TOXICOLOGICAL PROFILE FOR

DI-n-BUTYL PHTHALATE

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES

Public Health Service

Agency for Toxic Substances and Disease Registry

September 2001
DI-n-BUTYL PHTHALATE 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.
DI-n-BUTYL PHTHALATE iii

UPDATE STATEMENT

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

For information regarding the update status of previously released profiles, contact ATSDR at:

Agency for Toxic Substances and Disease Registry

Division of Toxicology/Toxicology Information Branch

1600 Clifton Road NE, E-29

Atlanta, Georgia 30333


DI-n-BUTYL PHTHALATE vi

*Legislative Background

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

Reauthorization Act (SARA) of 1986 (Public law 99-499) which amended the Comprehensive

Environmental Response, Compensation, and Liability Act of 1980 (CERCLA or Superfund). This

public law directed ATSDR to prepared toxicological profiles for hazardous substances most commonly

found at facilities on the CERCLA National Priorities List and that pose the most significant potential

threat to human health, as determined by ATSDR and the EPA. The availability of the revised priority

list of 275 hazardous substances was announced in the Federal Register on November 17, 1997 (62 FR

61332). For prior versions of the list of substances, see Federal Register notices dated April 29, 1996 (61

FR 18744); April 17, 1987 (52 FR 12866); October 20, 1988 (53 FR 41280); October 26, 1989 (54 FR

43619); October 17, 1990 (55 FR 42067); October 17, 1991 (56 FR 52166); October 28, 1992 (57 FR

48801); and February 28, 1994 (59 FR 9486). Section 104(i)(3) of CERCLA, as amended, directs the

Administrator of ATSDR to prepare a toxicological profile for each substance on the list.
DI-n-BUTYL PHTHALATE 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: 1-888-42-ATSDR or (404) 498-0110 Fax: (404) 498-0057

E-mail: atsdric@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.
DI-n-BUTYL PHTHALATE 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, 55 West Seegers Road, Arlington Heights, IL

60005 • Phone: 847-818-1800 • FAX: 847-818-9266.
DI-n-BUTYL PHTHALATE ix

CONTRIBUTORS

CHEMICAL MANAGER(S)/AUTHORS(S):

Jessilyn Taylor, M.S.

ATSDR, Division of Toxicology, Atlanta, GA

Lisa Ingerman, Ph.D., DABT

Syracuse Research Corporation, Saratoga, NY

D. Anthony Gray, Ph.D.

Syracuse Research Corporation, North Syracuse, NY

Susan Little, Ph.D.

Syracuse Research Corporation, Atlanta, GA

Richard Amata, Ph.D.

Syracuse Research Corporation, North Syracuse, NY

THE PROFILE HAS UNDERGONE THE FOLLOWING ATSDR INTERNAL REVIEWS:

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

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

end points.

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

substance-specific minimal risk levels (MRLs), reviews the health effects database of each

profile, and makes recommendations for derivation of MRLs.

3. Data Needs Review. The Research Implementation Branch reviews data needs sections to assure

consistency across profiles and adherence to instructions in the Guidance.

DI-n-BUTYL PHTHALATE xi

PEER REVIEW

A peer review panel was assembled for di-n-butyl phthalate. The panel consisted of the following

members: 

1. William J. Adams, Ph.D., Kennecott Utah Copper Corporation, Magna, Utah;

2. Martin Alexander, Ph.D., Cornell University, Ithaca, New York;

3. C. Clifford Conaway, Ph.D., American Health Foundation, Valhalla, New York; and

4. Robert Rubin, Ph.D., Environmental Health Sciences, John Hopkins School of Public Health,

Baltimore, Maryland

These experts have knowledge of di-n-butyl phthalate's physical and chemical properties, toxicokinetics,

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

humans. These 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. A list of databases reviewed

and a list of unpublished documents cited are also included in the administrative record.

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

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

DI-n-BUTYL PHTHALATE xiii

CONTENTS

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

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

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

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

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

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

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

1.1 WHAT IS DI-n-BUTYL PHTHALATE? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

1.2 WHAT HAPPENS TO DI-n-BUTYL PHTHALATE WHEN IT ENTERS THE

ENVIRONMENT? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2

1.3 HOW MIGHT I BE EXPOSED TO DI-n-BUTYL PHTHALATE? . . . . . . . . . . . . . . . . . . . . . 2

1.4 HOW CAN DI-n-BUTYL PHTHALATE ENTER AND LEAVE MY BODY? ............ 4

1.5 HOW CAN DI-n-BUTYL PHTHALATE AFFECT MY HEALTH? .................... 4

1.6 HOW CAN DI-n-BUTYL PHTHALATE AFFECT CHILDREN? ...................... 5

1.7 HOW CAN FAMILIES REDUCE THE RISK OF EXPOSURE TO DI-n-BUTYL

PHTHALATE? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

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

DI-n-BUTYL PHTHALATE? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

1.9 WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT MADE TO

PROTECT HUMAN HEALTH? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

1.10 WHERE CAN I GET MORE INFORMATION? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

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

2.1 BACKGROUND AND ENVIRONMENTAL EXPOSURES TO DI-n-BUTYL PHTHALATE

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

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

2.3 MINIMAL RISK LEVELS FOR DI-n-BUTYL PHTHALATE. . . . . . . . . . . . . . . . . . . . . . . . 12

3. HEALTH EFFECTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

3.1 INTRODUCTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

3.2 DISCUSSION OF HEALTH EFFECTS BY ROUTE OF EXPOSURE . . . . . . . . . . . . . . . . . 15

3.2.1 Inhalation Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17

3.2.1.1 Death . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17

3.2.1.2 Systemic Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17

3.2.1.3 Immunological and Lymphoreticular Effects . . . . . . . . . . . . . . . . . . . . . . 19

3.2.1.4 Neurological Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19

3.2.1.5 Reproductive Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19

3.2.1.6 Developmental Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19

3.2.1.7 Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20

3.2.2 Oral Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20

3.2.2.1 Death . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
DI-n-BUTYL PHTHALATE xiv

3.2.2.2 Systemic Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20

3.2.2.3 Immunological and Lymphoreticular Effects . . . . . . . . . . . . . . . . . . . . . . 40

3.2.2.4 Neurological Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40

3.2.2.5 Reproductive Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41

3.2.2.6 Developmental Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43

3.2.2.7 Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46

3.2.3 Dermal Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47

3.2.3.1 Death . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47

3.2.3.2 Systemic Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47

3.2.3.3 Immunological and Lymphoreticular Effects . . . . . . . . . . . . . . . . . . . . . . 49

3.2.3.4 Neurological Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49

3.2.3.5 Reproductive Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49

3.2.3.6 Developmental Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49

3.2.3.7 Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49

3.2.4 Other Routes of Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49

3.3 GENOTOXICITY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49

3.4 TOXICOKINETICS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51

3.4.1 Absorption . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51

3.4.1.1 Inhalation Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51

3.4.1.2 Oral Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51

3.4.1.3 Dermal Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51

3.4.2 Distribution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52

3.4.2.1 Inhalation Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52

3.4.2.2 Oral Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52

3.4.2.3 Dermal Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53

3.4.3 Metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53

3.4.3.1 Inhalation Exposure. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54

3.4.3.2 Oral Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54

3.4.3.3 Dermal Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54

3.4.4 Elimination and Excretion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56

3.4.4.1 Inhalation Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56

3.4.4.2 Oral Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56

3.4.4.3 Dermal Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56

3.4.5 Physiologically Based Pharmacokinetic (PBPK)/Pharmacodynamic (PD) 

Models . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56

3.5 MECHANISMS OF ACTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63

3.5.1 Pharmacokinetic Mechanisms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63

3.5.2 Mechanisms of Toxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63

3.5.3 Animal-to-Human Extrapolations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64

3.6 ENDOCRINE DISRUPTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65

3.7 CHILDREN’S SUSCEPTIBILITY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67

3.8 BIOMARKERS OF EXPOSURE AND EFFECT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70

3.8.1 Biomarkers Used to Identify or Quantify Exposure to Di-n-butyl Phthalate . . . . . . . 71

3.8.2 Biomarkers Used to Characterize Effects Caused by Di-n-butyl Phthalate . . . . . . . . 72

3.9 INTERACTIONS WITH OTHER CHEMICALS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72

3.10 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE . . . . . . . . . . . . . . . . . . . . . . . 72

3.11 METHODS FOR REDUCING TOXIC EFFECTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73

3.11.1 Reducing Peak Absorption Following Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73

3.11.2 Reducing Body Burden . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73

3.11.3 Interfering with the Mechanism of Action for Toxic Effects . . . . . . . . . . . . . . . . . . . 74

3.12 ADEQUACY OF THE DATABASE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74
DI-n-BUTYL PHTHALATE xv

3.12.1 Existing Information on Health Effects of Di-n-butyl Phthalate . . . . . . . . . . . . . . . . 74

3.12.2 Identification of Data Needs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76

3.12.3 Ongoing Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81

4. CHEMICAL AND PHYSICAL INFORMATION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83

4.1 CHEMICAL IDENTITY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83

4.2 PHYSICAL AND CHEMICAL PROPERTIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87

5.1 PRODUCTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87

5.2 IMPORT/EXPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87

5.3 USE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89

5.4 DISPOSAL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90

6. POTENTIAL FOR HUMAN EXPOSURE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93

6.1 OVERVIEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93

6.2 RELEASES TO THE ENVIRONMENT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93

6.2.1 Air . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95

6.2.2 Water . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96

6.2.3 Soil . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99

6.3 ENVIRONMENTAL FATE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100

6.3.1 Transport and Partitioning . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100

6.3.2 Transformation and Degradation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102

6.3.2.1 Air . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103

6.3.2.2 Water . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103

6.3.2.3 Sediment and Soil . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104

6.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT . . . . . . . . . . . . . . . 105

6.4.1 Air . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105

6.4.2 Water . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105

6.4.3 Sediment and Soil . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 107

6.4.4 Other Environmental Media . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 107

6.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE . . . . . . . . . . . . . . . . . . 111

6.6 EXPOSURES OF CHILDREN . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113

6.7 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES . . . . . . . . . . . . . . . . . . . . . . 115

6.8 ADEQUACY OF THE DATABASE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116

6.8.1 Identification of Data Needs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116

6.8.2 Ongoing Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119

7. ANALYTICAL METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121

7.1 BIOLOGICAL SAMPLES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122

7.2 ENVIRONMENTAL SAMPLES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122

7.3 ADEQUACY OF THE DATABASE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122

7.3.1 Identification of Data Needs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126

7.3.2 Ongoing Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 127

8. REGULATIONS AND ADVISORIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129

9. REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139

10. GLOSSARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 179
DI-n-BUTYL PHTHALATE xvi

APPENDICES

A. ATSDR MINIMAL RISK LEVEL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A-1

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

C. ACRONYMS, ABBREVIATIONS, AND SYMBOLS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . C-1
DI-n-BUTYL PHTHALATE xvii

LIST OF FIGURES

3-1. Levels of Significant Exposure to Di-n-butyl Phthalate - Oral . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35

3-2. Metabolic Scheme for Di-n-butyl Phthalate in Animals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55

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

Hypothetical Chemical Substance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59

3-4. Existing Information on Health Effects of Di-n-butyl Phthalate . . . . . . . . . . . . . . . . . . . . . . . . . . 75

6-1. Frequency of NPL Sites with Di-n-butyl Phthalate Contamination . . . . . . . . . . . . . . . . . . . . . . . . 94

DI-n-BUTYL PHTHALATE xix

LIST OF TABLES

3-1. Levels of Significant Exposure to Di-n-butyl Phthalate - Oral . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21

3-2. Levels of Significant Exposure to Di-n-butyl Phthalate - Dermal . . . . . . . . . . . . . . . . . . . . . . . . . 48

3-3. Genotoxicity of Di-n-butyl Phthalate In Vitro . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50

3-4. Tissue:Blood Partition Coefficients Used in the Keys et al. (2000) Model . . . . . . . . . . . . . . . . . . 61

3-5. Ongoing Studies on Di-n-butyl Phthalate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82

4-1. Chemical Identity of Di-n-butyl Phthalate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84

4-2. Physical and Chemical Properties of Di-n-butyl Phthalate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85

5-1. U.S. Production Volumes of Di-n-butyl Phthalate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88

5-2. Facilities that Produce, Process, or Use Di-n-butyl Phthalate . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91

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

Di-n-butyl Phthalate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97

6-2. Concentration of Di-n-butyl Phthalate in Paper and Board Packaging and Food Packaged in

Paper and Board . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 109

6-3. Concentration of Di-n-butyl Phthalate in Categories of Household Waste . . . . . . . . . . . . . . . . . 110

6-4. Estimated Daily Intake of Di-n-butyl Phthalate by the Population of Canada . . . . . . . . . . . . . . . 112

7-1. Analytical Methods for Determining Di-n-butyl Phthalate in Biological Samples . . . . . . . . . . . 123

7-2. Analytical Methods for Determining Di-n-butyl Phthalate in Environmental Samples . . . . . . . . 124

8-1. Regulations and Guidelines Applicable to Di-n-butyl Phthalate . . . . . . . . . . . . . . . . . . . . . . . . . 130

DI-n-BUTYL PHTHALATE 1

1. PUBLIC HEALTH STATEMENT

This public health statement tells you about di-n-butyl phthalate and the effects of exposure. 

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

the nation. These sites make up the National Priorities List (NPL) and are the sites targeted for

long-term federal cleanup activities. Di-n-butyl phthalate has been found in at least 471 of the

1,585 current or former NPL sites. However, the total number of NPL sites evaluated for this

substance is not known. As more sites are evaluated, the sites at which di-n-butyl phthalate is

found may increase. This information is important because exposure to this substance may harm

you and because these sites may be sources of exposure.

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

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

exposure. You are 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 di-n-butyl phthalate, many factors determine whether you’ll 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 the other chemicals you’re exposed to and your age, sex,

diet, family traits, lifestyle, and state of health.

1.1 WHAT IS DI-n-BUTYL PHTHALATE?

Di-n-butyl phthalate is an odorless and colorless or faintly yellow oily liquid that does not occur

in nature. It is a chemical that is added to hard plastics to make them soft. The plastics that

di-n-butyl phthalate is used most in are called polyvinyl chloride plastics and nitrocellulose

lacquers. These plastics are used to make many products that we use every day such as carpets,

paints, glue, insect repellents, hair spray, nail polish, and rocket fuel. In 1994, more than

17 million pounds (i.e., 7.8 million kilograms) of di-n-butyl phthalate were made.
DI-n-BUTYL PHTHALATE 2

1. PUBLIC HEALTH STATEMENT

Further information on the properties and uses of di-n-butyl phthalate can be found in Chapters 4

and 5.

1.2 WHAT HAPPENS TO DI-n-BUTYL PHTHALATE WHEN IT ENTERS THE

ENVIRONMENT?

Di-n-butyl phthalate enters the environment in many ways. Di-n-butyl phthalate is in many

items made of plastics such as carpets, paint, and nail polish. When paint dries or new carpets

are installed, a small amount of di-n-butyl phthalate enters the air. Di-n-butyl phthalate also gets

into air by sticking to dust particles. In air, di-n-butyl phthalate usually breaks down within a

few days, but not if it is stuck to dust. When it is on dust, di-n-butyl phthalate can move with the

wind for many miles before dust drops to the ground. Di-n-butyl phthalate can get into soil

when people throw out certain plastic items containing di-n-butyl phthalate and they get buried. 

In water and soil, bacteria break down di-n-butyl phthalate. This may happen in a day, or may

take up to a month. How long it takes to break down di-n-butyl phthalate in soil or water

depends on many factors. These factors include the outside temperature, because di-n-butyl

phthalate breaks down more slowly when it is cold than when it is hot. If di-n-butyl phthalate

does not break down in soil, it can get into groundwater and contaminate wells.

Further information on the uses of di-n-butyl phthalate and how it behaves in the environment

can be found in Chapters 5 and 6.

1.3 HOW MIGHT I BE EXPOSED TO DI-n-BUTYL PHTHALATE?

Because di-n-butyl phthalate has so many uses, it is widespread in the environment. Most

people are probably exposed to low levels in air. Some people may also be exposed to di-n-butyl

phthalate in water, food, or both. Most of the time, the largest source of exposure is from air that

contains di-n-butyl phthalate. Low levels (0.01 parts per billion [ppb]) are present around the

globe, and levels of 0.03 to 0.06 ppb are often found in city air. Higher levels can occur

temporarily inside homes and offices, especially when products containing di-n-butyl phthalate,

such as nail polish, are used or when new carpet containing di-n-butyl phthalate is installed. 
DI-n-BUTYL PHTHALATE 3

1. PUBLIC HEALTH STATEMENT

Di-n-butyl phthalate is present in some drinking water supplies, usually at levels of around 0.1 to

0.2 ppb.

Another way you can be exposed is by eating food containing di-n-butyl phthalate. Some

di-n-butyl phthalate in food comes from the materials used to package and store the food. Some

comes from di-n-butyl phthalate taken up by fish and shellfish. Levels of di-n-butyl phthalate in

food have been found to range from about 40 to 570 ppb.

The levels of di-n-butyl phthalate found in air, water, and food are usually low enough that they

are not expected to cause any harmful effects. You can read about this in Section 1.5. If you

were exposed to high levels of di-n-butyl phthalate, this might be of concern. Exposure to high

levels could occur at a number of places. For example, if you live near a factory that makes or

uses di-n-butyl phthalate, you could be exposed if the factory allowed di-n-butyl phthalate to

escape into the air that you breathe or into the water that you drink. If the factory spilled or

disposed of any di-n-butyl phthalate on the ground, you could also be exposed by getting the soil

on your skin. You could be exposed to elevated levels of di-n-butyl phthalate in these same

ways if you live near a chemical waste site that has allowed di-n-butyl phthalate to escape into

the environment. Di-n-butyl phthalate released into the air, water, and soil is also of concern

near garbage dumps and landfills. This is because large amounts of products that have di-n-butyl

phthalate in them are thrown away at these sites, and the di-n-butyl phthalate can slowly come

out of these products and get into air, water, or soil.

Further information on how you might be exposed to di-n-butyl phthalate is given in Chapter 6.

1.4 HOW CAN DI-n-BUTYL PHTHALATE ENTER AND LEAVE MY BODY?

If you eat or drink food or water containing di-n-butyl phthalate, nearly all of the di-n-butyl

phthalate rapidly enters your body through the digestive system. If you breathe air containing

di-n-butyl phthalate, it is likely that most of what you breathe in will enter your body through the

lungs, but this has not been studied in detail. Di-n-butyl phthalate can also enter the body

through the skin, although this occurs rather slowly. Inside the body, di-n-butyl phthalate is
DI-n-BUTYL PHTHALATE 4

1. PUBLIC HEALTH STATEMENT

changed into other chemicals. Most of these are quickly removed from the body in the urine. 

The rest are removed in the feces. Most of the di-n-butyl phthalate that enters the body is

removed within 24 hours, and virtually all of it is gone by 48 hours after exposure. 

More information on how di-n-butyl phthalate enters and leaves the body is given in Chapter 3.

1.5 HOW CAN DI-n-BUTYL PHTHALATE AFFECT MY HEALTH?

To protect the public from the harmful effects of toxic chemicals and to find ways to treat people

who have been harmed, scientists use many tests. 

