 

with 90% of the dose detected in the urine within 24 hours of administration (Plotnick and Weigel 1979). 

Less than 2% of the dose was found in the feces. Detectable tissue levels were not found 48 and 72 hours 

after administration. In mice administered 200 mg/kg for 70 days, 26.4, 13.3, and 19.0% of urinary 

metabolites excreted on day 70 were mandelic acid, phenylglyoxylic acid, and hippuric acid (Sbrana et al. 

1983). Approximately 80% of the dose was excreted in the first 24 hours. 
 

 

 

 

 

STYRENE 106 

3. HEALTH EFFECTS 

3.4.4.3 Dermal Exposure 

In a study of the absorption of liquid styrene applied to the forearms of male volunteers, about 13% of the 

absorbed dose was excreted as MA (Dutkiewicz and Tyras 1968). 

No studies were located regarding excretion in animals after dermal exposure to styrene. 

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. 1987a). 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 

1994; Leung 1993). PBPK models for a particular substance require estimates of the chemical-specific 

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 
 

 

 

STYRENE 107 

3. HEALTH EFFECTS 

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 styrene 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. 

Several investigators have developed toxicokinetic models for styrene (Csanády et al. 1994, 2003; 

Jonsson and Johanson 2002; Leavens and Bond 1996). The Csanády et al. (1994, 2003) model is useful 

for evaluating the carcinogenic risk associated with inhalation exposure to styrene. As discussed in 

Section 3.2.1.7, species differences exist in the metabolism of styrene in the lungs of rats, mice, and 

humans; these differences result in increased sensitivity of mice. Jonsson and Johanson (2002) developed 

a population-based PBPK model for styrene, which decreased the intraindividual variability for 

estimating the metabolic capacity for styrene in humans. Leavens and Bond (1996) described initial work 

on developing a model for co-exposure to 1,3-butadiene and styrene in mice. Some of these models 

provide strong support for the observed differences in styrene toxicity between rats, mice, and humans. 

As discussed further in Section 3.5.3, some have primarily focused on the species differences in the 

metabolism of styrene and metabolic differences between rats, mice, and humans. 
Figure 3-4. Conceptual Representation of a Physiologically Based 

Pharmacokinetic (PBPK) Model for a
 

Hypothetical Chemical Substance
 

Inhaled chemical Exhaled chemical 

Ingestion 

Lungs 

Liver 

Vmax GI Km Tract A 

V R 

E Fat T 

N E 

O R 

U Slowly I 

S perfused A 

tissues L 

Richly B perfused L B tissues O L Feces O O 

D O Kidney D 

Urine

Skin 

 Chemicals 

contacting skin 

Note: This is a conceptual representation of a physiologically based pharmacokinetic (PBPK) model for a 

hypothetical chemical substance. The chemical substance is shown to be absorbed via the skin, by inhalation, or by 

ingestion, metabolized in the liver, and excreted in the urine or by exhalation. 

Source: Adapted from Krishnan and Andersen 1994 

STYRENE 108 

3. HEALTH EFFECTS 
 

 

 

 

 

 

 

 

 

 

STYRENE 109 

3. HEALTH EFFECTS 

3.4.5.1 Summary of PBPK Models 

A number of investigators have developed toxicokinetic models for styrene. The earliest model was 

developed by Ramsey and Anderson (1984) to relate styrene exposure concentrations quantitatively to 

blood concentrations. A model developed by Csanády et al. (1994, 2003) is useful in describing the 

blood/tissue time course of styrene and styrene oxide in rats, mice, and humans following multiple routes 

of administration. A model developed by Sarangapani et al. (2002) expands these models and adds a 

description of styrene and styrene oxide levels in multiple compartments of the respiratory tract; this 

model is described below. 

Additionally, Jonsson and Johanson (2002) developed a population-based PBPK model for styrene, which 

decreased the intraindividual variability for estimating the metabolic capacity for styrene in humans. 

Leavens and Bond (1996) described initial work on developing a model for co-exposure to 1,3-butadiene 

and styrene in mice. 

3.4.5.2 Discussion of Model 

Risk assessment. The Sarangapani model quantifies the observed differences in the occurrence of 

lung tumors between rats, mice, and humans. 

Description of the model. The Sarangapani model is a mode of action based PBPK model 

developed to predict blood, liver, and respiratory tract tissue (particularly the terminal bronchioles) levels 

of styrene and styrene oxide and allow for interspecies extrapolations. The model has a nested 

architecture with a model for styrene and a linked submodel for styrene oxide. Both models consist of 

four respiratory tract tissue compartments (upper respiratory tract, conducting airways, terminal 

bronchioles, and pulmonary) and systemic tissue compartments for liver, fat, richly perfused tissue, and 

poorly perfused tissue. The metabolism of styrene to styrene 7,8-oxide and the detoxification of styrene 

7,8-oxide by epoxide hydrolase and glutathione S-transferase was modeled to occur in the liver and 

selected regions of the lung. The styrene oxide formed in the parent model in any tissue compartment 

was passed to the corresponding tissue compartment in the metabolite submodel; the schematic of the 

PBPK model is presented in Figure 3-5. Inhalation was the only exposure route considered in this model. 

Mass balance equations were used to account for the transport of styrene across the lumen and tissue 

subcompartments in the upper, conducting, and transitional airways and in the liver. Additionally mass 
Figure 3-5. Styrene and Styrene Oxide Models used in the Sarangapani PBPK 

Model 

Vm 

P450 EH+GST 

URT URT 

Vm 

Conducting airways Conducting airways 

Vm Vm - Va 

P450 

EH+GST T. Bronchioles T. Bronchioles 

Va 

Pulmonary Pulmonary 

Poorly perfused Poorly perfused 

Richly perfused Richly perfused 

Fat Fat 

Liver Liver 

P450 EH+GST 

Styrene Model Styrene Oxide Model 

EH = epoxide hydrase; GST = glutathione S-transferase; PBPK = physiologically based pharmacokinetic; 

T. Bronchioles = transitional bronchioles; URT = upper respiratory tract; Va = alveolar ventilation; Vm = minute 

ventilation or pulmonary ventilation; 

Source: Sarangapani et al. 2002 

STYRENE 110 

3. HEALTH EFFECTS 
 

 

STYRENE 111 

3. HEALTH EFFECTS 

balance equations were used to describe the production of styrene 7,8-oxide, elimination of styrene oxide, 

and kinetics of cytosolic glutathione in the liver and lung. Most of the physiological and flow parameters 

(Table 3-6) and respiratory tract-specific physiological parameters (Table 3-7) used in the model were 

obtained from the literature. Tissue volumes for the respiratory tract compartments were estimated by 

multiplying the appropriate surface areas with the tissue thickness. The kinetic constants used for hepatic 

and lung cytochrome P450, epoxide hydrolase, and glutathione S-transferase are presented in Table 3-8. 

Stereospecific kinetic parameters (Table 3-9) and steady-state concentrations of R-styrene oxide and 

S-styrene oxide were used to account for species differences in the stereospecific metabolism of styrene 

to styrene oxide. 

Validation of the model. Ten independent data sets ranging from closed chamber data to 

concentration measurements of styrene and styrene oxide in multiple tissues following multiple routes of 

exposure were used to validate various dose metrics in the mouse, rat, and human. The model provided 

good fit across species and at multiple target sites, including the whole lung for both styrene and styrene 

oxide. The model was not validated for styrene and styrene oxide levels in the transitional bronchioles 

due to the lack of experimental data. 

Target tissues. The model was used to predict steady-state styrene oxide levels in arterial blood and 

the terminal bronchioles. 

Species extrapolation. The model predicted that the levels of styrene oxide in the transitional 

bronchioles are approximately 10- and 100-fold lower in rats and humans, as compared to mice, thus 

suggesting that humans would be 100-fold less sensitive than mice to styrene-induced lung tumors. 

Interroute extrapolation. Interroute extrapolation was not attempted in this model. 

3.5 MECHANISMS OF ACTION 

3.5.1 Pharmacokinetic Mechanisms 

Styrene is rapidly absorbed through the respiratory tract (Ramsey and Andersen 1984; Ramsey and 

Young 1978; Ramsey et al. 1980; Withey and Collins 1979; Withey and Karpinski 1985) with a mean 

uptake of approximately 60–70% in humans (Johanson et al. 2000; Norström et al. 1992). A 

concentration-dependent uptake efficiency was found in the upper respiratory tract of rats and mice 
 

 

 

 

 

 

STYRENE 112 

3. HEALTH EFFECTS 

Table 3-6. Physiological and Flow Parameters Used in the Sarangapani PBPK
 

Model
 

Parameter Mouse Rat Human 

Body weight (g) 25 250 70,000 

Tissue volume as fraction of body weight 

Liver 5.5 3.66 2.6 

Richly perfused tissues 10 12.34 8.5 

Poorly perfused tissues 70 70 60 

Fat 7 6.5 21.4 

Blood 7.5 7.5 7.5 

Minute ventilation (mL/minute) 24 150 15,000 

Pulmonary ventilation (mL/minute) 12–1 75–110 10,500 

Cardiac output (mL/minute) 14 110 5,200 

Tissue blood flow as fraction of cardiac output 

Liver 15–30 15–30 22.7 

Richly perfused tissues 48 28.7 43 

Fat 5.9 7 5.2 

Upper airways 1.0 1.0 0.25 

Conducting airways 0.5 2.1 0.75 

Transitional airways 0.1 0.15 0.67 

Partition coefficients for styrene 

Blood:air 40 40 48 

Liver:blood 2 2 2 

Fat:blood 87 87 50 

Tissue:blood 1.3 1.3 1.3 

Partition coefficients for styrene 7,8-oxide 

Blood:air 2,000 2,000 2,000 

Liver:blood 1 1 1 

Fat:blood 14 14 14 

Tissue:blood 0.6 0.6 0.6 

Styrene:styrene oxide tissue-phase diffusivity (cm2/minute) 0.0002 0.0002 0.0002 

Styrene:styrene oxide air-phase diffusivity (cm2/minute) 6 6 6 

Source: Sarangapani et al. 2002 
 

 

 

 

 

 

 

 

 

 

STYRENE 113 

3. HEALTH EFFECTS 

Table 3-7. Respiratory Tract-Specific Physiological Parameters Used in the 

Sarangapani PBPK Model
 

Parameter Mouse Rat Human 

Tissue thickness (cm) 

Upper airway epithelium 0.005 0.005 0.005 

Conducting airway 0.0025 0.0025 0.0025 

epithelium 

Transitional airway 0.001 0.001 0.001 

epithelium 

Pulmonary airway 0.0003 0.00025 0.0005 

epithelium 

Mucus 0.0005 0.001 0.001 

Upper airway submucosa 0.01 0.01 0.01 

Conducting airway submucosa 0.005 0.005 0.005 

Transitional airway submucosa 0.002 0.002 0.002 

Surface area (cm2) 

Upper airway compartment 2.7 13.2 138 

Conducting airway 8.87 48.3 2,000 

compartment 

Transitional airway 0.48 5.5 ,6220 

compartment 

Pulmonary airway 500 3,400 540,000 

compartment 

Mass transfer coefficient 

(cm/min) 

Upper airway air-phase 7,200 7,200 1,980 

Conducting airway air- 312 228 181 

phase 

Transitional airway air- 1,136 481 158 

phase 

Tissue liquid phase 32 16 19.2 

Intracompartment clearance 10 40 400
 

(cm3/minute)
 

Lung microsomal protein 3.8 3.8 3.8
 

(mg/mL)
 

Liver microsomal protein 13 11 23
 

(mg/mL)
 

Lung cytosolic protein (mg/mL) 68 60 43
 

Liver cytosolic protein (mg/mL) 94 90 45
 

Source: Sarangapani et al. 2002 
 

 

 

STYRENE 114 

3. HEALTH EFFECTS 

Table 3-8. Kinetic Parameters Used in the Sarangapani PBPK Model 

Parameter Mouse Rat Human 

Vmax Cytochrome P450 

(nmol/minute/mL) 

Liver 200 50–150 50 

Upper airway 183 98 50 

Transitional airway 362 46.4 1.7 

Km Cytochrome P450 10 10 10 

(nmol/mL) 

Vmax Epoxide hydrolase 

(nmol/minute/mL) 

Liver 200 250 900 

Upper airway 250 250 500 

Transitional airway 250 250 500 

Km Epoxide hydrolase 100 100 100 

(nmol/mL) 

Vmax Glutatione S-transferase 

(nmol/minute/mL) 

Liver 11,000 6,300 1,400 

Upper airway 1,000 1,000 300 

Transitional airway 1,000 1,000 300 

Km Glutathione S-transferase 2,500 2,500 2,500 

for styrene (nmol/mL) 

Km Glutathione S-transferase 700 700 500 

for styrene oxide (nmol/mL) 

Liver glutathione basal 8,300 6,300 6,000 

concentration (nmol/mL) 

Upper airway glutathione basal 1,000 2,500 1,000 

concentration (nmol/mL) 

Transitional airway glutathione 1,000 1,000 1,000 

basal concentration (nmol/mL) 

Glutathione production rate 0.012 0.012 0.012 

(per minute) 

Source: Sarangapani et al. 2002 
 

 

STYRENE 115 

3. HEALTH EFFECTS 

Table 3-9. Stereospecific Kinetic Parameters for Styrene and Styrene Oxide 

Metabolism in Rodents Used in the Sarangapani PBPK Model
 

Mouse Rat 

Parameter R S R S 

Vmax Cytochrome P450-liver 

(nmol/minute/mL) 108.3 91.7 33.8 59.2 

Vmax Cytochrome P450­

terminal bronchioles 

(nmol/minute/mL) 211.8 88.2 130 250 

Km Cytochrome P450 

(nmol/mL) 10 10 10 10 

Km Epoxide hydrolase, liver 

(nmol/mL) 66.7 133.3 570 151 

Km Epoxide hydrolase, terminal 

bronchioles (nmol/mL) 125 125 200 50 

Km Epoxide hydrolase 

(nmol/mL) 29 155 29 155 

Vmax Glutatione S-transferaseliver (nmol/minute/mL) 4,400 6,600 2,400 3,600 

Vmax Glutatione S-transferaseterminal bronchioles 

(nmol/minute/mL) 400 600 400 600 

Km Glutathione S-transferase 

for styrene oxide (nmol/mL) 700 2,000 700 2,000 

Km Glutathione S-transferase 

for glutathione (nmol/mL) 2,500 2,500 2,500 2,500 

Source: Sarangapani et al. 2002 
 

 

 

 

 

 

STYRENE 116 

3. HEALTH EFFECTS 

(Morris 2000). In rats, the uptake efficiency was 23.7% at 5 ppm and 10.1% at 200 ppm; in mice, uptake 

efficiency decreased from 41.7% at 5 ppm to 9.6% at 200 ppm. Based on the decreased uptake efficiency 

observed in rats and mice following exposure to the cytochrome P450 inhibitor, metyrapone, Morris 

(2000) suggested that styrene was metabolized in situ and this metabolism enhanced styrene uptake. In 

humans, blood styrene levels reached steady state after 75 minutes of exposure to 70 ppm (Wigaeus et al. 

1983). The elimination of styrene from blood was biphasic, with a half-time of 1 minute for the rapid 

distribution phase and 40.8 minutes for the elimination phase. Styrene is rapidly distributed throughout 

the body with the highest concentrations found in adipose tissue. In rats, the styrene concentration in the 

adipose tissue was approximately 50-fold higher than in muscle; the biological half-time was 6.3 hours in 

adipose tissue and 2.4–2.0 hours in the blood, liver, kidney, spleen, muscle, and brain (Teramoto and 

Horiguchi 1979). In humans, styrene is primarily excreted in the urine as mandelic acid and 

phenylglyoxylic acid. The half-times of mandelic acid and phenylglyoxylic acid in the urine were 3.6 and 

8.8 hours, respectively, in humans exposed to 70 ppm for 2 hours (Wigaeus et al. 1983); another study 

reported elimination half-times of 2.2–4.2 hours for mandelic acid and 3.5–13.9 hours for 

phenylglyoxylic acid following a 2-hour exposure to 50 ppm styrene (Johanson et al. 2000). 

3.5.2 Mechanisms of Toxicity 

A large number of studies have investigated the mechanism of styrene carcinogenic activity, particularly 

the increased susceptibility of mice. Increases in malignant lung tumors have been observed in mice 

exposed to 160 ppm 6 hours/day, 5 days/week for approximately 2 years (Cruzan et al. 2001) and 

following gavage exposure to 300 mg/kg/day administered 5 days/week (NCI 1979b); however, 

neoplastic tumors have not been observed in rats exposed to concentrations as high as 1,000 ppm 

6 hours/day, 5 days/week for 2 years (Cruzan et al. 1998) or 2,000 mg/kg/day 5 days/week for 2 years 

(NCI 1979b), suggesting that mice are particularly sensitive. As reviewed by IARC (2002), Cohen et al. 

(2002), and Cruzan et al. (2002), genotoxic and nongenotoxic modes of action have been proposed. 

Although styrene itself does not appear to be DNA reactive, styrene 7,8-oxide is DNA reactive and has 

been shown to form stable N2 and O6 adducts of deoxyguanosine. Styrene oxide, DNA adducts, and 

genotoxic effects have been detected in humans, rats, and mice. Styrene has been shown to be mutagenic 

in bacteria, and exposure can result in increased frequency of sister chromatid exchange, chromosomal 

aberrations, micronucleated cells, and DNA strand breaks. However, elevated levels of blood styrene 

oxide do not explain the species differences in tumor formation. In humans, styrene 7,8-oxide is rapidly 

hydrolyzed by epoxide hydrolase as evidenced by the high levels of mandelic acid, phenylglyoxylic acid, 

and hippuric acid detected in the urine. Styrene 7,8-oxide is relatively stable in rats and mice, and 
 

 

 

 

 

 

 

 

 

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elevated levels have been detected in blood. The blood levels of styrene oxide in rats exposed to 1,000 

ppm is 100-fold higher than the levels in mouse exposed to 20–40 ppm; however, tumors have not been 

detected in rats. 

The nongenotoxic potential mode of action also implicates styrene 7,8-oxide and 4-vinylphenol (or its 

ring-oxidized metabolites) as the causative agents (Cruzan et al. 2002, 2005). The nongenotoxic 

mechanism involves cytotoxic damage to Clara cells in the lung. In the mouse lung, styrene is primarily 

metabolized by cytochrome P450, particularly the CYP2F2 isoform, in the Clara cell. The continued 

exposure to styrene 7,8-oxide and 4-vinylphenol results in Clara cell cytotoxicity, increased cell 

proliferation, bronchiolar epithelial hyperplasia, and eventually lung tumors. Intraperitoneal exposure 

data suggest that 4-vinylphenol may be more toxic to mouse Clara cells than styrene or styrene oxide 

(Cruzan et al. 2005). Several species differences account for the increased sensitivity of mice, compared 

to rats and likely humans. Humans appear to have a lower capacity to metabolize styrene in the lung 

compared to rats and a much lower capacity compared to mice; additionally, humans and rats have fewer 

Clara cells than mice. Mouse Clara cells metabolize higher levels of styrene than rat Clara cells; likely 

due to the higher levels of CYP2E1 and CYP2F2 found in mice (Cruzan et al. 2002). Mice produce a 

higher proportion of R-styrene oxide than S-styrene oxide, as compared to rats. It has been estimated that 

mice produce 15 times more R-styrene oxide than rats; in humans, the S enantiomer also predominates. 

This is particularly important since R-styrene oxide is a more potent pneumotoxicant than S-styrene 

oxide. In mice and rats, a portion of the styrene oxide generated is metabolized via glutathione 

conjugation. Mice appear to be more susceptible to glutathione depletion than rats, and glutathione 

depletion has been observed in mouse lung tissue at exposure concentrations of 80–300 ppm. 

Currently, the available data do not suggest that the nongenotoxic mode of action is not relevant to 

humans; a genotoxic mode of action have not been excluded for humans, and styrene is considered a 

possible human carcinogen by IARC (2002). 

3.5.3 Animal-to-Human Extrapolations 

Species differences exist in the metabolism of styrene in humans, rats, and mice; these differences are 

discussed in greater detail in Section 3.4.3. Although all three species predominantly metabolize styrene 

to styrene 7,8-oxide, there are species differences in the subsequent metabolism of styrene 7,8-oxide. As 

discussed in the metabolism section, styrene 7,8-oxide is primarily hydrolyzed to mandelic acid via 

epoxide hydrolase in humans. In rats and mice, styrene 7,8-oxide is also conjugated to form mercapturic 
 

 

 

 

 

 

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acids and styrene is metabolized to phenylacetic acid and/or 4-vinylphenol. In rats, 68–72% of the 

styrene metabolites in urine are generated from the epoxide hydrolase pathway and 26–35% are from the 

glutathione transferase pathway; in mice, 48–59 and 20–35% arise from the epoxide hydrolase and 

glutathione transferase pathways, respectively (Cruzan et al. 2002). In contrast, 95–100% of the styrene 

7,8-oxide is metabolized via the epoxide hydrolase pathway; only trace amounts of mercapturic acids 

have been detected in human urine. The difference in metabolism could result in significant increases in 

styrene 7,8-oxide levels in the body following exposure to high levels of styrene which may result in 

depletion of glutathione. Additionally, a small percentage of styrene can under ring oxidation resulting in 

the formation of 4-vinylphenol. Ring-opened compounds account for 4–8% of the urinary metabolites in 

mice, less than 1% in rats, and were not detected in humans. The production of 4-vinylphenol is 

potentially significant mode of action because it is considered to be more toxic to the liver and lung than 

styrene or styrene oxide (Cruzan et al. 2005b). 

However, these differences in the hepatic metabolism of styrene do not account for all of the observed 

species differences in styrene toxicity. As discussed in Section 3.2, mice appear to be especially sensitive 

to styrene toxicity in the liver, nasal olfactory, and lung. In the respiratory tract, the species differences 

between rats and mice are due to local metabolism of styrene to R-styrene oxide and/or other oxidized 

metabolites. The higher rate of metabolism in mice and higher production of the more reactive 

enantiomer likely result in increased susceptibility. The fact that humans have a more limited ability to 

metabolize styrene in the respiratory tract and possibly a higher potential to detoxify styrene oxide 

suggests that mice are not a good model for end points in which styrene oxide is the causative agent. 

3.6 TOXICITIES MEDIATED THROUGH THE NEUROENDOCRINE AXIS 

Recently, attention has focused on the potential hazardous effects of certain chemicals on the endocrine 

system because of the ability of these chemicals to mimic or block endogenous hormones. Chemicals 

with this type of activity are most commonly referred to as endocrine disruptors. However, appropriate 

terminology to describe such effects remains controversial. The terminology endocrine disruptors, 

initially used by (Thomas and Colborn 1992), was also used in 1996 when Congress mandated the EPA to 

develop a screening program for “...certain substances [which] may have an effect produced by a 

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 
 

 

 

 

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of chemicals as hormonally active agents. The terminology endocrine modulators has also been used to 

convey the fact that effects caused by such chemicals may not necessarily be adverse. Many scientists 

agree that chemicals with the ability to disrupt or modulate the endocrine system are a potential threat to 

the health of humans, aquatic animals, and wildlife. However, others think that endocrine-active 

chemicals do not pose a significant health risk, particularly in view of the fact that hormone mimics exist 

in the natural environment. Examples of natural hormone mimics are the isoflavinoid phytoestrogens 

(Adlercreutz 1995; Livingston 1978; Mayr et al. 1992). These chemicals are derived from plants and are 

similar in structure and action to endogenous estrogen. Although the public health significance and 

descriptive terminology of substances capable of affecting the endocrine system remains controversial, 

scientists agree that these chemicals may affect the synthesis, secretion, transport, binding, action, or 

elimination of natural hormones in the body responsible for maintaining homeostasis, reproduction, 

development, and/or behavior (EPA 1997). Stated differently, such compounds may cause toxicities that 

are mediated through the neuroendocrine axis. As a result, these chemicals may play a role in altering, 

for example, metabolic, sexual, immune, and neurobehavioral function. Such chemicals are also thought 

to be involved in inducing breast, testicular, and prostate cancers, as well as endometriosis (Berger 1994; 

Giwercman et al. 1993; Hoel et al. 1992). 

No in vitro studies were located regarding endocrine disruption of styrene. 

There is some evidence in styrene workers and in female rats that inhalation exposure to styrene may 

disrupt the tuberoinfundibular dopaminergic system. Significant alterations in serum prolactin levels 

have been observed in male and female workers exposed to air concentrations as low as 50 ppm 

(Bergamaschi et al. 1996, 1997; Luderer et al. 2004; Mutti et al. 1984b); a regression model predicts that 

exposure to ≥20 ppm would result in significant elevations in serum prolactin levels (Luderer et al. 2004). 

Elevated serum prolactin levels have also been observed in female rats acutely exposed to 150 ppm 

(Umemura et al. 2005); alterations have not been observed in male rats exposed to concentrations as high 

as 1,500 ppm (Jarry et al. 2002; Umemura et al. 2005). As noted by NTP (2006), the clinical significance 

of the increased serum prolactin levels, in the absence of other reproductive effects, is not known. 

Styrene exposure does not appear to adversely affect thyroid stimulating hormone levels in humans 

(Arfini et al. 1987) or rats (Umemura et al. 2005) or follicle stimulating hormone or luteinizing hormone 

in humans (Arfini et al. 1987). 

No significant alterations were observed in a gonadal sex differentiation assay using genetic male frogs 

exposed to styrene (Ohtani et al. 2001). 
 

 

 

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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 

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, 
 

 

 

 

 

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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). 

No studies were identified that examined the toxicity of styrene in children. Several occupational 

exposure studies have examined the developmental toxicity of styrene; these studies did not find 

statistically significant alterations in the occurrence of stillbirths, infant deaths, malformations, or birth 

weight (Ahlborg et al. 1987; Härkönen et al. 1984; Lemasters et al. 1989). However, an expert panel 

(NTP 2006) evaluating these data concluded that the human studies were not sufficient to evaluate 

developmental toxicity due to the low statistical power of the studies and the lack of adequate information 

on exposure. 

In general, animal studies have not found styrene-related developmental effects following inhalation 

exposure in rats (Murray et al. 1978), mice (Kankaanpää et al. 1980), rabbits (Murray et al. 1978), or 

hamsters (Kankaanpää et al. 1980) or oral exposure in rats (Daston et al. 1991; Murray et al. 1978); 

additionally, no developmental effects were observed in a rat two-generation study (Cruzan et al. 2005b). 

An expert panel determined that there was sufficient animal data to conclude that styrene does not cause 

developmental toxicity in rats following inhalation or oral exposure or in rabbits following inhalation 

exposure. No studies examined styrene toxicity following exposure of young laboratory animals. 

Studies in adults, particularly reinforced plastics industry workers, have identified the nervous system as 

the most sensitive target of styrene toxicity. Inconsistent results have been found in animal 

neurodevelopmental toxicity studies. Minor alterations in forelimb grip strength and swimming ability 

were observed in F2 offspring of rats exposed to 500 ppm styrene; however, the investigators (Cruzan et 

al. 2005a) attributed these alterations to a lower body weight rather than a neurodevelopmental effect of 

styrene. Another inhalation study found impaired righting reflex in the offspring of rats exposed to 
 

 

 

 

 

 

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300 ppm during gestation (Katakura et al. 2001). Similarly, impaired amphetamine-induced locomotor 

activity and apomorphine-induced stereotypy were observed in the offspring of rats orally administered 

200 mg/kg/day styrene during gestation and lactation (Zaidi et al. 1985). 

No human or animal data were located on the toxicokinetic properties of styrene in children or immature 

animals or possible age-related differences in the toxicokinetics of styrene. A lactational toxicokinetic 

model predicted that styrene can by transferred via maternal milk (Fisher et al. 1997). Subsequent 

sections of this chapter (Sections 3.8, 3.10, and 3.11) discuss the available information on biomarkers, 

interactions, and methods for reducing toxic effects. The available information is from adults and mature 

animals; no child-specific information was identified. It is likely that this information will also be 

applicable to children. 

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). 

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. Identification of 

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) may be difficult. Biomarkers of exposure 

to styrene 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 
 

 

 

 

 

 

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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 styrene are discussed in Section 3.8.2. 

A biomarker of susceptibility is an indicator of an inherent or acquired limitation of an organism's ability 

to respond to the challenge of exposure to a specific xenobiotic substance. It can be an intrinsic genetic or 

other characteristic or a preexisting disease that results in an increase in absorbed dose, a decrease in the 

biologically effective dose, or a target tissue response. If biomarkers of susceptibility exist, they are 

discussed in Section 3.10, Populations That Are Unusually Susceptible. 

3.8.1 Biomarkers Used to Identify or Quantify Exposure to Styrene 

The elimination of styrene via expired air may be used to identify exposure to styrene (Guillemin and 

Berode 1988; Stewart et al. 1968). Only a small percentage of unchanged styrene is expired after 

cessation of exposure. There are no adequate studies correlating post-exposure exhaled styrene with 

previous exposure levels. Assessment of occupational exposure involving measurement of unchanged 

styrene in urine has been reported (Dolara et al. 1984). In this study of workers, the styrene air 

concentrations were 3.8–14 ppm and the urinary concentrations of styrene were 0.7–4.1 μg/L. Urinary 

mutagenic activity was also evaluated in this study and was not a good indication of exposure to styrene. 

Only a small fraction of unchanged styrene is recovered in the urine. However, measurement of styrene 

in urine is a reliable indicator of styrene exposure if the exposure is recent (Dolara et al. 1984; Gobba et 

al. 1993; Guillemin and Berode 1988; Pezzagno et al. 1985). 

Analysis of unchanged styrene in blood may be used as a qualitative indicator of styrene exposure 

(Antoine et al. 1986). In one study, styrene was detected in the blood of humans exposed to 80 ppm 

(Ramsey et al. 1980). The maximum blood concentration at the end of exposure was 0.920.26 μg/mL. 

The half-life values for rapid and slow clearance curves were 0.58 and 13 hours, respectively. In another 

study, the concentration of styrene in blood (0.2–3.7 mg/L) increased with the level and duration of 

styrene exposure (Baselt 1988a). 
 

 

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The presence of styrene in adipose tissue is also an indicator of exposure. The concentration of styrene in 

the adipose tissue of two workers exposed to 7.5–20 ppm of styrene during a work week suggested a halflife of 5.2 days for one worker and 2.8 days for the other worker. The elimination time was estimated to 

be 5 weeks (Engstrom et al. 1978b). 

Levels of occupational exposure to styrene may also be estimated by measurement of styrene metabolites 

such as MA and PGA in urine (Bartolucci et al. 1986; Elia et al. 1980; Engstrom et al. 1976; Sedivec et 

al. 1984; Sollenberg et al. 1988). However, large intra-individual differences in MA and PGA urinary 

concentrations have been reported. A study of the inter- and intra-individual differences found that PGA 

levels were less variable than MA levels (Symanski et al. 2001) and variability was higher in post-shift 

urine samples compared to pre-shift urine samples. Expressing MA and PGA levels in units of mg per 

gram creatinine decreased the source intra-individual variability. Some studies found a good correlation 

between the time-weighted styrene exposure and urinary MA concentrations (Chua et al. 1993; Engstrom 

et al. 1976; Härkönen et al. 1974), while other studies found a better correlation with the sum of urinary 

MA and PGA at the end of the work period (Elia et al. 1980; Ong et al. 1994; Sollenberg et al. 1988). A 

good correlation between environmental styrene levels and urinary PGA levels has also been found (Chua 

et al. 1993). Total MA and PGA measured the morning after exposure may be a more reliable biological 

indicator of styrene exposure in factories where there is high variability in the environmental styrene 

concentration (Bartolucci et al. 1986). 

Reference levels of styrene urinary metabolites likely to be observed in workers exposed to the timeweighted average concentrations by inhalation have been reported. The American Conference of 

Governmental Industrial Hygienists (ACGIH 2008) recommends a biological exposure index of 400 mg/g 

creatinine for the sum of MA and PGA in urine. 

3.8.2 Biomarkers Used to Characterize Effects Caused by Styrene 

The nervous system is the most sensitive target of styrene toxicity in humans. Styrene affects both 

sensory (color vision, hearing, vestibular) and motor (nerve conduction velocity) function. Impaired 

performance on neurobehavioral tests and diminished color vision may be indicative of styrene exposure; 

however, these effects are not specific to styrene and have been observed following exposure to other 

solvents such as toluene. Several studies have found significant associations between performance on 

tests of color discrimination (Eguchi et al. 1995; Kishi et al. 2001) or reaction time (Mutti et al. 1984a) 

and levels of styrene urinary metabolites (mandelic acid and/or phenylglyoxylic acid). 
 

 

 

 

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Other investigators have proposed the use of genotoxicity biomarkers. Cytogenetic monitoring of 

peripheral lymphocytes as a biomarker of effect has been proposed (DeJong et al. 1988; Pero et al. 1982). 

Future biomarkers may include hemoglobin adducts. Using unscheduled DNA synthesis (UDS) as an 

indicator of DNA damage, the lymphocytes of 38 individuals occupationally exposed to styrene were 

evaluated. The induced UDS was significantly increased for the group exposed to 1–40 ppm styrene 

(Pero et al. 1982). Measurement of chromosome aberration in peripheral blood lymphocyte has been 

used for many years to monitor the biologic effects of genotoxic chemicals. However, due to high 

background levels of chromosomal aberration and exposures to other genotoxic workplace chemicals, the 

sensitivity of this biomarker for the effects of styrene is probably not adequate (DeJong et al. 1988). The 

role of hepatic glutathione in the toxicity of styrene has been proposed as inhibiting the covalent binding 

of styrene. This has been confirmed in animal studies by decreased glutathione in styrene-exposed 

animals (Parkki 1978). However, its use as a biomarker of effect in humans remains to be demonstrated 

since data on the adverse effects of styrene on the human liver are insufficient. 

3.9 INTERACTIONS WITH OTHER CHEMICALS 

Styrene metabolism is known to be inhibited by the presence of other chemicals such as toluene, 

trichloromethylene, and ethyl benzene. The biotransformation of styrene in rats to PGA, MA, and 

hippuric acid was suppressed by co-administration of toluene (Ikeda et al. 1972). This may be due to 

competitive inhibition of oxidative mechanisms. Similar results were reported by Ikeda and Hirayama 

(1978) in rats when styrene metabolism was inhibited by the administration of trichloroethylene. Urinary 

metabolites of styrene may be markedly reduced when humans or animals are concurrently exposed to 

organic solvents that inhibit styrene metabolism. 

In numerous polymer industries, workers are exposed to styrene and 1,3-butadiene, and several animal 

studies have found that styrene affects the metabolism and toxicity of 1,3-butadiene (Laib et al. 1992; 

Leavens and Bond 1996; Leavens et al. 1997) and 1,3-butadiene affects the metabolism of styrene 

(Leavens et al. 1996); however, the affect of 1,3-butadiene on styrene toxicity has not been well 

examined. In other industries, workers are co-exposed to styrene and acrylonitrile; in rats receiving an 

intraperitoneal dose of styrene and gavage dose of acrylonitrile, increases in serum creatinine and 

aspartate aminotransferase levels were observed, as compared to styrene-only exposure (Normandeau et 

al. 1984). 
 

 

 

 

 

 

 

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3.10 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE 

A susceptible population will exhibit a different or enhanced response to styrene than will most persons 

exposed to the same level of styrene 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 styrene, or compromised function of organs 

affected by styrene. Populations who are at greater risk due to their unusually high exposure to styrene 

are discussed in Section 6.7, Populations with Potentially High Exposures. 

Styrene is a hazardous substance found in the workplace with much lower levels found in the 

environment. Therefore, the populations at risk are workers in industries making polystyrene plastics, 

coating, polyester resins, and other products. Although no populations of unusually susceptible 

individuals have been identified for styrene, based on the targets of styrene toxicity, an assumption can be 

made that persons with pre-existing respiratory or neurological problems would be at risk for the irritant 

action and central nervous system effects of styrene, respectively. 

3.11 METHODS FOR REDUCING TOXIC EFFECTS 

This section will describe clinical practice and research concerning methods for reducing toxic effects of 

exposure to styrene. 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 styrene. 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 

styrene: 

Bronstein AC, Currance PL. 1988. Emergency care for hazardous materials exposure. St. Louis, MO: 

The C.V. Mosby Company, 221-222. 

Ellenhorn MJ, Barceloux DG. 1988. Medical toxicology: Diagnosis and treatment of human poisoning. 

New York, NY: Elsevier, 956-959. 

Haddad LM, Winchester JF. 1990. Clinical management of poisoning and drug overdose. 2nd ed. 

Philadelphia, PA: W.B. Saunders Company, 1226-1228. 

3.11.1 Reducing Peak Absorption Following Exposure 

Human exposure to styrene may occur by inhalation, ingestion, or dermal contact. General 

recommendations for reducing absorption of styrene following exposure include removing the exposed 
 

 

 

 

 

 

 

 

 

 

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individual from the contaminated area and removing the contaminated clothing. If the eyes and skin were 

exposed, they should be flushed with water. Since aspiration of styrene into the lung can cause 

pulmonary edema and hemorrhage, some authors advise against the use of emetics, but recommend 

administration of water for dilution of gastric lavage (Bronstein and Currance 1988; Haddad and 

Winchester 1990). Following acute inhalation exposure, administration of oxygen and use of mechanical 

ventilation to support respiration have been suggested (Bronstein and Currance 1988; Ellenhorn and 

Barceloux 1988; Haddad and Winchester 1990). Administration of aminophylline and inhaled 

bronchodilators may be required to treat bronchospasm (Ellenhorn and Barceloux 1988). Furthermore, 

cardiac monitoring has been suggested. Supportive treatment may be needed for neurological effects of 

styrene exposure (Haddad and Winchester 1990). 

3.11.2 Reducing Body Burden 

Styrene is metabolized by the body, and most styrene that is absorbed is excreted in the urine as 

metabolites of the parent compound. Styrene is cleared rapidly from the human body. Its half-life is 

several hours in the blood and about 2–4 days in subcutaneous adipose tissue (see Section 3.4). No 

method is commonly used to enhance the elimination of the absorbed dose of styrene. 

3.11.3 Interfering with the Mechanism of Action for Toxic Effects 

In humans, central nervous system depression and upper respiratory tract irritation were reported 

following acute exposure to higher styrene concentrations (see Section 3.2). Studies in animals indicate 

that chronic styrene exposure causes liver and kidney effects and may induce cancer. Styrene oxide was 

found to be the active mutagenic metabolite of styrene in several studies (de Raat 1978; Donner et al. 

1979; Norppa et al. 1979, 1980a, 1980b, 1981, 1984, 1988; Pohlova et al. 1985; Vainio et al. 1976). 

Based on these studies, it can be concluded that styrene is a typical indirect mutagen that needs metabolic 

activation to be able to bind covalently to macromolecules (e.g., nucleic acids). In one of the possible 

metabolic pathways, styrene oxide is further metabolized to hydroxyphenylethyl mercapturic acid. The 

reaction utilizes glutathione (Bond 1989). The mutagenic activity of styrene oxide was decreased in the 

presence of glutathione in S. typhimurium TA100 (Yoshikawa et al. 1980). This experiment, therefore, 

suggests that glutathione may reduce the mutagenic effects of styrene oxide. 

The formation of styrene oxide may also contribute to other effects following styrene exposure. 

Glutathione decreases the cytotoxicity of many reactive chemicals by acting as a scavenger of toxic 

metabolites. Exposure of rodents to high levels of styrene caused depletion of glutathione content in the 
 

 

 

 

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liver cells of these animals (Das et al. 1983; Vainio et al. 1979). Glutathione has been suggested to 

decrease the hepatotoxicity by preventing styrene oxide reaction with other endogenous macromolecules. 

Similarly, depletion of glutathione was found in all regions of rat brain following exposure to styrene 

oxide (Dixit et al. 1982; Trenga et al. 1991). The authors speculated that the depletion of brain 

glutathione may lead to an increased concentration of free styrene oxide with increased binding to cellular 

nucleophiles. This process would contribute to oxidative injury to neuronal and glial cells and may be a 

part of styrene-induced neurotoxicity. However, that styrene itself, being a lipophilic compound, may 

disrupt the nerve membrane function in a manner similar to anesthetic agents. 

Although results from in vitro studies in bacteria and in vivo animal studies demonstrate that exogenous 

glutathione precursors may decrease the effects of styrene toxicity, the benefit of this treatment is not 

known in humans. For low-level exposure cases, the endogenous glutathione levels are not likely to be 

decreased to a significant extent. Therefore, exogenous glutathione precursors such as N-acetylcysteine 

are not likely to be effective in mitigating the toxic effects of styrene. Exogenous doses of reducing 

agents may be useful following acute high dose exposure to styrene. In this case, a significant depletion 

of glutathione may occur as a result of the presence of high levels of styrene oxide. However, there are 

no clinical data available to date that support the use of this treatment. 

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 styrene is available. Where adequate information is not 

available, ATSDR, in conjunction with the National Toxicology Program (NTP), is required to assure the 

initiation of a program of research designed to determine the health effects (and techniques for developing 

methods to determine such health effects) of styrene. 

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. 
 

 

 

 

 

 

 

STYRENE 129 

3. HEALTH EFFECTS 

3.12.1 Existing Information on Health Effects of Styrene 

The existing data on health effects of inhalation, oral, and dermal exposure of humans and animals to 

styrene are summarized in Figure 3-6. The purpose of this figure is to illustrate the existing information 

concerning the health effects of styrene. 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. 

There is information on most categories of human toxicity via the inhalation route from occupational 

studies. However, there are limited data on humans exposed to styrene by the oral or dermal routes. Data 

from animal studies are more extensive, with studies available for most areas of toxicity resulting from 

exposure via the oral and inhalation routes. Little is known about the effects of dermal exposure to 

styrene in animals. 

3.12.2 Identification of Data Needs 

Acute-Duration Exposure. The possibility for brief human exposure to high concentrations of 

styrene exists in occupational settings, and might also exist near major spills. Exposure of the general 

public to episodic high concentrations of styrene at hazardous waste sites, in the home, or in the general 

environment is unlikely. The respiratory tract and central nervous system are the likely target organ 

systems for inhaled styrene (Alarie 1973; Carpenter et al. 1944; DeCeaurriz et al. 1983; Kankaanpää et al. 

1980; Murray et al. 1978; Seeber et al. 2004; Spencer et al. 1942; Stewart et al. 1968). Animal studies 

have reported hepatic (Cruzan et al. 1997, 2001; Morgan et al. 1993a, 1993b, 1993c; Vainio et al. 1979) 

and nasal (Cruzan et al. 2001) effects and hearing impairments (Campo et al. 2001; Crofton et al. 1994; 

Lataye et al. 2003). Available toxicokinetic data suggest that the mouse may be more sensitive to the 

hepatic and nasal toxicity of styrene than humans; thus, these data are not suitable for derivation of an 

acute-duration inhalation MRL. Studies have also examined potential reproductive (Salomaa et al. 1985) 

and developmental (Kankaanpää et al. 1980; Murray et al. 1978) effects; the highest doses tested in these 

studies were NOAELs. An acute-duration inhalation MRL based on a NOAEL for neurological effects in 

humans (Ska et al. 2003) was derived. Episodic high-level exposures to styrene from contaminated food 
Figure 3-6. Existing Information on Health Effects of Styrene 

Death 

Acute 

Intermediate

Chronic 

Immunologic/Lymphoretic

Systemic 

Neurologic

Reproductive

Developmental

Genotoxic

Cancer 

Inhalation 

Oral 

Dermal 

Human 

Systemic 

Death 

Acute 

Intermediate

Chronic 

Immunologic/Lymphoretic

Neurologic

Reproductive

Developmental

Genotoxic

Cancer 

Inhalation 

Oral 

Dermal 

Animal 

Existing Studies 

STYRENE 130 

3. HEALTH EFFECTS 
 

 

 

 

 

STYRENE 131 

3. HEALTH EFFECTS 

or water are unlikely. Few studies have examined the toxicity of styrene following exposure to an acute 

oral dose. Abdominal discomfort was observed in residents exposed to elevated levels of styrene in 

drinking water (Arnedo-Pena et al. 2003); concomitant inhalation exposure to styrene limits the utilization 

of this study for MRL derivation. A study in rats identified a LOAEL for neurotoxicity (Husain et al. 

1985) and another rat study examined potential developmental effects, but found no adverse effects 

(Daston et al. 1991). An acute-duration oral MRL was derived using the neurotoxicity study conducted 

by Husain et al. (1985). Although data on the toxicity of styrene following acute inhalation or oral 

exposure were considered adequate for the derivation of MRLs, the databases are limited to a few studies; 

additional studies confirming the dose-response relationships would increase the confidence in these 

MRLs. Dermal exposure to styrene at significant levels is unlikely except in the case of workplace spills 

and dermal absorption is probably low based on limited human studies. However, the almost complete 

lack of dermal toxicity data in animals and humans creates a degree of uncertainty on this issue. 

Therefore, single-dose dermal studies would be useful in determining target organs and thresholds for 

dermal exposure. In designing these types of studies, precautions should be taken to avoid concomitant 

inhalation exposure. 

Intermediate-Duration Exposure. Information on the toxicity of styrene in humans following 

intermediate-duration inhalation exposure is limited to a study examining potential reproductive effects in 

workers (Lindbohm et al. 1985); however, exposure information was not provided. Inhalation studies in 

animals have reported damage to the nasal olfactory epithelium in rats (Cruzan et al. 1997, 2005a, 2005b; 

Ohashi et al. 1986) and mice (Cruzan et al. 1997, 2001), liver damage in mice (Cruzan et al. 1997), eye 

irritation in rats (Cruzan et al. 1997) and guinea pigs (Spencer et al. 1942), ototoxicity in rats (Campo et 

al. 2001; Lataye et al. 2000; Loquet et al. 1999, 2000; Makitie et al. 2002; Pouyatos et al. 2002; Pryor et 

al. 1987; Yano et al. 1992), and impaired nerve conduction velocity (Yamamoto et al. 1997). A twogeneration study in rats did not find reproductive, developmental, or neurodevelopmental effects (Cruzan 

et al. 2005a, 2005b), but another study did find neurodevelopmental effects (Katakura et al. 1999, 2001). 

However, additional studies are needed, as the data are not considered sufficient to derive an 

intermediate-duration inhalation MRL. Chronic exposure studies provide strong evidence that the 

nervous system is the most sensitive target of styrene toxicity; studies examining neurological function of 

workers exposed to styrene for <1 year would provide valuable data for deriving an intermediate-duration 

inhalation MRL. Oral exposure studies of intermediate-duration are limited to a small number of animal 

studies and no human data; observed effects include impaired learning in rats (Bushnell 1994) and 

decreases in spermatozoa in rats (Srivastava et al. 1989, 1992a, 1992b). The results of the Srivastava 

studies have been questioned by the NTP Expert Panel (NTP 2006) because the findings are inconsistent 
 

 

 

STYRENE 132 

3. HEALTH EFFECTS 

with the lack of reproductive effects found in an inhalation two-generation study conducted by Cruzan et 

al. (2005b). The LOAELs identified in these studies were higher than the lowest LOAEL identified in an 

acute-duration neurotoxicity study (Husain et al. 1985). The intermediate-duration database was 

considered inadequate for derivation of an MRL because an intermediate-duration oral MRL based on the 

LOAELs identified in the intermediate-duration oral studies would be higher than the acute-duration oral 

MRL. Studies in animals are needed to establish dose-response relationships for neurotoxicity, the 

presumed sensitive end point. Additionally, more studies examining the potential reproductive toxicity of 

ingested styrene are needed to confirm the results of the Srivastava studies. One study examined the 

dermal toxicity of styrene in rabbits (Spencer et al. 1942); basic information on the adverse effects of 

intermediate-duration dermal exposure to styrene in animals is also needed due to the sparsity of available 

data. 

Chronic-Duration Exposure and Cancer. A large number of occupational exposure studies have 

examined the chronic toxicity of styrene. Systemic toxicity studies have examined endocrine 

(Bergamaschi et al. 1997; Mutti et al. 1984b), hematological (Checkoway and Williams 1982; Thiess and 

Friedheim 1978), hepatic (Hotz et al. 1980; Lorimer et al. 1978), or renal (Verplanke and Herber 1998; 

Viau et al. 1987; Vyskocil et al. 1989) end points; most studies relied on biomarkers of toxicity. The 

most widely examined end point is neurotoxicity and the available data suggest that this is the most 

sensitive end point. Examined neurological end points included color vision (Campagna et al. 1995, 

1996; Chia et al. 1994; Eguchi et al. 1995; Fallas et al. 1992; Gobba et al. 1991; Gong et al. 2002; Kishi et 

al. 2001; Mutti et al. 1984a), vestibular effects (Calabrese et al. 1996; Möller et al. 1990), hearing 

impairment (Morata et al. 2002; Morioka et al. 1999; Muijser et al. 1988; Śliwińska-Kowalska et al. 

2003), symptoms of neurotoxicity (Checkoway et al. 1992; Cherry et al. 1980; Edling et al. 1993; Viaene 

et al. 1998, 2001), performance on neurobehavioral tests (Cherry et al. 1980; Edling et al. 1993; 

Gamberale et al. 1976; Jegaden et al. 1993; Lindstrom et al. 1976; Mutti et al. 1984a; Tsai and Chen 

1996; Viaene et al. 1998, 2001), nerve conduction velocity (Behari et al. 1986; Murata et al. 1991; Rosen 

et al. 1978), olfactory alterations (Dalton et al. 2003, 2007), and EEG alterations (Härkönen et al. 1984; 

Seppäläinen and Härkönen 1976). Other human studies have examined reproductive (Härkönen and 

Holmberg 1982; Hemminki et al. 1980) and developmental (Ahlborg et al. 1987; Lemasters et al. 1989) 

end points. The chronic toxicity of styrene has also been examined in rat (Cruzan et al. 1998; Jersey et al. 

1978) and mouse (Cruzan et al. 2001) studies. The occupational exposure studies were considered 

adequate for derivation of a chronic-duration inhalation MRL for styrene. Further research to define the 

dose-response curve more fully and to identify a chronic inhalation NOAEL for neurological effects 

would be valuable and would help to reduce uncertainty in the MRL. Data on chronic oral exposure to 
 

 

 

 

 

 

STYRENE 133 

3. HEALTH EFFECTS 

styrene is only available through animal studies (Beliles et al. 1985; Conti et al. 1988; NCI 1979b; Quast 

et al. 1979). In these studies, the most sensitive indicator of toxicity appears to be Heinz body formation 

in red blood cells in dogs (Quast et al. 1979) and the EPA has calculated a chronic oral RfD based on this 

study (IRIS 2009). However, there is some doubt regarding the chronic oral NOAEL, and whether 

hematological effects are really more sensitive than neurological effects. Moreover, decreased survival 

has been noted in rats at exposure levels only slightly higher than the no-effect level for hematological 

effects (Conti et al. 1988). Therefore, no chronic oral MRL has been derived. Further studies on the 

effects of oral exposure, with special emphasis on neurological or neurobehavioral effects, would be 

valuable. Although chronic dermal exposure by the general public is not likely, there may be some 

potential for dermal contact with soil at hazardous waste sites. Therefore, data on long-term effects of 

dermal contact with styrene would be useful. 

Taken together, the animal and human data indicate that styrene may possibly be a weak human 

carcinogen. Although data from epidemiological studies are limited due to concurrent chemical 

exposures and small cohorts, the data are suggestive of some carcinogenic potential in humans (Antilla et 

al. 1998; Bond et al. 1992; Cheng et al. 2007; Coggon et al. 1987; Delzell et al. 1996, 2001; FrentzelBeyme et al. 1978; Gerin et al. 1998; Graff et al. 2005; Hodgson and Jones 1985; Kogevinas et al. 1993, 

1994; Kolstad et al. 1993, 1994, 1995; Macaluso et al. 1996; Matanoski and Schwartz 1987; Matanoski et 

al. 1990; McMichael et al. 1976; Meinhardt et al. 1982; Nicholson et al. 1978; Okun et al. 1985; Ott et al. 

1980; Sathiakumar et al. 2005; Wong 1990; Wong et al. 1994). Inhalation and oral exposure studies in 

rats have not found significant increases in the incidence of neoplastic tumors (Beliles et al. 1985; Conti 

et al. 1988; Cruzan et al. 1998; Jersey et al. 1978; Maltoni et al. 1979; NCI 1979b). However, inhalation 

and oral studies in mice have found significant increases in the incidence of neoplastic lung tumors 

(Cruzan et al. 2001; NCI 1979b). The available data suggest that toxicokinetic differences between rats, 

mice, and humans result in an increased sensitivity of mice. Clarification of the data is needed in several 

areas. Almost all of the available epidemiological studies involve concurrent exposures to other 

chemicals. The role of the metabolism of styrene in humans and animals needs to be clarified and the 

carcinogenic mechanisms needed to be further elucidated. Additional studies that account for these issues 

would be valuable. 

Genotoxicity. The results of genotoxicity tests for styrene both in vivo and in vitro are frequently 

conflicting, and the genotoxic potential of styrene is not clear (Andersson et al. 1980; Beliles et al. 1985; 

Hogstedt et al. 1979; Meretoja et al. 1977, 1978; Watanabe et al. 1981). The reasons for the mixed or 

conflicting genotoxicity results may be differences in the metabolism or detoxification of styrene in the 
 

 

 

 

 

 

 

 

STYRENE 134 

3. HEALTH EFFECTS 

various test systems employed. The role of the metabolite styrene oxide in genotoxicity assays on styrene 

should be fully evaluated, preferably in mammalian in vivo systems. Toxicokinetic studies evaluating the 

presence, level, and activity of styrene oxide in humans will influence the interpretation of genotoxicity 

studies on styrene and their relevance to public health. 

Reproductive Toxicity. Occupational exposure studies have examined male and female styrene 

workers to evaluate potential reproductive effects; however, most of these studies did not quantify styrene 

exposure or exposure to other compounds, thus, interpretation of results is difficult. Inconsistent results 

have been reported for spontaneous abortions with some studies reporting significant increases (Härkönen 

and Holmberg 1982; Hemminki et al. 1980; McDonald et al. 1988) and others reporting no effect 

(Härkönen and Holmberg 1982; Hemminki et al. 1980, 1984; Lindbohm et al. 1985). Oligomenorrhea 

was observed in one study of workers (Cho et al. 2001), but not in another study (Lemasters et al. 1985). 

Studies in male workers have found alterations in sperm parameters (Kolstad et al. 1999a), but no 

alterations in time-to-pregnancy (Kolstad et al. 2000; Sallmén et al. 1998) or fertility rates (Kolstad et al. 

1999c). A two-generation inhalation study (Cruzan et al. 2005b) and three-generation oral study (Beliles 

et al. 1985) in rats showed no styrene-related reproductive effects. However, testicular effects have been 

observed in an oral exposure study (Srivastava et al. 1989), but not in two inhalation studies (Cruzan et al. 

2005b; Salomaa et al. 1985). Additional reproductive data on occupationally-exposed males would be 

useful in evaluating the existing animal data that indicates altered testicular function and studies in 

females would be useful in evaluating the inconsistent findings in the existing studies. 

Developmental Toxicity. Data on the developmental effects of inhalation exposure to styrene are 

available in humans and animals. Occupational exposure studies (Ahlborg et al. 1987; Härkönen et al. 

1984; Lemasters et al. 1989) have not found increases in the occurrence of birth defects or decreases in 

birth weight. However, interpretation of the results are complicated by exposure to other chemicals and 

lack of information on exposure levels. Additional occupational studies are needed to adequately assess 

this end point. Developmental studies in animals via inhalation (Cruzan et al. 2005b; Kankaanpää et al. 

1980; Murray et al. 1978) or oral (Beliles et al. 1985) exposure have not found effects on fetal outcome, 

birth weight, or incidence of abnormalities. However, several studies have reported neurodevelopmental 

(Katakura et al. 1999, 2001; Zaidi et al. 1985) or reproductive (Srivastava et al. 1992a, 1992b) effects. 

Additional studies are needed to examine the potential effects on the nervous and reproductive systems of 

developing organisms. No studies examined the developmental toxicity of styrene following dermal 

exposure. 
 

 

 

 

 

 

 

 

 

 

STYRENE 135 

3. HEALTH EFFECTS 

Immunotoxicity. Occupational exposure studies have found alterations in lymphocyte subsets 

(Bergamaschi et al. 1995b; Biró et al. 2002), which may be indicative of reduced cell-mediated immunity 

and an impaired immune response to concanavalin (Tulinska et al. 2000). Limited data in animals 

indicate that inhalation (Ban et al. 2006) and oral (Sinitskij discussed in WHO 1983) exposure can also 

result in impaired immune response. No dermal exposure studies examining immunotoxicity were 

identified. Human and animal studies provide suggestive evidence that the immune system is a target; 

additional studies would be useful to further investigate the effect of styrene on immune function. 

Neurotoxicity. The neurotoxicity of styrene in workers in the reinforced plastic industry has been 

extensively examined (Behari et al. 1986; Calabrese et al. 1996; Campagna et al. 1995, 1996; Castillo et 

al. 2001; Checkoway et al. 1992; Cherry et al. 1980; Chia et al. 1994; Dalton et al. 2003; Edling et al. 

1993; Eguchi et al. 1995; Fallas et al. 1992; Fung and Clark 1999; Gamberale et al. 1976; Gobba et al. 

1991, 1995; Gong et al. 2002; Härkönen et al. 1984; Iregren et al. 2005; Jegaden et al. 1993; Kishi et al. 

2001; Lindstrom et al. 1976; Matikainen et al. 1993a, 1993b; Möller et al. 1990; Morata et al. 2002; 

Morioka et al. 1999; Muijser et al. 1988; Murata et al. 1991; Mutti et al. 1984a; Niklasson et al. 1993; 

Rosen et al. 1978; Seppäläinen and Härkönen 1976; Śliwińska-Kowalska et al. 2003; Štĕtkářová et al. 

1993; Triebig et al. 1985, 2001; Tsai and Chen 1996; Viaene et al. 1998, 2001; Yuasa et al. 1996). A 

variety of neurological effects have been observed in these studies including decreased color 

discrimination, slowed reaction time, altered performance on neurobehavioral tests of memory and 

learning, altered vestibular function, altered hearing, reduced nerve conduction velocity, and increased 

clinical symptoms such as dizziness, tiredness, memory loss, and feeling drunk. Additionally, several 

experimental studies have examined the effects of acute exposure on vestibular function (Ödkvist et al. 

1982; Stewart et al. 1968), clinical symptoms (Seeber et al. 2004; Ska et al. 2003; Stewart et al. 1968), 

color discrimination (Ska et al. 2003), and performance on neurobehavioral tests (Seeber et al. 2004; Ska 

et al. 2003). Animal studies have primarily focused on the damage to the organ of Corti and hearing loss 

(Campo et al. 2001; Crofton et al. 1994; Lataye et al. 2003; Loquet et al. 1999, 2000; Makitie et al. 2002; 

Pouyatos et al. 2002; Pryor et al. 1987; Yano et al. 1992), although nerve conduction velocity has also 

been examined (Kulig 1988; Yamamoto et al. 1997). The potential for neurotoxicity has not been 

examined in humans orally exposed to styrene and a limited number of end points have been examined in 

animals (Agrawal et al. 1982; Bushnell 1994; Husain et al. 1980, 1985; Khanna et al. 1994). The 

neurological effects observed in styrene workers were used as the basis of a chronic-duration inhalation 

MRL. Since this is based on a LOAEL, further studies which define the chronic NOAEL, as well as 

acute- and intermediate-duration NOAELs, would be valuable especially at levels of styrene causing 

problems with coordination and psychological function. These and other neurological effects may play a 
 

 

 

 

 

 

 

 

STYRENE 136 

3. HEALTH EFFECTS 

role in the rate of workplace accidents and the level of performance. Additional studies in mammalian 

animal models are needed to determine if styrene causes chronic damage to the central and/or peripheral 

nervous systems and to determine the associated mechanism of toxicity. Also, information is needed to 

determine if neurotoxicity is a sensitive end point from exposure to styrene via the oral route. 

Epidemiological and Human Dosimetry Studies. Numerous studies have examined the toxicity 

of styrene in workers, as discussed in other sections, most of these studies have focused on neurotoxicity 

and potential carcinogenicity of styrene. A common limitation of these studies is the poor 

characterization of exposure levels and possible exposure to other chemicals. Some studies provided no 

data on styrene exposure levels and other studies provide current exposure levels with limited or no data 

on past exposure levels. Occupational exposure and experimental studies also provide suggestive 

evidence of acute upper respiratory tract irritation and eye irritation (Carpenter et al. 1944; NIOSH 1983) 

Stewart et al. 1968) and possible endocrine effects (elevated levels of serum prolactin) (Arfini et al. 1987; 

Bergamaschi et al. 1996, 1997; Luderer et al. 2004; Mutti et al. 1984b); additional studies are needed to 

confirm the results of these studies and to establish dose-response relationships. Additionally, there are 

suggestive findings that styrene has the potential to induce reproductive effects (Cho et al. 2001; 

Härkönen and Holmberg 1982; Hemminki et al. 1980; Kolstad et al. 1999c; McDonald et al. 1988); 

however, poor characterization of styrene exposure, possible exposure to other compounds (particularly 

for the Cho et al. (2001) study), the low statistical power of the studies, and the lack of positive 

associations in the follow-up study (Hemminki et al. 1984) to the Hemminki et al. (1980) study limit the 

usefulness of the studies. Studies of males and female styrene workers examining a variety of 

reproductive end points and adequately characterized exposure would be useful. 

Biomarkers of Exposure and Effect. 

Exposure. Available studies indicate that there are good quantitative relationships between styrene 

metabolites (MA and PGA) in the urine and styrene exposure levels in humans (Bartolucci et al. 1986; 

Chua et al. 1993; Elia et al. 1980; Engstrom et al. 1976; Härkönen et al. 1978; Ong et al. 1994; Sedivec et 

al. 1984; Sollenberg et al. 1988; Symanski et al. 2001). Levels of styrene in blood have also been used as 

a biomarker of exposure (Antoine et al. 1986; Baselt et al. 1988a; Ramsey et al. 1980). 

Effect. There are currently no biomarkers specific for the effects of styrene that are not also typical of 

other central nervous system depressants. Further research is needed to evaluate potential biomarkers of 

effect in the areas of chromosome aberrations, psychomotor decrement, hepatic glutathione depletion, and 
 

 

 

 

 

 

 

 

 

 

 

 

STYRENE 137 

3. HEALTH EFFECTS 

adipose tissue retention of styrene. These potential biomarkers should be evaluated in terms of long-term 

or chronic exposure periods, and their specificity for exposure to styrene. 

Absorption, Distribution, Metabolism, and Excretion. Styrene oxide (styrene epoxide) has been 

identified as an intermediate metabolite of styrene (Drummond et al. 1989; Engstrom et al. 1976; Korn et 

al. 1984, 1987; Leibman 1975; Lof et al. 1983; Withey and Collins 1979; Young et al. 1979). However, 

styrene oxide has only been found in minute amounts in human studies (Lof et al. 1986a). The presence 

of styrene oxide, a mutagen and carcinogen, may account for some conflicting results and/or interspecies 

variation in mutagenicity tests and cancer bioassays. The role, if any, of styrene oxide in the overall 

toxicity of styrene needs to be evaluated by additional metabolism studies to confirm its presence, level, 

and duration in human tissues. The toxicokinetics of styrene exposure via inhalation are reasonably well 

defined. However, oral and dermal exposure data are needed to better characterize absorption rates and 

the elimination ratios of the metabolites (MA and PGA). 

Comparative Toxicokinetics. Interspecies variations in styrene metabolism have been established. 

Differences in the relative proportion of urinary metabolites, which is indicative of different metabolic 

pathways have been found in humans, mice, and rats. Additionally, there are differences in the kinetic 

constants for cytochrome P450 and epoxide hydrolase, which result in higher levels of reactive 

metabolites in the liver, lungs, and nasal epithelium. Also, mice appear to generate a higher proportion of 

R-styrene oxide than S-styrene oxide; the R-enantiomer is believed to be more cytotoxic. These 

metabolic differences are believed to result in mice being more sensitive than rats or humans to liver, 

lung, and nasal toxicity. Potential species differences in the neurotoxicity, the most sensitive end point in 

humans, have not been examined; if the neurological effects are due to styrene rather than one of its 

metabolites, the observed species differences may not be relevant. Efforts should continue to identify 

which animal model best approximates human metabolism of styrene. 

Methods for Reducing Toxic Effects. Recommended methods for the mitigation of acute effects 

of styrene intoxication include mechanical ventilatory support, administration of oxygen, and drug 

therapy for bronchospasm, if exposure is by inhalation (Bronstein and Currance 1988; Ellenhorn and 

Barceloux 1988). Thorough washing or flushing with water is recommended for dermal/ocular exposure. 

Supportive treatment is indicated for neurological effects of styrene exposure (Haddad and Winchester 

1990). No information was located concerning mitigation of effects of lower-level or longer-term 

exposure to styrene. Further information on techniques to mitigate such effects would be useful in 

determining the safety and effectiveness of possible methods for treating styrene-exposed populations in 
 

 

 

 

 

 

 

 

STYRENE 138 

3. HEALTH EFFECTS 

the vicinity of hazardous waste sites. This includes further studies on the mechanism(s) of styrene 

toxicity, so that methods may be developed to interfere with or block styrene's toxic actions in the body. 

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. 

No studies were identified that examined the toxicity of styrene in children or young laboratory animals. 

No consistently observed developmental effects have been reported in occupational exposure studies 

(Ahlborg et al. 1987; Härkönen et al. 1984; Lemasters et al. 1989) or in animal studies (Cruzan et al. 

2005b; Daston et al. 1991; Kankaanpää et al. 1980; Murray et al. 1978). The nervous system is the most 

sensitive target of styrene toxicity in adults. No adverse styrene-related effects were observed in 

neurobehavioral function tests in rats exposed to styrene during gestation and lactation (Cruzan et al. 

2005a); however, neurological effects have been observed in another inhalation study of rats exposed 

during gestation (Katakura et al. 2001) and in an oral gestation and lactation study (Zaidi et al. 1985). 

Possible neurological effects have not been assessed following post-weaning exposure; these data would 

be useful in evaluating whether growing children are more susceptible than adults to styrene-induced 

neurotoxicity. 

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 on styrene were identified in Federal Research in Progress database (FEDRIP 2007). 
 

 

 

 

 

STYRENE 139 

4. CHEMICAL AND PHYSICAL INFORMATION 

4.1 CHEMICAL IDENTITY 

Information regarding the chemical identity of styrene is located in Table 4-1. 

4.2 PHYSICAL AND CHEMICAL PROPERTIES 

Information regarding the physical and chemical properties of styrene is located in Table 4-2. 
STYRENE 140 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-1. Chemical Identity of Styrene 

Characteristic Information Reference 

Chemical name Styrene Verschueren 1983 

Synonym(s) cinnamene; Verschueren 1983; 

cinnamol; HSDB 2009 

ethenylbenzene; 

phenylethylene; 

styrol; 

vinylbenzene; 

Registered trade name(s) No data 

Chemical formula C8H8 Windholz 1983 

Chemical structure H IARC 1994 

C CH2 

Identification numbers: 

CAS registry 100-42-5 Sax and Lewis 1987 

NIOSH RTECS WL3675000 HSDB 2009 

EPA hazardous waste No data 

EINICS 202-851-5 ESIS 2009 

OHM/TADS 7216911 HSDB 2009 

DOT/UN/NA/IMDG shipping IMDG 3.3 HSDB 2009 

UN 2055 HSDB 2009 

HSDB 171 HSDB 2009 

NCI C02200 HSDB 2009 

CAS = Chemical Abstracts Service; DOT/UN/NA/IMDG = Department of Transportation/United Nations/North 

America/International Maritime Dangerous Goods Code; EPA = Environmental Protection Agency; ESIS = European 

chemical Substances Information System HSDB = Hazardous Substances Data Bank; NCI = National Cancer 

Institute; NIOSH = National Institute for Occupational Safety and Health; OHM/TADS = Oil and Hazardous 

Materials/Technical Assistance Data System; RTECS = Registry of Toxic Effects of Chemical Substances 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

STYRENE 141 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-2. Physical and Chemical Properties of Styrene 

Property Information Reference 

Molecular weight 104.15 O’Neil et al. 2001 

Lide 2005 

Color Colorless to yellowish Windholz 1983 

Physical state Liquid Sax and Lewis 1987 

Melting point -30.6 °C O’Neil et al. 2001 

Boiling point 145.2 °C Verschueren 2001; Weast 1985 

Density at 20 °C 0.9059 O’Neil et al. 2001 

Odor If pure, sweet and pleasant; Verschueren 2001 

commonly contains aldehydes which 

provide it with a penetrating, sharp, 

and unpleasant smell 

Odor threshold: 

Water 0.73 mg/L HSDB 2009 

0.011 mg/L Amoore and Hautala 1983 

Air 1.36 mg/m3 Amoore and Hautala 1983 

Solubility: 

Water at 15 °C 280 mg/L Verschueren 2001 

Water at 20 °C 300 mg/L 

Water at 40 °C 400 mg/L 

Organic solvents Soluble in alcohol, ether, acetone, Windholz 1983 

carbon disulfide 

Partition coefficients: 

Log Kow 2.95 Hansch et al. 1995; 

EPA 1984a 

Log Koc 2.96 Sabljic et al. 1995 

Vapor pressure at 20 °C 5 mmHg Verschueren 2001 

Henry's law constant at 25 °C 2.61x10-3 atm-m3/mol (calculated) EPA 1981 

Autoignition temperature 914 °F (490 °C) Sax and Lewis 1987 

Flashpoint 87 °F (31 °C) (closed cup) O’Neil et al. 2001; 

34.4°C (Tag open cup) Kirk-Othmer 2001 

Flammability limits No data 

0.9 (lower); 6.8 (higher) CEFIC 2008; 

1.1 (lower); 6.1 (higher) Kirk-Othmer 2001 

Conversion factors 1 mg/m3=0.23 ppm; Verschueren 2001 

1 ppm=4.33 mg/m3 

 

4. CHEMICAL AND PHYSICAL INFORMATION 

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STYRENE 142
 

 

 

 

 

 

 

 

 

 

 

 

STYRENE 143 

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

5.1 PRODUCTION 

In the United States, styrene is produced principally by the catalytic dehydrogenation of ethylbenzene. 

Hence, ethylbenzene is a common contaminant. Styrene is also produced by oxidation of ethylbenzene to 

ethylbenzene hydroperoxide, which is then reacted with propylene to produce propylene oxide and 

α-methylphenyl carbinol. The carbinol is then further dehydrated to produce styrene (Carlson and 

Erskine 1973; HSDB 2009; IARC 1979). The first route of manufacture (dehydrogenation of 

ethylbenzene) represents 90% of styrene production. The other described method is the second most 

commonly used route of styrene synthesis. Other methods of styrene production are rarely used. 

Styrene has been manufactured in the United States since 1938, with production increasing dramatically 

over the last 30 years. Since 1977, U.S. total styrene production has more than doubled. Production 

increased 16% in the decade between 1977 and 1987, but production increased >32% between 1987 and 

1999, and rose again by another 28% between the years 1999 and 2006 (HSDB 2009; SRI 2006). 

Specifically, U.S. production of styrene in 1978 was 6.8 billion pounds, and then in 1987, production was 

approximately 8 billion pounds (USITC 1987, 1988). In 1999, U.S. styrene production was over 

10 billion pounds, and in 2006, the production capacity in the United States was >13 billion pounds 

(HSDB 2009; SRI 2006). The annual U.S. styrene production capacity in 2008 was 12.2 billion pounds 

(SRI 2008). 

Information regarding the locations of the numerous styrene production facilities and the amounts of 

styrene that may be present on-site is presented in Table 5-1. Current domestic producers of styrene 

include Chevron Phillips Chemical Company LP (Aromatics and Styrenics Business Unit), St. James, 

Louisiana; Cos-Mar Company, Carville, Louisiana; the Dow Chemical Company, Freeport, Texas; 

INEOS Americas, LLC, Bayport, Texas and Texas City, Texas; LyondellBasell Industries, Channelview, 

Texas; and Westlake Styrene LP, Sulphur, Louisiana (SRI 2008). The production of styrene at these 

facilities is directed primarily for captive processes (on-site conversion to other materials) or for merchant 

sales to other entities (these include export). The information presented in Table 5-1 reflects the locations 

of these production plants, where it can be noted that the greatest production capacity occurs primarily in 

Texas and Louisiana. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

STYRENE 144 

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

Table 5-1. Facilities that Produce, Process, or Use Styrene 

Minimum Maximum 

Number of amount on site amount on site 

Statea facilities in poundsb in poundsb Activities and usesc 

AL 87 0 49,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

AR 58 100 49,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

AZ 54 0 999,999 1, 2, 3, 5, 6, 7, 8, 9, 10, 11, 12 

CA 192 0 499,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

CO 24 100 9,999,999 2, 3, 6, 7, 8, 9, 11, 12, 13 

CT 24 0 49,999,999 3, 5, 6, 7, 8, 9, 11, 12 

DE 22 100 999,999 1, 2, 3, 4, 6, 7, 8, 11, 12, 14 

FL 163 0 499,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

GA 106 0 499,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

GU 1 100 999 9 

HI 3 100 9,999 2, 3, 6, 7, 8, 10, 11 

IA 50 0 49,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 

ID 16 0 99,999 1, 2, 3, 6, 7, 8, 11, 12 

IL 111 0 499,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 

IN 169 0 99,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

KS 53 0 99,999,999 1, 2, 3, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

KY 68 0 499,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

LA 125 0 10,000,000,000 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

MA 34 0 499,999,999 2, 3, 4, 6, 7, 8, 9, 12, 13 

MD 39 100 9,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 

ME 17 100 99,999 2, 3, 6, 7, 8, 10, 11 

MI 107 0 99,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

MN 73 100 9,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 

MO 81 0 49,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 

MS 48 0 99,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 

MT 9 100 9,999,999 3, 6, 7, 8, 9, 10, 13 

NC 113 0 49,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 

ND 17 1,000 499,999,999 2, 3, 6, 7, 8, 9, 10, 11, 13 

NE 38 0 999,999 1, 2, 3, 6, 7, 8, 10, 11, 12, 13 

NH 27 100 499,999,999 2, 3, 5, 6, 7, 8, 10, 11, 12 

NJ 53 100 99,999,999 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 

NM 19 100 49,999,999 1, 2, 3, 6, 7, 8, 9, 11, 12 

NV 11 1,000 99,999,999 2, 3, 6, 7, 8, 10, 11 

NY 60 0 49,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

OH 205 0 499,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

OK 59 100 49,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

OR 57 100 49,999,999 1, 2, 3, 6, 7, 8, 9, 10, 11, 12 

PA 127 0 499,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 
 

 

 

 

 

 

 

 

 

 

 

 

 

STYRENE 145 

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

Table 5-1. Facilities that Produce, Process, or Use Styrene 

Minimum Maximum 

Number of amount on site amount on site 

Statea facilities in poundsb in poundsb Activities and usesc 

PR 29 0 9,999,999 1, 2, 3, 6, 7, 8, 10, 11, 12 

RI 31 100 999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 

SC 84 100 499,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 

SD 8 1,000 99,999 1, 2, 3, 6, 7, 8, 10, 11 

TN 105 0 499,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

TX 272 0 10,000,000,000 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

UT 42 0 99,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

VA 65 0 49,999,999 1, 2, 3, 4, 6, 7, 8, 9, 10, 11, 12 

VT 5 1,000 99,999 6, 7, 8 

WA 89 0 499,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 

WI 95 0 499,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 

WV 41 100 999,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 

WY 2 1,000 9,999 6, 8, 9 

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: TRI06 2008 (Data are from 2006) 
 

 

 

 

 

 

 

STYRENE 146 

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

5.2 IMPORT/EXPORT 

Imports of styrene have generally been <1% of U.S. domestic production volumes, with imported styrene 

amounts decreasing over the last decades, and exported amounts increasing during the same time period. 

Styrene imports were reported to be 26.4 million pounds for 1976, 320 million pounds in 1986 (Carlson 

and Erskine 1973; IARC 1979), but only 1 million pounds in 1999 (HSDB 2009). These trends indicate a 

higher capacity for domestic producers to meet industry needs. Styrene exports were <1 billion pounds in 

1978, but had exceeded 1 billion pounds by 1983. Exports have slowly increased such that recent export 

data indicate that the U.S. exports >2 billion pounds of styrene annually (HSDB 2009), also indicating 

that domestic production is more than capable to serve domestic needs. However, future styrene exports 

are forecast to drop off because of significant global oversupply, slowing economic growth, and the startup of new styrene facilities in the Middle East (Chemical Week 2008). 

5.3 USE 

Styrene is used predominantly (65% of total product) in the production of polystyrene plastics and resins 

(James and Castor 2005). In addition, fiberglass products used for boats are also made from polyester 

resins dissolved in styrene. Styrene is also used as an intermediate in the synthesis of materials used for 

ion exchange resins and to produce copolymers such as styrene-acrylonitrile (SAN) and acrylonitrilebutadiene-styrene (ABS), both representing approximately 9% of styrene use, and styrene-butadiene 

rubber (SBR), representing approximately 6% of styrene use. SBR is used for such products as car tires, 

hoses used for industrial applications, and shoes. A related polymer, styrene-butadiene latex 

(approximately 7%), is used in making carpet, coatings for paper, and as part of latex paints. SAN and 

ABS are used for materials such as piping, automotive components, refrigerator liners, plastic drinking 

glasses, and car battery enclosures. An additional 7% of styrene is formulated with unsaturated polyester 

resins in such things as boat hulls (fiberglass reinforcement materials). The remaining amounts of styrene 

produced are used for several types of applications, including less common thermoplastics and even for 

laboratory and water purification uses (ion-exchange resins) and glues and adhesives (James and Castor 

2005). Styrene copolymers are also frequently used in liquid toner for photocopiers and printers (HSDB 

2009). 

The Food and Drug Administration (FDA) permits styrene to be used as a direct additive for synthetic 

flavoring and an indirect additive in polyester resins, ion-exchange membranes, and in rubber articles (5% 

by weight maximum) intended for use with foods (HSDB 2009; IARC 1979; NIOSH 1983). 
 

STYRENE 147 

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

5.4 DISPOSAL 

Typical means of styrene disposal include absorption on vermiculite or similar material, followed by 

disposal in an EPA-permitted landfill. Incineration is also a useful disposal method, but this must be 

carefully controlled since pure styrene is highly flammable (HSDB 2009). No data were located 

regarding the quantities of styrene disposed by these means on a national level, but the state of 

Massachusetts reported that most styrene disposal occurred via incineration (95.5%), followed by smaller 

amounts being disposed of in landfills (0.5%), a slightly greater amount being subjected to solvent 

recovery (0.7%), and slightly more being transferred to waste/energy brokers (3.3%) (Keenan and 

Harriman 1993). The total amounts represented were ~250,000 pounds. Whether the data reported for 

Massachusetts are representative of the proportions disposed of by these means in other states is not 

known. 
STYRENE 148
 

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

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STYRENE 149 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.1 OVERVIEW 

Styrene has been identified in at least 251 of the 1,699 hazardous waste sites that have been proposed for 

inclusion on the EPA National Priorities List (NPL) (HazDat 2007). However, the number of sites 

evaluated for styrene is not known. The frequency of these sites can be seen in Figure 6-1. Of these sites, 

30 are located within the United States and one is located in the Commonwealth of Puerto Rico (not 

shown). 