One way to see if a chemical will hurt people is to learn how the chemical is absorbed, used, and

released by the body; for some chemicals, animal testing may be necessary. Animal testing may

also be used to identify health effects such as cancer or birth defects. Without laboratory

animals, scientists would lose a basic method to get information needed to make wise decisions

to protect public health. Scientists have the responsibility to treat research animals with care and

compassion. Laws today protect the welfare of research animals, and scientists must comply

with strict animal care guidelines.

Di-n-butyl phthalate appears to have relatively low toxicity, and large amounts are needed to

cause injury. Adverse effects on humans from exposure to di-n-butyl phthalate have not been

reported. In animals, eating large amounts of di-n-butyl phthalate can affect their ability to

reproduce. In male animals, sperm production can decrease after eating large amounts of

di-n-butyl phthalate. However, when exposure to di-n-butyl phthalate stops, sperm production

seems to return to near normal levels. The levels of di-n-butyl phthalate that cause toxic effects

in animals are about 10,000 times higher than the levels of di-n-butyl phthalate found in air,

food, or water. Exposure to high levels of di-n-butyl phthalate might cause similar effects in

humans as in animals, but this is not known. In animals, large amounts of di-n-butyl phthalate

repeatedly applied to the skin for a long time cause mild irritation. Although the available data

do not indicate that di-n-butyl phthalate causes cancer, this needs to be more thoroughly studied.
DI-n-BUTYL PHTHALATE 5

1. PUBLIC HEALTH STATEMENT

Additional information on the levels of exposure associated with harmful effects of di-n-butyl

phthalate can be found in Chapters 2 and 3.

1.6 HOW CAN DI-n-BUTYL PHTHALATE AFFECT CHILDREN?

This section discusses potential health effects from exposures during the period from conception

to maturity at 18 years of age in humans. Potential effects on children resulting from exposures

of the parents are also considered.

Very few studies have looked at how di-n-butyl phthalate can affect the health of children. It is

likely that the health effects seen in children exposed to di-n-butyl phthalate will be similar to

the effects seen in adults. We do not know whether children differ from adults in their

susceptibility to di-n-butyl phthalate. 

We do not know if exposure to di-n-butyl phthalate will result in birth defects or other

developmental effects in people. Birth defects have been observed in animals exposed to high

levels of di-n-butyl phthalate during development. The developing animal is sensitive to

di-n-butyl phthalate. Death, low body weights, skeletal deformities, cleft palate, and damage to

the testes have been observed in the offspring of animals ingesting large amounts of di-n-butyl

phthalate. 

We have no information to suggest that there are any differences between children and adults in

terms of how much di-n-butyl phthalate will enter the body, where di-n-butyl phthalate can be

found in the body, and how fast di-n-butyl phthalate will leave the body. We do not know if

di-n-butyl phthalate can be transferred from the mother to an infant in breast milk or whether it

can cross the placenta. 
DI-n-BUTYL PHTHALATE 6

1. PUBLIC HEALTH STATEMENT

1.7 HOW CAN FAMILIES REDUCE THE RISK OF EXPOSURE TO DI-n-BUTYL

PHTHALATE?

If your doctor finds that you have been exposed to significant amounts of di-n-butyl phthalate,

ask whether your children might also be exposed. Your doctor might need to ask your state

health department to investigate.

Di-n-butyl phthalate is used in many products that are made from plastic. It is also in products

like white glues and carpenter’s glues made from a plastic known as polyvinyl acetate emulsion. 

Di-n-butyl phthalate is also used in some paints, furniture lacquer, and nail polish. When it is in

anything, di-n-butyl phthalate is at a higher level when that product is new. There is less in

products that are old. Because di-n-butyl phthalate may be in some toys, there is a concern that

children chewing on such toys might be exposed. No measurements have yet been made to show

whether children are exposed in this way. 

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

EXPOSED TO DI-n-BUTYL PHTHALATE?

Tests are available that can detect di-n-butyl phthalate in blood and body tissues, and the major

breakdown products of di-n-butyl phthalate can be measured in urine. However, there is not

enough information at this time to use the results of such tests to predict the nature or severity of

any health effects that may result from exposure to di-n-butyl phthalate. Since special

equipment is needed, these tests cannot be performed routinely in your doctor's office. 

Further information on how di-n-butyl phthalate can be measured in exposed humans is

presented in Chapters 3 and 7.
DI-n-BUTYL PHTHALATE 7

1. PUBLIC HEALTH STATEMENT

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. Federal agencies that develop regulations for toxic

substances include the Environmental Protection Agency (EPA), the Occupational Safety and

Health Administration (OSHA), and the Food and Drug Administration (FDA). Recommendations provide valuable guidelines to protect public health but cannot be enforced by law. 

Federal organizations that develop recommendations for toxic substances include the Agency for

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

Safety and Health (NIOSH).

Regulations and recommendations can be expressed in not-to-exceed levels in air, water, soil, or

food that are usually based on levels that affect animals; then they are adjusted to help protect

people. Sometimes these not-to-exceed levels differ among federal organizations because of

different exposure times (an 8-hour workday or a 24-hour day), the use of different animal

studies, or other factors.

Recommendations and regulations are also periodically updated as more information becomes

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

provides it. Some regulations and recommendations for di-n-butyl phthalate include the

following:

The federal government has developed regulatory standards and advisories to protect individuals

from the potential health effects of di-n-butyl phthalate in the environment. EPA recommends

that levels of di-n-butyl phthalate in water not exceed 34 parts per million (34,000 ppb). Any

release of di-n-butyl phthalate to the environment in excess of 10 pounds must be reported to the

federal government. NIOSH has established a limit of 5 milligrams per cubic meter (5 mg/m3)

di-n-butyl phthalate in workplace air to protect the health of workers.
DI-n-BUTYL PHTHALATE 8

1. PUBLIC HEALTH STATEMENT

Additional information on governmental regulations regarding di-n-butyl phthalate can be found

in 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

Agency for Toxic Substances and Disease Registry

Division of Toxicology

1600 Clifton Road NE, Mailstop E-29

Atlanta, GA 30333

* Information line and technical assistance

Phone: 1-888-42-ATSDR (1-888-422-8737)

Fax: (404) 498-0057

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

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

hazardous substances.

* To order toxicological profiles, contact

National Technical Information Service

5285 Port Royal Road

Springfield, VA 22161

Phone: (800) 553-6847 or (703) 605-6000
DI-n-BUTYL PHTHALATE 9

2. RELEVANCE TO PUBLIC HEALTH

2.1 BACKGROUND AND ENVIRONMENTAL EXPOSURES TO DI-n-BUTYL PHTHALATE

IN THE UNITED STATES

Di-n-butyl phthalate is a colorless to faint yellow oily liquid that is not found naturally in the

environment. It has a slightly ester smell and a strong, bitter taste. It has moderately low solubility in

water, but is quite soluble in organic solvents such as alcohol, ether, benzene, and acetone. Di-n-butyl

phthalate is used in plastics to make them more flexible, and is found in a number of consumer products,

including home furnishings, paints, clothing, and cosmetic products. More than 8,500 tons (17 million

pounds) of di-n-butyl phthalate was produced in the United States in 1994 by a number of companies in

various locations.

Di-n-butyl phthalate is released to the environment during its production and use, with the vast majority

being released to underground injection wells. Di-n-butyl phthalate is not expected to volatilize

significantly from water to the atmosphere. In soils, migration to groundwater occurs, but is thought to be

limited to sites with low organic content. The half-life of di-n-butyl phthalate vapor in air is calculated to

be 14 daylight hours; in water and soils, >50% of di-n-butyl phthalate is degraded within 1–28 days.

The general population may be exposed to di-n-butyl phthalate from the air, water, and some foods. Air

is probably the main source of di-n-butyl phthalate exposure for the general population, but some

exposure may come from dairy products, fish, and seafood. Occupational exposures can occur through

skin contact and by inhalation of vapors and dust. It is not known if exposure of children to di-n-butyl

phthalate differs from that of adults. Di-n-butyl phthalate is present in some home furnishings, paints,

vinyl flooring and floor wax; however, it is not known if children are more likely than adults to be

exposed by increased contact with or proximity to these items. Children may also intentionally or

unintentionally ingest soil, which may contain low levels of di-n-butyl phthalate.

The level of di-n-butyl phthalate exposure for the general population is expected to be in the low ppb

range; in Canada, the estimated daily intake is 1.9–5.0 μg/kg body weight. Occupational exposure via

inhalation has been estimated to be 143 μg/kg body weight/workday for workers employed in phthalate

manufacturing.
DI-n-BUTYL PHTHALATE 10

2. RELEVANCE TO PUBLIC HEALTH

Populations residing near hazardous waste disposal sites or municipal landfills may be subject to higher

than average levels of di-n-butyl phthalate in ambient air or drinking water. No correlation of di-n-butyl

phthalate fallout rates with specific sources or transport routes was found in a monitoring study in

Sweden. However, di-n-butyl phthalate has been detected in leachate and groundwater near landfills and

in groundwater near rapid infiltration beds where secondary sewage effluent was disposed of. Di-n-butyl

phthalate has been identified in at least 471 of the 1,585 hazardous waste sites that have been proposed

for inclusion on the EPA National Priorities List (NPL). However, the number of sites evaluated for

di-n-butyl phthalate is not known. 

2.2 SUMMARY OF HEALTH EFFECTS

The primary effects seen in animals following exposure to di-n-butyl phthalate are developmental and

reproductive alterations. No data are available for developmental or reproductive effects in humans. 