Styrene is a widely used industrial chemical with reported atmospheric emissions of >51 million pounds 

annually in the United States (TRI06 2008). Styrene photodegrades in the atmosphere, with a half-life 

ranging between 7 and 16 hours (which are the degradation half-lives catalyzed by reactions with 

hydroxyl radical and ozone, respectively). Styrene is moderately mobile in soil and volatilizes from water 

to the atmosphere. Styrene will undergo biodegradation in most top soils and aquatic environments, but 

degradation will be much slower in environments that are anaerobic. Bioconcentration does not appear to 

be significant. 

The principal route of styrene exposure for the general population is probably by inhalation of 

contaminated indoor air. Mean indoor air levels of styrene have been reported in the range of 0.1– 

50 μg/m3

, and can be attributed to emissions from building materials, consumer products, and tobacco 

smoke. It should be pointed out that the workplace or home office may have substantially higher levels of 

airborne styrene, due to emissions from laser printers and photocopiers. General workplace styrene 

concentrations ranged from 89 to 1.5x106 μg/m3 (20–3.4x105 ppmv). The most significant exposure route 

in these settings is also likely by inhalation. The industries with the highest potential exposure are 

probably the reinforced plastics factories, boatbuilding facilities, and polystyrene factories. Exposure 

may also be high in areas near major spills. Exposure to styrene from hazardous waste sites is potentially 

important, but the magnitude of the problem is unknown. The potential for outdoor exposure to styrene is 

lower than indoor exposure, with reported mean air levels ranging from 0.28 to 20 μg/m3 (0.064– 

4.6 ppmv). 

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 
STYRENE 150 

6. POTENTIAL FOR HUMAN EXPOSURE 

Figure 6-1. Frequency of NPL Sites with Styrene Contamination 
 

 

 

 

STYRENE 151 

6. POTENTIAL FOR HUMAN EXPOSURE 

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 47.3 million pounds (21,500 metric tons) of styrene to the atmosphere from 

1,558 domestic manufacturing and processing facilities in 2006, accounted for 93% of the estimated total 

environmental releases from facilities required to report to the TRI (TRI06 2008). These releases are 

summarized in Table 6-1. 

Styrene may be emitted to the atmosphere from industrial production and usage processes, motor vehicle 

operation, combustion processes, building materials, and consumer products. Estimated atmospheric 

industrial styrene emissions reported to EPA for the 2005 TRI totaled 47.3 million pounds, with 

>38 million pounds released from point sources and >10 million pounds released as fugitive emissions 

(TRI06 2008). Styrene ranked 16th among air emissions for reported chemicals and chemical group 

compounds in the United States in 2005. Since EPA regulations that require reporting of toxic chemical 

emissions apply only to selected facilities producing and/or using substantial quantities of the chemical 

(EPA 1988a), the total air emissions of styrene are probably greater than those reported. Typical sources 

of industrial styrene emissions are those facilities producing styrene, polystyrene, other plastics, synthetic 

rubber, and resins (EPA 1975, 1987d; Graedel 1978; IARC 1979; NIOSH 1983). The number of facilities 

reporting styrene emissions to the TRI are listed in Table 6-1, along with number of reporting facilities in 

each state and Puerto Rico, and the primary routes of styrene release from those facilities. 

Styrene has been identified as a component of motor vehicle emissions from both gasoline- and dieselpowered engines (Hampton et al. 1982, 1983). Styrene emission rates ranging from 6.2 to 7.0 mg/km 
 

STYRENE 152 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-1. Releases to the Environment from Facilities that Produce, Process, or
 

Use Styrenea
 

Reported amounts released in pounds per yearb 

Total release 

On- and offStatec RFd Aire Waterf UIg Landh Otheri On-sitej Off-sitek site 

AL 37 1,493,262 501 0 4,259 0 1,493,763 4,259 1,498,021 

AR 27 656,082 0 0 32,770 1,455 656,082 34,225 690,307 

AZ 23 555,904 1,458 0 63,937 0 557,362 63,937 621,299 

CA 104 2,185,575 115 0 7,042 2,316 2,186,674 8,374 2,195,048 

CO 10 100,590 0 0 4,500 0 100,590 4,500 105,090 

CT 7 38,287 1 0 0 0 38,288 0 38,288 

DE 6 40,812 0 0 0 230 40,812 230 41,042 

FL 119 4,259,337 1 0 4,862 61,840 4,259,700 66,340 4,326,040 

GA 59 3,347,294 7 0 956 1,560 3,347,301 2,516 3,349,817 

IA 21 712,311 No data 0 4,044 253 712,311 4,297 716,608 

ID 3 166,603 No data 0 0 0 166,603 0 166,603 

IL 50 1,124,354 11 0 113,965 58 1,205,331 33,057 1,238,388 

IN 90 5,470,677 160 0 48,127 48,461 5,470,837 96,588 5,567,424 

KS 24 705,880 0 0 467 0 705,880 467 706,347 

KY 29 290,945 71 0 18,263 800 291,016 19,063 310,079 

LA 44 704,823 129 0 496,584 0 1,187,861 13,675 1,201,536 

MA 14 50,678 0 0 15,179 369 50,678 15,548 66,226 

MD 10 419,548 0 0 0 0 419,548 0 419,548 

ME 7 65,572 No data 0 0 1,747 65,572 1,747 67,319 

MI 43 1,656,863 49 0 9,627 2,638 1,656,928 12,249 1,669,177 

MN 30 1,128,972 0 0 1 1,410 1,128,972 1,411 1,130,383 

MO 31 820,328 0 0 0 1,841 820,328 1,841 822,169 

MS 13 536,877 10 0 310,794 0 536,887 310,794 847,681 

MT 3 1 No data 0 0 0 1 0 1 

NC 66 1,617,112 0 0 13,718 27,822 1,620,882 37,770 1,658,652 

ND 4 281,137 5 0 0 0 281,142 0 281,142 

NE 9 144,188 0 0 3,103 2 144,438 2,855 147,293 

NH 5 49,891 No data 0 0 0 49,891 0 49,891 

NJ 23 167,841 69 0 0 0 167,910 0 167,910 

NM 2 21,387 No data 0 6 0 21,387 6 21,393 

NV 7 47,800 0 0 1,959 0 47,800 1,959 49,759 

NY 18 99,248 360 0 83 113 99,608 196 99,804 

OH 123 1,583,501 17 0 388,345 4,834 1,583,518 393,179 1,976,697 

OK 25 574,291 0 0 110 0 574,291 110 574,401 

OR 21 901,084 0 0 3,617 0 901,084 3,617 904,701 

PA 60 1,154,378 25 0 89,876 8,555 1,154,403 98,431 1,252,834 
 

 

STYRENE 153 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-1. Releases to the Environment from Facilities that Produce, Process, or
 

Use Styrenea
 

Reported amounts released in pounds per yearb 

Total release 

On- and offStatec RFd Aire Waterf UIg Landh Otheri On-sitej Off-sitek site 

PR 5 43,422 0 0 32,400 99,360 43,422 131,760 175,182 

RI 4 61,640 No data 0 0 0 61,640 0 61,640 

SC 47 1,499,535 0 115 531,750 306 1,499,535 532,171 2,031,706 

SD 3 47,512 No data 0 0 0 47,512 0 47,512 

TN 47 4,495,679 255 0 89,127 119 4,495,934 89,246 4,585,179 

TX 166 4,271,673 754 425,575 97,903 237,905 4,698,326 335,484 5,033,810 

UT 8 45,615 No data 0 8 2 45,615 10 45,625 

VA 22 483,346 No data 0 776 0 483,346 776 484,122 

VT 1 12,441 No data 0 0 0 12,441 0 12,441 

WA 25 1,275,024 40 0 0 2,285 1,275,064 2,285 1,277,349 

WI 48 1,480,404 No data 0 30,095 16,686 1,480,404 46,781 1,527,186 

WV 14 393,651 5 0 20,828 1,000 393,736 21,748 415,484 

WY 1 14,559 No data 0 0 0 14,559 0 14,559 

Total 1,558 47,297,934 4,043 425,690 2,439,081 523,967 48,297,213 2,393,502 50,690,715 

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: TRI06 2008 (Data are from 2006) 
 

 

 

 

 

 

 

 

 

 

STYRENE 154 

6. POTENTIAL FOR HUMAN EXPOSURE 

distance for gasoline-powered vehicles and 1.4–2.1 mg/km for diesel trucks have been reported (Hampton 

et al. 1983). Styrene may also be emitted into the air by other combustion processes. Styrene has been 

identified in the stack emissions from waste incineration (Junk and Ford 1980), and Kleindienst et al. 

(1986) reported the presence of styrene in wood smoke emissions, but no quantitative data were reported. 

Emissions of styrene from building materials (carpets, floor tiles, insulation), office copiers, and 

consumer products (disinfectants, plastics, paint, cigarettes) may contribute significantly to indoor air 

pollution (Crump 1995). A styrene emission rate from glued carpet of 98 ng/minute/m2 was calculated by 

Wallace et al. (1987b), and Girman et al. (1986) identified styrene as a major emittant from adhesives 

used in the constructing and finishing of buildings. Hodgson et al. (1993) determined an average styrene 

emission rate from new carpets of 410 ng/minute/m2 over a 24-hour time period, but this was reduced to 

30 ng/minute/m2 when emissions were measured over 168 hours. Carpet cushioning material showed 

higher styrene emission rates of 2,300 ng/minute/m2 when measured over 6 hours, but this material also 

showed significantly lower emission rates of 83 ng/minute/m2 when measured over a longer span of 

96 hours (Schaeffer et al. 1996). Polystyrene products such as packaging materials, toys, housewares, and 

appliances that may contain small amounts of the monomer also contribute to air levels. The workplace 

or home office may have substantial levels of airborne styrene due to emissions from laser printers and 

photocopiers. In the case of laser printers, styrene concentrations measured in test chambers during 

printer operation were reported to be as high as 380 μg/m3 (87 ppmv) (Kagi et al. 2007). For 

photocopiers, emission rates from four different copiers averaged 3,300 μg/hour, but one copier had an 

emission rate of 12,000 μg/hour (Leovic et al. 1996). General workplace styrene concentrations ranged 

from 89 to 1.5x106 μg/m3 (20–3.4x105 ppmv). Styrene has also been detected in sidestream smoke 

emitted from cigarettes but concentrations were not reported (IARC 1979). 

6.2.2 Water 

Estimated releases of 4,043 pounds (~1.83 metric tons) of styrene to surface water from 1,558 domestic 

manufacturing and processing facilities in 2006, accounted for about 0.01% of the estimated total 

environmental releases from facilities required to report to the TRI (TRI06 2008). These releases are 

summarized in Table 6-1. 

The principal sources of styrene releases to water are industrial effluents. Styrene has been detected in 

effluents from chemical, textile, latex, and coal gasification plants (EPA 1976; Pellizzari et al. 1979). 

Styrene was also identified in one of 63 industrial effluents at a concentration of <10 μg/L (EPA 1979b). 
 

 

 

 

 

 

 

 

 

 

STYRENE 155 

6. POTENTIAL FOR HUMAN EXPOSURE 

Styrene occurred at concentrations up to 83 μg/L in coal gasification effluents (Pellizzari et al. 1979), and 

King and Sherbin (1986) reported styrene concentrations up to 970 μg/L in chemical plant effluents. The 

daily styrene loading from a single chemical plant into the St. Clair River (just south of Lake Huron on 

the Michigan/Ontario border) was estimated at 133 kg (King and Sherbin 1986). Styrene was detected 

(but not quantified) in the leachate from an industrial landfill in a study of 58 municipal and industrial 

landfill leachates (Brown and Donnelly 1988). Styrene has also been detected at trace concentrations in 

the River Elbe at two different sampling locations, with concentrations ranging from 6.1 to 46 ng/L (Gotz 

et al. 1998). 

6.2.3 Soil 

Estimated releases of 2.44 million pounds (~1,110 metric tons) of styrene to soils from 1,558 domestic 

manufacturing and processing facilities in 2006, accounted for about 5% of the estimated total 

environmental releases from facilities required to report to the TRI (TRI06 2008). An additional 

0.426 million pounds (~193 metric tons), constituting about 0.8% of the total environmental emissions, 

were released via underground injection (TRI06 2008). These releases are summarized in Table 6-1. 

Soil and sediments may become contaminated with styrene by chemical spills, landfill disposal of 

styrene-containing wastes, or discharge of styrene-contaminated water. A small amount of styrene is 

produced naturally through the activities of microorganisms, and some plants also produce styrene that 

may be released to soil. The amounts released to soil through these processes, however, are not expected 

to be significant in comparison to human activities that generate and release styrene to soil. 

6.3 ENVIRONMENTAL FATE 

6.3.1 Transport and Partitioning 

Should styrene be released to the environment, its vapor pressure indicates that it will partition to the 

atmosphere. In the atmosphere, styrene exists as a vapor. Styrene is an oily liquid that is slightly volatile; 

its vapor pressure has been determined to be approximately 5 mm Hg at 20 °C (Verschueren 2001). A 

small fraction of the styrene released to the atmosphere may dissolve into condensed water vapor such as 

clouds and raindrops. A Henry's law constant (H) is a measure of the tendency of a chemical to partition 

between its gas phase and water. A value for H has not been experimentally measured for styrene, but it 

may be estimated by dividing the vapor pressure of styrene by its solubility in water at the same 

temperature (EPA 1982a). In this case, the value of H is approximately 2.61x10-3 atm-m3

/mole at 25 °C. 
 

 

 

 

 

 

STYRENE 156 

6. POTENTIAL FOR HUMAN EXPOSURE 

Analogous air-water partition coefficients were measured at 37 °C, yielding a value of approximately 

5.4x10-1 atm-m3

/mole (Sato and Nakajima 1979). The magnitude of these values suggests that only a 

small fraction of vapor-phase styrene would dissolve into atmospheric water droplets. Physical processes 

such as precipitation and dry deposition would not be significant mechanisms for removing styrene from 

the atmosphere because of its high photochemical reactivity (EPA 1984b). 

Should styrene be released to lakes, rivers, streams, or other waterways, the magnitude of the estimated 

Henry's law constant (2.61x10-3 atm-m3

/mole, assuming a water solubility of 300 mg/L at 20 °C 

[Verschueren 2001]) and its water solubility suggest that a large fraction of the chemical dissolved in the 

water will volatilize into the atmosphere (depending on temperature gradients, relative humidity, air 

currents, and the extent of mixing of the solution). From a modeling perspective, it should be pointed out 

that the dependence of this process depends on an accurate determination of the chemical’s water 

solubility. In this case, while styrene is only sparingly soluble in water, the reported values are not 

precise, and range from 160 mg/L at 23 °C to 310 mg/L at 20 °C to 400 mg/L at 40 °C (Banerjee et al. 

1980; Valvani et al. 1981; Verschueren 2001). Therefore, estimated rates of volatilization have some 

uncertainty associated with them. Volatilization of styrene, however, has been measured in surface lake 

and distilled water samples such that different loadings of styrene were examined. When 2–10 mg of 

styrene was added to 1 L of lake water, 50% was lost to the atmosphere in 1–3 hours. For the distilled 

water, volatilization occurred more slowly, with 50% loss occurring within 6–7 hours (Fu and Alexander 

1992). The volatilization half-life of styrene in moving water that is 1 meter deep (assuming a solubility 

of 300 mg/L) may be on the order of 6 hours, based on the empirical relationship reported by Dilling 

(1977) for the volatilization of chlorinated hydrocarbons from water. The half-life of styrene in the Rhine 

River was estimated from field measurements at about 14 hours, but it was not known if the loss was due 

to volatilization, biodegradation, or photodegradation (Zoeteman et al. 1980). Volatilization from ponds 

and lakes is estimated to be slower, with half-life estimates ranging from 3 to 13 days (EPA 1984b). 

Styrene released to soils or sediments will also likely volatilize to the atmosphere, but the rate of this 

process depends on the characteristics of the soil or sediment. The extent of adsorption of sparingly 

water-soluble compounds such as styrene is often correlated with the organic carbon content of the 

adsorbent (i.e., the soil or sediment; Hassett et al. 1983). When adsorption is expressed as a function of 

organic-carbon content, an organic carbon/water partition coefficient (Koc) is generated, and may be used 

to rank the relative mobility of the chemical in soil. A Koc value for styrene has not been experimentally 

measured, but may be estimated from its solubility in water, using the empirical regression of Hassett et 

al. (1983). Assuming that the solubility of styrene is 300 mg/L, a calculated Koc value for styrene is 260. 
 

 

 

 

 

 

STYRENE 157 

6. POTENTIAL FOR HUMAN EXPOSURE 

The magnitude of this estimated Koc suggests that styrene is "moderately mobile" in soil (Roy and Griffin 

1985). In surface soils, where the amount of organic carbon will be highest, the movement of styrene will 

therefore be retarded by adsorption. In deeper subsurface environments where the amount of organic 

carbon may be lower, adsorption may not be as significant. The transport of styrene in aquifers by the 

movement of groundwater contaminant plumes has been observed (Colombani et al. 2009; Roberts et al. 

1980). Based on field measurements, the rate of movement of styrene in an aquifer was about 80 times 

slower than that of the groundwater (Roberts et al. 1980). The slower rate of movement was attributed to 

adsorption. No information was located to corroborate the estimated Koc value, and apparently, there are 

no studies in which the adsorption-desorption characteristics of styrene by soils and sediments have been 

measured. 

The octanol/water partition coefficient (Kow) reflects the partitioning of a chemical between octanol and 

water and is believed to be a good indication of the tendency for a chemical to accumulate in the fatty 

structures in plants and animal tissues (Kenaga and Goring 1980). The Kow of styrene has been measured 

to be 1,445 (Banerjee et al. 1980), 891 (log Kow=2.95) (Hansch et al. 1995), and 891 (Valvani et al. 1981), 

suggesting that styrene will partition to fat tissues. This is shown to be the case by the work of Engstrom 

et al. (1978a) and EPA (1986d). 

Even though styrene does tend to partition into fat, it does not tend to bioaccumulate to high levels, 

mainly because of its metabolism and excretion. A bioconcentration factor (BCF) relates the 

concentration of a chemical in an organism to the concentration of the chemical in the medium in which it 

is exposed. Based on the empirical regression of Kenaga (1980), the BCF for styrene is about 25. An 

experimentally-measured BCF for goldfish was 13.5 (Ogata et al. 1984). These low BCFs suggest that 

bioconcentration is not a significant fate of styrene released into the environment (EPA 1984b). No other 

measured BCFs were located to corroborate these reported values. 

6.3.2 Transformation and Degradation 

6.3.2.1 Air 

The major fate of atmospheric styrene is determined by the rate of photooxidation. Styrene may be 

transformed by direct photolysis, but the half-life of this process may be on the order of 50 years (EPA 

1984b). Kopczynski et al. (1972) found that styrene was not degraded by direct photolysis after 6 hours 

of exposure. 
 

 

 

 

 

 

 

STYRENE 158 

6. POTENTIAL FOR HUMAN EXPOSURE 

Styrene is more quickly photooxidized by ozone and hydroxyl radicals. The rate constant for the reaction 

of styrene with ozone at ambient temperatures (about 25 °C) has been measured and is approximately 

0.17–2.16x10-19 cm3

/molecule-second (Atkinson et al. 1982; EPA 1979a). Assuming that the mean 

concentration of ozone in the troposphere is 10x1012 molecules/cm3 (EPA 1980), the half-life of styrene 

would be approximately 13 hours. The rate constant for the reaction of styrene with hydroxyl radicals has 

been measured as 5.3x10-11 cm3

/molecule-second (Bignozzi et al. 1981). Assuming that the concentration 

of tropospheric hydroxyl radicals varies from 3x105 to 1x107 molecules/cm3 (Mac Leod et al. 1984), it 

follows that the atmospheric half-life of styrene would be between 0.5 and 17 hours. More recent studies 

provide a similar rate constant of 5.9x10-11 cm3

/molecule-second (Bunce and Dryfhout 1992) and 

5.8x10-12 cm3

/molecule-second (EPA 1993a), with a corresponding half-life of ~2.2 hours. Consequently, 

it is not expected that styrene will persist in the atmosphere, due to the combined and rapid effects of 

ozone- and hydroxyl radical-initiated atmospheric degradation processes. Transformation products 

resulting from such degradation processes include primarily oxygen-containing hydrocarbons such as 

phenol, phenylacetaldehyde, and phenoxy radical ( Sloane and Brudzynski 1979) or other compounds 

(Atkinson and Arey 2003), as well as other aromatic hydrocarbons such as the benzyl radical and other 

unsaturated hydrocarbons (Sloane and Brudzynski 1979). 

6.3.2.2 Water 

Little is known about abiotic transformations of styrene in water. The reaction of styrene with peroxy 

radicals appears to be too slow to be significant (EPA 1984b), and no relevant information regarding 

photochemical reactions in water was located. There is no information that styrene will hydrolyze in 

water, nor would its chemical structure suggest such potential. 

While little is known about the abiotic degradation potential of styrene in water, it has been shown to be 

biologically degraded in several types of aquatic systems including sewage treatment facilities, biofilm 

reactors, groundwater, and lakes. In sewage samples, styrene showed a range of biodegradability. In one 

study where styrene was added at a concentration of 1 mg/L, 20% of the added styrene was completely 

degraded (i.e., mineralized to CO2) within 3 days, with >60% degraded within 30 days (Fu and Alexander 

1992). In another sewage fate study, however, styrene was only slightly biodegraded; in five different 

evaluations, conducted for either 17 or 36 days, styrene degradation ranged from 6 to 23% (Pahren and 

Bloodgood 1961). Bridie et al. (1979) found that 42% of the styrene initially present degraded in 5 days 

when unadapted sewage was used as the source of microorganisms; when an adapted sewage was used, 
 

 

 

STYRENE 159 

6. POTENTIAL FOR HUMAN EXPOSURE 

80% degradation was observed. Very low concentrations of styrene (<10 μg/L) were completely 

degraded within 20 minutes in an aerobic biofilm reactor after acclimation, but the chemical was 

degraded much more slowly (~8% after 2 days) under methanogenic biofilm column conditions (Bouwer 

and McCarty 1984). When studied in groundwater, styrene biodegradation ranged between 4 and 12% 

per week (when added at 600–800 μg/L; Wilson et al. 1983) and a more recent study showed similar rates 

of degradation, with over 40% mineralization after 30 days (Fu and Alexander 1992). Styrene had a 

similar degradation potential in lake water, with ~35% degradation after 30 days (Fu and Alexander 

1992). 

6.3.2.3 Sediment and Soil 

Styrene is rapidly degraded in most soils when incubated under aerobic conditions, but it persists when 

soil conditions are anaerobic (e.g., waterlogged). Styrene was rapidly degraded when added to either a 

low organic-matter content landfill soil or a high organic-matter content loamy soil. When added at 

2 g/kg, >87% of the styrene was degraded in the landfill soil, and >95% was degraded in the loamy soil 

(measured over a period of 16 weeks; Sielicki et al. 1978). When styrene was added to the soils at higher 

concentrations (5 g/kg), degradation was slower and less was degraded, with ~60% degraded in both soils 

after a 16-week incubation. Fu and Alexander (1992) showed that styrene was biodegraded in loamy soil 

(when added at 2 mg/kg soil), with >50% degradation occurring over a 30-day incubation period, and the 

same soil in a later study showed similar amounts of degradation (40% degradation in 50 days; Fu et al. 

1994). In contrast to the findings in aerobic soils, this research group showed that styrene persisted when 

soil conditions were waterlogged and anaerobic (Fu and Alexander 1996). Other researchers, however, 

have been able to demonstrate degradation of styrene under anaerobic conditions by consortia of 

microbial cultures (Grbic-Galic et al. 1990). The relevance of these consortia studies to actual 

environmental samples is unknown. 

Several bacterial and fungal species have been isolated from soils that are capable of using styrene as a 

sole-carbon source (Braun-Lüllemann et al. 1997; Burback and Perry 1993; Hartmans 1995; Sielicki et al. 

1978; Warhurst and Fewson 1994), and these organisms degrade styrene by either side chain oxidation or 

aromatic ring attack. Initial biodegradation products included styrene oxide, 1-phenylethanol, 

2-phenylethanol, and then phenylacetaldehyde, acetophenone, and phenylethanediol, and then 

phenylacetic acid, with degradation proceeding towards normal metabolic intermediates such as 

acetaldehyde and pyruvate (Warhurst and Fewson 1994). 
 

 

 

 

 

 

 

 

 

 

STYRENE 160 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT 

Reliable evaluation of the potential for human exposure to styrene depends in part on the reliability of 

supporting analytical data from environmental samples and biological specimens. Concentrations of 

styrene 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 styrene 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 styrene in 

a variety of environmental media are detailed in Chapter 7. 

6.4.1 Air 

Styrene is a common contaminant of ambient urban air. Concentrations of styrene greater than rural air 

concentrations have been identified in urban and industrial source areas, near hazardous waste sites, in 

motor vehicle tunnels, in indoor air, and in workplace environments. A summary of monitoring data for 

these locations is presented in Table 6-2. The data suggest that indoor air concentrations of styrene can 

be considerably higher than outdoor concentrations. Cigarette smoke has also been implicated as a 

significant source of styrene in indoor air (EPA 1987e; Vainiotalo et al. 2008; Wallace et al. 1986a), as 

has the operation of photocopying machinery (Stefaniak et al. 2000; Leovic et al. 1996, 1998) and laser 

printers (Kagi et al. 2007). 

Monitoring studies in Minnesota detected styrene in over 1,400 air samples collected from a total of 

2,507 samples (there were 1,004 samples where styrene was below the detection limits) over an 8-year 

period. The average concentration detected was 0.1 μg/m3 (0.02 ppmv); the median concentration 

detected was 0.08 μg/m3 (0.02 ppmv); and the maximum detected amount was 1.49 μg/m3 (0.343 ppmv) 

(Pratt et al. 2000). Styrene monitoring in ambient air conducted in Chiba City, Japan over an 8-week 

period showed slightly higher mean concentrations, ranging from 0.11 to 0.36 μg/m3 (0.025–0.083 ppmv) 

(Uchiyama and Hasegawa 2000). 

6.4.2 Water 

Styrene is not frequently found in U.S. water supplies. Styrene was not detected in any of the 

>1,000 samples of drinking water analyzed during three federal surveys (EPA 1985a), but had been 

reported occasionally in drinking water supplies in several states (Coleman et al. 1984; EPA 1975, 1976; 

Kleopfer and Fairless 1972; Kool et al. 1982; Sanjivamurthy 1978) well water (EPA 1985b; Krill and 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

STYRENE 161 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-2. Styrene Concentrations in Representative Air Samples 

Concentration (μg/m3) 

Location Maximum Mean References 

Indoor 

Indoors, unspecified 6,500 0.4–8.9 EPA 1987e, 1988c; Fishbein 

0.3–50 1992; Sakaguchi and Akabayashi 

2003; Shields and Weschler 

1992; Wallace et al. 1986a 

New homes 14.3 0.9–2.6 Hodgson et al. 2000 

Remodeled buildings 167 0.1–10.1 Rothweiler et al. 1992; Zabiegala 

1999 

Workplaces 4.5x106 <1–1.5x106 Bartolucci et al. 1986; Cocheo et 

al. 1983; Correa et al. 2004; 

Fishbein 1992; Kagi et al. 2007; 

NIOSH 1983 

Photocopy centers 12,000a; 7,000a; Stefaniak et al. 2000; Leovic et al. 

220b 89b 1996, 1998 

Restaurants 3.3 1.6 Vainiotalo et al. 2008 

Outdoor 

Rural/suburban 53 0.28–0.34c; 0.43 EPA 1988c; Graedel 1978; Islam 

and Stancheva 1999; Kinney et 

al. 2002 

Urban 2,500 0.29–3.8; 20 EPA 1987e, 1988c; Fishbein 

1992; Grosjean and Fung 1984; 

Grosjean et al. 1998; Harkov et 

al. 1985; Wallace et al. 1986b 

Industrial source areas 25 1.3c–2.1 EPA 1978, 1983, 1988c 

Municipal waste sites 6,100 No data Assmuth and Kalevi 1992; Eitzer 

1995 

Hazardous waste sites 65 1.1–6.4 Harkov et al. 1985; La Regina 

and Bozzelli 1986 

Tunnels 46 1.1–6.6d Hampton et al. 1983; Zielinska et 

al. 1996 

a

Value provided is the emission rate, as μg/hour; the emission rate was measured during operation of copier in test
 

chambers.
 b

Value provided is the emission rate, as μg/hour; the emission rate was measured during the idle phase of copier
 

operation in test chambers.
 c

Median value
 d

Range of values, no mean given.
 
 

 

 

 

 

 

STYRENE 162 

6. POTENTIAL FOR HUMAN EXPOSURE 

Sonzogni 1986), river water (EPA 1976; Sheldon and Hites 1978), and Lake Erie (Konasewich et al. 

1978). Quantitative data were not available in these reports. A more recent survey provided by the EPA 

National Contaminant Occurrence Database (EPA 2006) noted that styrene was detected rarely in 

groundwater, where it was detected only 295 times out of over 174,000 analyses (<0.2% of the samples); 

detected concentrations ranged from <10 to 40 μg/L. Styrene concentrations in raw and treated waters 

ranged from 0.1 to ≥1.0 μg/L in an evaluation of organic compounds in Canadian water supplies at nine 

municipalities along the Great Lakes (Otson 1987). Styrene was rarely detected in aquifer materials in a 

large evaluation of U.S. groundwater and wells conducted by the U.S. Geological Survey (USGS). For 

>3,400 test evaluations of aquifer materials, there was a very low frequency of detections, with the 

median concentration being 0.015 μg/L. It was detected less frequently and also at low concentrations in 

domestic wells (0.014 μg/L), and at slightly higher concentrations in public wells (median=0.13 μg/L) 

(USGS 2006). 

Other bodies of water—those potentially highly contaminated and those that are used for direct 

ingestion—likewise do not usually contain styrene. Styrene is not commonly detected in groundwater 

even near superfund sites, and was not found in a drinking water evaluation of public water sources in 

Torino, Italy (Canter and Sabatini 1994; Zelano et al. 1998). In a study of wells near a superfund site in 

Florida, styrene was detected at a very low concentration (the maximum detected concentration was 

6.3 μg/L) near the site, but it was not detected in any treated water effluents (Canter and Sabatini 1994). 

Squillace et al. (1999) surveyed a vast number of drinking water wells in the United States over a 

10-year period. Styrene was detected in <1% of the 2,900 surveyed urban and suburban wells between 

1985 and 1995, and the concentrations detected were >2 orders of magnitude lower than the health 

advisory level. Styrene was only detected in rural wells, not in urban ones. Finally, Zelano et al. 

(1998) did not report the detection of any styrene in an evaluation of 21 public drinking water fountains 

in Torino, Italy. 

6.4.3 Sediment and Soil 

Limited data were located regarding estimation of styrene in sediments and soils (see Section 6.2.3). 

Water and sediment samples from the Lower Tennessee River were evaluated for styrene, and low 

concentrations (4.2 ppb) were found (Goodley and Gordon 1976). 
 

 

 

 

 

 

 

 

 

 

STYRENE 163 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.4.4 Other Environmental Media 

Styrene is a natural component of many foods; however, most styrene associated with food is the result of 

packaging of the food material in polystyrene containers. Styrene has been found as a natural component 

of roasted filberts, dried legumes, fried chicken, cooked pork, roasted beef, mussels, clams, eggs, 

nectarines, and Beaufort cheese (Dumont and Adda 1978; Kinlin et al. 1972; Lovegren et al. 1979; 

Takeoko et al. 1988; Tang et al. 1983, 2000), but detected concentrations were often very low (Tang et al. 

2000), except for turkey sausage, where detected levels were 100 ppb, and in some cheeses, where 

concentrations detected were up to 5,000 ppb (Tang et al. 2000). In contrast, styrene is a natural 

component of cinnamon, with concentrations up to 40,000 ppb (Tang et al. 2000). Data on styrene levels 

from an FDA monitoring study (1996–2000) of volatile organic compounds in food items are presented in 

Table 6-3 (Fleming-Jones and Smith 2003). 

Styrene may enter packaged foods by migration from polystyrene food containers and packaging 

materials, with concentrations ranging from <100 to >3,000 ppm, but common levels being much lower 

(5–30 ppb) (EPA 1985a; Tang et al. 2000). Concentrations of styrene measured in yogurt packaged in 

polystyrene containers ranged from 5.5 to 150 ppb (Withey 1976). Mean levels of styrene in foods 

packaged in plastic in the United Kingdom ranged from <1 to 180 ppb (Gilbert and Startin 1983). Similar 

concentrations of styrene were detected in other dairy products packaged in polystyrene containers (IARC 

1979). The rate of styrene migration into food is mainly a function of the diffusion coefficient of the 

monomer in the polymer and of the lipophilicity of the food (Till et al. 1987). For example, 4–6% of the 

free monomer in polystyrene packaging migrated into corn oil or sunflower oil within 10 days, while only 

0.3–0.6% migrated into milk, beef, or water. Similarly, migration of styrene from foam cups into liquids 

such as water, tea, or coffee was about 8 ng/cm2

, while migration into 8% ethanol (as might be 

encountered in wine or other alcoholic drinks) was 36 ng/cm2 (Varner and Breder 1981). However, 

Withey and Collins (1978) found no clear relationship between the styrene monomer content of 

packaging material (which varied widely) and the amount leached into food after comparable residence 

times. Levels of styrene ranged from 0.50 to 46.40 ppb in bottled water stored in 200–250 mL 

polystyrene containers (Al-Mudhaf et al. 2009). Concentrations in the water increased with time, 

indicating that the source was migration from the container walls. These authors did not detect styrene in 

bottled water stored in polyethylene terephthalate (PET) containers. 

Styrene has been identified as a component of cigarette smoke (EPA 1984b; Vainiotalo et al. 2008) and 

has been detected in concentrations of 18 μg/cigarette in the smoke of cigarettes made in the United 
 

STYRENE 164 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-3. Styrene Levels in Food Items 

Food Number of detections Minimum (ppb) Maximum (ppb) 

American cheese 4 2 11 

Cheddar cheese 3 4 70 

Mixed cuts 14 21 104 

Ground beef 6 4 13 

Pork bacon 7 6 85 

Cream cheese 2 2 3 

Frankfurters, beef 8 4 77 

Chocolate cake with icing 12 7 57 

Tuna canned in oil 1 2 2 

Fruit flavored cereal 3 2 10 

Eggs, scrambled 6 5 10 

Peanut butter 13 16 38 

Avocado, raw 8 3 550 

Popcorn, popped in oil 3 2 2 

Blueberry muffin 10 8 141 

Strawberries, raw 9 12 350 

Orange, raw 2 2 3 

Coleslaw with dressing 1 2 2 

Sweet roll/Danish 13 13 91 

Potato chops 6 2 16 

Popsicle 3 4 11 

Quarter pound hamburger, cooked 6 4 27 

Margarine 10 9 20 

Sandwich cookies 14 15 165 

Butter 12 11 28 

Chocolate chip cookies 12 15 111 

Sour cream 3 5 30 

Apple pie, fresh/frozen 9 10 40 

Chicken nuggets 12 10 66 

Graham crackers 6 4 21 

French fries 12 8 68 

Cheeseburger, quarter pound 5 5 22 

Cheese pizza 6 3 23 

Bologna 7 2 78 

Cheese and pepperoni pizza 7 8 20 

Olive/safflower oil 11 3 54 

Sugar cookies 14 24 142 

Cake doughnuts with icing 10 6 45 

Source: Fleming-Jones and Smith (2003). 
 

 

 

 

 

 

 

 

 

 

 

STYRENE 165 

6. POTENTIAL FOR HUMAN EXPOSURE 

States (IARC 1979). Indoor air concentrations of styrene may be significantly higher in homes of 

smokers than nonsmokers (EPA 1987e). 

6.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE 

Exposure to styrene may occur by inhalation, ingestion, or dermal absorption. The most likely mode of 

exposure of the general population to styrene is by inhalation of indoor air (EPA 1985a). Based on the 

EPA (1989e) estimate that the average person spends 20.4 hours/day indoors (inhaling about 17 m3 of air 

during that time based on an air inhalation rate of 20 m3

/day) and the range of mean indoor air 

concentrations presented in Table 6-2, typical indoor exposure levels to styrene may range from 1.7 to 

850 μg/day. Additional exposures may occur from inhalation of outdoor air and ingestion of food that 

was stored in polystyrene containers. Vitrac and Leblanc (2007) estimated a median styrene intake 

ranging from 1 to 35 μg/day per person for household exposures resulting from migration of this 

substance from food packaging. Based on estimated food consumption rates, Tang et al. (2000) reported 

an estimated annual general population exposure to styrene ranging from 0.8 to 4.5 mg/person from food. 

Outdoor air concentrations are likely to be lower in rural than urban areas and are likely to be small 

compared to indoor air concentrations. Exposure from municipal drinking water is probably insignificant. 

However, groundwater at hazardous waste sites where styrene has been detected may provide significant 

exposure to styrene if used as a local water supply. 

The exposure of the population to styrene varies significantly from the typical to the worst-case scenario. 

The daily general population exposure to styrene via food has been estimated at 0.2–1.2 μg/person and the 

exposure via inhalation has been estimated at 18–54 μg/person, with a total estimated exposure ranging 

from 18.2 to 55.2 μg/day. This is equivalent to 6.7–20.2 mg/year. Therefore, the primary route of 

exposure for the general population is via inhalation (Tang et al. 2000). Worst-case exposure estimates, 

on the other hand, are 0–0.5 μg/day from drinking water, 30 μg/day from food, and 65,000 μg/day from 

air (EPA 1985a). These estimates are based on the highest levels estimated or monitored and, therefore, 

reflect the highest potential exposure rather than typical exposure for the general population. 

Exposure of the general population to styrene is confirmed by human monitoring data. Styrene has been 

identified in adipose tissue at concentrations of 8–350 ng/g (EPA 1986d), in blood at a mean 

concentration of 0.4 μg/L (Antoine et al. 1986), and in exhaled breath at mean concentrations of 0.7– 

1.6 μg/m3 (EPA 1987e). 
 

 

 

 

 

 

 

 

 

STYRENE 166 

6. POTENTIAL FOR HUMAN EXPOSURE 

A large number of workers are potentially exposed to styrene. NIOSH estimates that approximately 

300,000 workers at 22,000 facilities may be exposed to styrene (NIOSH 1990); about 30,000 of these on 

a full-time basis (NIOSH 1983) and about 86,000 are females. The highest potential exposure occurs in 

the reinforced-plastics industry, where workers may be exposed to high air concentrations and also have 

dermal exposure to liquid styrene or resins (Dalton et al. 2007; Fustinoni et al. 2008; Lemasters et al. 

1985; NIOSH 1983; Rihs et al. 2008; Sato et al. 2009; Triebig et al. 2008; Van Rooij et al. 2008). 

Hemminki and Vianio (1984) estimated that heavily exposed workers in this industry in Finland might be 

exposed to up to 3 g of styrene per day. Van Rooij et al. (2008) estimated that styrene levels ranged from 

30 to 222 mg/m3 in the breathing zone of European open-mold process workers in 2003. Table 6-4 lists 

levels of styrene measured in the blood, urine, and surrounding air of reinforced plastic workers. Urinary 

levels of styrene metabolites are also included. Significant occupational exposures may also occur in 

other industrial settings, including styrene polymerization, rubber manufacturing, and styrene-polyester 

resin facilities (Engstrom et al. 1978b; NIOSH 1983; Rappaport and Fraser 1977) as well as in photocopy 

centers or facilities (Leovic et al. 1996, 1998; Stefaniak et al. 2000). Fustinoni et al. (2008) found that 

concentrations of styrene and its metabolites measured in the urine of 13 varnish workers were 

comparable to those measured in fiberglass reinforced plastic workers. 

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). 

Children can be exposed to styrene at home by inhalation of contaminated air and by food consumption. 

Inhalation-based exposures may occur in both urban and rural home environments, both of which may be 

contaminated by vehicular and industrial emissions. In addition, exposure to tobacco smoke may provide 
 

 

 

 

 

 

STYRENE 167 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-4. Concentrations of Styrene in the Surrounding Air, Blood, and Urine of
 

Reinforced Plastics Workers, Including Urinary Concentrations of the Styrene 

Metabolites, MA and PGA
 

Styrene MA PGA 

Urine Urine 

Air Blood Urine (mg/g (mg/g 

Occupation (ppm) (μg/L) (μg/L) creatinine) creatinine) Reference 

Boat building (n=248) Triebig et al. 2008 

Mean <10– 53.9– – 40.7– 10.6– 

40a 108 742 228 

Boat building (n=67) Sato et al. 2009 

Mean 51.7 – 47.0 300 120 

Minimum 0.3 – 5.2 0.00 0.00 

Maximum 133.5 – 189.2 1.81 0.48 

Boat building (n=88) Rihs et al. 2008 

Mean 55.1– 203.1– – – 83.8– 

82.0 264.2 190.0 

Minimum 0.2 55.8 – – 24.3 

Maximum 690.7 662.0 – – 591.3 

Unspecified reinforced Fustinoni et al. 

plastics (n=8) 2008 

Mean 4.20 – 1.9–7.5 32.29– 50.05– 

148.13 77.97 

Minimum 0.53 – 1.1 13.04 17.26 

Maximum 21.57 – 29.7 515.12 248.99 

Boat building (n=30) Dalton et al. 2007 

Mean 0.6–22a – – –b –b 

a

Levels were calculated based on urinary levels of MA+PGA.

b

Mean concentrations ranging from 10 to 463 mg/g creatinine were reported for the sum of MA+PGA in urine.
 

– = not reported; MA = mandelic acid; PGA = phenylglyoxylic acid 
 

 

 

 

 

 

 

STYRENE 168 

6. POTENTIAL FOR HUMAN EXPOSURE 

another route of styrene exposure, especially in homes where one or both parents, any siblings, or other 

relatives smoke. Children may be also be exposed to higher levels of styrene indoors at home during 

painting of indoor rooms, especially during winter months (such as over winter school vacations) when 

the child stays indoors more and during which time, windows may not be opened. 

From a food-based exposure perspective, infants may be exposed to styrene from consuming food items 

such as those listed in Table 6-3. In addition, it is possible that exposure may also result from 

consumption of infant formula or from nursing practices. In the 5-year FDA study on volatile organic 

compounds in foods (Fleming-Jones and Smith 2003), soy- and milk-based infant formula was included 

in the study; however, the results for styrene were not reported. Baby foods and infant formula are often 

stored in polystyrene containers and the migration of low levels of non polymerized styrene into food 

items from polystyrene containers has been demonstrated (EPA 1985a; Tang et al. 2000). In a study on 

chemicals in mother’s milk, styrene was identified, but not quantified, in 8 out of 12 samples of mother’s 

milk samples collected from mothers living in four U.S. urban areas (Pellizzari et al. 1982). Duffy and 

Gibney (2007) estimated the styrene exposure of Irish children between the ages of 5 and 12 years as a 

result of the migration of styrene from food packaging. The calculated mean styrene intake was 

0.122 μg/kg body weight-day when using 90th percentile migration values and 0.169 μg/kg when using 

maximum migration values. The authors note that these values are well below the provisional maximum 

tolerable daily intake of 40 μg/kg body weight-day established by the Joint FAO/WHO Expert Committee 

on Food Additives. Although children are exposed to styrene from the oral routes mentioned above, it 

has been estimated that >90% of human exposure to styrene arises due to inhalation routes (FlemingJones and Smith 2003; Tang et al. 2000). 

Aside from food-related intake, children’s exposure to styrene may differ from exposures to adults, 

especially during school, home, or play activities that may expose the children to styrene sources. For 

example, for elementary aged children (grades 2, 3, 4, and 5) attending inner city schools in Minneapolis, 

it was found that the lowest exposure to styrene occurred either outdoors or in school, and the highest 

exposure occurred at home. The latter can be substantially influenced (increased) if smoking occurs in 

the home. Exposures to styrene while outside, in either winter or spring, were very low (winter: 

0.0 μg/m3

; spring: 0.1 μg/m3), whereas exposures were much higher at school (winter: 31.3 μg/m3; 

spring: 39.7 μg/m3

), but were almost three times higher at home (winter: 91.9 μg/m3; spring: 91.9 μg/m3) 

(Adgate et al. 2004). These exposures led to blood level concentrations of styrene that were generally 

twice as high as the general population (Sexton et al. 2005). 
 

 

 

 

 

 

STYRENE 169 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.7 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES 

People working in various styrene industries are likely to have the highest exposures to styrene. Lower 

levels may be encountered near industrial facilities or hazardous waste sites emitting styrene to outdoor 

air. High indoor styrene concentrations in the home may be due to emissions from building materials, 

consumer products, tobacco smoke, photocopiers and laser printers. Smokers and those eating a high 

proportion of foods packaged in polystyrene may also have above average exposure to styrene, with the 

amounts estimated by smoking (100 μg from 20 cigarettes) more than doubling the normal estimated 

exposure to styrene (Tang et al. 2000). In addition, workers with long-term employment at photocopy 

centers may also be exposed to high concentrations of styrene. 

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 styrene 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 styrene. 

The following categories of possible data needs have been identified by a joint team of scientists from 

ATSDR, NTP, and EPA. They are defined as substance-specific informational needs that if met would 

reduce the uncertainties of human health assessment. This definition should not be interpreted to mean 

that all data needs discussed in this section must be filled. In the future, the identified data needs will be 

evaluated and prioritized, and a substance-specific research agenda will be proposed. 

6.8.1 Identification of Data Needs 

Physical and Chemical Properties. The solubility of an organic compound in water is indicative 

of how that chemical will partition between water, soil, and organisms (Banerjee et al. 1980; Hassett et al. 

1983; Valvani et al. 1981). Clarification of the exact solubility of styrene in water would be helpful 

because a range of values is currently reported (Table 4-2). The Henry's law constant and Koc value for 

styrene need to be verified experimentally to provide more accurate predictions of air-water and soilwater partitioning. 
 

 

 

 

 

 

 

STYRENE 170 

6. POTENTIAL FOR HUMAN EXPOSURE 

Production, Import/Export, Use, Release, and Disposal. According to the Emergency 

Planning and Community Right-to-Know Act of 1986, 42 U.S.C. Section 11023, industries are required 

to submit substance release and off-site transfer information to the EPA. The TRI, which contains this 

information for 2005, became available in May of 2007. This database is updated yearly and should 

provide a list of industrial production facilities and emissions. 

Substantial quantities of styrene are currently produced and used in the United States (Heylin 1989; 

HSDB 2009; SRI 1989; USITC 1988). Production and import quantities, producers, and uses are well 

documented, with 4.7x1012 g produced in 2000 (HSDB 2009), representing a slight increase in 

U.S. production since 1997 (3.12x1012 g). The United States has imported less styrene over the last 

several decades, with amounts decreasing more than an order of magnitude, from 1.4x1010 g imported in 

1978 to 5.7x108 g being imported in 2001 (HSDB 2009). Interestingly, styrene exports increased from 

3.6x1010 g in 1978 (representing 1% of total U.S. production) to >1.2x1012 g exported in 

2001 (representing >26% of total U.S. production) (HSDB 2009). 

Quantities of styrene disposed of by various disposal methods, other than those reported to the TRI, are 

not known. Styrene releases into water are regulated by EPA, but styrene is not listed as a hazardous 

waste constituent and, therefore, land disposal restrictions do not apply to this compound. Additional 

information on disposal methods used for styrene and styrene-containing products and the quantities 

disposed of by each method would help to better characterize the potential for human exposure to this 

compound from disposal at waste sites or other locations. 

Environmental Fate. Styrene will partition among the environmental media, with a tendency to 

volatilize from water to air and to adsorb to soils (EPA 1984b; Roberts et al. 1980; Sato and Nakajima 

1979). However, data on styrene volatilization from water and confirmation of the estimated Koc value by 

adsorption/desorption data would be useful to estimate more accurately the tendency of styrene to 

partition to air and soil. Confirmation of the Koc would also provide a more reliable basis for estimating 

the mobility of styrene in the various types of soil. 

Although the reaction mechanisms of styrene transformations in the atmosphere are fairly well 

understood (Atkinson et al. 1982; Bignozzi et al. 1981; EPA 1979a; Sloane and Brudzynski 1979), more 

information regarding the environmental fates of the transformation products would allow a more 

accurate prediction of the atmospheric fate of this compound. Biodegradation data are available for 

styrene under both aerobic and anaerobic conditions (Bridie et al. 1979; Grbic-Galic et al. 1990). 
 

 

 

 

 

 

STYRENE 171 

6. POTENTIAL FOR HUMAN EXPOSURE 

Bioavailability from Environmental Media. Styrene is known to be absorbed following inhalation, 

oral, and dermal contact (Dutkiewicz and Tyras 1968; Engstrom et al. 1978a, 1978b; Ramsey and 

Andersen 1984; Ramsey and Young 1978; Withey 1976; Withey and Collins 1979). Absorption rates via 

inhalation are known (Withey and Collins 1978). Additional data are needed to evaluate absorption rates 

following oral and dermal exposure. It is believed that absorption of styrene from the gut is believed to 

be generally rapid and therefore, contact with styrene contaminated food, soil, or water will probably also 

result in significant absorption. However, this may depend on the medium in which it is contained. 

Food Chain Bioaccumulation. Bioconcentration of styrene in aquatic organisms is not likely to be 

significant, based on both a measured BCF for a single goldfish species (BCF=13.5; Ogata et al. 1984) 

and an estimated BCF (EPA 1984b; Kenaga 1980; Ogata et al. 1984). No data on biomagnification of 

styrene in the food chain were located. Since significant bioaccumulation is unlikely, this lack of data 

may not be a major limitation. No data needs are identified at this time. 

Exposure Levels in Environmental Media. Reliable monitoring data for the levels of styrene in 

contaminated media at hazardous waste sites are needed so that the information obtained on levels of 

styrene in the environment can be used in combination with the known body burden of styrene to assess 

the potential risk of adverse health effects in populations living in the vicinity of hazardous waste sites. 

Monitoring data for styrene in environmental compartments are extensive, and historical and recent data 

are available for air (EPA 1987e, 1988c; Uchiyama and Hasegawa 2000), groundwater (Canter and 

Sabatini 1994; Squillace et al. 1999), and rivers (Gotz et al. 1998; Rathbun 2000). Additional data on 

styrene levels in water and soil, especially in the vicinity of hazardous waste sites, would be useful in 

assessing the potential for human exposure. Estimates of human intake from food, air, water, and soil 

have been made (EPA 1985a; Tang et al. 2000) and will undoubtedly be revised as additional data 

become available. 

Exposure Levels in Humans. Styrene has been detected in human blood, breath, milk, and adipose 

tissue of the general population (Antoine et al. 1986; EPA 1986d, 1987e; Pellizzari et al. 1982) and 

metabolites of styrene have been detected in urine of workers exposed to styrene (Elia et al. 1980; 

Sollenberg et al. 1988). However, data generated by biological monitoring of populations in the vicinity 

of waste sites with the most sensitive methods (Section 7.1) would be useful in assessing the magnitude 

of human exposures from this source. 
 

 

 

 

 

STYRENE 172 

6. POTENTIAL FOR HUMAN EXPOSURE 

This information is necessary for assessing the need to conduct health studies on these populations. 

Exposures of Children. Additional studies on the exposure of children to styrene would improve 

understanding of any mechanisms and pathways for styrene exposure and subsequent effects on this 

subpopulation. The exposure study report by Adgate et al. (2004) and the corresponding blood level 

study by Sexton et al. (2005) provide a good understanding for styrene exposures and uptake in one 

metropolitan area in the Midwestern United States, but additional reports investigating exposures and 

uptake, for example, in other climates, would be beneficial. 

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 styrene 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 

No current ongoing studies located in the Federal Research in Progress (FEDRIP) database were related 

to the potential for human exposure. The Computer Retrieval of Information on Scientific Projects 

(CRISP 2007) National Institutes of Health database identified one study. Scott Ensign of Utah State 

University proposed to investigate microbial pathways of short-chain hydrocarbon metabolism and the 

properties of the enzymes, cofactors, and regulatory elements associated with these pathways. The work 

will be sponsored by the National Institutes of Health/National Institute of General Medical Sciences and 

will investigate the central roles of carboxylation and novel cofactors/enzymes in bacterial 

hydrocarbon/epoxide/ketone metabolism of these chemicals, including styrene, by pursuing the 

biochemical, structural, and genetic characterization of these processes (CRISP 2007). 

As part of the Third National Health and Nutrition Evaluation Survey (NHANES III), the Environmental 

Health Laboratory Sciences Division of the National Center for Environmental Health, Centers for 
 

STYRENE 173 

6. POTENTIAL FOR HUMAN EXPOSURE 

Disease Control and Prevention, will be analyzing human blood samples for styrene and other volatile 

organic compounds. These data will give an indication of the frequency of occurrence and background 

levels of these compounds in the general population. 
STYRENE 174
 

6. POTENTIAL FOR HUMAN EXPOSURE 

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STYRENE 175 

7. ANALYTICAL METHODS 

The purpose of this chapter is to describe the analytical methods that are available for detecting, 

measuring, and/or monitoring styrene, its metabolites, and other biomarkers of exposure and effect to 

styrene. 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. 

As a volatile material, styrene is readily determined by gas chromatographic (GC) analysis. As a 

hydrocarbon, styrene is detected very sensitively by flame ionization detection (FID); its aromatic nature 

enables some selectivity by photoionization detection (PID); and it can be specifically identified by mass 

spectrometry (MS). Styrene is usually collected from the gas phase or from vapor evolved from the 

sample matrix on a column of solid sorbent, such as Tenax®. Cryogenic (low temperature) collection and 

sorption in organic liquids are also possible. 

Capillary gas chromatography, also known broadly as high-resolution gas chromatography (HRGC), has 

greatly facilitated the analysis of compounds such as styrene that can be measured by gas chromatography 

and has resulted in vast improvements in resolution and sensitivity. It has made the choice of a stationary 

phase less important than is the case with the use of packed columns. The instrumental capability to 

separate volatile analytes by HRGC is, for the most part, no longer the limiting factor in their analysis. 

The specific analytical methods used to quantify styrene in biological and environmental media samples 

are summarized below. 

7.1 BIOLOGICAL MATERIALS 

Methods have been described for the determination of styrene in expired air (Kneip and Crable 1988a; 

Stewart et al. 1968; Wallace and Pellizzari 1995; Wallace et al. 1996), blood (Antoine et al. 1986; Ashley 

et al. 1992; Bartolucci et al. 1986; Chambers et al. 2006; Guillemin and Berode 1988; Withey and Collins 

1977), urine (Dolara et al. 1984; Ghittori et al. 1987; Pezzagno et al. 1985), adipose tissue (Engstrom et 
 

 

 

 

 

 

 

 

 

STYRENE 176 

7. ANALYTICAL METHODS 

al. 1978a), and other tissues (heart, lungs, liver, spleen, kidney, brain) (Withey and Collins 1977) 

(Table 7-1). These methods generally require styrene release from the sample matrix and collection on a 

column of solid sorbent or collection as headspace gas; more recent methods permit the exhaled breath to 

be delivered directly, via a breath interface, to the mass spectrometer (Wallace et al. 1996). Cryogenic 

collection is also possible (Romieu et al. 1999). Of the available methods for detecting styrene, FID is the 

most sensitive, and MS is the most specific, the latter of which can be made more sensitive by tandem MS 

approaches (MS/MS) (Wallace et al. 1996). Levels of detection are in the low parts per billion range for 

breath samples (Stewart et al. 1968; Wallace et al. 1996) and parts per trillion range for blood samples 

(Ashley et al. 1992; Chambers et al. 2006). 

The major metabolites of styrene in humans are mandelic acid (MA) and phenylglyoxylic acid (PGA). 

Detection of these metabolites in urine is the most commonly performed procedure as an indicator of 

exposure to styrene. Procedures have been described for their measurement in urine (Baselt 1988a; 

Dolara et al. 1984; Engstrom et al. 1976; Kneip and Crable 1988b, 1988c; Korn et al. 1984; Pezzagno et 

al. 1985; Sedivec et al. 1984; Sollenberg et al. 1988). Generally, these styrene metabolites are converted 

to volatile derivatives and measured gas chromatographically or determined directly by high performance 

liquid chromatography (HPLC). Two other styrene metabolites that may result from exposure to styrene 

are 4-vinylphenol (Pfaffli et al. 1981) and styrene glycol (phenyl ethylene glycol) (Guillemin and Berode 

1988), but methods for the detection of these metabolites in biological materials have not been worked 

out in detail. Sensitive methods are also available for measuring styrene oxide in blood (Kessler et al. 

1990; Langvardt and Nolan 1991), although these techniques are probably more useful in research on 

styrene toxicity than in detecting or quantifying styrene exposure. 

Methods for detection of styrene and its metabolites in biological materials are summarized in Table 7-1. 

7.2 ENVIRONMENTAL SAMPLES 

Styrene determined in environmental samples is usually collected on solid sorbents (from air; Zielinska et 

al. 1996) or on solid sorbents after purging in a gas stream (water, soil, solid waste samples; Miermans et 

al. 2000)). Styrene from such samples is measured very sensitively by GC/FID and very specifically by 

GC/MS. Methods for the determination of styrene in environmental samples have been standardized by 

the American Society for Testing and Materials (ASTM 1988a, 1988b), EPA (1986a, 1986b, 1989c, 

1989d, 2003), and NIOSH (1984). Relatively low detection limits can be achieved for the determination 

of styrene in environmental samples and the accuracy appears to be acceptable for those limited cases in 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

STYRENE 177 

7. ANALYTICAL METHODS 

Table 7-1. Analytical Methods for Determining Styrene in Biological Materials 

Sample matrix Preparation method 

Analytical 

method 

Sample 

detection 

limit 

Percent 

recovery Reference 

Styrene analyte 

Adipose tissue Evaporation into nitrogen, 

collection as vapor 

GC No data No data Engstrom et al. 

1978a 

Breatha Collection in Saran bag GC/FID 0.05 ppm No data Stewart et al. 

1968 

Breath Sorption onto silicagel, 

desorption into headspace 

GC 0.1 ppm No data Kneip and Crable 

1988a 

Breath Collection in Tedlar bag, 

followed by sorption of 

VOCs (including styrene) 

onto Tenax 

GC/MS Low ppb No data Wallace et al. 

1996 

Breath Collection onto personal 

monitoring badge, followed 

by solvent extraction 

GC/FID 0.9 ppbb No data Romieu et al. 

1999 

Blood Purge at 40–50 °C with 

helium, collection on 

Tenax-GC/silica 

GC/MS No data CV<5% Antoine et al. 

1986 

Blood Headspace analysis GC/FID No data No data Bartolucci et al. 

1986 

Blood Collection in vacutainer GC No data No data Guillemin and 

with EDTA as Berode 1988 

anticoagulant, headspace 

analysis 

Blood Headspace analysis GC 0.02 μg/mL No data Withey and 

Collins 1977 

Blood Vacutainer collection, 

followed by purge and trap 

GC/MS 9 ppt (95% 

CI: 4– 

21 ppt) 

95–121% Ashley et al. 1992 

Blood Vacutainer collection, 

followed by static 

headspace sampling using 

solid-phase microextraction 

GC/MS 30 ppt 

(98.15% 

mean 

accuracy) 

No data Chambers et al. 

2006 

Serum Headspace analysis and 

solid-phase microextraction 

GC/FID 0.013 μg/mL No data Barua et al. 2008 

Heart, lungs, liver, 

spleen, kidney, 

brain 

Hemogenate prepared for 

headspace analysis 

GC 0.01 μg/g No data Withey and 

Collins 1977 

Urine Headspace from sample 

maintained and 37 °C for 

GC/MS No data No data Ghitori et al. 1987 

2 hours 

Urine Sorption on XAD-2, elution 

with n-hexane 

HPLC/UV <0.7 μg/L 72±10% Dolara et al. 1984 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

STYRENE 178 

7. ANALYTICAL METHODS 

Table 7-1. Analytical Methods for Determining Styrene in Biological Materials 

Sample 

Analytical detection Percent 

Sample matrix Preparation method method limit recovery Reference 

Urine Headspace analysis GS/MS No data No data Pezzagno et al. 

1985 

Styrene metabolite analyte 

Urine for MA Extraction with ethyl GC/FID No data No data Korn et al. 1984 

acetate, derivatization to 

isopropyl ester 

Urine for MA Extraction with diethyl GC No data No data Engstron et al. 

ether, silylation 1976 

Urine for MA and Extraction and GC/FID 0.05 ppm 94% MA, Bartolucci et al. 

PGA metabolites derivatization 98% PGA 1986 

Urine for MA Acidification, extraction, HRGC/FID 10 mg/L No data Kneip and Crable 

metabolite derivatization 1988b 

Urine for PGA Reduction, acidification, HRGC/FID 10 mg/L No data Kneip and Crable 

metabolite extraction, derivatization 1988c 

Urine for MA and Extraction with ethyl GC 10 mg/L No data Sedivec et al. 

PGA metabolites acetate, derivatization to 1984 

methyl esters with 

diazomethane 

Urine for MA and Extraction with ethyl GC/FID No data 97–99% Baselt 1988a 

PGA metabolites acetate, evaporation relative 

derivatization recovery 

Urine for MA and Acidification, extraction, HPLC/UV 1.1– 99.6– Onchoi et al. 

PGA metabolites evaporation 17.0 ng/mL 100.9% 2008 

Urine for MA, Direct injection HPLC/UV <1 μg/mLc <3% Regnaud et al. 

PGA, and deviation 1987 

hippuric acid from true 

metabolites value at 

5 μg/mL 

Urine for MA and Extraction and HRGC/FID No data No data Korn et al. 1987 

PGA (stereo­ derivatization 

selective) 

Blood for styrene Extraction with GC/FID 1 ng/mL 72±8% Kessler et al. 

oxide n-hexanone, concentration 1990 

by evaporation 

Blood for styrene Extraction with benzene GC/MS 10 ng/g 92±21% Langvardt and 

oxide Nolan 1991 

a

Unless otherwise designated, analyses are for styrene.

b

Values were reported for benzene; authors indicated that other VOCs had similar levels of detection
 c

Detection limits were 0.63 μg/mL for mandelic acid, 0.78 μg/mL for phenylglyoxylic acid, and 0.52 μg/mL for hippuric 

acid. 

CV = coefficient of variation; CI = confidence interval; EDTA = ethylene diamine tetra acetic acid; FID = flame 

ionization detector; GC = gas chromatography; HPLC = high-performance liquid chromatography; HRGC = highresolution gas chromatography; MA = mandelic acid; MS = mass spectrometry; PGA = phenylglyoxylic acid; 

UV = ultraviolet; VOC = volatile organic compound 
 

 

 

 

 

 

STYRENE 179 

7. ANALYTICAL METHODS 

which accuracy data are available. For example, the most sensitive for styrene detection limits were 

0.002 μg/L in water, 4 μg/kg in soil, and 500 μg/kg in solid waste. No significant reports were found 

pertaining to styrene degradation products in environmental samples. Information on methods for the 

determination of styrene in environmental samples is summarized in Table 7-2. 

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 styrene 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 styrene. 

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. Styrene and its primary 

metabolites, MA and PGA, can be detected in several human tissues (blood, urine, adipose tissue, and in 

several organs [Table 7-1]), as well as in exhaled breath. The detection limits range in the parts per 

billion to parts per trillion range (Ashley et al. 1992; Chambers et al. 2006). Approaches have been 

developed to provide more efficient and rapid assessment of exposure, such as where the subject breathes 

for short periods of time into different types of sample collectors (tedlar bags, evacuated canisters, even 

directly into a mass spectrometer interface [Wallace et al. 1996]), allowing samples to be collected 

efficiently for subsequent or immediate analysis. Personal monitoring badges containing charcoal have 

also been developed for longer-term assessment of exposure to styrene and other volatiles, which have 

been calibrated for comparison to levels detected in the subjects’ blood (Romieu et al. 1999). 

The concentration of the metabolites, MA and PGA, in urine has been found to correlate with average 

exposure levels in air (Härkönen et al. 1978), and so may be used as a biomarker of exposure. However, 
 

 

 

 

 

 

 

 

 

 

 

 

 

STYRENE	 180 

7. ANALYTICAL METHODS 

Table 7-2. Analytical Methods for Determining Styrene in Environmental Samples 

Sample Analytical Sample Percent 

matrix Preparation method method detection limit recovery Reference 

Food	 Homogenization, 

headspace sampling 

Air	 Retention by activated 

carbon 

Air	 Retention by activated 

carbon, elution with 

carbon disulfide 

Air	 Retention by activated 

carbon, elution with 

carbon disulfide 

Wastewater	 Stable isotope dilution 

method, followed by 

solvent extraction 

Water	 Purge by helium, 

collection on activated 

charcoal/silica gel/Tenax® 

Water	 Purge by helium, 

collection on activated 

charcoal/silica gel/Tenax® 

Water	 Purge by helium, 

collection on activated 

charcoal/silica gel/Tenax® 

Water	 Purge by helium, 

collection on activated 

charcoal/silica gel/Tenax® 

Water	 Purge and trap with 

nitrogen or helium 

Water Purge and trap 

Water	 Purge by helium, and trap 

at low temperature 

Water	 Purge and trap on 

VOCARB or equivalent 

Soil, low	 Purge by helium, 

level	 collection on solid, 

thermal desorption 

Solid waste,	 Purge by helium, 

nonwater	 collection on solid, 

miscible	 thermal desorption 

GC/MS 1 μg/kg 

GCa No data 

GCb No data 

HRGC/FID 0.01 mg/sample 

GC/MS 10 μg/L 

GC/PID 0.01 μg/L 

GC/PID 0.008 μg/L 

HRGC/MS 0.20 μg/L 

HRGC/MS 0.04 μg/L 

GC/PID 0.01 μg/L 

GC/PID 0.01 μg/L 

GC/FID 0.002 μg/L 

GC/MS 0.039 μg/L 

GC/MS 4 μg/kg 

GC/MS 500 μg/kgc 

No data 

No data 

No data 

No data 

No data 

96–104% 

No data 

120% (at 

1 μg/L) 

102% 

104% 

104% 

No data 

94–110% 

No data 

No data 

Gilbert and Startin 

1983 

ASTM 1988a 

ASTM 1988b 

NIOSH 1984 

EPA 2001 

EPA 1989f 

EPA 1989g 

EPA 1989h 

EPA 1989i 

EPA 1995 

EPA 1996 

Miermans et al. 

2000 

USGS 1998 

EPA 1986c 

EPA 1986c 
 

STYRENE 181 

7. ANALYTICAL METHODS 

Table 7-2. Analytical Methods for Determining Styrene in Environmental Samples 

Sample Analytical Sample Percent 

matrix Preparation method method detection limit recovery Reference 

Solid waste Purge by helium, GC/MS 500 μg/kgc No data EPA 1986b 

collection on solid, 

thermal desorption 

a

Absorption characteristics for sampling atmospheric vapor with activated carbon for subsequent analysis by GC.

b

Generic method for the determination of organics.
 c

Estimation from detection limits in water.
 

FID = flame ionization detector; GC = gas chromatography; HRGC = high-resolution gas chromatography;
 

MS = mass spectrometry; PID = photoionization detection; UV = ultraviolet
 
 

 

 

 

STYRENE 182 

7. ANALYTICAL METHODS 

measurements of MA and PGA are not specific for this purpose (Bartolucci et al. 1986) and these 

metabolites can result from the metabolism of other organic substances, particularly ethylbenzene (Baselt 

1988b). Levels of MA and PGA in biological samples from the general population probably are below 

the detection limits of methods that are currently used (Baselt 1988a). However, it is likely that normal 

background levels of these metabolites in unexposed individuals are too low to be of any significance. 

Although new and improved methods for the determination of styrene and its metabolites in biological 

samples need not have a high priority, additional work on standardization of these methods for use in 

biological samples accompanied by additional studies involving interlaboratory comparisons of recovery, 

accuracy, and precision data would be useful. 

Clinical means have been proposed to indicate exposure to styrene. In general, these are not sufficiently 

sensitive, specific, or well characterized. The most common symptom of exposure, impairment of central 

nervous system function, is not unique to styrene. Neither cytogenetic monitoring of peripheral 

lymphocytes nor unscheduled DNA synthesis have been sufficiently well characterized as biomarkers of 

exposure to styrene. 

There is currently some information that can be used to correlate levels of biomarkers of exposure to 

styrene in biological media with adverse health effects. Central nervous system depression has been 

correlated with a urinary MA concentration of ≥800 mg/L and a decrement in psychomotor performance 

in association with a concentration of ≥1,200 mg/L (Härkönen et al. 1978). The styrene concentrations in 

air producing these effects and urinary MA levels were relatively high. Studies to determine if effects at 

lower levels of exposure could also be correlated to metabolite levels in urine would be valuable. 

However, the design of studies involving controlled inhalation exposures in humans is precluded by the 

potential carcinogenicity of styrene. 

Methods for Determining Parent Compounds and Degradation Products in Environmental 

Media. In an occupational setting, the medium that is of most concern for human exposure to styrene is 

air, although at Superfund sites, contaminated groundwater may pose a danger. Methods are well 

developed for the determination of styrene in water and air with excellent selectivity and sensitivity 

(ASTM 1988a, 1988b; EPA 1989f, 1989g, 1989i, 1995, 1996; NIOSH 1984; USGS 1998). Methods for 

the determination of styrene in soil and waste samples are not as well developed and may require 

additional testing and validation (EPA 1986b, 1986c, 2001). 
 

 

 

 

 

STYRENE 183 

7. ANALYTICAL METHODS 

The detection limits for styrene in environmental media cited in Table 7-2 (0.01 mg/sample, typically 

10 L, NIOSH 1984; 0.002 μg/L in water, Miermans et al. 2000; and 4 μg/kg in soil, EPA 1986c) are low 

enough to enable the determination of styrene in any environmental medium likely to pose a hazard to 

health based upon information currently available in the literature. These detection limits are probably 

below most ambient background levels of styrene. 

Sampling methodologies for compounds such as styrene pose typical collection problems that include the 

collection of samples that are nonrepresentative, may be of insufficient sample volume, may contain 

interfering materials that result in low sample recovery, or may contain interfering contaminating 

chemicals. Other sampling methods may be labor-intensive, or require tedious extraction and purification 

procedures (Green and Le Pape 1987; Miermans et al. 2000). Methods that measure organic compounds 

such as styrene in situ in water and other environmental media without the need for sampling and 

extraction procedures to isolate the analyte prior to analysis are desirable. One such method has been 

patented, but no commercial products have been identified (see below). 

In regard to methods for determining parent styrene and degradation products in environmental media, the 

following conclusions may be drawn: Because styrene can be detected instrumentally and determined in 

air and normal water samples with totally adequate selectivity and sensitivity, no additional data are 

needed at this time. A moderate need exists to improve methodologies to determine styrene in soil, 

sludges, and solid wastes. Styrene degradation products are a different matter in that little information is 

available on their determination in environmental samples. In air, these compounds should consist 

predominantly of photochemical oxidation products, whereas in water and soil samples, they are expected 

to be biodegradation products. Additional research is needed on the determination of these materials. 

7.3.2 Ongoing Studies 

No current ongoing studies were found in the Federal Research in Progress database (FEDRIP 2007) 

regarding the development of analytical methods for the detection of styrene or its metabolites. 

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 styrene and 

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. 
STYRENE 184 

7. ANALYTICAL METHODS 

In addition to the detection and identification of styrene using chromatographic means, where current 

detection limits approach analytical thresholds, other technologies may offer additional routes for 

detection of styrene in samples, especially for aquatic environmental samples. Immunoassay-based 

methods of analysis offer rapid analysis times, high sensitivity, and often high selectivity for various 

organic pollutants and other chemicals of concern. While styrene and its metabolites are considered 

important chemicals to monitor using such techniques, no known assays have been commercialized, even 

though one patent has been issued for a method that claims to detect styrene and other VOCs by 

immunoassay (patent 5,358,851, issued in 1994 [Peck 1994]). No additional information was found 

regarding the continued development (or use or application) of this technology. 
 

 

 

 

 

 

 

 

 

STYRENE 185 

8. REGULATIONS, ADVISORIES, AND GUIDELINES
 

MRLs are substance specific estimates, which are intended to serve as screening levels, are used by 

ATSDR health assessors and other responders to identify contaminants and potential health effects that 

may be of concern at hazardous waste sites. 

ATSDR has derived an acute-duration inhalation MRL of 5 ppm for styrene. This MRL is based on a 

NOAEL of 49 ppm for alterations in tests of reaction time, memory, attention, color discrimination, and 

olfactory threshold in subjects exposed to styrene for 6 hours (Ska et al. 2003) and an uncertainty factor 

of 10 to account for human variability. 

ATSDR has derived a chronic-duration inhalation MRL of 0.2 ppm for styrene. This MRL is based on a 

minimal LOAEL of 20 ppm estimated from a meta-analysis of data (Benignus et al. 2005) from 

occupational exposure studies demonstrating alterations in choice reaction time and color discrimination 

in styrene workers. The minimal LOAEL was adjusted for intermittent exposure (8 hours/day, 

5 days/week) and divided by an uncertainty factor of 30 (3 for use of a minimal LOAEL and 10 for 

human variability). 

EPA (IRIS 2009) has derived an inhalation reference concentration (RfC) of 1 mg/m3 (0.2 ppm) based on 

a NOAELHEC value of 34 mg/m3 in a cross-sectional study in workers finding central nervous system 

effects in workers exposed to >22 ppm (Mutti et al. 1984a) and an uncertainty factor of 30 (3 for the use 

less than chronic study, 3 for human variability, and 3 for database inadequacies). 

ATSDR has derived an acute-duration oral MRL of 0.1 mg/kg/day for styrene. This MRL is based on a 

LOAEL of 100 mg/kg/day for impaired learning in rats exposed to styrene for 14 days (Husain et al. 

1985) and an uncertainty factor of 1,000 (10 for use of a LOAEL, 10 for extrapolation from rats to 

humans, and 10 for human variability). 

EPA (IRIS 2009) has established an oral reference dose (RfD) of 0.2 mg/kg/day based on a NOAEL of 

200 mg/kg/day from a subchronic oral toxicity study in beagle dogs in which red blood cell and liver 

effects was observed (Quast et al. 1979). The uncertainty factor used in this assessment was 1,000 (10 for 

interspecies extrapolation, 10 for human variability variation, and 10 for extrapolation of subchronic 

effects to chronic effects). 
 

STYRENE 186 

8. REGULATIONS AND ADVISORIES 

The international and national regulations, advisories, and guidelines regarding styrene in air, water, and 

other media are summarized in Table 8-1. 
 

 

 

 

 

 

STYRENE 187 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations, Advisories, and Guidelines Applicable to Styrene 

Agency Description Information Reference 

INTERNATIONAL 

Guidelines: 

IARC Carcinogenicity classification Group 2Ba IARC 2006 

WHO Air quality guidelines WHO 2000 

TWA based on effects other than 0.26 mg/m3 

cancer or odor/annoyance using an 

averaging time of 1 week 

Based on sensory effects or 

annoyance reactions, using an 

averaging time of 30 minutes 

Detection threshold 0.07 mg/m3 

Recognition threshold 0.21–0.28 mg/m3 

Guideline value 0.07 mg/m3 

Drinking water quality guidelines 0.02 mg/Lb WHO 2004 

NATIONAL 

Regulations and 

Guidelines: 

a. Air 

ACGIH TLV (8-hour TWA) 85 mg/m3 ACGIH 2008 

STEL (15-minute TWA) 170 mg/m3 

AIHA ERPG-1c 213 mg/m3 AIHA 1995 

ERPG-2c 1,065 mg/m3 

ERPG-3c 4,260 mg/m3 

EPA AEGL-1d EPA 2007a 

10 minutes 85 mg/m3 

30 minutes 85 mg/m3 

60 minutes 85 mg/m3 

4 hours 85 mg/m3 

8 hours 85 mg/m3 

AEGL-2d 

10 minutes 980 mg/m3 

30 minutes 682 mg/m3 

60 minutes 554 mg/m3 

4 hours 554 mg/m3 

8 hours 554 mg/m3 
 

 

 

 

 

 

 

 

 

 

STYRENE	 188 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations, Advisories, and Guidelines Applicable to Styrene 

Agency Description	 Information Reference 

NATIONAL (cont.)

 EPA AEGL-3d EPA 2007a 

10 minutese

 8,094 mg/m3 

(1,862 ppm) 

30 minutese

 8,094 mg/m3 

(1,862 ppm) 

60 minutese

 4,686 mg/m3 

(1,078 ppm) 

4 hours 1,448 mg/m3 

(333 ppm) 

8 hours 1,448 mg/m3 

(333 ppm) 

Level of distinct odor awareness 2.3 mg/m3 

(0.5 ppm) 

EPA Hazardous air pollutant Yes EPA 2007c 

42 USC 7412
 

NIOSH REL (10-hour TWA) 50 ppm NIOSH 2005
 

STEL (15-minute TWA) 100 ppm

 IDLH 700 ppm
 

OSHA PEL (8-hour TWA) for general industry 100 ppm	 OSHA 2006c 

29 CFR 1910.1000, 

Table Z-2 

Acceptable ceiling concentration 200 ppm 

Acceptable maximum peak above 600 ppm 

the acceptable ceiling concentration 

for an 8-hour shift for a maximum 

duration of 5 minutes in any 3 hours 

PEL (8-hour TWA) for shipyard industry 100 ppm OSHA 2006a 

29 CFR 1915.1000 

PEL (8-hour TWA) for construction 100 ppm OSHA 2006b 

industry 29 CFR 1926.55, 

Appendix A 

b. Water 

EPA Designated as hazardous substances in Yes EPA 2007b 

accordance with Section 311(b)(2)(A) of 40 CFR 116.4 

the Clean Water Act 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

STYRENE 189 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations, Advisories, and Guidelines Applicable to Styrene 

Agency Description Information Reference 

NATIONAL (cont.) 

EPA Drinking water standards and health 

advisories 

EPA 2006 

1-day health advisory for a 10-kg 

child 

20 mg/L 

10-day health advisory for a 10-kg 

child 

2 mg/L 

DWEL 7 mg/L 

Lifetime 

10-4 Cancer risk 

0.1 mg/L 

No data 

Master Testing List Yesf EPA 2007d 

National primary drinking water 

standards 

EPA 2003 

MCLG 0.1 mg/L 

MCL 0.1 mg/L 

Public health goal 0.1 mg/L 

Reportable quantities of hazardous 

substances designated pursuant to 

Section 311 of the Clean Water Act 

1,000 pounds EPA 2007e 

40 CFR 117.3 

c. Food 

FDA Bottled drinking water 0.1 mg/L FDA 2006a 

21 CFR 165.110 

Food additives permitted for direct 

addition to food for human consumption 

Yes FDA 2007b 

21 CFR 172 

Indirect food additives: adhesives and Yes FDA 2006b 

components of coatings 

EAFUS Yesh 

21 CFR 175 

FDA 2007a 

d. Other 

ACGIH Carcinogenicity classification A4i ACGIH 2008 

Biological exposure indices (end of shift 

at end of workweek) 

Sum of mandelic acid and phenyl 

glyoxylic acid in urine 

400 mg/g creatinine 

Styrene in venous blood 0.2 mg/L 

EPA Carcinogenicity classification 

RfC 

No data 

1 mg/m3 

(0,2 ppm) 

IRIS 2009 

RfD 0.2 mg/kg/day 

Superfund, emergency planning, and 

community right-to-know 

Designated CERCLA hazardous 

substance 

Yesj EPA 2007f 

40 CFR 302.4 

Reportable quantity 1,000 pounds 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

STYRENE 190 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations, Advisories, and Guidelines Applicable to Styrene 

Agency Description Information Reference 

NATIONAL (cont.) 