Animal studies have shown that the development of the male reproductive system, especially the

seminiferous epithelium of the testes, may be disrupted by in utero exposure to high doses of di-n-butyl

phthalate during the critical period for reproductive development. Other developmental effects may also

occur following in utero or perinatal exposure, and include increases in postimplantation losses, decreases

in the number of live fetuses per litter, decreases in fetal and pup body weights, and increases in

incidences of external, skeletal, and internal malformations. Reproductive effects are also seen in adult

animals exposed to di-n-butyl phthalate. Fertility is reduced in male and female animals, and is related to

testicular atrophy and seminiferous tubule damage in males; the mechanism in females is not known. 

Reproductive alterations may also extend to the offspring of exposed animals, and may include reduced

fecundity and decreased sperm production. Minor liver, hematological, and renal effects, as well as

changes in body weight, have also been observed in exposed rats.

Species differences in susceptibility to testicular damage have been noted. More severe testicular damage

was seen in rats and guinea pigs than in mice and hamsters at the same dose level. This is thought to be

due, at least in part, to differing levels of β-glucuronidase activity that may result in different levels of the

free primary metabolite, mono-n-butyl phthalate, in the testes (see Section 3.5 Mechanisms of Action).

Developmental Effects. No human data are available for developmental effects of di-n-butyl

phthalate. Animal studies have shown that acute- and intermediate-duration oral exposure to di-n-butyl

phthalate causes a number of developmental effects, including increases in postimplantation losses,

decreases in the number of live fetuses per litter, decreases in fetal/pup body weights, increases in
DI-n-BUTYL PHTHALATE 11

2. RELEVANCE TO PUBLIC HEALTH

incidences of external, skeletal, and internal malformations, and altered reproductive development in the

offspring. The lowest levels at which these effects were seen were varied widely. Decreases in the

number of live pups/litter were seen following doses as low as 80 mg/kg/day in rats and 1,950 mg/kg/day

in mice. Decreases in ano-genital distance, increases in undescended testes, and increases in abortions

were seen at 500 mg/kg/day in rats, and increases in the incidence of external and skeletal malformations

were seen at 750 mg/kg/day in rats. As discussed in Section 2.3, increased incidence of retained nipples

and areolas (an anti-androgenic effect) in male rat pups exposed in utero is the basis for the acute-duration

minimal risk level (MRL) for oral exposure. The lowest dose level resulting in disruption of androgenregulated reproductive development in rats was 100 mg/kg/day. This is well above the levels expected to

be encountered by the general population or at a well-regulated workplace.

Reproductive Effects. No human data are available for reproductive effects of di-n-butyl phthalate.

Animal studies have shown that di-n-butyl phthalate affects fertility in both males and females. 

Decreases in fertility indices, reduced pregnancy rates, and shortened length of gestation have been seen

in rodents exposed to di-n-butyl phthalate before or during gestation. Testicular atrophy has been

observed in male rats, mice, and guinea pigs, but not hamsters, acutely exposed to di-n-butyl phthalate;

however, rats are much more sensitive to the testicular effects than other animals examined (see

Section 3.5 Mechanisms of Action). 

Hepatic Effects. Mild liver effects have been seen in rats and mice orally exposed to di-n-butyl

phthalate for acute or intermediate durations. These effects were increased liver weight, increased

microsomal enzyme activity, inhibition of mitochondrial respiration, liver necrosis, and peroxisome

proliferation. The lowest dose level at which effects were seen was 348 mg/kg/day.

Hematological Effects. Hematological effects have been observed in rats and mice exposed orally to

high dose levels of di-n-butyl phthalate. These included anemia, decreased hematocrit, hemoglobin, and

red blood cell levels.

Renal Effects. Renal effects of di-n-butyl phthalate were limited to decreased kidney weight in mice

and increased kidney weight in rats exposed to high dose levels.
DI-n-BUTYL PHTHALATE 12

2. RELEVANCE TO PUBLIC HEALTH

2.3 MINIMAL RISK LEVELS FOR DI-n-BUTYL PHTHALATE.

Inhalation MRLs

Information on the toxicity of inhaled di-n-butyl phthalate is sparse. Hypertension and hyperbilirubinemia were reported in workers exposed to 1.7–66 mg/m3

 di-n-butyl phthalate. Because the

workers were exposed to other plasticizers, these effects cannot be definitively attributed to di-n-butyl

phthalate exposure. Animal inhalation data are limited to a study that examined organ weight changes

and hematological and serum chemistry parameters in rats exposed to di-n-butyl phthalate. Although

organ weight (lung and brain) effects were observed, the toxicological significance of the alterations

cannot be determined without histopathological examination of these tissues. In absence of reliable data,

acute-, intermediate-, or chronic-duration inhalation MRLs were not derived. 

Oral MRLs

C An MRL of 0.5 mg/kg/day has been derived for acute-duration oral exposure (14 days or less)

to di-n-butyl phthalate.

The acute-duration oral MRL was based on a no-observed-adverse-effect level (NOAEL) of

50 mg/kg/day for developmental effects in the offspring of rats exposed to di-n-butyl phthalate on

gestational days 12–21 and an uncertainty factor of 100 (10 for extrapolation from animals to humans and

10 for human variability). In this study, groups of 20 pregnant Sprague-Dawley rats (except 11 in the

500 mg/kg/day group) were treated with 0, 0.5, 5, 50, 100, or 500 mg/kg/day di-n-butyl phthalate by

gavage in corn oil on gestational days 12–21. No developmental effects or clinical signs of toxicity were

seen in pups exposed to 50 mg/kg/day or less in utero. The only treatment-related effect seen in the

100 mg/kg/day group was retained areolas and nipples in males (normally seen only in females) on

postpartum day 14. This effect was dose-dependent, being more prominent at 500 mg/kg/day. 

Permanence of retained areolas and nipples was not assessed. Other statistically significant effects, seen

only in males at 500 mg/kg/day level, were decreased ano-genital distance (12% decrease) and anogenital distance/body weight at birth; smaller epididymides, dorsolateral prostate, and levator

ani-bulbocavernosus muscle at sexual maturity; and decreased testes weight. Malformations of the male

reproductive tract included absent or malformed epididymis, absent or malformed vas deferens,

hypospadia, and unilaterally absent seminal vesicle. Histopathological lesions of the testis seen were

seminiferous tubule degeneration, focal interstitial hyperplasia, and interstitial cell adenoma. In males, no

significant changes were seen in age at preputial separation, or body, kidney, liver, adrenal, ventral
DI-n-BUTYL PHTHALATE 13

2. RELEVANCE TO PUBLIC HEALTH

prostate, vas deferens, seminal vesicle, or other organ weights (other than those listed above). In female

pups, no significant differences from controls were seen in age of onset of vaginal opening, body, liver,

kidney, adrenal, ovary, or uterus weight, or gross morphology of the reproductive organs at sexual

maturity.

Studies that have examined the acute toxicity of orally administered di-n-butyl phthalate have primarily

focused on reproductive and developmental end points. Testicular atrophy, decreased testes weight, and

decreased number of spermatocytes have been observed in rats, mice, and guinea pigs exposed to doses of

1,000 mg/kg/day and higher; a NOAEL of 500 mg/kg/day was identified. The developmental effects

consisted of increases in post-implantation losses, decreases in fetal body weight, increases in external,

skeletal, and internal malformations, and androgen-regulated developmental alterations (reduced anogenital distance, increased number of retained nipples, decreased androgen-dependent tissue weights,

delayed preputial separation). The smallest lowest-observed-adverse-effect level (LOAEL) for

developmental toxicity was identified in a study in which increases in the incidence of retained areolas

and nipples were observed in the offspring of rats exposed orally by gavage to $100 mg/kg/day di-n-butyl

phthalate on gestational days 12–21. The NOAEL for this effect is 50 mg/kg/day. Although the systemic

toxicity of di-n-butyl phthalate has not been adequately assessed following acute oral exposure, the

results of intermediate-duration studies suggest that developmental toxicity would occur at similar or

lower LOAELs than hepatic effects (the most sensitive systemic effect). 

An intermediate-duration oral MRL was not derived for di-n-butyl phthalate. Systemic, reproductive, and

developmental effects have been observed in animals. The liver appears to be the most sensitive systemic

target in rats and mice exposed to di-n-butyl phthalate in the diet for 13 weeks. The hepatic effects

consisted of cytoplasmic alterations suggestive of glycogen depletion, peroxisomal enzyme induction,

decreased lipid deposition in the liver, decreased serum triglyceride and cholesterol levels, and inhibition

of mitochondrial respiration. The reproductive effects consisted of testicular atrophy (including decreases

in testes weight and degeneration of seminiferous tubule germinal epithelium) with decreases in

spermatogenesis. Reproductive effects have been observed at 250 mg/kg/day and higher. Serious

developmental effects have been observed in intermediate-duration studies. Decreases in fetal/pup

survival, decreases in pup body weight, and impaired reproductive development in the male offspring

(testicular degeneration and atrophy) have been observed. The lowest LOAEL for developmental toxicity

is 80 mg/kg/day; decreases in fetal survival were observed at this dose. 

The available intermediate-duration data suggest that developmental toxicity is the most sensitive toxic

end point and should be used to derive an intermediate-duration MRL. The lowest LOAEL identified for
DI-n-BUTYL PHTHALATE 14

2. RELEVANCE TO PUBLIC HEALTH

developmental toxicity is 80 mg/kg/day for decreases in the average number of pups per litter in rats

exposed to dietary di-n-butyl phthalate in a continuous breeding study; a NOAEL was not identified. The

80 mg/kg/day is considered a serious LOAEL and is not appropriate for MRL derivation. Thus, an

intermediate oral MRL was not derived for di-n-butyl phthalate.

No chronic-duration oral studies for humans or animals were identified; thus, a chronic oral MRL was not

derived. 