EPA Effective date of toxic chemical 01/01/2000 EPA 2007g 

release reporting 40 CFR 372.65 

NTP Carcinogenicity classification No data NTP 2005 

a

Group 2B: possibly carcinogenic to humans 

b

Concentrations of the substance at or below the health-based guideline value may affect the appearance, taste, or 

odor of the water, leading to consumer complaints (WHO 2004).

c

ERPG-1 is the maximum airborne concentration below which nearly all individuals could be exposed for up to 1 hour 

without experiencing other than mild, transient health effects; ERPG-2 is the maximum airborne concentration below 

which nearly all individuals could be exposed for up to 1 hour without experiencing irreversible or other serious 

adverse effects; and ERPG-3 is the maximum airborne concentration below which nearly all individuals could be 

exposed for up to 1 hour without life-threatening health effects (AIHA 1995). d

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, however, the effects are not disabling and are transient and reversible upon cessation of exposure; 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; and 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 

(EPA 2007a).

e

Safety considerations against the hazard of explosion must be taken into account. 

f

Styrene was recommended to the MTL by the U.S. EPA’s Office of Pollution Prevention and Toxics on the basis of 

the SIDS. Styrene was added to the MTL in 1993 and the chemical testing program is currently underway by way of 

a VTA. The testing needs include health effects, environmental effects, and environmental fate and exposure. 

g

Potential health effects from exposure above the MCL include liver, kidney, or circulatory system problems. 

Common sources of contaminant in drinking water include discharges from rubber and plastic factories and leaching 

from landfills (EPA 2003).

h

The EAFUS list of substances contains ingredients added directly to food that FDA has either approved as food 

additives or listed or affirmed as GRAS. 

i

A4: not classifiable as a human carcinogen 

j

Designated CERCLA hazardous substance pursuant to Section 311(b)(2) of the Clean Water Act and Section 112 of 

the Clean Air Act. 

ACGIH = American Conference of Governmental Industrial Hygienists; AEGL = acute exposure guideline levels; 

AIHA = American Industrial Hygiene Association; CERCLA = Comprehensive Environmental Response, 

Compensation, and Liability Act; CFR = Code of Federal Regulations; DWEL = drinking water equivalent level; 

EAFUS = Everything Added to Food in the United States; EPA = Environmental Protection Agency; 

ERPG = emergency response planning guidelines; FDA = Food and Drug Administration; GRAS = Generally 

Recognized As Safe; IARC = International Agency for Research on Cancer; IDLH = immediately dangerous to life or 

health; IRIS = Integrated Risk Information System; MCL = maximum contaminant level; MCLG = maximum 

contaminant level goal; MTL = Master Testing List; 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; SIDS = Screening Information Data Sets; STEL = short-term expsoure limit; TLV = threshold limit values; 

TWA = time-weighted average; USC = United States Code; VTA = Voluntary Testing Agreement; WHO = World 

Health Organization 
 

 

 

 

 

 

_________________________ 

STYRENE 191 

9. REFERENCES
 

ACGIH. 2008. Styrene. Threshold limit values for chemical substances and physical agents and 

biological exposure indices. Cincinnati, OH: American Conference of Governmental Industrial 

Hygienists, 53, 108. 

Adgate JL, Church TR, Ryan AD, et al. 2004. Outdoor, indoor, and personal exposure to VOCs in 

children. Environ Health Perspect 112:1386-1392. 

Adinolfi M. 1985. The development of the human blood-CSF-brain barrier. Dev Med Child Neurol 

27(4):532-537. 

Adlercreutz H. 1995. Phytoestrogens: Epidemiology and a possible role in cancer protection. Environ 

Health Perspect Suppl 103(7):103-112. 

Agency for Toxic Substances and Disease Registry. 1989. Decision guide for identifying substancespecific data needs related to toxicological profiles; Notice. Agency for Toxic Substances and Disease 

Registry, Division of Toxicology. Fed Regist 54(174):37618-37634. 

Agrawal AK, Srivastava SP, Seth PK. 1982. Effect of styrene on dopamine receptors. Bull Environ 

Contam Toxicol 39:400-403. 

Ahlborg G, Bjerkedal T, Egenaes J. 1987. Delivery outcome among women employed in the plastics 

industry in Sweden and Norway. Am J Ind Med 12:507-517. 

AIHA. 1995. Styrene. Emergency Response Planning Guidelines (ERPG). Fairfax, VA: American 

Industrial Hygiene Association. 

Alarie Y. 1973. Sensory irritation of the upper airways by airborne chemicals. Toxicol Appl Pharmacol 

24:279-297. 

Ali SF, Hong JS, Wilson WE, et al. 1983. Effect of acrylamide on neurotransmitter metabolism and 

neuropeptide levels in several brain regions and upon circulating hormones. Arch Toxicol 52:35-43. 

Aliberti LM, Severini G. 1987. Urinary enzyme excretion in subjects exposed to styrene. Ann Clin 

Biochem 24:114. 

Al-Mudhaf JF, Alsharifi FA, Abu-Shady ASI. 2009. A survey of organic contaminants in household and 

bottled drinking water in Kuwait. Sci Total Environ 407(5):1658-1668. 

Altman PL, Dittmer DS. 1974. Biological handbooks: Biology data book. Vol. III. 2nd ed. Bethesda, 

MD: Federation of American Societies for Experimental Biology, 1987-2008, 2041. 

Amoore JE, Hautala E. 1983. Odor as an aid to chemical safety: Odor thresholds compared with 

threshold limit values and volatilities for 214 industrial chemicals in air and water dilution. J Appl 

Toxicol 3:272-290. 

* Not cited in text 
 

 

 

 

 

 

 

 

 

STYRENE 192 

9. REFERENCES 

Andersen ME, Krishnan K. 1994. Relating in vitro to in vivo exposures with physiologically based tissue 

dosimetry and tissue response models. In: Salem H, ed. Animal test alternatives: Refinement,
 

reduction, replacement. New York, NY: Marcel Dekker, Inc., 9-25.
 

Andersen ME, Clewell HJ, Gargas ML, et al. 1987a. Physiologically based pharmacokinetics and the 

risk assessment process for methylene chloride. Toxicol Appl Pharmacol 87(2):185-205.
 

Andersson HC, Tranberg EA, Uggla AH, et al. 1980. Chromosomal aberrations and sister-chromatid 

exchanges in lymphocytes of men occupationally exposed to styrene in a plastic-boat factory. Mutat Res 

73:387-401.
 

Antilla A, Pukkala E, Riala R, et al. 1998. Cancer incidence among Finnish workers exposed to aromatic
 

hydrocarbons. Int Arch Occup Environ Health 71:187-193.
 

Antoine SR, DeLeon IR, O'Dell-Smith RM. 1986. Environmentally significant volatile organic
 

pollutants in human blood. Bull Environ Contam Toxicol 36:364-371.
 

Anwar WA, Shamy MY. 1995. Chromosomal aberrations and micronuclei in reinforced plastics workers 

exposed to styrene. Mutat Res 327:41-47.
 

Apostoli P, Brugnone F, Perbellini L, et al. 1983. Occupational styrene exposure: Environmental and 

biological monitoring. Am J Ind Med 4:741-754.
 

Arfini G, Mutti A, Vescovi P, et al. 1987. Impaired dopaminergic modulation of pituitary secretion in
 

workers occupationally exposed to styrene: Further evidence from PRL response to TRH stimulation. J 

Occup Med 29:826-830.
 

Arnedo-Pena A, Bellido-Blasco J, Villamarin-Vazquez JL, et al. 2003. Acute health effects after 

accidental exposure to styrene from drinking water in Spain. Environ Health 2(6):1-9.
 

Artuso M, Angotzi G, Bonassi S, et al. 1995. Cytogenetic biomonitoring of styrene-exposed plastic boat
 

builders. Arch Environ Contam Toxicol 29:270-274.
 

Ashley DL, Bonin MA, Cardinali FL, et al. 1992. Determining volatile organic compounds in human 

blood from a large sample population by using purge and trap gas chromatography/mass spectrometry.
 

Anal Chem 64:1021-1029.
 

Assmuth T, Kalevi K. 1992. Concentrations and toxicological significance of trace organic compounds
 

in municipal solid waste landfill gas. Chemosphere 24(9):1207-1216.
 

ASTM. 1988a. D 3686-84. Standard practice for sampling atmospheres to collect organic compound 

vapors. (Activated charcoal tube adsorption method). In: Storer RA, Cornillot JL, Richardson D, et al., 

eds. 1988 Annual book of ASTM standards. Vol. 11.03. Section 11: Water and environmental
 

technology. Philadelphia, PA: American Society for Testing and Materials, 234-240.
 

ASTM. 1988b. D3687-84. Standard practice for analysis of organic compound vapors collected by the
 

activated charcoal tube absorption method. In: Storer RA, Cornillot JL, Richardson D, et al., eds. 1988
 

Annual book of ASTM standards. Vol. 11.03. Section 11. Water and environmental technology.
 

Philadelphia, PA: American Society for Testing and Materials, 241-246.
 
 

 

 

 

 

 

 

 

 

 

 

STYRENE 193 

9. REFERENCES 

Atkinson R, Arey J. 2003. Atmospheric degradation of volatile organic compounds. Chem Rev 

103:4605-4638. 

Atkinson R, Aschmann SM, Fitz DR, et al. 1982. Rate constants for the gas-phase reactions of O3 with 

selected organics at 296K. Int J Chem Kinet 14:13-18. 

*Axelson O, Gustavson J. 1978. Some hygienic and clinical observations on styrene exposure. Scand J 

Work Environ Health 4:215-219. 

Ban M, Langonne I, Huguet N, et al. 2006. Inhaled chemicals may enhance allergic airway inflammation 

in ovalbumin-sensitised mice. Toxicology 226:161-171. 

Banerjee S, Yalkowsky SH, Valvani SC. 1980. Water solubility and octanol/water partition coefficients 

of organics. Limitations of the solubility-partition coefficient correlation. Environ Sci Technol 

14:1227-1229. 

Barnes DG, Dourson M. 1988. Reference dose (RfD): Description and use in health risk assessments. 

Regul Toxicol Pharmacol 8(4):471-486. 

Bartolucci GB, De Rosa E, Gori GP, et al. 1986. Biomonitoring of occupational exposure to styrene. 

Appl Ind Hyg 1:125-131. 

Barua R, Chi LH, Fitzpatrick R, et al. 2008. Determination of volatile organic compounds in biological 

samples using headspace solid-phase microextraction and gas chromatography: Toluene and styrene. J 

Anal Toxicol 32(5):379-386. 

Baselt RC. 1988a. Styrene. In: Biological monitoring methods for industrial chemicals. 2nd ed. 

Littleton, MA: PSG Publishing, Inc., 265-267. 

Baselt RC. 1988b. Ethylbenzene. In: Biological monitoring methods for industrial chemicals. 2nd ed. 

Littleton, MA: PSG Publishing, Inc., 146-148. 

Basirov AA. 1975. [Biochemical indexes of the gastric juice in the early diagnosis of stomach illness 

under the effect of toxic substances (1,3-butadiene and styrene).] Azerb Med Zh 52:60-66. (Russian) 

Behari M, Choudhary C, Roy S, et al. 1986. Styrene-induced peripheral neuropathy: A case report. Eur 

Neurol 25:424-427. 

Beliles RP, Butala JH, Stack CR, et al. 1985. Chronic toxicity and three-generation reproduction study 

of styrene monomer in the drinking water of rats. Fundam Appl Toxicol 5:855-868. 

Belvedere G, Tursi F. 1981. Styrene oxidation to styrene oxide in human blood erythrocytes and 

lymphocytes. Res Commun Chem Pathol Pharmacol 33:273-282. 

Benignus VA, Geller AM, Boyes WK, et al. 2005. Human neurobehavioral effects of long-term 

exposure to styrene: A meta-analysis. Environ Health Perspect 113:532-538. 

*Bergamaschi E, Mutti A, Cavazzini S, et al. 1995a. Peripheral markers of neurochemical effects among 

styrene-exposed workers. Neurotoxicology 16(3):545. 
 

 

 

 

 

 

 

 

 

 

STYRENE 194 

9. REFERENCES 

Bergamaschi E, Mutti A, Cavazzini S, et al. 1996. Peripheral markers of neurochemical effects among 

styrene-exposed workers. Neurotoxicology 17(3-4):753-759. 

Bergamaschi E, Smargiassi A, Mutti A, et al. 1995b. Immunological changes among workers 

occupationally exposed to styrene. Int Arch Occup Environ Health 67:165-171. 

Bergamaschi E, Smargiassi A, Mutti A, et al. 1997. Peripheral markers of catecholaminergic dysfunction 

and symptoms of neurotoxicity among styrene-exposed workers. Int Arch Occup Environ Health 

69:209-214. 

Berger GS, ed. 1994. Epidemiology of endometriosis. In: Endometriosis: Modern surgical 

management of endometriosis. New York, NY: Springer-Verlag, 3-7. 

Berode M, Droz PO, Guillemin M. 1985. Human exposure to styrene: VI. Percutaneous absorption in 

human volunteers. Int Arch Occup Environ Health 55:331-336. 

BFR. 2006. High daily intakes of cinnamon: Health risks cannot be ruled out. Bundesinstitut fur 

Risikobewertung. BfR Health Assessment No. 044/2006. 

http://www.bfr.bund.de/cm/245/high_daily_intakes_of_cinnamon_health_risk_cannot_be_ruled_out.pdf. 

August 17, 2007. 

Bigbee WL, Grant SG, Langlois RG, et al. 1996. Glycophorin a somatic cell mutation frequencies in 

Finnish reinforced plastics workers exposed to styrene. Cancer Epidemiol Biomarkers Prev 5:801-810. 

Bignozzi CA, Maldotti A, Chiorboli C, et al. 1981. Kinetics and mechanisms of reactions between 

aromatic olefins and hydroxyl radicals. Int J Chem Kinet 13:1235-1242. 

Biró A, Pallinger E, Major J, et al. 2002. Lymphocyte phenotype analysis and chromosome aberration 

frequency of workers occupationally exposed to styrene, benzene, polycyclic aromatic hydrocarbons or 

mixed solvents. Immunol Lett 81:133-140. 

Bond GG, Bodner KM, Olsen GW, et al. 1992. Mortality among workers engaged in the development or 

manufacture of styrene-based products-an update. Scand J Work Environ Health 18:145-154. 

Bond JA. 1989. Review of toxicology of styrene. CRC Crit Rev Toxicol 19:227-249. 

Bouwer EJ, McCarty PL. 1984. Modeling of trace organics biotransformation in the subsurface. Ground 

Water 22:433-440. 

Braun-Lüllemann A, Majcherczyk A, Huttermann A. 1997. Degradation of styrene by white-rot fungus. 

Appl Microbiol Biotechnol 47:150-155. 

Bridie AL, Wolff CJ, Winter M. 1979. BOD and COD of some petrochemicals. Water Res 13:627-630. 

Bronstein AC, Currance PL. 1988. Emergency care for hazardous materials exposure. St. Louis, MO: 

The C.V. Mosby Company, 221-222. 

Brown KW, Donnelly KC. 1988. An estimation of the risk associated with the organic constituents of 

hazardous and municipal waste landfill leachates. Haz Waste Haz Mater 5:1-30. 
 

 

 

 

 

 

 

 

 

 

STYRENE 195 

9. REFERENCES 

Brugnone F, Perbellini L, Wang GZ, et al. 1993. Blood styrene concentrations in a "normal" population 

and in exposed workers 16 hours after the end of the workshift. Int Arch Occup Environ Health 

65:125-130. 

Bunce NJ, Dryfhout HG. 1992. Diurnal and seasonal modeling of the tropospheric half-lives of 

polycyclic aromatic hydrocarbons. Can J Chem 70:1966-1970. 

Burback BL, Perry JJ. 1993. Biodegradation and biotransformation of groundwater pollutant mixtures 

by Mycobacterium vaccae. Appl Environ Microbiol 59(4):1025-1029. 

Bushnell PJ. 1994. Styrene impairs serial spatial reversal learning in rats. J Am Coll Toxicol 

13(4):279-300. 

Calabrese G, Martini A, Sessa G, et al. 1996. Otoneurological study in workers exposed to styrene in the 

fiberglass industry. Int Arch Occup Environ Health 68(4):219-223. 

Campagna D, Gobba F, Mergler D, et al. 1996. Color vision loss among styrene-exposed workers 

neurotoxicological threshold assessment. Neurotoxicology 17(2):367-373. 

Campagna D, Mergler D, Huel G, et al. 1995. Visual dysfunction among styrene-exposed workers. 

Scand J Work Environ Health 21:382-390. 

Campo P, Lataye R, Loquet G, et al. 2001. Styrene-induced hearing loss: A membrane insult. Hear Res 

154(1-2):170-180. 

Canter LW, Sabatini DA. 1994. Contamination of public ground water supplies by Superfund sites. Int J 

Environ Stud 46:35-57. 

Cantoni L, Salmona M, Facchinetti T, et al. 1978. Hepatic and extrahepatic formation and hydration of 

styrene oxide in vitro in animals of different species and sex. Toxicol Lett 2:179-186. 

Carlson EM, Erskine MG. 1973. Styrene. Chemical economics handbook. Menlo Park, CA: Standford 

Research Institute. 

Carlson GP, Mantick NA, Powley MW. 2000. Metabolism of styrene by human liver and lung. J 

Toxicol Environ Health A 59:591-595. 

Carlsson A. 1981. Distribution and elimination of 14-C styrene in rat. Scand J Work Environ Health 

7:45-50. 

Carpenter CP, Shaffer CB, Weil CS, et al. 1944. Studies on the inhalation of 1,3-butadiene; with a 

comparison of its narcotic effect with benzol, toluol, and styrene, and a note on the elimination of styrene 

by the human. J Ind Hyg Toxicol 26:69-78. 

Castillo L, Baldwin M, Sassine MP, et al. 2001. Cumulative exposure to styrene and visual functions. 

Am J Ind Med 39:351-360. 

CEFIC. 2008. Styrene monomer: Environmental, health, safety, transport and storage guidelines. 

European Chemical Industry Council. http://www.styrenemonomer.org/environment-health-safetyguidelines.pdf. March 25, 2009. 
 

 

 

 

 

 

 

 

 

 

 

 

 

STYRENE 196 

9. REFERENCES 

*Chakrabarti SK, Labelle L, Tuchweber B. 1987. Studies on the subchronic nephrotoxic potential of 

styrene in Sprague-Dawley rats. Toxicology 44:355-365. 

Chambers DM, McElprang DO, Waterhouse MG, et al. 2006. An improved approach for accurate 

quantitation of benzene, toluene, ethylbenzene, xylene, and styrene in blood. Anal Chem 78:5375-5383. 

Checkoway H, Williams TM. 1982. A hematology survey of workers at a styrene-butadiene synthetic 

rubber manufacturing plant. Am Ind Hyg Assoc J 43:164-169. 

Checkoway H, Costa LG, Camp J, et al. 1992. Peripheral markers of neurochemical function among 

workers exposed to styrene. Br J Ind Med 49:560-565. 

Chemical Week. 2008. Styrene. Product focus. Chem Week September 1/8:41. 

Chen S. 2001. Styrene. In: Kirk-Othmer encyclopedia of chemical technology. John Wiley & Sons, 

Inc. http://www.mrw.interscience.wiley.com/emrw/9780471238966/kirk/article/styrchen.a01/current/pdf. 

May 30, 2007. 

Chen GD, Chi LH, Kostyniak PJ, et al. 2007. Styrene induced alterations in biomarkers of exposure and 

effects in the cochlea: Mechanisms of hearing loss. Toxicol Sci 98(1):167-177. 

Chen GD, Tanaka C, Henderson D. 2008. Relation between outer hair cell loss and hearing loss in rats 

exposed to styrene. Hear Res 243(1-2):28-34. 

Cheng H, Sathiakumar N, Graff J, et al. 2007. 1,3-Butadiene and leukemia among synthetic rubber 

industry workers: Exposure-response relationships. Chem Biol Interact 166:15-24. 

Cherry N, Waldron HA, Wells GG, et al. 1980. An investigation of the acute behavioral effects of 

styrene on factory workers. Br J Ind Med 37:234-240. 

Chia SE, Jeyaratnam J, Ong CN, et al. 1994. Impairment of color vision among workers exposed to low 

concentrations of styrene. Am J Ind Med 26:481-488. 

Chmielewski J, Renke W. 1975. Clinical and experimental studies on the pathogenesis of toxic effects of 

styrene. II. The effect of styrene on the respiratory system. Bull Inst Marit Trop Med Gdynia 

26:299-302. 

Cho SI, Damokosh AI, Ryan LM, et al. 2001. Effects of exposure to organic solvents on menstrual cycle 

length. J Occup Environ Med 43(6):565-575. 

Chua SC, Lee BL, Liau LS, et al. 1993. Determination of mandelic acid and phenylglyoxylic acid in the 

urine and its use in monitoring of styrene exposure. J Anal Toxicol 17(3):129-132. 

Clay P. 2004. Styrene monomer does not induce unscheduled DNA synthesis in the mouse liver 

following inhalation exposure. Mutagenesis 19(6):489-492. 

Clewell HJ, Andersen ME. 1985. Risk assessment extrapolations and physiological modeling. Toxicol 

Ind Health 1(4):111-131. 

Cocheo V, Bellomo ML, Bombi GG. 1983. Rubber manufacture: Sampling and identification of 

volatile pollutants. Am Ind Hyg Assoc J 44:521-527. 
 

 

 

 

 

STYRENE 197 

9. REFERENCES 

Coggon D, Osmond C, Pannett B, et al. 1987. Mortality of workers exposed to styrene in the 

manufacture of glass-reinforced plastics. Scand J Work Environ Health 13:94-99. 

Coleman WE, Munch JW, Streicher RP, et al. 1984. The identification and measurement of components 

in gasoline, kerosene, and No. 2 fuel oil that partition into the aqueous phase after mixing. Arch Environ 

Contam Toxicol 13:171-178. 

Colombani N, Mastrocicco M, Cargini A, et al. 2009. Modeling the fate of styrene in a mixed petroleum 

hydrocarbon plume. J Contam Hydrol 105(1-2):39-55. 

Compton-Quintana PJ, Jensen RH, Bigbee WL, et al. 1993. Use of the glycophorin A human mutation 

assay to study workers exposed to styrene. Environ Health Perspect 99:297-301. 

Conner MK, Alarie Y, Dombroske RL. 1980. Sister chromatid exchange in Murine alveolar 

macrophages, bone marrow, and regenerating liver cells induced by styrene inhalation. Toxicol Appl 

Pharmacol 55:37-42. 

Conti B, Maltoni C, Perino G, et al. 1988. Long-term carcinogenicity bioassays on styrene administered 

by inhalation, ingestion and injection and styrene oxide administered by ingestion in Sprague-Dawley 

rats, and para-methylstyrene administered by ingestion in Sprague-Dawley rats and Swiss mice. Ann NY 

Acad Sci 534:203-234. 

Correa SM, Torres AR, Arbilla G. 2004. Aromatic volatile organic compounds emissions in a tire 

recapping unit. Bull Environ Contam Toxicol 72:255-260. 

CRISP. 2007. Styrene: Computer Retrieval of Information on Scientific Projects Database. Bethesda, 

MD: National Institutes of Health, Division of Research Grants. 

Crofton KM, Lassiter TL, Rebert CS. 1994. Solvent-induced ototoxicity in rats: An atypical selective 

mid-frequency hearing deficit. Hear Res 80:25-30. 

Crump D. 1995. Volatile organic compounds in indoor air. Issues Environ Sci Technol 4:109-124. 

Cruzan G, Carlson GP, Johnson KA. 2002. Styrene respiratory tract toxicity and mouse lung tumors are 

mediated by CYP2F-generated metabolites. Regul Toxicol Pharmacol 35:308-319. 

Cruzan G, Carlson GP, Turner M, et al. 2005b. Ring-oxidized metabolites of styrene contribute to 

styrene-induced Clara-cell toxicity in mice. J Toxicol Environ Health 68A:229-237. 

Cruzan G, Cushman JR, Andrews LS, et al. 1997. Subchronic inhalation studies of styrene in CD rats 

and CD-1 mice. Fundam Appl Toxicol 35(2):152-165. 

Cruzan G, Cushman JR, Andrews LS, et al. 1998. Chronic toxicity/oncogenicity study of styrene in CD 

rats by inhalation exposure for 104 weeks. Toxicol Sci 46:266-281. 

Cruzan G, Cushman JR, Andrews LS, et al. 2001. Chronic toxicity/oncogenicity study of styrene in CD1 mice by inhalation exposure for 104 weeks. J Appl Toxicol 21:185-198. 

Cruzan G, Faber WD, Johnson KA, et al. 2005a. Developmental neurotoxicity study of styrene by 

inhalation in Crl-CD rats. Birth Defects Res B Dev Reprod Toxicol 74(3):221-232. 
 

 

 

 

 

 

 

 

 

 

 

 

 

STYRENE 198 

9. REFERENCES 

Csanády GA, Kessler W, Hoffmann HD, et al. 2003. A toxicokinetic model for styrene and its 

metabolite styrene-7,8-oxide in mouse, rat, and human with special emphasis on the lung. Toxicol Lett 

138:75-102. 

Csanády GA, Mendrala AL, Noland RJ, et al. 1994. A physiologic pharmacokinetic model for styrene 

and styrene-7,8-oxide in mouse, rat and man. Arch Toxicol 68:143-157. 

Dalton P, Cowart B, Dilks D, et al. 2003. Olfactory function in workers exposed to styrene in the 

reinforced-plastics industry. Am J Ind Med 44(1):1-11. 

Dalton P, Lees PS, Gould M, et al. 2007. Evaluation of long-term occupational exposure to styrene 

vapor on olfactory function. Chem Senses 32(8):739-747. 

Das M, Dixit R, Mushtaq M, et al. 1981. Effect of styrene on hepatic mixed function oxidases, 

glutathione content and glutathione-S-transferase activity in rats. Drug Chem Toxicol 4:219-227. 

Das M, Srivastava SP, Seth PK. 1983. Effect of styrene on glutathione content and some xenobiotic 

metabolizing enzymes of rat kidney. Acta Pharmacol Toxicol (Copenh) 52:47-50. 

Daston GP, Overmann GJ, Taubeneck MW, et al. 1991. The role of metallothionein induction and 

altered zinc status in maternally mediated developmental toxicity: Comparison of the effects of urethane 

and styrene in rats. Toxicol Appl Pharmacol 110:450-463. 

DeCeaurriz J, Desiles JP, Bonnet P, et al. 1983. Concentration-dependent behavioral changes in mice 

following short-term inhalation exposure to various industrial solvents. Toxicol Appl Pharmacol 

67:383-389. 

DeJong G, van Sittert NJ, Natarajan AT. 1988. Cytogenetic monitoring of industrial populations 

potentially exposed to genotoxic chemicals and of control populations. Mutat Res 204:451-464. 

Delzell E, Macalluso M, Sathiakumar N, et al. 2001. Leukemia and exposure to 1,3-butadiene, styrene 

and dimethyldithiocarbamate among workers in the synthetic rubber industry. Chem Biol Interact 

135-136:515-534. 

Delzell E, Sathiakumar N, Hovinga M, et al. 1996. A follow-up study of synthetic rubber workers. 

Toxicology 113:182-189. 

DeMeester C, Duverger-van Bogaert M, Lambotte-Vandepaer M, et al. 1981. Mutagenicity of styrene in 

the Salmonella typhimurium test system. Mutat Res 90:443-450. 

de Raat VK. 1978. Induction of sister chromatid exchanges by styrene and its presumed metabolite 

styrene oxide in the presence of rat liver homogenate. Chem Biol Interact 20:163-170. 

Dilling WL. 1977. Interphase transfer processes. II. Evaporation rates of chloro methanes, ethanes, 

ethylenes, propanes, and propylenes from dilute aqueous solutions. Comparisons with theoretical 

predictions. Environ Sci Technol 11:405-409. 

Dixit R, Das M, Mushtaq M, et al. 1982. Depletion of glutathione content and inhibition of glutathioneS-transferase and aryl hydrocarbon hydroxylase activity of rat brain following exposure to styrene. 

Neurotoxicology 3:142-145. 
 

 

 

 

 

 

 

 

STYRENE 199 

9. REFERENCES 

Dogra RKS, Chandra K, Chandra S, et al. 1992. Host resistance assays as predictive models in styrene 

immunomodulation. Int J Immunopharmacol 14(6):1003-1009. 

Dolara P, Caderni G, Lodovici M, et al. 1984. Determination of styrene in the urine of workers 

manufacturing polystyrene plastics. Ann Occup Hyg 28:195-199. 

Donner M, Sorsa M, Vainio H. 1979. Recessive lethals induced by styrene and styrene oxide in 

Drosophila melanogaster. Mutat Res 67:373-376. 

Drummond L, Caldwell J, Wilson HK. 1989. The metabolism of ethylbenzene and styrene to mandelic 

acid: Stereochemical considerations. Xenobiotica 19:199-207. 

Duffy E, Gibney MJ. 2007. Use of a food-consumption database with packaging information to estimate 

exposure to food-packaging migrants: Epoxidized soybean oil and styrene monomer. Food Addit 

Contam 24(2):216-225. 

Dumont JP, Adda J. 1978. Occurrence of sesquiterpenes in mountain cheese volatiles. J Agric Food 

Chem 26:364-367. 

Dunkel VC, Zeiger E, Brusick D, et al. 1985. Reproducibility of microbial mutagenicity assays: II. 

Testing of carcinogens and noncarcinogens in Salmonella typhimurium and Escherichia coli. Environ 

Mut 7(Suppl 5):1-248. 

Dutkiewicz T, Tyras H. 1968. Skin absorption of toluene, styrene, and xylene by man. Br J Ind Med 

25:243. 

Edling C, Anundi H, Johanson G, et al. 1993. Increase in neuropsychiatric symptoms after occupational 

exposure to low levels of styrene (Comment in: Occup Environ Med 51(4):286-287). Br J Ind Med 

50(9):843-850. 

Eguchi T, Kishi R, Harabuchi I, et al. 1995. Impaired colour discrimination among workers exposed to 

styrene: Relevance of a urinary metabolite. Occup Environ Med 52:534-538. 

Eitzer BD. 1995. Emissions of volatile organic chemicals from municipal solid waste composting 

facilities. Environ Sci Technol 29:896-902. 

Elia VJ, Anderson LA, MacDonald TJ, et al. 1980. Determination of urinary mandelic and 

phenylglyoxylic acids in styrene exposed workers and a control population. Am Ind Hyg Assoc J 

41:922-926. 

Ellenhorn MJ, Barceloux DG. 1988. Styrene. In: Medical toxicology: Diagnosis and treatment of 

human poisoning. New York, NY: Elsevier, 956-959. 

Engelhardt G, Gamer A, Vodicka P, et al. 2003. A re-assessment of styrene-induced clastogenicity in 

mice in a subacute inhalation study. Arch Toxicol 77:56-61. 

Engstrom J, Astrand I, Wigaeus E. 1978b. Exposure to styrene in a polymerization plant: Uptake in the 

organism and concentration in subcutaneous adipose tissue. Scand J Work Environ Health 4:324-329. 
 

 

 

 

 

 

 

 

 

 

STYRENE 200 

9. REFERENCES 

Engstrom J, Bjurstrom R, Astrand I, et al. 1978a. Uptake, distribution and elimination of styrene in man: 

Concentration in subcutaneous adipose tissue. Scand J Work Environ Health 4:315-323. 

Engstrom K, Harkonen H, Kalliokoski P, et al. 1976. Urinary mandelic acid concentration after 

occupational exposure to styrene and its use as a biological exposure test. Scand J Work Environ Health 

2:21-26. 

EPA. 1975. Identification of organic compounds in effluents from industrial sources. Washington, DC: 

U.S. Environmental Protection Agency, Office of Toxic Substances. EPA560375002. 

EPA. 1976. Frequency of organic compounds identified in water. Athens, GA: U.S. Environmental 

Protection Agency, Office of Research and Development. EPA600476062. PB265470. 

EPA. 1978. Environmental monitoring near industrial sites: Brominated chemicals. Part I. Research 

Triangle Park, NC: U.S. Environmental Protection Agency, Office of Toxic Substances. PB286484. 

EPA. 1979a. Atmospheric reaction products of organic compounds. Washington, DC: U.S. 

Environmental Protection Agency, Office of Toxic Substances. EPA5601279001. PB301384. 

EPA. 1979b. Identification of organic compounds in industrial effluent discharges. Athens, GA: U.S. 

Environmental Protection Agency, Office of Research and Development. EPA600479016. PB294794. 

EPA. 1980. Fate of toxic and hazardous materials in the air environment. Research Triangle Park, NC: 

U.S. Environmental Protection Agency, Office of Research and Development. EPA600380084. 

PB80221948. 

EPA. 1981. Treatability manual. Vol. I. Treatability data. Washington, DC: U.S. Environmental 

Protection Agency, Office of Research and Development. EPA600282001A. 

EPA. 1982a. Aquatic fate process data for organic priority pollutants. Washington, DC: U.S. 

Environmental Protection Agency, Office of Water Regulations and Standards. EPA440481014. 

PB87169090. 

*EPA. 1982b. Chemical information rules; manufacturers reporting; preliminary assessment 

information. U.S. Environmental Protection Agency. Fed Regist 47:26992, 27007. 

EPA. 1983. Volatile organic chemicals in the atmosphere: An assessment of available data. Research 

Triangle Park, NC: U.S. Environmental Protection Agency, Office of Research and Development. 

EPA600383027A. 

EPA. 1984a. Drinking water criteria document for styrene. Cincinnati, OH: U.S. Environmental 

Protection Agency, Environmental Criteria and Assessment Office. EPA600X84195. 

EPA. 1984b. Health and environmental effects profile for styrene. Cincinnati, OH: U.S. Environmental 

Protection Agency, Environmental Criteria and Assessment Office. EPA600X84325. 

EPA. 1985a. Drinking water criteria document for styrene. Final draft. Cincinnati, OH: U.S. 

Environmental Protection Agency, Office of Health and Environmental Assessment. ECAOCIN409. 

EPA. 1985b. Synthetic organic compound sampling survey of public water supplies. Washington, DC: 

U.S. Environmental Protection Agency. PB85214427. 
 

 

 

 

 

 

 

 

 

STYRENE 201 

9. REFERENCES 

EPA. 1986a. National primary drinking water regulations; synthetic organic chemicals, inorganic 

chemicals and microorganisms; correction. U.S. Environmental Protection Agency. Fed Regist 

51(25):4618. 

EPA. 1986b. Gas chromatography/mass spectrometry for volatile organics, method 8240. In: Test 

methods for evaluating solid waste. Vol. IA: Laboratory manual, physical/chemical methods. 3rd ed. 

SW-846. Washington, DC: U.S. Environmental Protection Agency, Office of Solid Waste and 

Emergency Response. 

EPA. 1986c. Method 8020. Aromatic volatile organics. In: Test methods for evaluating solid waste. 

3rd ed. SW-846. Washington, DC: U.S. Environmental Protection Agency, Office of Solid Waste and 

Emergency Response. 

EPA. 1986d. Broad scan analysis of the FY82 national human adipose tissue survey specimens. Vol. I. 

Executive summary. Washington, DC: U.S. Environmental Protection Agency, Office of Toxic 

Substances. EPA560586035. 

*EPA. 1987a. Styrene: Health advisory. Washington, DC: U.S. Environmental Protection Agency, 

Office of Drinking Water. 

*EPA. 1987b. National primary drinking water regulations; synthetic organic chemicals, monitoring for 

unregulated contaminants. Part II. U.S. Environmental Protection Agency. Fed Regist 52:25710. 

*EPA. 1987c. List (phase 1) of hazardous constituents for ground water monitoring, final rule. U.S. 

Environmental Protection Agency: Fed Regist 52(131):25942-25952. 

EPA. 1987d. Toxic air pollutant/source crosswalk: A screening tool for locating possible sources 

emitting toxic air pollutants. Research Triangle Park, NC: U.S. Environmental Protection Agency, 

Office of Air Quality Planning and Standards. EPA450487023a. PB88161146. 

EPA. 1987e. The Total Exposure Assessment Methodology (TEAM) study: Summary and analysis. 

Vol. I. Washington, DC: U.S. Environmental Protection Agency, Office of Research and Development. 

EPA600687002a. PB088100060. 

EPA. 1988a. Toxic chemical release reporting: Community right to know. U.S. Environmental 

Protection Agency. Fed Regist 53:4500-4501. 

EPA. 1988b. Drinking water criteria document for styrene. Final draft. Cincinnati, OH: U.S. 

Environmental Protection Agency, Office of Health and Environmental Assessment. ECAOCIN409. 

EPA. 1988c. National ambient volatile organic compounds (VOCs) database update. Research Triangle 

Park, NC: U.S. Environmental Protection Agency. EPA600338010a. PB88195631. 

*EPA. 1989a. List of hazardous substances and reportable quantities. U.S. Environmental Protection 

Agency. Fed Regist 54(155):33425-33484. 

*EPA. 1989b. National primary and secondary drinking water regulations. U.S. Environmental 

Protection Agency. Fed Regist 54:22064, 22090. 
 

 

 

 

 

 

 

 

 

 

 

STYRENE 202 

9. REFERENCES 

EPA. 1989c. The toxics-release inventory: A national perspective. Washington, DC: U.S. 

Environmental Protection Agency, Office of Toxic Substances. EPA560489005. 

EPA. 1989d. Interim methods for development of inhalation reference doses. Washington, DC: U.S. 

Environmental Protection Agency, Office of Health and Environmental Assessment. EPA600888066F. 

EPA. 1989e. Exposure factors handbook. Washington, DC: U.S. Environmental Protection Agency, 

Office of Health and Environmental Assessment. EPA600889043. 

EPA. 1989f. Method 503.1 volatile aromatic and unsaturated organic compounds in water by purge and 

trap gas chromatography. U.S. Environmental Protection Agency, Office of Research and Development. 

EPA. 1989g. Methods 508, 501.1, 502.2. Methods for the determination of organic compounds in 

drinking water. Cincinnati, OH: U.S. Environmental Protection Agency, Environmental Monitoring and 

Support Laboratory. EPA600488039. 

EPA. 1989h. Method 524.1. Measurement of purgeable organic compounds in water by packed column 

gas chromatography/mass spectrometry. Methods for the determination of organic compounds in 

drinking water. Cincinnati, OH: U.S. Environmental Protection Agency, Office of Research and 

Development. EPA600488039. 

EPA. 1989i. Method 524.2. Measurement of purgeable organic compounds in water by capillary 

column gas chromatography/mass spectrometry. In: Methods for the determination of organic 

compounds in drinking water. Cincinnati, OH: U.S. Environmental Protection Agency, Office of 

Research and Development. EPA600488039. 

EPA. 1990. Interim methods for development of inhalation reference concentrations. Washington, DC: 

U.S. Environmental Protection Agency, Office of Health and Environmental Assessment, Office of 

Research and Development, Environmental Criteria and Assessment Office. EPA600890066A. 

PB90238890. 

EPA. 1993a. Determination of rates of reaction in the gas-phase in the troposphere. Theory and practice. 

5. Rate of indirect photoreaction: Evaluation of the atmospheric oxidation computer program of 

Syracuse Research Corporation for estimating the second-order rate constant for the reaction of an 

organic chemical with hydroxyl radicals. Washington, DC: U.S. Environmental Protection Agency. 

EPA744R93001. 

EPA. 1993b. Final report on literature review of atmospheric transformation products of Clean Air Act 

Title III hazardous air pollutants. Research Triangle Park: U.S. Environmental Protection Agency. 

EPA600R94088. 

EPA. 1995. Method 502.2. Volatile organic compounds in water by purge and trap capillary column gas 

chromatography with photoionization and electrolytic conductivity detectors in series. Cincinnati, OH: 

U.S. Environmental Protection Agency. 

EPA. 1996. Method 8021B: Aromatic and halogenated volatiles by gas chromatography using 

photoionization and/or electrolytic conductivitiy detectors. Washington, DC: U.S. Environmental 

Protection Agency, Office of Solid Waste. 

EPA. 1997. Special report on environmental endocrine disruption: An effects assessment and analysis. 

Washington, DC: U.S. Environmental Protection Agency, Risk Assessment Forum. EPA630R96012. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

STYRENE 203 

9. REFERENCES 

EPA. 2001. Method 1625. Semivolatile organic compounds by isotope dilution GCMS. U.S. 

Environmental Protection Agency. Code of Federal Regulations. 40 CFR Part 136, App. A. 

EPA. 2003. National primary drinking water regulations. Washington, DC: U.S. Environmental 

Protection Agency, Office of Ground Water and Drinking Water. EPA816F03016. 

http://www.epa.gov/safewater/mcl.html. March 07, 2006. 

EPA. 2005. Toxic chemical release inventory reporting forms and instructions: Revised 2004 version. 

Section 313 of the Emergency Planning and Community Right-to-Know Act (Title III of the Superfund 

Amendments and Reauthorization Act of 1986). U.S. Environmental Protection Agency. Office of 

Environmental Information. EPA260B05001. 

EPA. 2006. Drinking water standards and health advisories. Washington, DC: U.S. Environmental 

Protection Agency, Office of Water. EPA822R04005. http://epa.gov/waterscience/criteria/drinking/. 

April 11, 2007. 

EPA. 2007a. Acute exposure guideline levels (AEGLs) Washington, DC: U.S. Environmental 

Protection Agency, Office of Pollution Prevention and Toxics. 

EPA. 2007b. Designated as hazardous substances in accordance with Section 311(b)(2)(A) of the Clean 

Water Act. U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 116.4. 

http://www.epa.gov/epacfr40/chapt-I.info/chi-toc.htm. April 11, 2007. 

EPA. 2007c. Hazardous air pollutants. Clean Air Act. U.S. Environmental Protection Agency. United 

States Code. 42 USC 7412. http://www.epa.gov/ttn/atw/orig189.html. April 11, 2007. 

EPA. 2007d. Master testing list. Washington, DC: U.S. Environmental Protection Agency, Office of 

Pollution Prevention and Toxics. http://www.epa.gov/opptintr/chemtest/pubs/mtl.htm. May 10, 2007. 

EPA. 2007e. Reportable quantities of hazardous substances designated pursuant to Section 311 of the 

Clean Water Act. U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 117.3. 

http://www.epa.gov/epacfr40/chapt-I.info/chi-toc.htm. April 11, 2007. 

EPA. 2007f. Superfund, emergency planning, and community right-to-know programs. Designation, 

reportable quantities, and notifications. U.S. Environmental Protection Agency. Code of Federal 

Regulations. 40 CFR 302.4. http://www.epa.gov/epacfr40/chapt-I.info/chi-toc.htm. April 11, 2007. 

EPA. 2007g. Superfund, emergency planning, and community right-to-know programs. Toxic chemical 

release reporting. U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 372.65. 

http://www.epa.gov/epacfr40/chapt-I.info/chi-toc.htm. April 11, 2007. 

ESIS. 2009. Styrene. European chemical Substances Information System. European Commission. 

http://ecb.jrc.ec.europa.eu/esis/. March 17, 2009. 

Fallas C, Fallas J, Maslard P, et al. 1992. Subclinical impairment of colour vision among workers 

exposed to styrene. Br J Ind Med 49(10):679-682. 

FDA. 2006a. Beverages. Bottled water. U.S. Food and Drug Administration. Code of Federal 

Regulations. 21 CFR 165.110. http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm. 

April 11, 2007. 
 

 

 

 

 

 

STYRENE 204 

9. REFERENCES 

FDA. 2006b. Indirect food additives: Adhesives and components of coatings. U.S. Food and Drug 

Administration. Code of Federal Regulations. 21 CFR 175. 

http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm. May 10, 2007. 

FDA. 2007a. Everything added to food in the United States (EAFUS). Washington, DC: U.S. Food and 

Drug Administration. http://vm.cfsan.fda.gov/~dms/eafus.html. April 11, 2007. 

FDA. 2007b. Food additives permitted for direct addition to food for human. Code of Federal 

Regulations. 21 CFR 172. Washington, DC: U.S. Food and Drug Administration. 

http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm. May 15, 2007. 

FEDRIP. 2007. Styrene. Federal Research in Progress database. Springfield, VA: National Technical 

Information Service. 

Fishbein L. 1992. Exposure from occupational versus other sources. Scand J Work Environ Health 

18(1):5-16. 

Fisher J, Mahle D, Bankston L, et al. 1997. Lactational transfer of volatile chemicals in breast milk. Am 

Ind Hyg Assoc J 58(6):425-431. 

Fleming-Jones ME, Smith RE. 2003. Volatile organic compounds in foods: A five-year study. J Agric 

Food Chem 51(27):8120-8127. 

Flodin U, Ekberg K, Andersson L. 1989. Neuropsychiatric effects of low exposure to styrene. Br J Ind 

Med 46:805-808. 

Fomon SJ. 1966. Body composition of the infant: Part 1: The male reference infant. In: Faulkner F, 

eds. Human development. Philadelphia, PA: WB Saunders, 239-246. 

Fomon SJ, Haschke F, Ziegler EE, et al. 1982. Body composition of reference children from birth to age 

10 years. Am J Clin Nutr 35(Suppl 5):1169-1175. 

Frentzel-Beyme R, Thiess AM, Wieland R. 1978. Survey of mortality among employees engaged in 

manufacture of styrene and polystyrene at the BASF Ludwigshafen works. Scand J Work Environ Health 

4:231-239. 

Fu MH, Alexander M. 1992. Biodegradation of styrene in samples of natural environments. Environ Sci 

Technol 26:1540-1544. 

Fu MH, Alexander M. 1996. Biodegradation of styrene in waterlogged soils and aquifer solids. Soil Sci 

161(12):846-851. 

Fu MH, Mayton H, Alexander M. 1994. Desorption and biodegradation of sorbed styrene in soil and 

aquifer solids. Environ Toxicol Chem 13(5):749-753. 

Fujita H, Koizumi A, Furusawa T, et al. 1987. Decreased erythrocyte β-aminolevulinate dehydratase 

activity after styrene exposure. Biochem Pharmacol 36:711-716. 

Fung F, Clark RF. 1999. Styrene-induced peripheral neuropathy. Clin Toxicol 37(1):91-97. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

STYRENE 205 

9. REFERENCES 

Fustinoni S, Campo L, Manini P, et al. 2008. An integrated approach to biomonitoring exposure to 

styrene and styrene-(7,8)-oxide using a repeated measurements sampling design. Biomarkers 13(6):560-

578. 

Gamberale F, Lisper HO, Olson BA. 1976. The effect of styrene vapour on the reaction time of workers 

in the plastic boat industry. In: Horvath M, ed. Adverse effects of environmental chemicals and 

psychomotor drugs. Neurophysiological and behavioral tests. London, England: Elsevier Scientific 

Pub., 135-148. 

Gargas ML, Burgess RJ, Voisard DE, et al. 1989. Partition coefficients of low-molecular-weight volatile 

chemicals in various liquids and tissues. Toxicol Appl Pharmacol 98:87-99. 

Gerin M, Siemiatycki J, Desy M, et al. 1998. Associations between several sites of cancer and 

occupational exposure to benzene, toluene, xylene, and styrene: Results of a case-control study in 

Montreal. Am J Ind Med 34:144-156. 

Geuskens RBM, van der Klaauw MM, van der Tuin J, et al. 1992. Exposure to styrene and health 

complaints in the Dutch glass-reinforced plastics industry. Ann Occup Hyg 36:47-57. 

Ghittori S, Imbriani M, Pezzagno G, et al. 1987. The urinary concentration of solvents as a biological 

indicator of exposure: Proposal for the biological equivalent exposure limit for nine solvents. Am Ind 

Hyg Assoc J 48:786-790. 

Gilbert J, Startin JR. 1983. A survey of styrene monomer levels in foods and plastic packaging by 

coupled mass spectrometry-automatic headspace gas chromatography. J Sci Food Agric 34:647-652. 

Giwercman A, Carlsen E, Keiding N, et al. 1993. Evidence for increasing incidence of abnormalities of 

the human testis: A review. Environ Health Perspect Suppl 101(2):65-71. 

Gobba F, Cavalleri F, Bontadi D, et al. 1995. Peripheral neuropathy in styrene-exposed workers. Scand 

J Work Environ Health 21:517-520. 

Gobba F, Galassi C, Ghittori S, et al. 1993. Urinary styrene in the biological monitoring of styrene 

exposure. Scand J Work Environ Health 19:175-182. 

Gobba F, Galassi C, Imbriani M, et al. 1991. Acquired dyschromatopsia among styrene-exposed 

workers (Comment in: J Occup Med 34(5):563-564). J Occup Med 33(7):761-765. 

Gong YY, Kishi R, Katakura Y, et al. 2002. Relation between colour vision loss and occupational 

styrene exposure level. Occup Environ Med 59(12):824-829. 

Goodley PC, Gordon M. 1976. Characterization of industrial organic compounds in water. Trans KY 

Acad Sci 37(1-2):11-15. 

Gosselin RE, Smith RP, Hodge HC, et al. 1984. Clinical toxicology of commercial products. 5th ed. 

Baltimore, MD: Williams and Wilkins, II-152. 

Gotz R, Bauer OR, Friesel P, et al. 1998. Organic trace compounds in the water of the River Elbe near 

Hamburg. Part II. Chemosphere 36:2103-2118. 
 

 

 

 

 

 

 

 

 

 

STYRENE 206 

9. REFERENCES 

Graedel TE. 1978. Aromatic compounds: Benzene and derivatives. In: Chemical compounds in the 

atmosphere. New York, NY: Academic Press, 105-113. 

Graff JJ, Sathiakumar N, Macaluso M, et al. 2005. Chemical exposures in the synthetic rubber industry 

and lymphohematopoietic cancer mortality. J Occup Environ Med 47(9):916-932. 

Grbic-Galic D, Churchman-Eisel N, Mrakovic I. 1990. Microbial transformation of styrene by anaerobic 

consortia. J Appl Bacteriol 69:247-260. 

Green DR, Le Pape D. 1987. Stability of hydrocarbon samples on solid-phase extraction columns. Anal 

Chem 59:699-703. 

Green T, Lee R, Toghill A, et al. 2001a. The toxicity of styrene to the nasal epithelium of mice and rats: 

Studies on the mode of action and relevance to humans. Chem Biol Interact 137:185-202. 

Grosjean D, Fung K. 1984. Hydrocarbons and carbonyls in Los Angeles air. J Air Pollut Control Assoc 

34:537-543. 

Grosjean E, Grosjean D, Rasmussen RA. 1998. Ambient concentrations, sources, emission rates, and 

photochemical reactivity of C2-C10 hydrocarbons in Porto Alegre, Brazil. Environ Sci Technol 

32(14):2061-2069. 

Guillemin MP, Bauer D. 1979. Human exposure to styrene. III. Elimination kinetics of urinary 

mandelic and phenylglyoxylic acids after single experimental exposure. Int Arch Occup Environ Health 

44:249-263. 

Guillemin MP, Berode M. 1988. Biological monitoring of styrene: A review. Am Ind Hyg Assoc J 

49:497-505. 

Guzelian PS, Henry CJ, Olin SS, eds. 1992. Similarities and differences between children and adults: 

implications for risk assessment. Washington DC: International Life Sciences and Press Institute Press. 

Haddad LM, Winchester JF. 1990. Clinical management of poisoning and drug overdose. 2nd ed. 

Philadelphia, PA: W.B. Saunders Company, 1226-1228. 

Hallier E, Goergens HW, Hallier K, et al. 1994. Intervention study on the influence of reduction of 

occupational exposure to styrene on sister chromatid exchanges in lymphocytes. Int Arch Occup Environ 

Health 66(3):167-172. 

Hallier E, Goergens HW, Karels H, et al. 1995. A note on individual differences in the urinary excretion 

of optical enantiomers of styrene metabolites and of styrene-derived mercapturic acids in humans. Arch 

Toxicol 69(5):300-305. 

Hampton CV, Pierson WR, Harvey TM, et al. 1982. Hydrocarbon gases emitted from vehicles on the 

road. 1. A qualitative gas chromatography/mass spectrometry survey. Environ Sci Technol 16:287-298. 

Hampton CV, Pierson WR, Schuetzie D, et al. 1983. Hydrocarbon gases emitted from vehicles on the 

road. 2. Determination of emission rates from diesel and spark-ignition vehicles. Environ Sci Technol 

17:699-708. 
 

 

 

 

 

 

 

 

STYRENE 207 

9. REFERENCES 

Hansch C, Leo A, Hoekman D. 1995. Exploring QSAR. Hydrophobic, electronic, and steric constants. 

Washington, DC: American Chemical Society, 40. 

Hansteen IL, Jelmert O, Torgrimsen T, et al. 1984. Low human exposure to styrene in relation to 

chromosome breaks, gaps and sister-chromatid exchanges. Hereditas 100:87-91. 

Härkönen H, Holmberg PC. 1982. Obstetric histories of women occupationally exposed to styrene. 

Scand J Work Environ Health 8:74-77. 

Härkönen H, Lehtniemi A, Aitio A. 1984. Styrene exposure and the liver. Scand J Work Environ Health 

10:59-61. 

Härkönen H, Kalliokoski P, Hietala S, et al. 1974. Concentrations of mandelic and phenlyglyoxylic acid 

in urine as indicators of styrene exposure. Work Environ Health 11:162-169. 

Härkönen H, Lindstrom K, Seppäläinen AM, et al. 1978. Exposure-response relationship between 

styrene exposure and central nervous functions. Scand J Work Environ Health 4:53-59. 

Harkov R, Gianti SJ, Bozzelli JW, et al. 1985. Monitoring volatile organic compounds at hazardous and 

sanitary landfills in New Jersey. J Environ Sci Health A20:491-501. 

Hartmans S. 1995. Microbial degradation of styrene. In: Singh VP, ed. Biotransformations: Microbial 

degradation of health risk compounds. Amsterdam: Elsevier Science, 227-238. 

Hassett JJ, Banwart WL, Griffin RA. 1983. Correlation of compound properties with sorption 

characteristics of nonpolar compounds by soils and sediments: Concepts and limitations. In: Francis 

CW, Auerbach SI, eds. Environmental and solid wastes: Characterization, treatment, and disposal. 

Boston, MA: Butterworths, 161-176. 

HazDat. 2007. Styrene. HazDat Database: ATSDR’s Hazardous Substance Release and Health Effects 

Database. Atlanta, GA: Agency for Toxic Substances and Disease Registry. 

http://www.atsdr.cdc.gov/hazdat.html. May 21, 2007. 

Hemminki K, Franssila E, Vainio H. 1980. Spontaneous abortions among female chemical workers in 

Finland. Int Arch Occup Environ Health 45:123-126. 

Hemminki K, Lindbohm ML, Hemminki T, et al. 1984. Reproductive hazards and plastics industry. In: 

Jarvisalo J, Pfaffli P, Vainio H, eds. Industrial hazards of plastics and synthetic elastomers. New York, 

NY: Alan R. Liss, Inc., 79-87. 

Heylin M, ed. 1989. Production by the U.S. chemical industry: Growth maintains a strong pace. Chem 

Eng News 67:38-45. 

Hodgson AT, Rudd AF, Beal D, et al. 2000. Volatile organic compound concentrations and emission 

rates in new manufactures and site-built houses. Indoor Air 10:178-192. 

Hodgson JT, Jones RD. 1985. Mortality of styrene production, polymerization and processing workers at 

a site in northwest England. Scand J Work Environ Health 11:347-352. 

Hoel DG, Davis DL, Miller AB, et al. 1992. Trends in cancer mortality in 15 industrialized countries, 

1969-1986. J Natl Cancer Inst 84(5):313-320. 
 

 

 

 

 

 

 

 

 

STYRENE 208 

9. REFERENCES 

Hogstedt B, Akesson B, Axell K, et al. 1983. Increased frequency of lymphocyte micronuclei in workers 

producing reinforced polyester resin with low exposure to styrene. Scand J Work Environ Health 9:241-

246. 

Hogstedt B, Hender K, Mark-Vendel E, et al. 1979. Increased frequency of chromosome aberrations in 

workers exposed to styrene. Scand J Work Environ Health 5:333-335. 

Hotz P, Guillemin MP, Lob M. 1980. Study of some hepatic effects (induction and toxicity) caused by 

occupational exposure to styrene in the polyester industry. Scand J Work Environ Health 6:206-215. 

HSDB. 2009. Styrene. Hazardous Substances Data Bank. National Library of Medicine. 

http://toxnet.nlm.nih.gov. March 17, 2009. 

Husain R, Srivastava SP, Mushtaq M, et al. 1980. Effect of styrene on levels of serotonin, noradrenaline, 

dopamine and activity of acetyl cholinesterase and monoamine oxidase in rat brain. Toxicol Lett 7:47-50. 

Husain R, Srivastava SP, Seth PK. 1985. Some behavioral effects of early styrene intoxication in 

experimental animals. Arch Toxicol 57:53-55. 

Hynes DE, DeNicola DB, Carlson GP. 1999. Metabolism of styrene by mouse and rat isolated lung 

cells. Toxicol Sci 51:195-201. 

IARC. 1979. Styrene, polystyrene and styrene-butadiene copolymers. IARC monographs on the 

evaluation of the carcinogenic risk of chemicals to humans. Vol. 19. Some monomers, plastics and 

synthetic elastomers, and acrolein. Geneva, Switzerland: International Agency for Research on Cancer, 

World Health Organization, 231-274. 

IARC. 1994. IARC monographs on the evaluation of the carcinogenic risk of chemicals to humans. 

Lyon, France: International Agency for Research on Cancer, 233-320. 

IARC. 2002. IARC monographs on the evaluation of carcinogenic risk to humans. Vol. 82. Some 

traditional herbal medicines, some mycotoxins, naphthalene and styrene. Lyon, France: International 

Agency for Research on Cancer, 437-550. 

IARC. 2006. Agents Reviewed by the IARC Monographs. Volumes 1–96. Lyon, France: International 

Agency for Research on Cancer. http://monographs.iarc.fr/ENG/Classification/index.php. April 11, 

2007. 

Ikeda M, Hirayama T. 1978. Possible metabolic interaction of styrene with organic solvents. Scand J 

Work Environ Health 4:41-46. 

Ikeda M, Ohtsuji H, Imamura T. 1972. In vivo suppression of benzene and styrene oxidation by coadministered toluene in rats and effects of phenobarbital. Xenobiotica 2:101-106. 

Iregren A, Johnson AC, Nylen P. 2005. Low-level styrene exposure and color vision in Swedish styrene 

workers. Environ Toxicol Pharmacol 20(3):506. 

IRIS. 2009. Styrene. Integrated Risk Information System. Washington, DC: U.S. Environmental 

Protection Agency. http://www.epa.gov/iris/subst/index.html. March 26, 2009. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

STYRENE 209 

9. REFERENCES 

Islam MA, Stancheva E. 1999. Volatile organic compounds in the ambient air of Rousse, Bulgaria. 

Water Air Soil Pollut 115:309-320. 

Jablonicka A, Karelova J, Polakova H, et al. 1988. Analysis of chromosomes in peripheral blood 

lymphocytes of styrene-exposed workers. Mutat Res 206:167-169. 

James DH, Castor WM. 2005. Styrene. In: Ullman’s encyclopedia of industrial chemistry. 

http://www.mrw.interscience.wiley.com/emrw/9783527306732/ueic/article/a25_329/current/pdf. May 

30, 2007. 

Jantunen K, Maki-Paakkanen J, Norppa H. 1986. Induction of chromosome aberrations by styrene and 

vinylacetate in cultured human lymphocytes: Dependence on erythrocytes. Mutat Res 159:109-116. 

Jarry H, Metten M, Gamer AO, et al. 2002. Effects of 5-day styrene inhalation on serum prolactin and 

dopamine levels and on hypothalamic and striatal catecholamine concentrations in male rats. Arch 

Toxicol 76:657-663. 

Jegaden D, Amann D, Simon JF, et al. 1993. Study of the neurobehavioural toxicity of styrene at low 

levels of exposure. Int Arch Occup Environ Health 64(7):527-531. 

Jersey GM, Balmer J, Quast J, et al. 1978. Two-year chronic inhalation toxicity and carcinogenicity 

study on monomeric styrene in rats - final report. Dow Chemical Company. Submitted to the U.S. 

Environmental Protection Agency under TSCA Section 8E. OTS8EHQ-0692-4867. 

Johanson CE. 1980. Permeability and vascularity of the developing brain: Cerebellum vs. cerebral 

cortex. Brain Res 190(1):3-16. 

Johanson G, Ernstgard L, Gullstrand E, et al. 2000. Styrene oxide in blood, hemoglobin adducts, and 

urinary metabolites in human volunteers exposed to 13C8-styrene vapors. Toxicol Appl Pharmacol 

168:36-49. 

Johnston R, Mensik D, Linscombe A, et al. 1983. An evaluation of styrene vapor inhalation in pigs. 

Report of Dow Chemical U.S.A., Freeport, TX. 

Jonsson F, Johanson G. 2002. Physiologically based modeling of the inhalation kinetics of styrene in 

humans using a Bayesian population approach. Toxicol Appl Pharmacol 179:35-49. 

Junk GA, Ford CS. 1980. A review of organic emissions from selected combustion processes. 

Chemosphere 9:187-230. 

Kagi N, Fujii S, Horiba Y, et al. 2007. Indoor air quality for chemical and ultrafine particle contaminants 

from printers. Build Environ 42(5):1949-1954. 

Kankaanpää JT, Eovaara E, Hemminki K, et al. 1980. The effect of maternally inhaled styrene on 

embryonal and foetal development in mice and Chinese hamsters. Acta Pharmacol Toxicol 47:127-129. 

Karakaya AE, Karahalil B, Yilmazer M, et al. 1997. Evaluation of genotoxic potential of styrene in 

furniture workers using unsaturated polyester resins. Mutat Res 392:261-268. 

Katakura Y, Kishi R, Ikeda T, et al. 1999. Effects of prenatal exposure to styrene on neurochemical 

levels in rat brain. Toxicol Lett 105:239-249. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

STYRENE 210 

9. REFERENCES 

Katakura Y, Kishi R, Ikeda T, et al. 2001. Effects of prenatal styrene exposure on postnatal development 

and brain serotonin and catecholamine levels in rats. Environ Res 85(1):41-47. 

*Katoh T, Higashi K, Inoue N. 1989. Subchronic effects of styrene and styrene oxide on lipid 

peroxidation and the metabolism of glutathione in rat liver and brain. J Toxicol Sci 14:1-9. 

Keenan C, Harriman E. 1993. Styrene use in Massachusetts. Lowell, MA: University of Massachusetts. 

Toxic Use Reduction Institute. 

Kenaga EE. 1980. Predicted bioconcentration factors and soil sorption coefficients of pesticides and 

other chemicals. Ecotoxicol Environ Safety 4:26-38. 

Kenaga EE, Goring CAI. 1980. Relationship between water solubility, soil sorption, octanol-water 

partitioning, and concentration of chemicals in biota. ASTM Spec Tech Publ 707:78-115. 

Kessler W, Jiang X, Filser JG. 1990. Direct determination of styrene-7,8-oxide in blood by gas 

chromatography with flame ionization detector. J Chromatog 534:67-75. 

Khanna VK, Husain R, Seth PK. 1994. Effect of protein malnutrition on the neurobehavioural toxicity of 

styrene in young rats. J Appl Toxicol 14(5):351-356. 

Kim H, Wang RS, Elovaara E, et al. 1997. Cytochrome P450 isozymes responsible for the metabolism 

of toluene and styrene in human liver microsomes. Xenobiotica 27(7):657-665. 

King L, Sherbin G. 1986. Point sources of toxic organics to the upper St. Clair River. Water Poll Res J 

Canada 21:433-446. 

Kinlin TE, Muralidhara R, Pittet AO, et al. 1972. Volatile components of roasted filberts. J Agric Food 

Chem 20:1021-1028. 

Kinney PL, Chillrud SN, Ramstrom S, et al. 2002. Exposures to multiple air toxics in New York City. 

Environ Health Perspect 110(Suppl 4):539-546. 

*Kishi R, Chen BQ, Katakura Y, et al. 1995. Effect of prenatal exposure to styrene on the 

neurobehavioral development, activity, motor coordination, and learning behavior of rats. Neurobehav 

Toxicol Teratol 17(2):121-130. 

Kishi R, Eguchi T, Yuasa J, et al. 2001. Effects of low-level occupational exposure to styrene on color 

vision: Dose relation with a urinary metabolite. Environ Res 85(1):25-30. 

*Kishi R, Katakura Y, Ikeda T, et al. 1992. Neurochemical effects in rats following gestational exposure 

to styrene. Toxicol Lett 63:141-146. 

Kleopfer RD, Fairless BJ. 1972. Characterization of organic components in a municipal water supply. 

Environ Sci Technol 6:1036-1037. 

Kligerman AD, Allen JW, Bryant MF, et al. 1992. Cytogenetic studies of mice exposed to styrene by 

inhalation. Mutat Res 280:35-43. 
 

 

 

 

 

 

 

 

 

 

 

STYRENE 211 

9. REFERENCES 

Kneip TJ, Crable JV. 1988a. Styrene in expired air. In: Methods for biological monitoring. 

Washington, DC: American Public Health Association, 457-462. 

Kneip TJ, Crable JV. 1988b. Mandelic acid in urine. In: Methods for biological monitoring. 

Washington, DC: American Public Health Association, 387-391. 

Kneip TJ, Crable JV. 1988c. Phenylglyoxylic acid in urine. In: Methods for biological monitoring. 

Washington, DC: American Public Health Association, 393-399. 

Kogevinas M, Ferro G, Andersen A, et al. 1994. Cancer mortality in a historical cohort study of workers 

exposed to styrene. Scand J Work Environ Health 50:251-261. 

Kogevinas M, Ferro G, Saracci R, et al. 1993. Cancer mortality in an international cohort of workers 

exposed to styrene. IARC Sci Publ (127):289-300. 

Kohn AN. 1978. Ocular toxicity of styrene. Am J Ophthalmol 85:569-570. 

Kolstad HA, Bisanti L, Roeleveld N, et al. 1999c. Time to pregnancy for men occupationally exposed to 

styrene in several European reinforced plastics companies. Scand J Work Environ Health 25:66-69. 

Kolstad HA, Bisanti L, Roeleveld N, et al. 2000. Time to pregnancy among male workers of the 

reinforced plastics industry in Denmark, Italy and the Netherlands. Scand J Work Environ Health 

26(4):353-358. 

Kolstad HA, Bonde JP, Spano M, et al. 1999a. Change in semen quality and sperm chromatin structure 

following occupational styrene exposure. Int Arch Occup Environ Health 72:135-141. 

Kolstad HA, Bonde JPE, Spano M, et al. 1999b. Sperm chromatin structure and semen quality following 

occupational styrene exposure. Scand J Work Environ Health 25:70-73. 

Kolstad HA, Juel K, Olsen J, et al. 1995. Exposure to styrene and chronic health effects: Mortality and 

incidence of solid cancers in the Danish reinforced plastics industry. Occup Environ Med 52:320-327. 

Kolstad HA, Lynge E, Olsen J. 1993. Cancer incidence in the Danish reinforced plastics industry. IARC 

Sci Publ (127):301-308. 

Kolstad HA, Lynge E, Olsen J, et al. 1994. Incidence of lymphohematopoietic malignancies among 

styrene-exposed workers of the reinforced plastics industry. Scand J Work Environ Health 20:272-278. 

Komori M, Nishio K, Kitada M, et al. 1990. Fetus-specific expression of a form of cytochrome P-450 in 

human livers. Biochemistry 29(18):4430-4433. 

Konasewich D, Traversy W, Zar H. 1978. Status report on organic and heavy metal contaminants in the 

Lakes Erie, Michigan, Huron and Superior basins. Great Lakes Water Quality Board. 

Kool HJ, van Kreijl CF, Zoeteman BC. 1982. Toxicology assessment of organic compounds in drinking 

water. Crit Rev Environ Control 12:307-357. 

Korn M, Wodarz R, Drysch K, et al. 1987. Stereometabolism of styrene in man. Urinary excretion of 

chiral styrene metabolites. Arch Toxicol 60:86-88. 
 

 

 

 

 

 

 

 

 

 

 

 

 

STYRENE 212 

9. REFERENCES 

Korn M, Wodarz R, Schoknecht W, et al. 1984. Styrene metabolism in man: Gas chromatographic 

separation of mandelic acid enantiomers in the urine of exposed persons. Arch Toxicol 55:59-63. 

Krill RM, Sonzogni WC. 1986. Chemical monitoring of Wisconsin's groundwater. J Am Water Works 

Assoc 78:70-75. 

Krishnan K, Andersen ME. 1994. Physiologically based pharmacokinetic modeling in toxicology. In: 

Hayes AW, eds. Principles and methods of toxicology. 3rd ed. New York, NY: Raven Press, Ltd.,149-

188. 

Krishnan K, Anderson ME, Clewell HJ, et al. 1994. Physiologically based pharmacokinetic modeling of 

chemical mixtures. In: Yang RSH, eds. Toxicology of chemical mixtures. New York, NY: Academic 

Press, 399-437. 

Kulig BM. 1988. The neurobehavioral effects of chronic styrene exposure in the rat. Neurotoxicol 

Teratol 10:511-517. 

Laffon B, Pasaro E, Mendez J. 2002. Evaluation of genotoxic effects in a group of workers exposed to 

low levels of styrene. Toxicology 171(2-3):175-186. 

Laib RJ, Tucholski M, Filser JG, et al. 1992. Pharmacokinetic interaction between 1,3-butadiene and 

styrene in Sprague-Dawley rats. Arch Toxicol 66(5):310-314. 

Langvardt PW, Nolan RJ. 1991. Determination of styrene 7,8-oxide in whole rat blood by gas 

chromatography-mass spectrometry. J Chromatog 567:93-103. 

Lataye R, Campo P, Barthelemy C, et al. 2001. Cochlear pathology induced by styrene. Neurotoxicol 

Teratol 23(1):71-79. 

Lataye R, Campo P, Loquet G. 2000. Combined effects of noise and styrene exposure on hearing 

function in the rat. Hear Res 139:86-96. 

Lataye R, Campo P, Pouyatos B, et al. 2003. Solvent ototoxicity in the rat and guinea pig. Neurotoxicol 

Teratol 25(1):39-50. 

Leavens TL, Bond JA. 1996. Pharmacokinetic model describing the disposition of butadiene and styrene 

in mice. Toxicology 113(1-3):310-313. 

Leavens TL, Farris GM, James RA, et al. 1997. Genotoxicity and cytotoxicity in male B6C3F1 mice 

following exposure to mixtures of 1,3-butadiene and styrene. Environ Mol Mutagen 29:335-345. 

Leeder JS, Kearns GL. 1997. Pharmacogenetics in pediatrics: Implications for practice. Pediatr Clin 

North Am 44(1):55-77. 

Leibman KC. 1975. Metabolism and toxicity of styrene. Environ Health Perspect 11:115-119. 

Lemasters GK, Carson A, Samuels SJ. 1985. Occupational styrene exposure for twelve product 

categories in the reinforced-plastics industry. Am Ind Hyg Assoc J 46:434-441. 
 

 

 

 

 

 

 

 

STYRENE 213 

9. REFERENCES 

Lemasters GK, Samuels SJ, Morrison JA, et al. 1989. Reproductive outcomes of pregnant workers 

employed at 36 reinforced plastics companies. II. Lowered birth weight. J Occup Med 31:115-120. 

Leovic KW, Sheldon LS, Whitaker DA, et al. 1996. Measurement of indoor air emissions from dryprocess photocopy machines. J Air Waste Manage Assoc 46:821-829. 

Leovic KW, Whitaker D, Northeim C, et al. 1998. Evaluation of a test method for measuring indoor air 

emissions from dry-process photocopiers. J Air Waste Manage Assoc 48:915-923. 

Leung HW. 1993. Physiologically-based pharmacokinetic modelling. In: Ballantyne B, Marro T, 

Turner P, eds. General and applied toxicology. Vol. 1.1 New York, NY: Stockton Press, 153-164. 

Lide CR. 2005. Styrene. In: CRC Handbook of chemistry and physics. 86th ed. Boca Raton, FL: 

Taylor & Francis, 3-464. 

Lindbohm ML, Hemminki K, Kyyronen P. 1985. Spontaneous abortions among women employed in the 

plastics industry. Am J Ind Med 8:579-586. 

Lindstrom K, Harkonen H, Hernberg S. 1976. Disturbances in psychological functions of workers 

occupationally exposed to styrene. Scand J Work Environ Health 3:129-139. 

Livingston AL. 1978. Forage plant estrogens. J Toxicol Environ Health 4(2-3):301-324. 

Lof A, Johanson G. 1993. Dose-dependent kinetics of inhaled styrene in man. IARC Sci Publ 

(127):89-99. 

Lof A, Gullstrand E, Byfalt Nordqvist M. 1983. Tissue distribution of styrene, styrene glycol and more 

polar styrene metabolites in the mouse. Scand J Work Environ Health 9:419-430. 

Lof A, Gullstrand E, Lundgren E, et al. 1984. Occurrence of styrene-7,8-oxide and styrene glycol in 

mouse after the administration of styrene. Scand J Work Environ Health 10:179-187. 

Lof A, Lundgren E, Byfalt Nordqvist M. 1986b. Kinetics of styrene in workers from a plastics industry 

after controlled exposure: A comparison with subjects not previously exposed. Br J Ind Med 

43:537-543. 

Lof A, Lundgren E, Nydahl EM, et al. 1986a. Biological monitoring of styrene metabolites in blood. 

Scand J W Environ Health 12:70-74. 

Loquet G, Campo P, Lataye R. 1999. Comparison of toluene-induced and styrene-induced hearing 

losses. Neurotoxicology 21(6):689-697. 

Loquet G, Campo P, Lataye R, et al. 2000. Combined effects of exposure to styrene and ethanol on the 

auditory function in the rat. Hear Res 148(1-2):173-180. 

Lorimer WV, Lilis R, Fischbein A, et al. 1978. Health status of styrene-polystyrene polymerization 

workers. Scand J Work Environ Health 4:220-226. 

Lovegren NV, Fisher GS, Legendre MG, et al. 1979. Volatile constituents of dried legumes. J Agric 

Food Chem 27:851-853. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

STYRENE 214 

9. REFERENCES 

Luderer U, Tornero-Velez R, Shay T, et al. 2004. Temporal association between serum prolactin 

concentration and exposure to styrene. Occup Environ Med 61(4):325-333. 

Macaluso M, Larson R, Delzell E, et al. 1996. Leukemia and cumulative exposure to butadiene, styrene 

and benzene among workers in the synthetic rubber industry. Toxicology 113:190-202. 

Mackay CJ, Kelman GR. 1986. Choice reaction time in workers exposed to styrene vapour. Human 

Toxicol 5:85-89. 

Mac Leod H, Jourdain JL, Poulet G, et al. 1984. Kinetic study of reactions of some organic sulfur 

compounds with OH radicals. Atmos Environ 18:2621-2626. 

Maestri L, Ghittori S, Imbriani M. 1997a. Determination of specific mercapturic acids as an index of 

exposure to environmental benzene, toluene, and styrene. Ind Health 35:489-501. 

Maki-Paakkanen J. 1987. Chromosome aberrations, micronuclei and sister-chromatid exchanges in 

blood lymphocytes after occupational exposure to low levels of styrene. Mutat Res 189:39-406. 

Maki-Paakkanen J, Walles S, Osterman-Golkar S, et al. 1991. Single-strand breaks, chromosome 

aberrations, sister-chromatid exchanges, and micronuclei in blood lymphocytes of workers exposed to 

styrene during the production of reinforced plastics. Environ Mol Mutagen 17(1):27-31. 

Makitie A, Pirvola U, Pyykko I, et al. 2002. Functional and morphological effects of styrene on the 

auditory system of the rat. Arch Toxicol 76:40-47. 

Maltoni C, Ciliberti A, Carretti D. 1982. Experimental contributions in identifying brain potential 

carcinogens in the petrochemical industry. Ann NY Acad Sci 381:216-249. 

Maltoni C, Failla G, Kassapidis G. 1979. First experimental demonstration of the carcinogenic effects of 

styrene oxide. Med Lav 5:358-362. 

Matanoski G, Schwartz L. 1987. Mortality of workers in styrene-butadiene polymer production. J 

Occup Med 29:675-680. 

Matanoski G, Elliott E, Tao X, et al. 1997. Lymphohematopoietic cancers and butadiene and styrene 

exposure in synthetic rubber manufacture. Ann N Y Acad Sci 837:157-169. 

Matanoski G, Francis M, Correa-Villasenor A, et al. 1993. Cancer epidemiology among styrenebutadiene rubber workers. IARC Sci Publ (127):363-374. 

Matanoski G, Santos-Burgoa C, Schwartz L. 1990. Mortality of a cohort of workers in the styrenebutadiene polymer manufacturing industry. Environ Health Perspect 86:107-117. 

Matikainen E, Forsman-Gronholm L, Pfaffli P, et al. 1993a. Nervous system effects of occupational 

exposure to styrene: A clinical and neurophysiological study. Environ Res 61(1):84-92. 

Matikainen E, Forsman-Gronholm L, Pfaffli P, et al. 1993b. Neurotoxicity in workers exposed to 

styrene. IARC Sci Publ (127):153-161. 

Mattie DR, Bates GD, Jepson GW, et al. 1994. Determination of skin: Air partition coefficients for 

volatile chemicals: Experimental method and applications. Fundam Appl Toxicol 22:51-57. 
 

 

 

 

 

 

 

 

 

 

 

STYRENE 215 

9. REFERENCES 

Mayr U, Butsch A, Schneider S. 1992. Validation of two in vitro test systems for estrogenic activities 

with zearalenone, phytoestrogens and cereal extracts. Toxicology 74(2-3):135-149. 

McDonald AD, Lavoie J, Côté R. 1988. Spontaneous abortion in women employed in plastics 

manufacture. Am J Ind Med 14:9-14. 

McMichael AJ, Spirtas R, Gamble JF, et al. 1976. Mortality among rubber workers: relationship to 

specific jobs. J Occup Med 18:178-185. 

Meinhardt TJ, Lemen RA, Crandall MS, et al. 1982. Environmental epidemiologic investigation of the 

styrene-butadiene rubber industry: Mortality patterns with discussion of the hematopoietic and lymphatic 

malignancies. Scand J Work Environ Health 8:250-259. 

Mendrala AL, Langvardt PW, Nitschke KD, et al. 1991. In vitro metabolism of styrene and styrene 

oxide in human and animal tissues. Midland, MI: Dow Chemical Company, 1-63. 

Meretoja T, Jarventaus H, Sorsa M, et al. 1978. Chromosome aberrations in lymphocytes of workers 

exposed to styrene. Scand J Work Environ Health 4:259-264. 

Meretoja T, Vainio H, Sorsa M, et al. 1977. Occupational styrene exposure and chromosomal 

aberrations. Mutat Res 56:193-197. 

Miermans CJH, van der Velde LE, Frintrop PCM. 2000. Analysis of volatile organic compounds, using 

the purge and trap injector coupled to a gas chromatograph/ion-trap mass spectrometer: Review of the 

results in Dutch surface water of the Rhine, Meuse, Northern Delta area and Westerscheldt over the 

period 1992-1997. Chemosphere 40:39-48. 

Möller C, Ödkvist L, Larsby B, et al. 1990. Otoneurological findings in workers exposed to styrene. 

Scand J Work Environ Health 16:189-194. 

Morata TC, Johnson AC, Nylen P, et al. 2002. Audiometric findings in workers exposed to low levels of 

styrene and noise. J Occup Environ Med 44(9):806-814. 

Morgan DL, Cooper SW, Carlock DL, et al. 1991. Dermal absorption of neat and aqueous volatile 

organic chemicals in the Fischer 344 rat. Environ Res 55:51-63. 

Morgan DL, Mahler JF, Dill JA, et al. 1993a. Styrene inhalation toxicity studies in mice: II. Sex 

differences in susceptibility of B6C3F1 mice. Fundam Appl Toxicol 21:317-325. 