A chronic MRL for DNB was not derived. There were no adequate chronic-duration oral studies

identified for humans or animals. EPA verified an RfD based on a study by Smith (1953). In this study,

10 rats were fed diets containing 0.01-1.25 % dibutyl phthalate. Half of the high dose group died within

the first week of exposure. ATSDR did not have confidence in this study to derive an MRL due to the

lack of detail and apparent conflict in the reported results. EPA also had low confidence in the study; the

RfD received a low rating.
DI-n-BUTYL PHTHALATE 15

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 di-n-butyl

phthalate. 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

lowest-observed-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 
DI-n-BUTYL PHTHALATE 16

3. HEALTH EFFECTS

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

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

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

effects to human health. 

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

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

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

associated with more subtle effects in humans or animals (LOAEL) 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.

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

made for di-n-butyl phthalate. 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 1990b),

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

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

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

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

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

significant human exposure improve, these MRLs will be revised.

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.
DI-n-BUTYL PHTHALATE 17

3. HEALTH EFFECTS

3.2.1 Inhalation Exposure

3.2.1.1 Death

No studies regarding death in humans following inhalation exposure to di-n-butyl phthalate were located.

Studies in rats calculate acute inhalation LC50 values for rats of 25 g/m3

 (NTP 1995) and 4.25 g/m3 (NTP

1995), and for mice of 25 g/m3

 (NTP 1995). No other studies regarding death in animals following

inhalation exposure to di-n-butyl phthalate were located.

3.2.1.2 Systemic Effects

No studies regarding gastrointestinal, musculoskeletal, endocrine, dermal, or ocular effects in humans or

animals following inhalation exposure to di-n-butyl phthalate were located.

Respiratory Effects. No studies regarding respiratory effects in humans following inhalation

exposure to di-n-butyl phthalate were located.

Information on the potential of di-n-butyl phthalate to induce respiratory effects is limited to a study by

Kawano (1980a), which found an increase in relative lung weight in rats exposed to 50 mg/m3

 di-n-butyl

phthalate 6 hours/day for 6 months (Kawano 1980a); lung weight was not altered in the 0.5 mg/m3

 group. 

The toxicological significance of the altered lung weight is difficult to assess in the absence of a study

that examined histopathology.

Walseth and Nilsen (1984) reported a decrease in lung cytochrome P450 in rats exposed to 28.4 or

79.5 mg/m3

 but not 5.7 mg/m3, di-n-butyl phthalate for 5 of 6 consecutive days, although no statistical

significance was indicated.

Cardiovascular Effects. There is a limited amount of information available on the cardiovascular

toxicity of di-n-butyl phthalate in humans. Hypertension was reported in workers exposed to di-n-butyl

phthalate for 0.5–19 years at concentrations of 1.7–66 mg/m3

; the frequency increased with length of

employment (Milkov et al. 1973). These workers were also exposed to other plasticizers, so the effects

seen may not have been caused by di-n-butyl phthalate exposure.
DI-n-BUTYL PHTHALATE 18

3. HEALTH EFFECTS

Hematological Effects. No studies regarding hematological effects in humans following inhalation

exposure to di-n-butyl phthalate were located.

No alterations in hematocrit, hemoglobin, or erythrocyte levels were observed in rats exposed to

50 mg/m3

 di-n-butyl phthalate 6 hours/day for 6 months (Kawano 1980a).

Hepatic Effects. Data on the hepatotoxicity of di-n-butyl phthalate is limited to a report of hyperbilirubinemia among workers exposed to 1.7–66 mg/m3

 for 0.5–19 years; the frequency increased with

length of employment (Milkov et al. 1973). These workers were also exposed to other plasticizers, so the

effects seen may not have been caused by di-n-butyl phthalate exposure.

Relative liver weight was not affected in rats exposed to 50 mg/m3

 di-n-butyl phthalate mist 6 hours/day

for 6 months (Kawano 1980a). Small fluctuations in several serum chemistry parameters (serum

enzymes, urea nitrogen, cholesterol) were noted in this study, but these were not clearly dose- or timedependent.

Renal Effects. No studies regarding renal effects in humans following inhalation exposure to

di-n-butyl phthalate were located.

Relative kidney weight did not differ from controls in rats exposed to 50 mg/m3

 di-n-butyl phthalate

6 hours/day for 6 months (Kawano 1980a).

Endocrine Effects. No studies regarding endocrine effects in humans or animals following inhalation

exposure to di-n-butyl phthalate were located.

Body Weight Effects. No studies regarding body weight effects in humans following inhalation

exposure to di-n-butyl phthalate were located.

An approximate 13% decrease in body weight gain was observed in rats exposed to 50 mg/m3

 di-n-butyl

phthalate 6 hours/day for 6 months (Kawano 1980a).
DI-n-BUTYL PHTHALATE 19

3. HEALTH EFFECTS

3.2.1.3 Immunological and Lymphoreticular Effects

No studies regarding immunological effects in humans following inhalation exposure to di-n-butyl

phthalate were located. Small fluctuations in white cell counts and percent neutrophils were found in rats

exposed to 0.5 and 50 mg/m3

 di-n-butyl phthalate 6 hours per day for 6 months, but the changes were not

dose- or time-dependent (Kawano 1980a), and do not appear to be clinically significant.

3.2.1.4 Neurological Effects

Workers exposed to di-n-butyl phthalate for 0.5–19 years at concentrations of 1.7–66 mg/m3

 experienced

neurological symptoms (pain, numbness, spasms, weakness) and exhibited reflex disturbances, elevated

thresholds for pain sensitivity and olfactory stimulation, and depression of vestibular function (Milkov et

al. 1973). The frequency and severity of these effects increased with increased duration of exposure. The

workers were also exposed to other plasticizers, so these neurological effects may not have been caused

by di-n-butyl phthalate exposure.

In rats, a statistically significant increase in brain weight as a percent of body weight was observed

following exposure to 50 mg/m3

 di-n-butyl phthalate for 6 months (Kawano 1980a). However, a

significant decrease in body weight gain was reported for this dose group, and the absolute brain weight

increase was small (1.58 g versus 1.47 g in controls).

3.2.1.5 Reproductive Effects

No studies regarding reproductive effects in humans following inhalation exposure to di-n-butyl phthalate

were located. In rats, exposure to 0.5 or 50 mg/m3

 6 hours/day for 6 months caused no changes in relative

testicular weight (Kawano 1980a).

3.2.1.6 Developmental Effects

No studies regarding developmental effects in humans or animals following inhalation exposure to

di-n-butyl phthalate were located.
DI-n-BUTYL PHTHALATE 20

3. HEALTH EFFECTS

3.2.1.7 Cancer

No studies regarding cancer effects in humans or animals following inhalation exposure to di-n-butyl

phthalate were located.

3.2.2 Oral Exposure

Table 3-1 and Figure 3-1 summarize the health effects observed following oral exposure of animals to

di-n-butyl phthalate. These effects are discussed below. 

3.2.2.1 Death

No studies regarding death in humans following oral exposure to di-n-butyl phthalate were located. 

Di-n-butyl phthalate has low acute toxicity in animals. Single doses of 8,000 mg/kg killed four of nine

rats in one study (Smith 1953), but other studies indicate the acute oral LD50 in rats and mice is in excess

of 20,000 mg/kg (Hardin et al. 1987; White et al. 1983). The cause of death in these studies was not

reported. In mice, an LD10 of 2,500 mg/kg was reported by Hardin et al. (1987).

In a 52-week study in rats, half of the animals given 625 mg/kg/day in feed died during the first week of

the study; the cause of death was not determined. No deaths were observed at 125 mg/kg/day (Smith

1953). No deaths were reported in rats or mice that received up to 2,964 or 4,278 mg/kg/day,

respectively, in the feed for 13 weeks (NTP 1995). However, pregnant rats may be more susceptible to

the lethal effects of di-n-butyl phthalate, as 1–2 rats per treatment group died when exposed to 630 to

3000 mg/kg/day for 1 to 9 days during gestation (Ema et al. 1993, 1994; Saillenfait et al. 1998).

The highest NOAEL values and all reliable LOAEL values for death in each species and duration

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

3.2.2.2 Systemic Effects

No studies regarding systemic effects in humans following oral exposure to di-n-butyl phthalate were

located. 
















DI-n-BUTYL PHTHALATE 37

3. HEALTH EFFECTS

Respiratory Effects. No histological alterations were observed in the respiratory tract tissues of rats

and mice exposed to up to 2,964 and 4,278 mg/kg/day, respectively, di-n-butyl phthalate in the diet for

13 weeks (NTP 1995).

Cardiovascular Effects. No histological alterations were observed in the heart of rats and mice

exposed to up to 2,964 and 4,278 mg/kg/day, respectively, di-n-butyl phthalate in the diet for 13 weeks

(NTP 1995).

Gastrointestinal Effects. No histological alterations were observed in the gastrointestinal tract

tissues of rats and mice exposed to up to 2,964 and 4,278 mg/kg/day, respectively, di-n-butyl phthalate in

the diet for 13 weeks (NTP 1995).

Hematological Effects. Minimally severe anemia was observed in male rats exposed to

$369 mg/kg/day di-n-butyl phthalate in the diet for 13 weeks (NTP 1995). The study authors noted that

hemoconcentration by dehydration (as evidenced by higher albumin concentrations) may have masked

the effects, and that the anemia may have been more severe than the data indicated. No hematological

effects were observed in the female rats. Decreases in erythrocyte, hemoglobin, and hematocrit levels

were also observed in male rats exposed to 752 mg/kg/day in the diet (Schilling et al. 1992) and a

decrease in hematocrit was observed in female mice exposed to 2,137 mg/kg/day di-n-butyl phthalate in

the diet (NTP 1995). 