Morgan DL, Mahler JF, Dill JA, et al. 1993b. Styrene inhalation toxicity studies in mice: III. Strain 

differences in susceptibility. Fundam Appl Toxicol 21:326-333. 

Morgan DL, Mahler JF, O'Connor RW, et al. 1993c. Styrene inhalation toxicity studies in mice: I. 

Hepatotoxicity in B6C3F1 mice. Fundam Appl Toxicol 20:325-335. 

Morioka I, Kuroda M, Miyashita K, et al. 1999. Evaluation of organic solvent ototoxicity by the upper 

limit of hearing. Arch Environ Health 54(5):341-346. 

Morris JB. 2000. Uptake of styrene in the upper respiratory tract of the CD mouse and Sprague-Dawley 

rat. Toxicol Sci 54:222-228. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

STYRENE 216 

9. REFERENCES 

Morselli PL, Franco-Morselli R, Bossi L. 1980. Clinical pharmacokinetics in newborns and infants:
 

Age-related differences and therapeutic implications. Clin Pharmacokinet 5(6):485-527.
 

Muijser H, Hoogendijk EM, Hooisma J. 1988. The effects of occupational exposure to styrene on highfrequency hearing thresholds. Toxicology 49:331-340.
 

Murata K, Araki S, Yokoyama K. 1991. Assessment of the peripheral, central, and autonomic nervous 

system function in styrene workers. Am J Ind Med 20:775-784.
 

Murray FJ, John JA, Balmer MF, et al. 1978. Teratologic evaluation of styrene given to rats and rabbits
 

by inhalation or by gavage. Toxicology 11:335-343.
 

Mutti A, Mazzucchi A, Rustichelli P, et al. 1984a. Exposure-effect and exposure-response relationships 

between occupational exposure to styrene and neuropsychological functions. Am J Ind Med 5:275-286.
 

Mutti A, Vescovi PP, Falsoi M, et al. 1984b. Neuroendocrine effects of styrene on occupationally
 

exposed workers. Scand J Work Environ Health 10:225-228.
 

Nakajima T, Elovaara E, Gonzalez FJ, et al. 1993. Characterization of the human cytochrome P450 

isozymes responsible for styrene metabolism. IARC Sci Publ (127):101-108.
 

Nakajima T, Wang R-S, Elovaara E, et al. 1994. CYP2C11 and CYP2B1 are major cytochrome 

P450 forms involved in styrene oxidation in liver and lung microsomes from untreated rats, respectively.
 

Biochem Pharmacol 48(4):637-642.
 

NAS/NRC. 1989. Report of the oversight committee. Biologic markers in reproductive toxicology.
 

Washington, DC: National Academy of Sciences, National Research Council, National Academy Press,
 

15-35.
 

*NCI. 1979a. Bioassay of a solution of β-nitrostyrene and styrene for possible carcinogenicity.
 

Bethesda, MD: National Cancer Institute, Division of Cancer Cause and Prevention. DHEW Publication
 

No. (NIH) 79-1726.
 

NCI. 1979b. Bioassay of styrene for possible carcinogenicity. Bethesda, MD: National Cancer Institute,
 

Division of Cancer Cause and Prevention. Technical Report Series No. 185. NCI-CG-TR-185. NIH 79-

1741. PB300977.
 

Nicholson WJ, Selikoff IJ, Seidman H. 1978. Mortality experience of styrene-polystyrene 

polymerization workers: Initial findings. Scand J Work Environ Health 4:247-252.
 

Niklasson M, Tham R, Larsby B, et al. 1993. Effects of toluene, styrene, trichloroethylene, and
 

trichloroethane on the vestibulo- and opto-oculo motor system in rats. Neurotoxicol Teratol 15:327-334.
 

NIOSH. 1983. Criteria for a recommended standard: Occupational exposure to styrene. Cincinnati, OH:
 

U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control, 

National Institute for Occupational Safety and Health. PB84148295. 

NIOSH. 1984. Method 1501: Hydrocarbons, aromatic. In: NIOSH manual of analytical methods. Vol. 

2. Cincinnati, OH: U.S. Department of Health and Human Services, National Institute for Occupational 

Safety and Health. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

STYRENE 217 

9. REFERENCES 

NIOSH. 1990. Styrene. Estimated numbers of employees potentially exposed to specific agents by 

2-digit Standard Industrial Classification (SIC). National Occupational Exposure Survey conducted from 

1981-1983. Centers for Disease Control. National Institute for Occupational Safety and Health. 

http://www.cdc.gov/noes/. August 09, 2007. 

NIOSH. 2005. NIOSH pocket guide to chemical hazards. Atlanta, GA: National Institute for 

Occupational Safety and Health, Centers for Disease Control and Prevention. 

http://www.cdc.gov/niosh/npg/. May 15, 2007. 

Nordenson I, Beckman L. 1984. Chromosomal aberrations in lymphocytes of workers exposed to low 

levels of styrene. Hum Hered 34:178-182. 

Normandeau J, Chakrabarti S, Brodeur J. 1984. Influence of simultaneous exposure to acrylonitrile and 

styrene on the toxicity and metabolism of styrene in rats. Toxicol Appl Pharmacol 75:346-349. 

Norppa H. 1981. Styrene and vinyltoluene induce micronuclei in mouse bone marrow. Toxicol Lett 

8:247-251. 

Norppa H, Maki-Paakkanen J, Jantunen K, et al. 1988. Mutagenicity studies on styrene and vinyl 

acetate. Ann NY Acad Sci 534:671-678. 

Norppa H, Sorsa M, Pfaffli P, et al. 1979. Effects of styrene oxide on chromosome aberrations, sister 

chromatid exchange and hepatic drug biotransformation in Chinese hamsters in vivo. Chem Biol Interact 

26:305-315. 

Norppa H, Sorsa M, Pfaffli P, et al. 1980a. Styrene and styrene oxide induce SCEs and are metabolized 

in human lymphocyte cultures. Carcinogenesis 1:357-361. 

Norppa H, Sorsa M, Vainio H. 1980b. Chromosomal aberrations in bone marrow of Chinese hamsters 

exposed to styrene and ethanol. Toxicol Lett 5:241-244. 

Norppa H, Vainio H, Sorsa M. 1981. Chromosome aberrations in lymphocytes of workers exposed to 

styrene. Am J Ind Med 2:299-304. 

Norppa H, Vainio H, Sorsa M. 1983. Metabolic activation of styrene by erythrocytes detected as 

increased sister-chromatid exchanges in cultured human lymphocytes. Cancer Res 43:3579-3582. 

Norppa H, Vainio H, Sorsa M, et al. 1984. Erythrocyte-dependent metabolic activation of styrene and 

induction of sister-chromatid exchange in cultured human lymphocytes. Arch Toxicol Suppl 7:286-290. 

Norström A, Lof A, Aringer L, et al. 1992. Determination of N-acetyl-S-(2-phenyl-2-hydroxyethyl) 

cysteine in human urine after experimental exposure to styrene. Chemosphere 24(11):1553-1561. 

NRC. 1993. Pesticides in the diets of infants and children. Washington, DC: National Research 

Council. National Academy Press. PB93216091. 

NTP. 2005. Introduction. Report on carcinogens. 11th ed. Research Triangle Park, NC: U.S. 

Department of Health and Human Services, Public Health Service, National Toxicology Program. 

http://ntp.nieh.nih.gov/ntp/roc/eleventh/intro.pdf. May 23, 2007. 
 

 

 

 

 

 

 

 

 

 

 

STYRENE 218 

9. REFERENCES 

NTP. 2006. NTP-CERHR monograph on the potential human reproductive and developmental effects of 

styrene. National Toxicology Program. NIH Publication No. 06-4475. 

Ödkvist LM, Edling C, Hellquist H, et al. 1985. Influence of vapours on the nasal mucosa among 

industry workers. Rhinology 23:121-127. 

Ödkvist LM, Larsby B, Tham R, et al. 1982. Vestibulo-oculomotor disturbances in humans exposed to 

styrene. Acta Otolaryngol 94:487-493. 

Ogata M, Fujisawa K, Ogino Y, et al. 1984. Partition coefficients as a measure of bioconcentration 

potential of crude oil compounds in fish and shellfish. Bull Environ Contam Toxicol 33:561-567. 

Ohashi Y, Nakai Y, Ikeoka H, et al. 1986. Degeneration and regeneration of respiratory mucosa of rats 

after exposure to styrene. J Appl Toxicol 6:405-412. 

Ohtani H, Ichikawa Y, Iwamoto E, et al. 2001. Effects of styrene monomer and trimer on gonadal sex 

differentiation of genetic males of the frog Rana rugosa. Environ Res 87(3):175-180. 

Okun AH, Beaumont JJ, Meinhardt TJ, et al. 1985. Mortality patterns among styrene-exposed 

boatbuilders. Am J Ind Med 8:193-205. 

Onchoi C, Kongtip P, Yoosook W, et al. 2008. High performance liquid chromatography for 

determination of urinary metabolites of toluene, xylene and styrene and its application. Southeast Asian J 

Trop Med Public Health 39(6):1164-1171. 

O’Neil MJ, Smith A, Heckelman PE, et al., eds. 2001. Styrene. In: The Merck index. An encyclopedia 

of chemicals, drugs, and biologicals. 13th ed. Whitehouse Station, NJ: Merck & Co., Inc., 1578. 

Ong CN, Shi CY, Chia SE, et al. 1994. Biological monitoring of exposure to low concentrations of 

styrene. Am J Ind Med 25(5):719-730. 

OSHA. 2006a. Air contaminants. Occupational safety and health standards for shipyard employment. 

Occupational Safety and Health Administration. Code of Federal Regulations. 29 CFR 1915.1000. 

http://www.osha.gov/comp-links.html. April 11, 2007. 

OSHA. 2006b. Gases, vapors, fumes, dusts, and mists. Safety and health regulations for construction. 

Occupational Safety and Health Administration. Code of Federal Regulations. 29 CFR 1926.55, 

Appendix A. http://www.osha.gov/comp-links.html. April 11, 2007. 

OSHA. 2006c. Toxic and Hazardous Substances. Occupational safety and health standards. 

Occupational Safety and Health Administration. Code of Federal Regulations. 29 CFR 1910.1000, Table 

Z-2. http://www.osha.gov/comp-links.html. May 15, 2007. 

Otson R. 1987. Purgeable organics in Great Lakes raw and treated water. Int J Environ Anal Chem 

31:41-53. 

Ott MG, Kolesar RC, Schamweber HC, et al. 1980. A mortality survey of employees engaged in the 

development or manufacture of styrene-based products. J Occup Med 22:445-460. 
 

 

 

 

 

 

STYRENE 219 

9. REFERENCES 

Owen GM, Brozek J. 1966. Influence of age, sex and nutrition on body composition during childhood 

and adolescence. In: Falkner F, ed., eds. Human development. Philadelphia, PA: WB Saunders, 

222-238. 

Pahren HR, Bloodgood DE. 1961. Biological oxidation of several vinyl compounds. J Water Pollut 

Control Fed 33:233-238. 

Parkki MG. 1978. The role of glutathione in the toxicity of styrene. Scand J Work Environ Health 

4(Suppl 2):53-59. 

Peck DP. 1994. Immunoassay for aromatic ring containing compounds. United States Patent no. 

5,358,851. Date of patent June 06, 1991. http://patft.uspto.gov/netacgi/nphParser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearchbool.html&r=7&f=G&l=50&co1=AND&d=PTXT&s1=5358851&OS=5358851&RS=5358851. May 30, 

2007. 

Pellizzari ED, Castillo NP, Willis S, et al. 1979. Identification of organic components in aqueous 

effluents from energy-related processes. ASTM Spec Tech Publ 686:256-274. 

Pellizzari ED, Hartwell TD, Harris BS, et al. 1982. Purgeable organic compounds in mother's milk. Bull 

Environ Contam Toxicol 28:322-328. 

Pero RW, Bryngelsson T, Hogstedt B, et al. 1982. Occupational and in vitro exposure to styrene 

assessed by unscheduled DNA synthesis in resting human lymphocytes. Carcinogenesis 3:681-685. 

Pezzagno G, Ghittori S, Imbriani M, et al. 1985. Urinary elimination of styrene in experimental and 

occupational exposure. Scand J Work Environ Health 11:371-379. 

Pfaffli P, Hesso A, Vainio H, et al. 1981. 4-Vinylphenol excretion suggestive of arene oxide formation 

in workers occupationally exposed to styrene. Toxicol Appl Pharmacol 60:85-90. 

Plotnick HB, Weigel WW. 1979. Tissue distribution and excretion of 14C-styrene in male and female 

rats. Res Commun Chem Pathol Pharmacol 24:515-524. 

Pohlova H, Rossner P, Sram RJ. 1985. Cytogenetic analysis of human peripheral blood lymphocytes in 

culture exposed in vitro to styrene and styrene oxide. J Hyg Epidem Microbiol Immunol 29:269-274. 

Ponomarkov V, Tomatis L. 1978. Effects of long-term oral administration of styrene to mice and rats. 

Scand J Work Environ Health 4(Suppl 2):127-135. 

Pouyatos B, Campo P, Lataye R. 2002. Use of DPOAEs for assessing hearing loss caused by styrene in 

the rat. Hear Res 165(1-2):156-164. 

Pratt GC, Palmer K, Wu CY, et al. 2000. An assessment of air toxics in Minnesota. Environ Health 

Perspect 108(9):815-825. 

Prince MM, Stayner LT, Smith RJ, et al. 1997. A re-examination of risk estimates from the NIOSH 

Occupational Noise and Hearing Survey (OHNS). J Acoust Soc Am 101(2):950-963. 

Pryor GT, Rebert CS, Howd RA. 1987. Hearing loss in rats caused by inhalation of mixed xylenes and 

styrene. J Appl Toxicol 7:55-61. 
 

 

 

 

 

 

 

 

STYRENE 220 

9. REFERENCES 

Quast JF, Humiston CG, Kalnins RV, et al. 1979. Results of a toxicity study of monomeric styrene 

administered to beagle dogs by oral intubation for 19 months. Midland, MI: Toxicology Research 

Laboratory, 199. 

Ramsey JC, Andersen ME. 1984. A physiologically based description of the inhalation 

pharmacokinetics of styrene in rats and humans. Toxicol Appl Pharmacol 73:159-175. 

Ramsey JC, Young JD. 1978. Pharmacokinetics of inhaled styrene in rats and humans. Scand J Work 

Environ Health 4(Suppl 2):84-91. 

Ramsey JC, Young JD, Karbowski RJ, et al. 1980. Pharmacokinetics of inhaled styrene in human 

volunteers. Toxicol Appl Pharmacol 53:54-63. 

Rappaport SM, Fraser DA. 1977. Air sampling and analysis in a rubber vulcanization area. Am Ind Hyg 

Assoc J 38:205-210. 

Rathbun Re. 2000. Transport, behavior and fate of volatile organic compounds in streams. Crit Rev 

Environ Sci 30:129-295. 

Regnaud L, Sirois G, Colin P, et al. 1987. Simultaneous ion-pairing liquid chromatographic 

determination of the major metabolites of styrene and carbamazepine and of unchanged carbamazepine in 

urine. J Liq Chromatogr 10(11):2369-2382. 

Rihs HP, Triebig G, Werner P, et al. 2008. Association between genetic polymorphisms in styrenemetabolizing enzymes and biomarkers in styrene-exposed workers. J Toxicol Environ Health A 71(13-

14):866-873. 

Riihimaki V, Pfaffli P. 1978. Percutaneous absorption of solvent vapors in man. Scand J Work Environ 

Health 4:73-85. 

Roberts PV, McCarty PL, Reinhard M, et al. 1980. Organic contaminant behavior during groundwater 

recharge. J Water Pollut Control Fed 52(1):161-172. 

Romieu I, Ramirez M, Meneses F, et al. 1999. Environmental exposure to volatile organic compounds 

among workers in Mexico City assessed by personal monitors and blood concentrations. Environ Health 

Perspect 107:511-515. 

Rosen I, Haeger-Aronsen B, Rehnstrom S, et al. 1978. Neurophysiological observations after chronic 

styrene exposure. Scand J Work Environ Health 4(Supp. 2):184-194. 

Rosengren LE, Haglid KG. 1989. Long term neurotoxicity of styrene. A quantitative study of glial 

fibrillary acidic protein (GFA) and S-100. Br J Ind Med 46:316-320. 

Rothweiler H, Wager PA, Schlatter C. 1992. Volatile organic compounds and some very volatile organic 

compounds in new and recently renovated buildings in Switzerland. Atmos Environ 26(12):2219-2225. 

Roy WR, Griffin RA. 1985. Mobility of organic solvents in water-saturated soil materials. Environ Geol 

Water Sci 7:241-247. 
 

 

 

 

 

 

 

 

 

 

 

 

 

STYRENE 221 

9. REFERENCES 

Ruder AM, Ward EM, Dong M, et al. 2004. Mortality patterns among workers exposed to styrene in the 

reinforced plastic boatbuilding industry: An update. Am J Ind Med 45(2):165-176. 

Sabljic A, Gusten H, Hermens J. 1995. QSAR modelling of soil sorption. Improvements and 

systematics of log Koc vs. log Kow correlations. Chemosphere 31:4489-4514. 

Sakaguchi J, Akabayashi S. 2003. Field survey of indoor air quality in detached houses in Niigata 

Prefecture. Indoor Air 13:42-49. 

Sallmén M, Lindbohm M-L, Anttila A, et al. 1998. Time to pregnancy among the wives of men exposed 

to organic solvents. Occup Environ Med 55:24-30. 

Salomaa S, Donner M, Norppa H. 1985. Inactivity of styrene in the mouse sperm morphology test. 

Toxicol Lett 24:151-155. 

Sanjivamurthy VA. 1978. Analysis of organics in Cleveland water supply. Water Res 12:31-33. 

Santos-Burgoa C, Matanoski GM, Zeger S, et al. 1992. Lymphohematopoietic cancer in styrenebutadiene polymerization workers. Am J Epidemiol 136(7):843-854. 

Sarangapani R, Teeguarden JG, Cruzan G, et al. 2002. Physiologically based pharmacokinetic modeling 

of styrene and styrene oxide respiratory-tract dosimetry in rodents and humans. Inhal Toxicol 14:789-

834. 

Sathiakumar N, Graff J, Macaluso M, et al. 2005. An updated study of mortality among North American 

synthetic rubber industry workers. Occup Environ Med 62(12):822-829. 

Sato A, Nakajima T. 1979. Partition coefficients of some aromatic hydrocarbons and ketones in water, 

blood and oil. Br J Ind Med 36:231-234. 

Sato T, Kishi R, Gong Y, et al. 2009. Effects of styrene exposure on vibration perception threshold. 

Neurotoxicology 30:97-102. 

Savolainen H, Pfaffli P. 1978. Accumulation of styrene monomer and neurochemical effects of longterm inhalation exposure in rats. Scand J Work Environ Health 4:78-83. 

Sax NI, Lewis RJ. 1987. Hawley's condensed chemical dictionary. 11th ed. New York: Van Nostrand 

Reinhold Company, 1101. 

Sbrana I, Lascialfari D, Rossi AM, et al. 1983. Bone marrow cell chromosomal aberrations and styrene 

biotransformation in mice given styrene on a repeated oral schedule. Chem Biol Interact 45:349-357. 

Schaeffer VH, Bhooshan B, Chen S-B, et al. 1996. Characterization of volatile organic chemical 

emissions from carpet cushions. J Air Waste Manage Assoc 46:813-820. 

Sedivec V, Flek J, Mraz M. 1984. Urinary excretion of mandelic and phenylglyoxylic acids after human 

exposure to styrene vapour. J Hyg Epid Microbiol Immunol 28:241-255. 

Seeber A, Blaszkewicz M, Golka K, et al. 2004. Neurobehavioral effects of experimental exposures to 

low levels of styrene. Toxicol Lett 151:183-192. 
 

 

 

 

 

 

 

 

 

 

STYRENE 222 

9. REFERENCES 

Seeber A, Bruckner T, Triebig G. 2009a. Occupational styrene exposure and nuerobehavioural 

functions: A cohort study with repeated measurements. Int Arch Occup Environ Health 82(8):969-984. 

Seeber A, Bruchner T, Triebig G. 2009b. Occupational styrene exposure, colour vision and contrast 

sensitivity: a cohort study with repeated measurements. Int Arch Occup Environ Health 82(6):757-770. 

Seppäläinen AM, Härkönen H. 1976. Neurophysiological findings among workers occupationally 

exposed to styrene. Scand J Work Environ Health 3:140-146. 

Setchell BP, Waites GMH. 1975. The blood testis barrier. In: Creep RO, Astwood EB, Geiger SR, eds. 

Handbook of physiology: Endocrinology V. Washington, DC: American Physiological Society, 143-

172. 

Sexton K, Adgate JL, Church TR, et al. 2005. Children's exposure to volatile organic compounds as 

determined by longitudinal measurements in blood. Environ Health Perspect 113(3):342-349. 

Shamy MY, Osman HH, Kandeel KM, et al. 2002. DNA single strand breaks induced by low levels of 

occupational exposure to styrene: The gap between standards and reality. J Environ Pathol Toxicol 

Oncol 21(1):57-61. 

Sheldon LS, Hites RA. 1978. Organic compounds in the Delaware River. Environ Sci Tech 12:1188-

1194. 

Shields HC, Weschler CJ. 1992. Volatile organic compounds measured at a telephone switching center 

form 5/30/85-12/6/88: A detailed case study. J Air Waste Manage Assoc 42:792-804. 

Shugaev BB. 1969. Concentrations of hydrocarbons in tissues as a measure of toxicity. Arch Environ 

Health 18:878-882. 

Sielicki M, Focht DD, Martin JP. 1978. Microbial transformations of styrene and [14C] styrene in soil 

and enrichment cultures. Appl Environ Microbiol 35:124-128. 

Simula AP, Priestly BG. 1992. Species differences in the genotoxicity of cyclophosphamide and styrene 

in three in vivo assays. Mutat Res 271:49-58. 

Sinha AK, Jersey GC, Linscombe VA, et al. 1983. Cytogenetic evaluation of bone marrow cells from 

rats exposed to styrene vapor for one year. Fundam Appl Toxicol 3:95-98. 

Sjöborg S, Fregert S, Trulsson L. 1984. Contact allergy to styrene and related chemicals. Contact 

Dermatitis 10:94-96. 

Ska B, Vyskocil A, Tardif R, et al. 2003. Effects of peak concentrations on the neurotoxicity of styrene 

in volunteers. Hum Exp Toxicol 22:407-415. 

Śliwińska-Kowalska M, Zamyslowska-Szmytke E, Szymczak W, et al. 2003. Ototoxic effects of 

occupational exposure to styrene and co-exposure to styrene and noise. J Occup Environ Med 

45(1):15-24. 

Sloane TM, Brudzynski RJ. 1979. Competition between reactive sites in the reactions of oxygen atoms 

and hydroxyl radicals with phenylacetylene and styrene. J Am Chem Soc 101 (March 14):1495-1499. 
 

 

 

 

 

 

 

 

 

 

STYRENE 223 

9. REFERENCES 

Sollenberg J, Bjurstrom R, Wrangskag K, et al. 1988. Biological exposure limits estimated from 

relations between occupational styrene exposure during a workweek and excretion of mandelic and 

phenylglyoxylic acids in urine. Int Arch Occup Environ Health 60:365-370. 

Somorovská M, Jahnova E, Tulinska J, et al. 1999. Biomonitoring of occupational exposure to styrene in 

a plastic lamination plant. Mutat Res 428(1-2):255-269. 

Spencer HC, Irish DD, Adams EM, et al. 1942. The response of laboratory animals to monomeric 

styrene. J Ind Hyg Toxicol 24:295-301. 

Squillace PJ, Moran MJ, Lapman WW, et al. 1999. Volatile organic compounds in untreated ambient 

groundwater of the United States, 1985-1995. Environ Sci Technol 33(23):4176-4187. 

SRI. 1989. Directory of chemical producers: United States of America. Menlo Park, CA: SRI 

International, 968. 

SRI. 2006. Directory of chemical producers. United Status of America. Menlo Park, CA: SRI 

Consulting, 894. 

SRI. 2008. [Styrene] Directory of Chemical Producers. United States. Menlo Park, CA: SRI 

Consulting. Access Intelligence, LLC., 856. 

Srivastava S, Das M, Mushtaq M, et al. 1982. Hepatic effects of orally administered styrene in rats. J 

Appl Toxicol 2:219-222. 

Srivastava S, Seth PK, Srivastava SP. 1989. Effect of styrene administration on rat testis. Arch Toxicol 

63:43-46. 

Srivastava S, Seth PK, Srivastava SP, et al. 1992a. Biochemical and morphological studies in testes of 

rat offspring of mothers exposed to styrene during lactation. Pharmacol Toxicol 70:314-316. 

Srivastava S, Seth PK, Srivastava SP. 1992b. Effect of styrene on testicular enzymes of growing rat. Ind 

J Exp Biol 30:399-401. 

Stefaniak AB, Breysse PN, Murray MPM, et al. 2000. An evaluation of employee exposure to volatile 

organic compounds in three photocopy centers. Environ Res 83:162-173. 

Štĕtkářová I, Urban P, Prochazka B, et al. 1993. Somatosensory evoked potentials in workers exposed to 

toluene and styrene. Br J Ind Med 50(6):520-527. 

Stewart RD, Dodd HC, Baretta ED, et al. 1968. Human exposure to styrene vapor. Arch Environ Health 

16:656-662. 

Sumner SJ, Fennell TR. 1994. Review of the metabolic fate of styrene. Crit Rev Toxicol 24(Suppl 

1):S11-S33. 

Symanski E, Bergamaschi E, Mutti A. 2001. Inter-and intra-individual sources of variation in levels of 

urinary styrene metabolites. Int Arch Occup Environ Health 74:336-344. 

Takeoko GR, Flath RA, Guntert M, et al. 1988. Nectarine volatiles: Vacuum steam distillation versus 

headspace. J Agric Food Chem 36:553-560. 
 

 

 

 

 

 

 

STYRENE 224 

9. REFERENCES 

Tang J, Jin QZ, Shen GH, et al. 1983. Isolation and identification of volatile compounds from fried 

chicken. J Agric Food Chem 31:1287-1292. 

Tang W, Hemm I, Eisenbrand G. 2000. Estimation of human exposure to styrene and ethylbenzene. 

Toxicology. Toxicology 144(1-3):39-50. 

Teramoto K, Horiguchi S. 1979. Absorption, distribution and elimination of styrene in man and 

experimental animals. Arh Hig Rada Toksikol 30:431-437. 

Thiess AM, Friedheim M. 1978. Morbidity among persons employed in styrene production, 

polymerization and processing plants. Scand J Work Environ Health 4 (Suppl 2):203-214. 

Thiess AM, Schwegler H, Fleig I. 1980. Chromosome investigations in lymphocytes of workers 

employed in areas in which styrene-containing unsaturated polyester resins are manufactured. Am J Ind 

Med 1:205-210. 

Thomas K, Colborn T. 1992. Organochlorine endocrine disruptors in human tissue. In: Colborn T, 

Clement C, eds. Chemically induced alterations in sexual and functional development: The 

wildlife/human connection. Princeton, NJ: Princeton Scientific Publishing, 365-394. 

Till D, Schwope AD, Ehntholt DJ, et al. 1987. Indirect food additive migration from polymeric food 

packaging materials. CRC Crit Rev Toxicol 18:215-243. 

Tomanin R, Ballarin C, Bartolucci GB, et al. 1992. Chromosome aberrations and micronuclei in 

lymphocytes of workers exposed to low and medium levels of styrene. Int Arch Occup Environ Health 

64:209-215. 

Toppila E, Forsman P, Pyykko I, et al. 2006. Effect of styrene on postural stability among reinforced 

plastic boat plant workers in Finland. J Occup Environ Med 48(2):175-180. 

Trenga CA, Kunkel DD, Eaton DL, et al. 1991. Effects of styrene oxide on rat brain glutathione. 

Neurotoxicity 12:165-178. 

TRI06. 2008. TRI explorer: Providing access to EPA’s toxics release inventory data. Washington, DC: 

Office of Information Analysis and Access. Office of Environmental Information. U.S. Environmental 

Protection Agency. Toxics Release Inventory. http://www.epa.gov/triexplorer/. February 19, 2009. 

Triebig G, Bruckner T, Seeber A. 2009. Occupational styrene exposure and hearing loss: A cohort study 

with repeated measurements. Int Arch Occup Environ Health 82(4):463-480. 

Triebig G, Lehrl S, Weltle D, et al. 1989. Clinical and neurobehavioral study of the acute and chronic 

neurotoxicity of styrene. Br J Ind Med 46:799-804. 

Triebig G, Schaller KH, Valentin H. 1985. Investigations on neurotoxicity of chemical substances at the 

workplace. Int Arch Occup Environ Health 56:239-247. 

Triebig G, Bruckner T, Seeber A. 2009. Occupational styrene exposure and hearing loss: A cohort study 

with repeated measurements. Int Arch Occup Environ Health 82(4):463-480. 
 

 

 

 

 

 

 

 

 

 

STYRENE 225 

9. REFERENCES 

Triebig G, Stark T, Ihrig A, et al. 2001. Intervention study on acquired color vision deficiencies in 

styrene-exposed workers. J Occup Environ Med 43(5):494-500. 

Tsai SP, Chen JD. 1996. Neurobehavioural effects of occupational exposure to low-level styrene. 

Neurotoxicol Teratol 18(4):463-469. 

Tulinska J, Dusinska M, Jahnova E, et al. 2000. Changes in cellular immunity among workers 

occupationally exposed to styrene in a plastics lamination plant. Am J Ind Med 38(5):576-583. 

Uchiyama S, Hasegawa S. 2000. Investigation of a long-term sampling period for monitoring volatile 

organic compounds in ambient air. Environ Sci Technol 34:4656-4661. 

Umemura T, Kurahashi N, Kondo T, et al. 2005. Acute effects of styrene inhalation on the 

neuroendocrinological system of rats and the different effects in male and female rats. Arch Toxicol 

79(11):653-659. 

USGS. 1998. Methods of analysis by the U.S. Geological Survey National Water Quality Laboratory: 

Determination of 86 volatile organic compounds in water by gas chromatography/mass spectrometry, 

including detections less than reporting limits. Denver, CO: U.S. Geological Survey, 97-829. 

USGS. 2006. Volatile organic compounds in the nation’s ground water and drinking water supply wells. 

Reston, VA: U.S. Geological Survey. 

USITC. 1987. Synthetic organic chemicals: United States production and sales, 1986. Washington, DC: 

U.S. International Trade Commission. USITC Publication 2009, 26, 39. 

USITC. 1988. Synthetic organic chemicals: United States production and sales, 1987. Washington, DC: 

U.S. International Trade Commission. USITC Publication 2118, 3-2, 3-14. 

Vainio H, Jarvisalo J, Taskinen E. 1979. Adaptive changes caused by intermittent styrene inhalation on 

xenobiotic biotransformation. Toxicol Appl Pharmacol 49:7-14. 

Vainio H, Paakkonen R, Ronnholm K, et al. 1976. A study on the mutagenic activity of styrene and 

styrene oxide. Scand J Work Environ Health 3:147-151. 

Vainiotalo S, Vaananen V, Vaaranrinta R. 2008. Measurement of 16 volatile organic compounds in 

restaurant air contaminated with environmental tobacco smoke. Environ Res 108(3):280-288. 

Valvani SC, Yalkowsky SH, Roseman TJ. 1981. Solubility and partitioning IV: Aqueous solubility and 

octanol-water partition coefficients of liquid nonelectrolytes. J Pharm Sci 70:502-507. 

Van Rooij JG, Kasper A, Triebig G, et al. 2008. Trends in occupational exposure to styrene in the 

European glass fibre-reinforced plastics industry. Ann Occup Hyg 52(5):337-349. 

Varner SL, Breder CV. 1981. Headspace sampling and gas chromatographic determination of styrene 

migration from food-contact polystyrene cups into beverages and food stimulants. J Assoc Off Anal 

Chem 64:1122-1130. 

Verplanke AJW, Herber RFM. 1998. Effects on the kidney of occupational exposure to styrene. Int 

Arch Occup Environ Health 71:47-52. 
 

 

 

 

 

 

 

 

 

 

 

 

 

STYRENE 226 

9. REFERENCES 

Verschueren K. 1983. Handbook of environmental data on organic chemicals. 2nd ed. New York: Van 

Nostrand Reinhold Company, 1055-1057. 

Verschueren K. 2001. Handbook of environmental data on organic chemicals. Vol. 2. 4th ed. New 

York, NY: John Wiley & Sons, Inc., 1899-1902. 

Viaene MK, Pauwels W, Veulemans H, et al. 2001. Neurobehavioural changes and persistence of 

complaints in workers exposed to styrene in a polyester boat building plant: Influence of exposure. 

Occup Environ Med 58(2):103-112. 

Viaene M, Veulemans H, Masschelein R. 1998. Experience with a vocabulary test for workers 

previously and still exposed to styrene. Scand J Work Environ Health 24(4):308-311. 

Viau C, Bernard A, De Russis R, et al. 1987. Evaluation of the nephrotoxic potential of styrene in man 

and in rat. J Appl Toxicol 7(5):313-316. 

Vieira I, Sonnier M, Cresteil T. 1996. Developmental expression of CYP2E1 in the human liver: 

Hypermethylation control of gene expression during the neonatal period. Eur J Biochem 238(2):476-483. 

Vitrac O, Leblanc JC. 2007. Consumer exposure to substances in plastic packaging. I. Assessment of 

the contribution of styrene from yogurt pots. Food Addit Contam 24(2):194-215. 

Vodicka P, Bastlova T, Vodickova L, et al. 1995. Biomarkers of styrene exposure in lamination 

workers: Levels of {IO}{+6}-guanine DNA adducts, DNA strand breaks and mutant frequencies in the 

hypoxanthine guanine phosphoribosyltransferase gene in T-lymphocytes. Carcinogenesis 

16(7):1473-1481. 

Vodicka P, Koskinen M, Vodickova L, et al. 2001a. DNA adducts, strand breaks and micronuclei in 

mice exposed to styrene by inhalation. Chem Biol Interact 137:213-227. 

*Vodicka P, Soucek P, Tates AD, et al. 2001b. Association between genetic polymorphisms and 

biomarkers in styrene-exposed workers. Mutat Res 482(1-2):89-103. 

Vodicka P, Tuimala J, Stetina R, et al. 2004. Cytogenetic markers, DNA single-strand breaks, urinary 

metabolites, and DNA repair rates in styrene-exposed lamination workers. Environ Health Perspect 

112:867-871. 

Vyskocil A, Emminger S, Malir F, et al. 1989. Lack of nephrotoxicity of styrene at current TLV level 

(50 ppm). Int Arch Occup Environ Health 61:409-411. 

Wallace L, Buckley T, Pellizzari E, Gordon S. 1996. Breath measurements as volatile organic 

compounds biomarkers. Environ Health Perspect 104:861-869. 

Wallace LA, Pellizzari ED. 1995. Recent advances in measuring exhaled breath and estimating exposure 

and body burden for volatile organic compounds. Environ Health Perspect 103:95-98. 

Wallace LA, Pellizzari ED, Hartwell TD, et al. 1986a. Total exposure assessment methodology (TEAM) 

study: Personal exposures, indoor-outdoor relationships, and breath levels of volatile organic compounds 

in New Jersey. Environ Int 12:369-387. 
 

 

 

 

 

 

 

 

 

 

 

STYRENE 227 

9. REFERENCES 

Wallace LA, Pellizzari ED, Leaderer B, et al. 1987b. Emissions of volatile organic compounds from 

building materials and consumer products. Atmos Environ 21:385-393. 

Wallace LA, Pellizzari ED, Sheldon L, et al. 1986b. The total exposure assessment methodology 

(TEAM) study: Direct measurement of personal exposures through air and water for 600 residents of 

several U.S. cities. In: Cohen Y, ed. Pollutants in a multimedia environment. New York, NY: Plenum 

Publishing Corporation, 289-315. 

Walles SAS, Orsen I. 1983. Single-strand breaks in DNA of various organs of mice induced by styrene 

and styrene oxide. Cancer Lett 21:9-15. 

Walles SAS, Edling C, Anundi H, et al. 1993. Exposure dependent increase in DNA single strand breaks 

in leucocytes from workers exposed to low concentrations of styrene. Br J Ind Med 50:570-574. 

Warhurst AM, Fewson CA. 1994. Microbial metabolism and biotransformation of styrene. J Appl 

Bacteriol 77:597-606. 

Watanabe T, Endo A, Sato K, et al. 1981. Mutagenic potential of styrene in man. Ind Health 19:37-45. 

Weast RC, ed. 1985. CRC handbook of chemistry and physics. Boca Raton, FL: CRC Press, Inc., 

C-498. 

Welp E, Kogevinas M, Andersen A, et al. 1996c. Exposure to styrene and mortality from nervous 

system diseases and mental disorders. Am J Epidemiol 144(7):623-633. 

Wenker MAM, Kezic S, Monster AC, et al. 2001. Stereochemical metabolism of styrene in volunteers. 

Int Arch Occup Environ Health 74:359-365. 

West JR, Smith HW, Chasis H. 1948. Glomerular filtration rate, effective renal blood flow, and maximal 

tubular excretory capacity in infancy. J Pediatr 32:10-18. 

WHO. 1983. Environmental health criteria 26: Styrene. Geneva: World Health Organization. 

http://www.inchem.org/documents/ehc/ehc/ehc26.htm. April 05, 2007. 

WHO. 2000. Air quality guidelines. 2nd ed. Geneva, Switzerland: World Health Organization. 

http://www.euro.who.int/Document/AIQ/AirQualRepMtg.pdf. March 08, 2006. 

WHO. 2004. Guidelines for drinking-water quality. Vol. 1. Recommendations. 3rd ed. Geneva, 

Switzerland: World Health Organization. http://www.who.int/water_sanitation_health/dwq/gdwq3/en/. 

March 08, 2006. 

Widdowson EM, Dickerson JWT. 1964. Chemical composition of the body. In: Comar CL, Bronner F, 

eds. Mineral metabolism: An advanced treatise. Volume II: The elements Part A. New York, NY: 

Academic Press. 

Wigaeus E, Lof A, Bjurstrom R, et al. 1983. Exposure to styrene: Uptake, distribution, metabolism and 

elimination in man. Scand J Work Environ Health 9:479-488. 

Wilson JT, McNabb JF, Wilson BH, et al. 1983. Biotransformation of selected organic pollutants in 

ground water. Developments in Industrial Microbiology 24:225-233. 
 

 

 

 

 

 

 

 

 

STYRENE 228 

9. REFERENCES 

Windholz, M, ed. 1983. Styrene. The Merck index. 10th ed. Rahway, NJ: Merck and Co., Inc., 1270. 

Wintrobe MM, Thorn GW, Adams RD, et al., eds. 1970. Harrison's principles of internal medicine. Vol. 

2. 6th ed. New York, NY: McGraw-Hill, Inc., 1614-1615. 

Withey JR. 1976. Quantitative analysis of styrene monomer in polystyrene and foods including some 

preliminary studies of the uptake and pharmacodynamics of the monomer in rats. Environ Health 

Perspect 17:125-133. 

Withey JR, Collins PG. 1977. Pharmacokinetics and distribution of styrene monomer in rats after 

intravenous administration. J Toxicol Environ Health 3:1011-1020. 

Withey JR, Collins PG. 1978. Styrene monomer in foods: A limited Canadian survey. Bull Environ 

Contam Toxicol 19:86-94. 

Withey JR, Collins PG. 1979. The distribution and pharmacokinetics of styrene monomer in rats by the 

pulmonary route. J Environ Pathol Toxicol 2:1329-1342. 

Withey JR, Karpinski K. 1985. Fetal distribution of styrene in rats after vapor phase exposures. Biol 

Res Pregnancy 6:59-64. 