Biochemical parameters and histopathological evaluation of the spleen of rats showed no effects at doses

up to 1,200 mg/kg/day (Nikonorow et al. 1973; Smith 1953). Increased absolute and relative spleen

weight was observed in rats at a dose of 2,500 mg/kg/day (Murakami et al. 1986a, 1986b), but without

additional information on histopathological changes and evaluation of hematological parameters, the

significance of this isolated finding cannot be determined.

Musculoskeletal Effects. No studies regarding musculoskeletal effects in animals following oral

exposure to di-n-butyl phthalate were located.
DI-n-BUTYL PHTHALATE 38

3. HEALTH EFFECTS

Hepatic Effects. In animals, minimal effects on the liver were observed after acute exposure to

di-n-butyl phthalate. Increased absolute liver weight was observed in rats and mice given di-n-butyl

phthalate at 2% in the diet (1,000–2,600 mg/kg/day) for 7 days (Oishi and Hiraga 1980a, 1980b) or in rats

and mice that received at least 359 or 2137 mg/kg/day, respectively, in the diet for 13 weeks (NTP 1995). 

Increased relative liver weight in animals was observed in several studies with di-n-butyl phthalate at

doses of 348 mg/kg/day and higher for 21 days or more (Bell 1982; BIBRA 1986; Murakami et al. 1986a,

1986b; Nikonorow et al. 1973). In these studies, the increases in relative liver weight may simply reflect

body weight decreases caused by di-n-butyl phthalate in those animals.

Slight, but statistically significant, increases in microsomal enzyme activity levels were observed in the

livers of rats given di-n-butyl phthalate by gavage for 5 days at doses of 2.8 and 27.8 mg/kg/day, but not

at 278 mg/kg/day (Walseth and Nilsen 1986). The authors considered di-n-butyl phthalate to be a weak

inducer of microsomal enzymes. Increased microsomal enzyme activity was observed in the livers of rats

exposed to 1,000 mg/kg/day in the diet for 7 days (Kawashima et al. 1983).

Longer exposure to di-n-butyl phthalate was found to interfere with mitochondrial respiration. 

Mitochondrial respiration was inhibited in rats fed di-n-butyl phthalate at 2,500 mg/kg/day for 35 days

(Murakami et al. 1986b). Evaluation of liver tissue by electron microscopy revealed an increase in the

number of mitochondria, suggesting that the organ is compensating for the inhibitory effects of the

di-n-butyl phthalate on mitochondrial function (Murakami et al. 1986a). NTP (1995) reported

hepatocellular cytoplasmic alterations, consistent with glycogen depletion, in rats and mice exposed to

720 and 1601 mg/kg/day, respectively, di-n-butyl phthalate in the diet for 13 weeks. Liver necrosis was

noted at doses of 470 mg/kg/day and higher, an effect possibly related to the effects of di-n-butyl

phthalate on liver mitochondria (Murakami et al. 1986a). Other studies using higher doses have found no

liver necrosis (BIBRA 1986; Nikonorow et al. 1973; NTP 1995). No explanation for the discrepant

results is evident.

Decreases in serum triglyceride and cholesterol levels were observed in rats exposed to dietary di-n-butyl

phthalate for 13 weeks (NTP 1995). Although the mechanism for these alterations is not known, this

finding may be associated with peroxisome proliferation. 

Proliferation of peroxisomes and increases in peroxisomal enzymes have been reported in rat liver cells by

several investigators (BIBRA 1986; Murakami et al. 1986a) at doses of 2,131 mg/kg/day for 21 days or

more. In rats exposed for 13 weeks, induction of peroxisomal enzyme activity (acyl CoA oxidase) was
DI-n-BUTYL PHTHALATE 39

3. HEALTH EFFECTS

observed at doses of 353 mg/kg/day, but not 176 mg/kg/day (NTP 1995). This response may contribute to

the increase in liver weight discussed above, especially in males (Murakami et al. 1986a, 1986b).

Renal Effects. Oral exposure to di-n-butyl phthalate has been reported to cause decreased kidney

weight after 7 days of exposure of mice to 2,600 mg/kg/day (Oishi and Hiraga 1980a) and increased

kidney weight after 21 days of exposure of rats to 1,248 mg/kg/day (BIBRA 1986). Relative kidney

weights were increased in male and female rats administered 359 and 712 mg/kg/day, respectively, for

13 weeks, and absolute and relative kidney weights were increased in female mice exposed to

238 mg/kg/day for 13 weeks (NTP 1995); decreased absolute kidney weights in male and female rats and

male mice were considered secondary to body weight changes. No histopathologic lesions of the kidney

have been observed in rats exposed to di-n-butyl phthalate (BIBRA 1986; Nikonorow et al. 1973; NTP

1995).

Endocrine Effects. No histological alterations in endocrine tissue have been observed in rats and

mice exposed to up to 2,964 and 4,278 mg/kg/day, respectively, di-n-butyl phthalate in the diet for

13 weeks (NTP 1995). Phthalates are a class of chemicals that have been implicated as having estrogenic

properties. There is in vitro evidence of the weak estrogenic behavior of di-n-butyl phthalate; however,

in vivo results do not support these findings. Studies in rats indicate that di-n-butyl phthalate has antiandrogenic properties (Ema et al. 1998, 2000b; Gray et al. 1999; Mylchreest et al. 1999, 2000). These are

discussed in Section 3.6 Endocrine Disruption.

Dermal Effects. No studies regarding dermal effects in humans or animals following oral exposure to

di-n-butyl phthalate were located.

Ocular Effects. No studies regarding ocular effects in humans following oral exposure to di-n-butyl

phthalate were located.

No changes to the refracting media of the eye were noted in Wistar rats receiving 1,075 (male) or

1,111 (female) mg/kg/day di-n-butyl phthalate in the feed for 3 months (Schilling et al. 1992).
DI-n-BUTYL PHTHALATE 40

3. HEALTH EFFECTS

Body Weight Effects. Several studies have evaluated the effect of oral exposure of animals to

di-n-butyl phthalate on body weight (BIBRA 1986; Gray et al. 1982; Lamb et al. 1987; Murakami et al.

1986, 1986b; Nikonorow et al. 1973; NTP 1984, 1995; Oishi and Hiraga 1980a; Smith 1953). Decreases

in body weight gain were only observed at higher doses (8,000 mg/kg/day) in the acute-duration studies

(Gray et al. 1982; Smith 1953). Decreases in body weight gain have been observed at lower doses

following repeated exposure: 250 mg/kg/day in rats exposed for 34–36 days (Murakami et al. 1986a),

720 mg/kg/day in rats for 13 weeks (NTP 1995), and 353 mg/kg/day in mice exposed for 13 weeks (NTP

1995).

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

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

Metabolic Effects. No studies regarding metabolic effects in humans or animals following oral

exposure to di-n-butyl phthalate were located. 

3.2.2.3 Immunological and Lymphoreticular Effects

No studies regarding immunological effects in humans or animals following oral exposure to di-n-butyl

phthalate were located.

3.2.2.4 Neurological Effects

No studies regarding neurological effects in humans following oral exposure to di-n-butyl phthalate were

located.

Male and female Wistar rats exposed to 1,075 and 1,111 mg/kg/day di-n-butyl phthalate, respectively, in

the feed for 3 months showed no signs of neurological impairment, as assessed by a functional

observational battery of sensory and motor function parameters (Schilling et al. 1992). No gross or

histological lesions of the brain were noted in rats or mice exposed to up to 2,964 or 4,000 mg/kg/day,

respectively, for 13 weeks, or exposed throughout gestation, lactation, and then for 13 weeks. 
DI-n-BUTYL PHTHALATE 41

3. HEALTH EFFECTS

3.2.2.5 Reproductive Effects

A weak, negative correlation was reported between sperm density and di-n-butyl phthalate concentration

in semen from male university students (Murature et al. 1987). However, lack of data and inadequate

data analysis in this study prevent the establishment of a causal relationship between sperm density and

di-n-butyl phthalate. No other studies regarding reproductive effects in humans following oral exposure

to di-n-butyl phthalate were located.

Oral exposure to di-n-butyl phthalate had adverse effects on the male reproductive system in several

animal species (rats, mice, and guinea pigs). Testicular atrophy (including decreases in testicular weight,

decreases in spermatocytes and spermatogonia, and sloughing of germ cells) have been observed in

Sprague-Dawley or Wistar rats receiving 1,000 mg/kg/day or higher for 4 or 5 days (Cater et al. 1977;

Gray and Gangolli 1986), 2,400 mg/kg/day for 1 or 7 days via gavage (Fukuoka et al. 1989, 1990), or

2,100 mg/kg/day in the diet for 7 days (Oishi and Hiragi 1980b). Gray et al. (1999) found that LongEvans hooded rats exposed to 250 mg/kg/day from weaning through puberty and young adulthood also

showed testicular atrophy and reduced sperm production. Fukuoka et al. (1990) observed sloughing of

the germ cells in the seminiferous tubules 6 hours after dosing with di-n-butyl phthalate. Three to seven

days after a single gavage dose was administered, more severe damage including dissociation of mature

germ cells (i.e., spermatozoa, spermatids, and spermatocytes) from seminiferous tubule germinal

epithelium was observed (Fukuoka et al. 1990). 