Wolf MA, Rowe VK, McCollister DD, et al. 1956. Toxicological studies of certain alkylated benzenes 

and benzene: Experiments on laboratory animals. AMA Arch Ind Health 14:387-398. 

Wong O. 1990. A cohort mortality study and a case-control study of workers potentially exposed to 

styrene in the reinforced plastics and composites industry. Br J Ind Med 47:753-762. 

Wong O, Trent LS, Whorton MD. 1994. An updated cohort mortality study of workers exposed to 

styrene in the reinforced plastics and composites industry. Occup Environ Med 51:386-396. 

Yager JW, Paradisin WM, Rappaport SM. 1993. Sister-chromatid exchanges in lymphocytes are 

increased in relation to longitudinally measured occupational exposure to low concentrations of styrene. 

Mutat Res 319:155-165. 

Yamamoto T, Teramoto K, Horiguchi S. 1997. Effects of styrene on peripheral nerve conduction 

velocities in rats. J Occup Health 39:319-324. 

Yang WP, Hu BH, Chen GD, et al. 2008. Protective effect of N-acetyl-L-cysteine (L-NAC) against 

styrene-induced cochlear injuries. Acta Otolaryngol [Epub ahead of print]:1-8. 

Yano BL, Dittenber DA, Albee RR, et al. 1992. Abnormal auditory brainstem responses and cochlear 

pathology in rats induced by an exaggerated styrene exposure regimen. Toxicol Pathol 20(1):1-6. 

Yoshikawa K, Isobe M, Watabe T, et al. 1980. Studies on metabolism and toxicity of styrene: III. The 

effect of metabolic inactivation by rat-liver S9 on the mutagenicity of phenyloxirane toward Salmonella 

typhimurium. Mutat Res 78:219-226. 

Young JD, Ramsey JC, Blau GE, et al. 1979. Pharmacokinetics of inhaled or intraperitoneally 

administered styrene in rats. In: Toxicology and Occupational Medicine. New York, NY: 

Elsevier/North-Holland, 297-310. 
 

 

 

 

 

 

 

 

STYRENE 229 

9. REFERENCES 

Yuasa J, Kishi R, Eguchi T, et al. 1996. Study of urinary mandelic acid concentration and peripheral 

nerve conduction among styrene workers. Am J Ind Med 30:41-47. 

Zaidi NF, Agrawal AK, Srivastava SP, et al. 1985. Effect of gestational and neonatal styrene exposure 

on dopamine receptors. Neurobehav Toxicol Teratol 7:23-28. 

Zelano V, Rizzi S, Gastaldi D, et al. 1998. Volatile organic compounds in drinking water. Ann Chim 

88:449-460. 

Ziegler EE, Edwards BB, Jensen RL, et al. 1978. Absorption and retention of lead by infants. Pediatr 

Res 12(1):29-34. 

Zielinska B, Sagebiel JC, Harshfield G, et al. 1996. Volatile organic compounds up to C20 emitted from 

motor vehicles; measurement methods. Atmos Environ 30:2269-2286. 

Zoeteman BC, Harmsen K, Linders JB, et al. 1980. Persistent organic pollutants in river water and 

groundwater of the Netherlands. Chemosphere 9:231-241. 
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STYRENE 231 

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. 
 

 

 

 

STYRENE 232 

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. 
 

 

STYRENE 233 

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. 
 

 

 

STYRENE 234 

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 
 

 

 

 

 

 

 

 

 

 

STYRENE 235 

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. 
 

 

 

 

 

 

 

STYRENE 236 

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. 
 

 

 

 

 

 

STYRENE A-1 

APPENDIX A. ATSDR MINIMAL RISK LEVELS AND WORKSHEETS 

The Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) [42 U.S.C. 

9601 et seq.], as amended by the Superfund Amendments and Reauthorization Act (SARA) [Pub. L. 99– 

499], requires that the Agency for Toxic Substances and Disease Registry (ATSDR) develop jointly with 

the U.S. Environmental Protection Agency (EPA), in order of priority, a list of hazardous substances most 

commonly found at facilities on the CERCLA National Priorities List (NPL); prepare toxicological 

profiles for each substance included on the priority list of hazardous substances; and assure the initiation 

of a research program to fill identified data needs associated with the substances. 

The toxicological profiles include an examination, summary, and interpretation of available toxicological 

information and epidemiologic evaluations of a hazardous substance. During the development of 

toxicological profiles, Minimal Risk Levels (MRLs) are derived when reliable and sufficient data exist to 

identify the target organ(s) of effect or the most sensitive health effect(s) for a specific duration for a 

given route of exposure. An MRL is an estimate of the daily human exposure to a hazardous substance 

that is likely to be without appreciable risk of adverse noncancer health effects over a specified duration 

of exposure. MRLs are based on noncancer health effects only and are not based on a consideration of 

cancer effects. These substance-specific estimates, which are intended to serve as screening levels, are 

used by ATSDR health assessors to identify contaminants and potential health effects that may be of 

concern at hazardous waste sites. It is important to note that MRLs are not intended to define clean-up or 

action levels. 

MRLs are derived for hazardous substances using the no-observed-adverse-effect level/uncertainty factor 

approach. They are below levels that might cause adverse health effects in the people most sensitive to 

such chemical-induced effects. MRLs are derived for acute (1–14 days), intermediate (15–364 days), and 

chronic (365 days and longer) durations and for the oral and inhalation routes of exposure. Currently, 

MRLs for the dermal route of exposure are not derived because ATSDR has not yet identified a method 

suitable for this route of exposure. MRLs are generally based on the most sensitive chemical-induced end 

point considered to be of relevance to humans. Serious health effects (such as irreparable damage to the 

liver or kidneys, or birth defects) are not used as a basis for establishing MRLs. Exposure to a level 

above the MRL does not mean that adverse health effects will occur. 

MRLs are intended only to serve as a screening tool to help public health professionals decide where to 

look more closely. They may also be viewed as a mechanism to identify those hazardous waste sites that 

are not expected to cause adverse health effects. Most MRLs contain a degree of uncertainty because of 
 

STYRENE A-2 

APPENDIX A 

the lack of precise toxicological information on the people who might be most sensitive (e.g., infants, 

elderly, nutritionally or immunologically compromised) to the effects of hazardous substances. ATSDR 

uses a conservative (i.e., protective) approach to address this uncertainty consistent with the public health 

principle of prevention. Although human data are preferred, MRLs often must be based on animal studies 

because relevant human studies are lacking. In the absence of evidence to the contrary, ATSDR assumes 

that humans are more sensitive to the effects of hazardous substance than animals and that certain persons 

may be particularly sensitive. Thus, the resulting MRL may be as much as 100-fold below levels that 

have been shown to be nontoxic in laboratory animals. 

Proposed MRLs undergo a rigorous review process: Health Effects/MRL Workgroup reviews within the 

Division of Toxicology and Environmental Medicine, expert panel peer reviews, and agency-wide MRL 

Workgroup reviews, with participation from other federal agencies and comments from the public. They 

are subject to change as new information becomes available concomitant with updating the toxicological 

profiles. Thus, MRLs in the most recent toxicological profiles supersede previously published levels. 

For additional information regarding MRLs, please contact the Division of Toxicology and 

Environmental Medicine, Agency for Toxic Substances and Disease Registry, 1600 Clifton Road NE, 

Mailstop F-62, Atlanta, Georgia 30333. 
 

 

 

 

 

 

 

 

 

 

 

 

STYRENE A-3 

APPENDIX A 

MINIMAL RISK LEVEL (MRL) WORKSHEET 

Chemical Name: Styrene 

CAS Numbers: 100-42-5 

Date: June 2010 

Profile Status: Final Draft Post-Public Comment 

Route: [X] Inhalation [ ] Oral 

Duration: [X] Acute [ ] Intermediate [ ] Chronic 

Graph Key: 17 

Species: Human 

Minimal Risk Level: 5 [ ] mg/kg/day [X] ppm 

Reference: Ska B, Vyskocil A, Tardif R, et al. 2003. Effects of peak concentrations on the neurotoxicity 

of styrene in volunteers. Hum Exper Toxicol 22:407-415. 

Experimental design: Groups of 24 healthy men (aged 20–50 years) were exposed to 1 ppm (control 

exposure), 24 ppm, and 24 ppm with four 15-minute exposures to peak concentrations of 49 ppm, 

49 ppm, or 49 ppm with four 15-minute exposures to peak concentrations of 98 ppm for 6 hours. The 

subjects were exposed to each concentration with a 2-week period between each session. The subjects 

did not have a history of styrene exposure. At the end of the exposure session the subjects were tested for 

color discrimination (using the Lanthony D-15 desaturated panel), vision contrast, olfactory threshold, 

simple reaction time, color word stress (response time), symbol digit matching, digit span memory, and 

continuous tracking. The subjects were also given a questionnaire to assess mood and symptoms. 

Effect noted in study and corresponding doses: No significant styrene-related alterations in performance 

on color discrimination, olfactory threshold, neurobehavioral tests, mood, or subjective symptoms were 

found. 

Dose and end point used for MRL derivation: 

[X] NOAEL [ ] LOAEL 

A NOAEL of 49 ppm for the lack of alterations in tests of simple reaction time, choice reaction time, 

memory, or attention. 

Uncertainty Factors used in MRL derivation: 

[ ] 10 for use of a LOAEL 

[ ] 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? No, because the subjects were only 

exposed once for 6 hours; adjusting this NOAEL from intermittent exposure to continuous exposure 

0.04 ppm) may result in an overly conservative MRL. 
 

 

 

 

 

 

STYRENE A-4 

APPENDIX A 

Other additional studies or pertinent information that lend support to this MRL: Exposure to 99 ppm for 

7 hours or 376 ppm for 1 hour (Stewart et al. 1968) resulted in eye irritation in experimental subjects; 

nasal irritation was also reported at 376 ppm. A significant inhibition of the vestibular-oculomotor

system was observed in subjects exposed to 87 ppm for 1 hour (Ödkvist et al. 1982). Studies by Stewart 

et al. (1968) found alterations in tests of balance or coordination in subjects exposed to 376 ppm for 

1 hour, but not after exposure to 99 ppm for 7 hours or 216 ppm for 1 hour; the test used in the Stewart et

al. (1968) studies is probably less sensitive than those used by Ödkvist et al. (1982). No significant 

alterations in performance on neurobehavioral tests were observed in subjects exposed to 20 ppm for 

3 hours (Seeber et al. 2004). 

The available data suggest that the nervous system is the most sensitive target of styrene toxicity 

following acute-duration inhalation exposure. The lowest LOAEL for a relevant end point in humans is

87 ppm for vestibular impairment in subjects exposed to styrene for 1 hour (Ödkvist et al. 1982). A 

similar LOAEL (80 ppm) was identified for nasal effects in mice exposed to styrene for 3 days (Cruzan et 

al. 2001); this effect was not considered suitable as the basis of an MRL. As stated previously, mice 

appear to have a greater capacity than humans to generate the reactive metabolite, styrene oxide, in the 

nasal cavity and a lower capacity to detoxify styrene oxide (Green et al. 2001a). The identification of the 

nervous system as the critical target of toxicity for styrene is supported by a large number of occupational 

exposure studies. Delays in reaction time have been observed in workers exposed to 21.9–92 ppm 

(Cherry et al. 1980; Fallas et al. 1992; Gamberale et al. 1976; Jegaden et al. 1993; Mutti et al. 1984a; Tsai 

and Chen 1996) and vestibular effects have been observed at 18–36 ppm (Calabrese et al. 1996; Möller et 

al. 1990; Toppila et al. 2006). 

Agency Contact (Chemical Manager): Selene Chou 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

STYRENE A-5 

APPENDIX A 

MINIMAL RISK LEVEL (MRL) WORKSHEET 

Chemical Name: Styrene 

CAS Numbers: 100-42-5 

Date: June 2010 

Profile Status: Final Draft Post-Public Comment 

Route: [X] Inhalation [ ] Oral 

Duration: [ ] Acute [ ] Intermediate [X] Chronic 

Graph Key: 61 

Species: Human 

Minimal Risk Level: 0.2 [ ] mg/kg/day [X] ppm 

Reference: Benignus VA, Geller AM, Boyes WK, et al. 2005. Human neurobehavioral effects of longterm exposure to styrene: a meta-analysis. Environ Health Perspect 113:532-538. 

Experimental design: Benignus et al. (2005) used data from occupational exposure studies examining 

color vision impairment (Campagna et al. 1996; Eguchi et al. 1995; Gobba et al. 1991; Gong et al. 2002; 

Kishi et al. 2001) and delays in choice reaction time (Jegaden et al. 1993; Mutti et al. 1984a; Triebig et al. 

1989; Tsai and Chen 1996). Average styrene exposure concentrations for each study were estimated from 

individual data reported in the papers; for studies reporting individual data as urinary mandelic acid 

levels, standardized methods for converting to styrene exposure levels were used. Cumulative styrene 

exposure was estimated by multiplying exposure level by length of employment. A common metric of 

effect magnitude (percentage of baseline) was calculated for the different neurological effects. 

Effect noted in study and corresponding doses: A significant linear relationship between choice reaction 

time and cumulative styrene exposure was found; cumulative exposure accounted for 91% of the variance 

in reaction time. Similarly, a significant relationship between CCI and cumulative styrene exposure was 

found, with cumulative exposure accounting for 35% of the variance in CCI. Using the regression 

equations for these two effects, the investigators estimated that exposure to 150 ppm for 8 work-years 

would result in a 50% increase in choice reaction time and a 17% increase in CCI score; exposure to 

20 ppm for 8 work-years would result in a 6.5% increase in choice reaction time and a 2.23% increase in 

CCI score. As discussed in Benignus et al. (2005), a 7% decrease in reaction time would prevent 58,000– 

70,000 injuries per year from automobile accidents. The investigators also noted that CCI increases with 

age, and the rate of increase is about 10% per 13 years of age; thus, a 2.23% decrease in color perception 

would be roughly equivalent to 2.9 additional years of age. Based on this analysis, 20 ppm is considered 

a LOAEL for neurological effects. 

Dose and end point used for MRL derivation: 

[ ] NOAEL [X] LOAEL 

A minimal LOAEL of 20 ppm in the Benignus et al. (2005) meta-analysis was selected as the point of 

departure for the chronic-duration inhalation MRL. The LOAEL was classified as a minimal LOAEL 

based on the findings of Triebig et al. (2001) that alterations in color vision were reversible and the 

workers were not aware of any changes in color vision. 
 

 

 

 

STYRENE A-6 

APPENDIX A 

Uncertainty Factors used in MRL derivation: 30 

[X] 3 for use of a minimal LOAEL
 

[ ] 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? Yes. 

LOAELADJ = 20 ppm x 8 hours/24 hours x 5 days/7 days 

LOAELADJ = 4.8 ppm 

Other additional studies or pertinent information that lend support to this MRL: A large number of 

occupational exposure studies have examined the toxicity of styrene; however, most of these studies have 

focused on the potential neurotoxicity of styrene, which appears to be the most sensitive effect. Two 

common limitations of the occupational exposure studies are: (1) the range of current styrene levels for 

the workers is typically large and it is difficult to ascribe the observed effects to the mean or median 

exposure level and (2) historical exposure to higher styrene levels are not adequately taken into 

consideration. The use of urinary levels of mandelic acid, phenylglyoxylic acid, or mandelic acid plus 

phenylglyoxylic acid levels as biomarkers for styrene exposure eliminates another common limitation of 

styrene occupational exposure studies, which is poor characterization of styrene exposure levels due to 

the lack of personal air samples and the workers’ use of respirators with or without canisters. 

A variety of neurological effects have been reported in workers at reinforced plastic manufacturing 

facilities, including decreased color discrimination, slowed reaction time, impaired performance on other 

neurobehavioral tests, permanent hearing threshold shifts, vestibular effects, altered nerve conduction 

velocity, and increases in subjective symptoms. A summary of the results of studies for some of these 

neurological effects is presented in Table A-1 (more details regarding these studies and other studies of 

neurological effects in styrene workers are presented in Table 3-2). An alteration in color discrimination 

is one of the more consistently found neurological effects; it may also be one of the more sensitive 

effects. Color discrimination was typically measured using the Lanthony desaturated panel D-15 test in 

which the subjects were asked to arrange 15 painted caps in a line with definite chromatic sequence; the 

TCDS and CCI are used to quantitatively analyze the results. LOAEL values of 6–93 ppm have been 

identified; however, these LOAELs often reflect the mean exposure level or the lower end of the range of 

exposure levels. Other neurological effects that have been frequently found include alterations in 

performance on neurobehavioral tests, particularly reaction time, in workers exposed to ≥21 ppm; 

vestibular alterations at ≥18 ppm; and increased frequency of clinical symptoms (e.g., tiredness and 

headaches in workers exposed to ≥6 ppm). Hearing loss and alterations in nerve conduction velocity have 

also been reported in some studies, but the finding is not consistent across studies. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

STYRENE A-7
 

APPENDIX A
 

Table A-1. Results of Selected Human Neurotoxicity Studies 

Result Reference NOAEL (ppm) LOAEL (ppm) 

Decreased color Chia et al. (1994) 6 

discrimination Kishi et al. (2001) 4 10 

Gong et al. (2002) 10 

Gobba et al. (1991) 16 

Triebig et al. 2001 20 

Iregren et al. (2005) 22 

Fallas et al. (1992) 24.3 

Campagna et al. (1996) 265 

Eguchi et al. (1995) 8 93 

Neurological symptoms Flodin et al. (1989) 6 

Edling et al. (1993) 8.6 

Checkoway et al. (1992) 10.8 18.9 

Cherry et al. 1980 92 

Vestibular effects Möller et al. (1990) 18 

Toppila et al. (2006) 24.8 

Calabrese et al. (1996) 36 

Reaction time Edling et al. (1993) 8.6 21.9 

Tsai and Chen (1996) 21.9 

Jegaden et al. (1993) 22.68 

Fallas et al. (1992) 24.3 

Mutti et al. (1984a) 25 

Gamberale et al. (1976) 4,755 

Cherry et al. (1980) 92 

Non-neurological effects observed in styrene workers include obstructive lung effects (Chmielewski and 

Renke 1975), mild hematological alterations (Checkoway and Williams 1982; Stengel et al. 1990; Thiess 

and Friedheim 1978), and impaired immune response to concanavalin (Somorowská et al. 1999; Tulinska 

et al. 2000). Although exposure levels were not reported in all of these studies, effects were typically 

observed at styrene concentrations of >20 ppm. Clinical chemistry studies did not find alterations 

indicative of impaired liver (Härkönen et al. 1984; Hotz et al. 1980; Lorimer et al. 1978; Thiess and 

Friedheim 1978) or kidney (Verplanke and Herber 1998; Viau et al. 1987; Vyskocil et al. 1989) function 

in workers exposed to ≥24 ppm. 

Chronic-duration studies in laboratory animals identify the nasal olfactory epithelium as the most 

sensitive end point. Atrophic and/or degenerative changes were observed in rats exposed to 50 ppm 

styrene 6 hours/day, 5 days/week for 104 weeks (Cruzan et al. 1998) and respiratory metaplasia in the 

nasal olfactory epithelium were observed in mice exposed to 20 ppm 6 hours/day, 5 days/week for 98– 

104 weeks (Cruzan et al. 2001). As noted previously, mice do not appear to be a good model for potential 

respiratory effects in humans. 

In addition to the studies included in the Benignus et al. (2005) meta-analysis, a LOAEL of 20 ppm is 

supported by a color discrimination study conducted by Triebig et al. (2001). In this study, significant 
 

STYRENE A-8 

APPENDIX A 

increases in CCI values were observed in styrene workers with urinary mandelic acid plus 

phenylglyoxylic acid levels of ≥472 mg/g creatinine (approximately 20 ppm air styrene concentration), 

when compared to >95th percentile age-dependent reference CCI values. An advantage of the Triebig et 

al. (2001) study is that individual exposure and CCI data were reported, which diminishes the problem of 

ascribing an observed effect to the mean or median concentration and the study addresses the issue of 

biological relevance because the CCI scores were compared to the 95th percentile of age-dependent 

reference values rather than values in the control group. 

In comparisons between styrene workers and a control group employed at the same facility without 

styrene exposure, Triebig et al. (2001) found no significant differences in CCI scores between workers 

and controls when the tests were conducted on a Monday morning, but CCI scores were significantly 

different when measured on a Thursday afternoon. Within the styrene-exposed workers, CCI scores on 

Monday morning and Thursday afternoon were not significantly different. After a 4-week nonexposure 

period, the CCI scores were significantly reduced in the styrene workers. After styrene exposure levels 

were lowered, no difference between workers and controls was observed on Monday morning or 

Thursday afternoon. However, among styrene workers, there were significant differences between 

Monday morning and Thursday afternoon measurements and between Monday morning and postvacation levels. These findings provide suggestive evidence that the alterations in color discrimination 

were reversible. 

Agency Contact (Chemical Manager): Selene Chou 
 

 

 

 

 

 

 

 

 

STYRENE A-9 

APPENDIX A 

MINIMAL RISK LEVEL (MRL) WORKSHEET 

Chemical Name: Styrene 

CAS Numbers: 100-42-5 

Date: June 2010 

Profile Status: Final Draft Post-Public Comment 

Route: [ ] Inhalation [X] Oral 

Duration: [X] Acute [ ] Intermediate [ ] Chronic 

Graph Key: 3 

Species: Rat 

Minimal Risk Level: 0.1 [X] mg/kg/day [ ] ppm 

Reference: Husain R, Srivastava SP, Seth PK. 1985. Some behavioral effects of early styrene 

intoxication in experimental animals. Arch Toxicol 57:53-55. 

Experimental design: Groups of 15 male Wistar rats were administered by gavage 0, 100, or 

200 mg/kg/day styrene in ground nut oil for 14 consecutive days. Spontaneous motor activity for a period 

of 10 minutes was measured 24 hours after the last dose. After baseline activity was measured, the rats 

received an intraperitoneal injection of 2.5 mg/kg amphetamine, and amphetamine-induced spontaneous 

motor activity was measured. Two days after exposure termination, acquisition training was initiated 

using a Cook's pole climbing apparatus. Learning was assessed by measuring the number of times the rat 

climbed the pole after the conditioned stimulus to avoid the foot-shock unconditioned stimulus. The rats 

were tested for 4 days. Noradrenaline, dopamine, and serotonin levels were measured in seven regions of 

the brain in six rats/group killed after the acquisition training. 

Effect noted in study and corresponding doses: No overt signs of toxicity were observed. No significant 

alterations in locomotor activity were observed with or without amphetamine induction. Significantly 

greater increases in percent avoidance response (indicative of impaired learning) were observed at 

100 and 200 mg/kg/day; no difference was found between the two styrene groups. The effects were 

observed on test days 3 and 4. Significant increases in the level of serotonin in the hypothalamus (70%), 

hippocampus (51%), and midbrain (29%) were observed at 200 mg/kg/day. Styrene did not affect brain 

noradrenaline and dopamine levels. 

Dose and end point used for MRL derivation: 

[ ] NOAEL [X] LOAEL 

A LOAEL of 100 mg/kg/day for impaired learning 

Uncertainty Factors used in MRL derivation: 

[X] 10 for use of a LOAEL 

[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. 
 

 

 

 

 

STYRENE A-10 

APPENDIX A 

Was a conversion used from intermittent to continuous exposure? Not applicable. 

Other additional studies or pertinent information that lend support to this MRL: A limited number of 

studies have examined the acute toxicity of orally-administered styrene; these studies have examined 

potential neurotoxicity and developmental toxicity. No developmental effects were observed in rats 

administered a single dose of 300 mg/kg on gestational day 11 (Daston et al. 1991) or administered 

300 mg/kg/day (administered as two daily doses of 150 mg/kg) on gestational days 6–15 (Murray et al. 

1978). Impaired learning was observed in rats administered via gavage 100 or 200 mg/kg/day for 14 days 

(Husain et al. 1985); increases in serotonin levels in the hypothalamus, hippocampus, and midbrain were 

also observed at 200 mg/kg/day. In another study, increases in dopamine receptor binding was observed 

in rats administered a single gavage dose of 200 mg/kg (Agrawal et al. 1982). 

Although there is a limited acute toxicity database, longer-term oral studies support the selection of 

neurotoxicity as the principal effect. The lowest LOAEL identified for a systemic effect is 

400 mg/kg/day for Heinz body formation in dogs administered styrene by gavage for 561 days (Quast et 

al. 1979); the identified NOAEL was 200 mg/kg/day. Decreased spermatozoa counts were observed in 

adult rats administered 400 mg/kg 6 days/week for 60 days (Srivastava et al. 1989), young rats exposed 

via lactation on postnatal days 1–21 (maternal dose of 400 mg/kg/day) (Srivastava et al. 1992a), and 

young rats administered 200 mg/kg 6 days/week on postnatal days 1–61 (Srivastava et al. 1992b); the 

NOAELs identified in these three studies were 200, 200, and 100 mg/kg, respectively. Marked 

degeneration of the seminiferous tubules was also observed in the adult rats administered 400 mg/kg 

(Srivastava et al. 1989). Impaired learning was also observed in rats administered 500 mg/kg 

5 days/week for 8 weeks (Bushnell 1994); a NOAEL was not identified in this study. The extensive 

inhalation toxicity database for styrene also supports the selection of neurotoxicity as the most sensitive 

target of toxicity; both the acute- and chronic-duration inhalation MRLs are based on neurological effects 

in humans. Neurological effects observed in chronically exposed styrene workers include decreased color 

discrimination, slowed reaction time, increased prevalence of neurological symptoms, and ototoxicity 

(hearing and vestibular effects). 

Agency Contact (Chemical Manager): Selene Chou 
 

 

 

 

 

 

 

 

 

STYRENE	 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. 
 

 

 

 

 

STYRENE 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. 
 

 

 

 

 

 

 

 

STYRENE	 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"). 
 

 

 

 

 

 

STYRENE	 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. 
STYRENE	 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

234

→ 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). 

STYRENE B-8
 

APPENDIX B 

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STYRENE C-1 

APPENDIX C. ACRONYMS, ABBREVIATIONS, AND SYMBOLS 

ACGIH American Conference of Governmental Industrial Hygienists 

ACOEM American College of Occupational and Environmental Medicine 

ADI acceptable daily intake 

ADME absorption, distribution, metabolism, and excretion 

AED atomic emission detection 

AFID alkali flame ionization detector 

AFOSH Air Force Office of Safety and Health 

ALT alanine aminotransferase 

AML acute myeloid leukemia 

AOAC Association of Official Analytical Chemists 

AOEC Association of Occupational and Environmental Clinics 

AP alkaline phosphatase 

APHA American Public Health Association 

AST aspartate aminotransferase 

atm atmosphere 

ATSDR Agency for Toxic Substances and Disease Registry 

AWQC Ambient Water Quality Criteria 

BAT best available technology 

BCF bioconcentration factor 

BEI Biological Exposure Index 

BMD/C benchmark dose or benchmark concentration 

BMDX dose that produces a X% change in response rate of an adverse effect 

BMDLX 95% lower confidence limit on the BMDX 

BMDS Benchmark Dose Software 

BMR benchmark response 

BSC Board of Scientific Counselors 

C centigrade 

CAA Clean Air Act 

CAG Cancer Assessment Group of the U.S. Environmental Protection Agency 

CAS Chemical Abstract Services 

CDC Centers for Disease Control and Prevention 

CEL cancer effect level 

CELDS Computer-Environmental Legislative Data System 

CERCLA Comprehensive Environmental Response, Compensation, and Liability Act 

CFR Code of Federal Regulations 

Ci curie 

CI confidence interval 

CL ceiling limit value 

CLP Contract Laboratory Program 

cm centimeter 

CML chronic myeloid leukemia 

CPSC Consumer Products Safety Commission 

CWA Clean Water Act 

DHEW Department of Health, Education, and Welfare 

DHHS Department of Health and Human Services 

DNA deoxyribonucleic acid 

DOD Department of Defense 

DOE Department of Energy 

DOL Department of Labor 
 

 

STYRENE C-2 

APPENDIX C 

DOT Department of Transportation 

DOT/UN/ Department of Transportation/United Nations/ 

NA/IMDG North America/Intergovernmental Maritime Dangerous Goods Code 

DWEL drinking water exposure level 

ECD electron capture detection 

ECG/EKG electrocardiogram 

EEG electroencephalogram 

EEGL Emergency Exposure Guidance Level 

EPA Environmental Protection Agency 

F Fahrenheit 

F1 first-filial generation 

FAO Food and Agricultural Organization of the United Nations 

FDA Food and Drug Administration 

FEMA Federal Emergency Management Agency 

FIFRA Federal Insecticide, Fungicide, and Rodenticide Act 

FPD flame photometric detection 

fpm feet per minute 

FR Federal Register 

FSH follicle stimulating hormone 

g gram 

GC gas chromatography 

gd gestational day 

GLC gas liquid chromatography 

GPC gel permeation chromatography 

HPLC high-performance liquid chromatography 

HRGC high resolution gas chromatography 

HSDB Hazardous Substance Data Bank 

IARC International Agency for Research on Cancer 

IDLH immediately dangerous to life and health 

ILO International Labor Organization 

IRIS Integrated Risk Information System 

Kd adsorption ratio 

kg kilogram 

kkg metric ton 

Koc organic carbon partition coefficient 

Kow octanol-water partition coefficient 

L liter 

LC liquid chromatography 

LC50 lethal concentration, 50% kill 

LCLo lethal concentration, low 

LD50 lethal dose, 50% kill 

LDLo lethal dose, low 

LDH lactic dehydrogenase 

LH luteinizing hormone 

LOAEL lowest-observed-adverse-effect level 

LSE Levels of Significant Exposure 

LT50 lethal time, 50% kill 

m meter 

MA trans,trans-muconic acid 

MAL maximum allowable level 

mCi millicurie 
STYRENE C-3 

APPENDIX C 

MCL maximum contaminant level 

MCLG maximum contaminant level goal 

MF modifying factor 

MFO mixed function oxidase 

mg milligram 

mL milliliter 

mm millimeter 

mmHg millimeters of mercury 

mmol millimole 

mppcf millions of particles per cubic foot 

MRL Minimal Risk Level 

MS mass spectrometry 

NAAQS National Ambient Air Quality Standard 

NAS National Academy of Science 

NATICH National Air Toxics Information Clearinghouse 

NATO North Atlantic Treaty Organization 

NCE normochromatic erythrocytes 

NCEH National Center for Environmental Health 

NCI National Cancer Institute 

ND not detected 

NFPA National Fire Protection Association 

ng nanogram 

NHANES National Health and Nutrition Examination Survey 

NIEHS National Institute of Environmental Health Sciences 

NIOSH National Institute for Occupational Safety and Health 

NIOSHTIC NIOSH's Computerized Information Retrieval System 

NLM National Library of Medicine 

nm nanometer 

nmol nanomole 

NOAEL no-observed-adverse-effect level 

NOES National Occupational Exposure Survey 

NOHS National Occupational Hazard Survey 

NPD nitrogen phosphorus detection 

NPDES National Pollutant Discharge Elimination System 

NPL National Priorities List 

NR not reported 

NRC National Research Council 

NS not specified 

NSPS New Source Performance Standards 

NTIS National Technical Information Service 

NTP National Toxicology Program 

ODW Office of Drinking Water, EPA 

OERR Office of Emergency and Remedial Response, EPA 

OHM/TADS Oil and Hazardous Materials/Technical Assistance Data System 

OPP Office of Pesticide Programs, EPA 

OPPT Office of Pollution Prevention and Toxics, EPA 

OPPTS Office of Prevention, Pesticides and Toxic Substances, EPA 

OR odds ratio 

OSHA Occupational Safety and Health Administration 

OSW Office of Solid Waste, EPA 

OTS Office of Toxic Substances 
STYRENE C-4 

APPENDIX C 

OW Office of Water 

OWRS Office of Water Regulations and Standards, EPA 

PAH polycyclic aromatic hydrocarbon 

PBPD physiologically based pharmacodynamic 

PBPK physiologically based pharmacokinetic 

PCE polychromatic erythrocytes 

PEL permissible exposure limit 

pg picogram 

PHS Public Health Service 

PID photo ionization detector 

pmol picomole 

PMR proportionate mortality ratio 

ppb parts per billion 

ppm parts per million 

ppt parts per trillion 

PSNS pretreatment standards for new sources 

RBC red blood cell 

REL recommended exposure level/limit 

RfC reference concentration 

RfD reference dose 

RNA ribonucleic acid 

RQ reportable quantity 

RTECS Registry of Toxic Effects of Chemical Substances 

SARA Superfund Amendments and Reauthorization Act 

SCE sister chromatid exchange 

SGOT serum glutamic oxaloacetic transaminase 

SGPT serum glutamic pyruvic transaminase 

SIC standard industrial classification 

SIM selected ion monitoring 

SMCL secondary maximum contaminant level 

SMR standardized mortality ratio 

SNARL suggested no adverse response level 

SPEGL Short-Term Public Emergency Guidance Level 

STEL short term exposure limit 

STORET Storage and Retrieval 

TD50 toxic dose, 50% specific toxic effect 

TLV threshold limit value 

TOC total organic carbon 

TPQ threshold planning quantity 

TRI Toxics Release Inventory 

TSCA Toxic Substances Control Act 

TWA time-weighted average 

UF uncertainty factor 

U.S. United States 

USDA United States Department of Agriculture 

USGS United States Geological Survey 

VOC volatile organic compound 

WBC white blood cell 

WHO World Health Organization 

> greater than 

≥ greater than or equal to 
STYRENE C-5 

APPENDIX C 

= 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 
STYRENE C-6
 

APPENDIX C 

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STYRENE D-1 

APPENDIX D. INDEX
 

absorbed dose ....................................................................................................................................104, 106, 123, 127
 

adipose tissue............................................................................... 99, 100, 105, 116, 123, 127, 137, 165, 171, 175, 179
 

adsorption ..........................................................................................................................................................156, 170
 

aerobic ...............................................................................................................................................................159, 170
 

alanine aminotransferase .............................................................................................................................................49
 

ambient air.................................................................................................................................................................160
 

anaerobic....................................................................................................................................................149, 159, 170
 

aspartate aminotransferase...................................................................................................................................49, 125
 

bioaccumulation ........................................................................................................................................................171
 

bioconcentration factor..............................................................................................................................................157
 

biodegradation ...................................................................................................................................149, 156, 159, 183
 

biological half-time....................................................................................................................................................116
 

biomarker............................................................................................... 16, 53, 122, 123, 125, 132, 136, 175, 179, 182
 

blood cell count ...........................................................................................................................................................86
 

breast milk .......................................................................................................................................................5, 99, 166
 

cancer............................................................................................................. 12, 72, 73, 74, 75, 90, 121, 127, 137, 187
 

carcinogen................................................................................................................................5, 12, 117, 133, 137, 190
 

carcinogenic......................................................................................................... 12, 23, 72, 76, 90, 107, 116, 133, 190
 

carcinogenicity ............................................................................................................ 12, 75, 76, 77, 91, 101, 136, 182
 

carcinoma ..............................................................................................................................................................76, 90
 

cardiovascular..................................................................................................................................................47, 78, 91
 

cardiovascular effects ............................................................................................................................................47, 78
 

CCI (see color confusion index)..............................................................................................17, 19, 54, 55, 61, 62, 63
 

chromosomal aberrations...............................................................................................................................92, 96, 116
 

clearance....................................................................................................................................................104, 113, 123
 

color confusion index (see CCI) ......................................................................................................................17, 61, 62
 

color discrimination....................................................... 9, 13, 14, 15, 16, 17, 18, 19, 20, 21, 53, 54, 62, 124, 135, 185
 

death ................................................................................................................................ 11, 23, 53, 70, 72, 74, 77, 190
 

deoxyribonucleic acid (see DNA)................................................................................................................................95
 

dermal effects ..............................................................................................................................................................91
 

developmental effects ........................................................................ 10, 14, 20, 70, 71, 89, 90, 92, 121, 131, 134, 138
 

DNA (see deoxyribonucleic acid).............................................................................. 92, 94, 95, 96, 116, 123, 125, 182
 

dopamine ...................................................................................................................................................20, 21, 88, 90
 

elimination half-time .................................................................................................................................................116
 

enantiomer........................................................................................................................... 77, 103, 104, 117, 118, 137
 

endocrine ......................................................................................................................... 50, 78, 91, 118, 119, 132, 136
 

endocrine effects............................................................................................................................................50, 69, 136
 

fetus .....................................................................................................................................................................11, 120
 

follicle stimulating hormone..........................................................................................................................51, 69, 119
 

gastrointestinal effects ...........................................................................................................................................47, 86
 

general population ............................................................................................... 24, 149, 165, 168, 171, 173, 182, 190
 

genotoxic ...............................................................................................................................23, 96, 116, 117, 125, 133
 

genotoxicity .................................................................................................................................................92, 125, 133
 

groundwater................................................................................................................... 3, 157, 158, 162, 165, 171, 182
 

half-life ................................................................................................ 99, 105, 122, 123, 124, 127, 149, 156, 157, 158
 

hematological effects...............................................................................................................................47, 48, 86, 133
 

hematopoietic ............................................................................................................................................12, 73, 74, 75
 

hepatic effects..................................................................................................................................................11, 49, 86
 

hydroxyl radical.................................................................................................................................................149, 158
 

immune system....................................................................................................................................................22, 135
 

immunological...........................................................................................................................................22, 23, 87, 88
 

immunological effects ...........................................................................................................................................22, 87
 

Kow .....................................................................................................................................................................141, 157
 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

STYRENE D-2 

APPENDIX D 

LD50 .............................................................................................................................................................................77
 

leukemia ..........................................................................................................................................................72, 73, 74
 

lymphatic ...................................................................................................................................................12, 73, 74, 75
 

menstrual .....................................................................................................................................................................69
 

metabolic effects..........................................................................................................................................................25
 

micronuclei............................................................................................................................................................92, 96
 

milk................................................................................................................................................5, 122, 163, 168, 171
 

mucociliary ..................................................................................................................................................................47
 

musculoskeletal effects................................................................................................................................................48
 

neonatal .................................................................................................................................................................16, 71
 

neoplastic.........................................................................................................................................12, 76, 90, 116, 133
 

neurobehavioral ................................................................................. 9, 13, 15, 16, 53, 57, 63, 119, 124, 132, 135, 138
 

neurochemical..............................................................................................................................................................16
 

neurodevelopmental...........................................................................................................11, 16, 71, 90, 121, 131, 134
 

neurological effects.......................................9, 16, 17, 19, 21, 22, 52, 53, 68, 88, 89, 92, 127, 129, 132, 135, 137, 138
 

non-Hodgkin’s lymphoma ...........................................................................................................................................72
 

ocular effects ...................................................................................................................................................51, 78, 91
 

odds ratio .............................................................................................................................................61, 65, 69, 70, 75
 

partition coefficients ..................................................................................................................................................156
 

pharmacodynamic......................................................................................................................................................106
 

pharmacokinetic................................................................................................... 77, 104, 105, 106, 107, 108, 110, 120
 

photolysis...................................................................................................................................................................157
 

rate constant...............................................................................................................................................................158
 

renal effects .....................................................................................................................................................50, 87, 91
 

reproductive effects ............................................................................................. 11, 68, 69, 89, 92, 119, 131, 134, 136
 

respiratory effects ............................................................................................................................................17, 25, 78
 

retention.........................................................................................................................................................58, 96, 137
 

solubility....................................................................................................................................................155, 156, 169
 

spermatozoa.................................................................................................................................11, 20, 22, 89, 90, 131
 

systemic effects .........................................................................................................................................15, 25, 78, 91
 

T3...........................................................................................................................................................................26, 79
 

thyroid .................................................................................................................................................................51, 119
 

thyroid stimulating hormone................................................................................................................................51, 119
 

toxicokinetic ................................................................................................................ 23, 107, 109, 122, 129, 133, 137
 

tumors...................................................................................................................... 12, 76, 90, 109, 111, 116, 117, 133
 

vapor pressure............................................................................................................................................................155
 

volatilization ......................................................................................................................................................156, 170
 

weanling ......................................................................................................................................................................91