Srivastava et al. (1990) found a minimal amount of seminiferous tubular damage (approximately 5% of

tubules affected) in Wistar rats following gavage administration of 250 mg/kg/day in groundnut oil for

15 days, more moderate tubular damage (20% affected) with decreased testicular weight at

500 mg/kg/day, and marked degeneration of seminiferous tubules at 1,000 mg/kg/day. Similarly, Gray et

al. (1999) found testicular atrophy, with accompanying decreased sperm production, in Long-Evans rats

following gavage administration of 500, but not 250 mg/kg/day, di-n-butyl phthalate in corn oil from

weaning into adulthood; no histological data were provided. In contrast, NTP (1995) did not find

testicular alterations in rats exposed to 359 mg/kg/day in the diet for 13 weeks. Testicular atrophy was

observed at 720 mg/kg/day and hypospermia at 1,540 mg/kg/day. The different routes of exposure

(gavage versus diet) may explain the different results in these studies. 
DI-n-BUTYL PHTHALATE 42

3. HEALTH EFFECTS

The testicular effects of acute exposure of rats to di-n-butyl phthalate appear to be at least in part

reversible. Tanino et al. (1987) showed that 2 weeks after discontinuation of the administration of

di-n-butyl phthalate (2,400 mg/kg/day for 7 days), some regeneration of seminiferous tubules had

occurred. Three weeks after treatment, active spermatogenesis was observed in almost all tubules. 

However, vacuolation of germinal epithelium and decreased number of sperm were still evident.

Species and sex differences in the reproductive toxicity of di-n-butyl phthalate are evident. While severe

seminiferous tubular atrophy was observed in rats and guinea pigs at 2,000 mg/kg/day for 7–9 days, only

focal atrophy was reported in mice at the same dose, and no effects on the testes were seen in Syrian

hamsters (Gray et al. 1982). Testicular atrophy was observed in rats following intermediate-duration

exposure to 720 mg/kg/day (NTP 1995); this effect was not observed in mice exposed to 3,689 mg/kg/day

(NTP 1995). The species differences may be related to the greater ability of some species to conjugate

the primary metabolite of di-n-butyl phthalate (see Section 3.3.3.2).

No histopathological alterations in reproductive tissues or effects on estrus cycling were observed in

female rats following a 13-week exposure to doses as high as 2,943 mg/kg/day (NTP 1995), and no

statistically significant differences from controls in number of implantation sites or live pups per litter

were seen in Sprague-Dawley rats exposed to up to 500 mg/kg/day on gestational days 12–21

(Mylchreest et al. 2000). However, pregnancy rate (nonpregnancy=no detectable implantation sites) was

decreased in female Wistar rats (bred to untreated males) receiving 1,250 or 1,500 mg/kg/day di-n-butyl

phthalate via gavage administration on gestational days 0–8, and preimplantation losses were increased at

1,500 mg/kg/day (Ema et al. 2000a). Also, a cross-over mating study (NTP 1995) in mice suggests that

di-n-butyl phthalate may impair fertility in exposed females. Decreases in fertility and average number of

litters per breeding pair and live pups per litter were observed in female mice exposed to 1,950 mg/kg/day

and mated with control males. 

In a three-generation study in Long-Evans rats, exposure of the first generation (F0) males to

250 mg/kg/day di-n-butyl phthalate via gavage administration from weaning through early adulthood

statistically significantly delayed preputial separation (an index of puberty) in a dose-dependent manner

(39.5, 42.6, 43.4, and 44.4 days in the 0, 250, 500, and 1,000 mg/kg/day groups, respectively) (Gray et al.

1999). In the same study, exposure to $500 mg/kg/day resulted in decreased fertility in (F0) males and

females (bred to untreated rats), and caused mid-gestation abortions in females bred to untreated males

(Gray et al. 1999). Infertility in males was related to testicular atrophy and reduced sperm production. 
DI-n-BUTYL PHTHALATE 43

3. HEALTH EFFECTS

Reproductive malformations in second generation (F1) male pups (exposed to di-n-butyl phthalate only

in utero and via lactation) included testicular nondescent and hypospadias. Reduced fecundity was seen

in similarly treated (250 or 500 mg/kg/day) (F1) mating pairs under continuous breeding conditions,

which may have been caused, at least in part, by reduced cauda epididymal sperm counts in (F1) males. 

The highest NOAEL and all reliable LOAEL values for reproductive effects are recorded in Table 3-1 and

plotted in Figure 3-1.

3.2.2.6 Developmental Effects

No studies were located regarding developmental effects in humans following oral exposure to di-n-butyl

phthalate.

A number of studies have examined the developmental toxicity of di-n-butyl phthalate in animals

following acute- and intermediate-duration oral exposure (Ema et al. 1993, 1994, 1995a, 1997a, 1997b,

1998, 2000a, 2000b; Gray et al. 1999; Hardin 1987; IRDC 1984; Mylchreest et al. 1998b, 1999, 2000,

NTP 1995; Saillenfait et al. 1998). The observed developmental effects include increases in

postimplantation losses, decreases in the number of live fetuses per litter, decreases in fetal/pup body

weights, increases in incidences of external, skeletal and internal malformations, and altered reproductive

development in the offspring. A series of gavage-administration studies, conducted by Ema and

associates, reported postimplantation losses and decreases in the number of live fetuses in Wistar rats

receiving gavage doses of 630 mg/kg/day on gestational days 7–15 (Ema et al. 1993) or 750 mg/kg/day

on gestational days 0–8 (Ema et al. 2000a), 7–9 (Ema et al. 1994, 1995a), 10–12 (Ema et al. 1994,

1995a), or 13–15 (Ema et al. 1994); no losses were reported after dosing with 500 mg/kg/day on

gestational days 7–15 (Ema et al. 1993). In a series of single gavage dose studies by Ema et al. (1997a),

postimplantation losses were observed in rats dosed with 1,500 mg/kg/day di-n-butyl phthalate on

gestational days 6, 8, 9, 10, 12, 13, 14, 15, and 16. At doses of 750 mg/kg/day (administered on

gestational days 7–15), >80% of the litters were totally resorbed; decreases in maternal body weight and

food consumption were also observed at this dosage (Ema et al. 1993). Approximately 10–20% of the

litters were completely resorbed when the dams were dosed with 750 mg/kg/day for 3 days during

gestation (between gestational days 7 and 17) (Ema et al. 1994, 1995a); 20–100% were totally resorbed at

1,500 mg/kg/day (Ema et al. 1994, 2000b); no litters were totally resorbed following exposure to up to

1,500 mg/kg/day on gestational days 18–20 (Ema et al. 2000b). Maternal food consumption and body
DI-n-BUTYL PHTHALATE 44

3. HEALTH EFFECTS

weight gain were decreased at 500 mg/kg/day or greater (Ema et al., 2000b). Hardin et al. (1987) also

reported fetal losses (no viable litters) in mice receiving gavage doses of 2,500 mg/kg/day on gestational

days 6–13. A pilot study conducted by Saillenfait et al. (1998) also found postimplantation losses in

Sprague-Dawley rats receiving single gavage doses of 2,000 mg/kg/day on gestational days 13, 14, or 15

(loss per litter of 23.04, 64.46, or 37.55%, respectively). Increased pup losses have also been observed in

intermediate-duration studies. Female Long-Evans rats treated with 500 mg/kg/day di-n-butyl phthalate

from weaning through puberty and gestation aborted their litters around mid-gestation (Gray et al. 1999). 

Rats exposed to 250 or 500 mg/kg/day di-n-butyl phthalate in utero and via lactation produced fewer pups

than controls (means of 108, 78, and 59 pups/breeding pair over 11 breeding cycles for control, 250, and

500 mg/kg/day, respectively) when mated with similarly treated rats under continuous breeding

conditions (Gray et al. 1999). A decrease in the number of live pups per litter was observed in rats

exposed via the diet to 950 mg/kg/day on gestational days 1–21 (NTP 1995). Decreases in the number of

live pups per litter were also observed in continuous breeding studies conducted for NTP (1995) in which

rats and mice were exposed to 80 and 1,950 mg/kg/day, respectively, di-n-butyl phthalate in the diet for

112 or 98 days, respectively. A NOAEL for this effect was not identified in the rat study; the mouse

study identified a NOAEL of 580 mg/kg/day. Another developmental toxicity study conducted for NTP

(1995) reported decreased survival in the pups of rats and mice exposed to di-n-butyl phthalate in the diet

throughout gestation, lactation, and postnatal days 28–56. The LOAELs identified in the rat and mouse

studies were 960 and 1,380 mg/kg/day, respectively; the NOAELs for pup survival were 720 and

920 mg/kg/day, respectively.

Decreased body weights have been observed in the offspring of rats following acute- or intermediateduration exposure (Ema et al. 1993, 1994, 1995a, 1997a, 2000a, 2000b; NTP 1995). Dose-related

decreases in fetal body weights were observed in rats receiving gavage doses of 500 mg/kg/day or higher

di-n-butyl phthalate on gestational days 0–8 (Ema et al. 2000a) or 630 mg/kg/day or higher on gestational

days 7–15 (Ema et al. 1993). Decreases in body weights were also observed in the fetuses of rats

receiving gavage doses of 750 mg/kg/day on gestational days 7–9, 10–12, or 13–15 (Ema et al. 1994,

1995a), 1,000 mg/kg/day on gestational days 12–14 or 18–20 (Ema et al. 2000b), or 1,500 mg/kg/day on

gestational days 6, 7, 8, 9, 10, 11, 16, or 15–17 (Ema et al. 1997a, 2000b). Body weight was not affected

when the dams were exposed on gestational days 12, 13, 14, or 15. Similarly, rat pups exposed in utero

to up to 500 mg/kg/day on gestational days 12–21 had no significant decrease in body weight (Mylchreest

et al. 2000). Several of the NTP (1995) developmental toxicity studies found decreases in pup body

weight. The identified LOAELs were 240 mg/kg/day (NOAEL of 120 mg/kg/day) in rats exposed
DI-n-BUTYL PHTHALATE 45

3. HEALTH EFFECTS

throughout gestation, lactation, and postnatal days 28–56, 950 mg/kg/day in rats exposed throughout

gestation and lactation, and in mice exposed to 460 mg/kg/day (NOAEL of 230 mg/kg/day) throughout

gestation, lactation, and postnatal days 28–56.

External and skeletal malformations have been observed in the offspring of rats exposed to di-n-butyl

phthalate for acute durations (Ema et al. 1993, 1994, 1995, 1997a; Saillenfait et al. 1998). Increases in

the incidence of skeletal and/or external malformation have been observed in a number of gavage

administration studies conducted by Ema and associates. The skeletal effects, primarily fusion or absence

of cervical vertebral arches, were observed in the fetuses of rats exposed to 750 mg/kg/day on gestational

days 7–9 or 13–15 (Ema et al. 1994, 1995a). External malformations (cleft palate) were observed in

fetuses of rats receiving 750 mg/kg/day gavage doses of di-n-butyl phthalate on gestational days 13–15,

but not on days 7–9 or 10–12 (Ema et al. 1994, 1995a). Saillenfait et al. (1998) also found increases in

the occurrence of skeletal variations (accessory 14th rib) and malformations (fused sternebrae) in the

fetuses of rats receiving a single gavage dose of 1,000 or 2,000 mg/kg/day, respectively, on gestational

day 14. A serial study conducted by Ema et al. (1997a) was designed to identify the critical periods for

skeletal and external malformations in rats receiving a single gavage dose of 1,500 mg/kg/day on one of

gestational days 6–16; maternal toxicity (death or decreases in adjusted body weight gain) was not

observed in this study. Increases in external malformations were only observed in the fetuses exposed on

gestational day 15 and skeletal malformations were observed in fetuses exposed on gestational days 8, 9,

or 15.

Acute- and intermediate-duration studies have reported reproductive effects in rat offspring (Ema et al.

1998, 2000a, 2000b; Gray et al. 1999; IRDC 1984; Mylchreest et al. 1998b, 1999, 2000; NTP 1995). 

Rats exposed to 500 mg/kg/day di-n-butyl phthalate on gestational days 12–21 exhibited a number of

developmental reproductive abnormalities, including retained nipple buds or areolas, decreased anogenital

distance and anogenital distance/body weight ratio, absent or malformed epididymis, absent or malformed

vas deferens, and hypospadias (Mylchreest et al. 2000). Only retained nipple buds/areolas were seen in

rats exposed to 100 mg/kg/day, and no developmental effects were seen at 50 mg/kg/day or less. This

study was used to derive an acute-duration oral MRL for di-n-butyl phthalate. In an acute-duration study

by Ema et al. (1998), an increased incidence of undescended testes (an internal malformation) and

decreased anogenital distance and anogenital distance/body weight ratio were observed in the fetuses of

rats receiving gavage doses of 555 or 661 mg/kg/day on gestational days 11–21; no effects were observed

at 331 mg/kg/day. Effects seen in other acute-duration studies involving gestational or gestational/
DI-n-BUTYL PHTHALATE 46

3. HEALTH EFFECTS

lactational exposure to 250–1,500 mg/kg/day included retained nipple buds or areolas, decreased

anogenital distance and anogenital distance/body weight ratio, absent or malformed epididymis,

degeneration of seminiferous epithelium, absent or malformed vas deferens, decreased androgendependent tissue weights (ventral prostate, epididymis, cauda epididymis, testes, glans penis, and levator

ani-bulbocavernosus), hypospadias, increased incidence of cryptorchidism, and delayed preputial

separation (Ema et al. 2000a, 2000b; Gray et al. 1999; Mylchreest et al. 1999). The reproductive effects

observed in the intermediate-duration studies are similar to those observed in adult rats orally exposed to

di-n-butyl phthalate, including degeneration and atrophy of the seminiferous tubules and hypospermia. 

Degeneration and atrophy of the seminiferous tubules were observed in the offspring of rats receiving

daily gavage doses of 250 mg/kg/day on gestational days 3–21 and lactational days 2–20 (Mylchreest et

al. 1998b). Male offspring of rat dams exposed to 250 mg/kg/day di-n-butyl phthalate or higher from

weaning through mating, gestation, and lactation showed reduced cauda epididymal sperm counts and

increased incidence of urogenital malformations (Gray et al. 1999). Female offspring in the same study

(Gray et al. 1999) showed increased incidence of uterine abnormalities (partial agenesis or lack of

implants in one uterine horn). Two studies conducted for NTP (1995) and a study by IRDC (1984)

examined reproductive organs of F1 rats exposed to di-n-butyl phthalate in utero, during lactation, and for

7 (IRDC 1984), 10 (NTP 1995), or 13 weeks postweaning. IRDC (1984) and NTP (1995) reported

testicular degeneration/atrophy in the F1 rats exposed to 500 (IRDC 1984) or 571 (NTP 1995) mg/kg/day;

this effect was not observed in offspring of rats only exposed in utero and during lactation (IRDC 1984). 

Decreases in epididymal, cauda epididymal, testes, seminal vesicle, prostate gland, and ovary weights,

testicular degeneration, and hypospermia were observed in the F1 rats exposed to 509 mg/kg/day in utero,

during lactation, and through delivery of the F2 generation (10 weeks) (NTP 1995). 

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. 

3.2.2.7 Cancer

No studies regarding carcinogenic effects of di-n-butyl phthalate in humans after oral exposure to

di-n-butyl phthalate were located. Rats exposed for 15–21 months to doses of 100–500 mg/kg/day were

reported not to develop cancer, but no details of the study or the examination for tumors were provided 
DI-n-BUTYL PHTHALATE 47

3. HEALTH EFFECTS

(Krauskopf 1973). No other studies on the carcinogenic effects of chronic ingestion of di-n-butyl

phthalate were located.

3.2.3 Dermal Exposure

Available data on the effects of dermal exposure to di-n-butyl phthalate are presented in Table 3-2. These

studies are discussed below.

3.2.3.1 Death

No studies regarding death in humans following dermal exposure to di-n-butyl phthalate were located. 

The subchronic (90-day) dermal LD50 in rabbits has been reported to be >4,200 mg/kg/day (Lehman

1955).

3.2.3.2 Systemic Effects

No studies regarding respiratory, cardiovascular, gastrointestinal, hematological, musculoskeletal,

hepatic, ocular, metabolic, or body weight effects in humans or animals following dermal exposure to

di-n-butyl phthalate were located.

Renal Effects. No information concerning renal effects in humans following dermal exposure to

di-n-butyl phthalate was located. Histological evidence of slight kidney damage was noted in rabbits

after 90 days of dermal application of 4,200 mg/kg/day (Lehman 1955). No details about the study or

specifics about the type of kidney damage were given. In this study, a NOAEL of 2,100 mg/kg/day was

identified.

Dermal Effects. Some cosmetic preparations containing di-n-butyl phthalate cause slight irritation to

human skin (Cosmetic Ingredient Review Panel 1985). A single dermal application of 520 mg/kg/day of

di-n-butyl phthalate was reported to be slightly irritating to skin and "quite irritating" to mucous

membranes of rabbits (Lehman 1955). In a 90-day study, doses up to 4,200 mg/kg/day were described as

slightly irritating, and slight dermatitis was reported. No data were presented, and the no-effect level was

not given. 

DI-n-BUTYL PHTHALATE 49

3. HEALTH EFFECTS

3.2.3.3 Immunological and Lymphoreticular Effects

Di-n-butyl phthalate does not appear to be a skin sensitizer. A variety of cosmetic materials (e.g.,

deodorants, nail polish) containing 4.5–9% di-n-butyl phthalate were not skin sensitizers when tested on

50–250 individuals per sample (Cosmetic Ingredient Review Committee 1985). In a 90-day study in

rabbits, there was no indication that di-n-butyl phthalate was a skin sensitizer (Lehman 1955).

No studies regarding the following health effects in humans or experimental animals after dermal

exposure to di-n-butyl phthalate were located:

3.2.3.4 Neurological Effects

3.2.3.5 Reproductive Effects

3.2.3.6 Developmental Effects

3.2.3.7 Cancer

3.2.4 Other Routes of Exposure

No relevant studies for other routes of exposure were located.

3.3 GENOTOXICITY

Genotoxic Effects. Available in vitro genotoxicity data are summarized in Table 3-3. Di-n-butyl

phthalate has tested negative or marginally positive in prokaryotic (Agarwal et al. 1985; Seed 1982) and

eukaryotic (Barber et al. 2000) gene mutation, chromosomal aberration (Ishidate and Odashima 1977),

and DNA damage (Kleinsasser et al. 2000) studies. These results suggest that di-n-butyl phthalate may be

weakly mutagenic in vitro. The significance of these findings to the intact mammalian organism is not

known because in vivo genotoxicity studies have not been conducted.
Table 3-3. Genotoxicity of Di-n-butyl Phthalate In Vitro

Results

Species (test system) End point With activation Without activation Reference

Prokaryotic organisms:

Salmonella typhimurium Gene mutation – – Florin et al. 19

Zeiger et al. 1

S. typhimurium – (+) Seed 1982S. typhimurium – + Agarwal et al. 

Eukaryotic organisms:

Fungi:

Saccharomyces cerevisiae Gene mutation – – Shahin and V

Mammalian cells:

Human oropharyngeal mucosa Single-strand DNA breaks No data + Kleinsasser e

Human nasal mucosa Single-strand DNA breaks No data + Kleinsasser eMouse lymphoma Gene mutation + – Barber et al. 2Mouse lymphoma Gene mutation + – Hazleton BioteChinese hamster ovary cells Chromosomal aberrations No data (+) Ishidate and OBalb 3T3 Cell transformation No data – Barber et al. 2Balb 3T3 Cell transformation No data – Litton Bionetic

– = negative result; (+) = marginally positive; + = positive result
DI-n-BUTYL PHTHALATE 51

3. HEALTH EFFECTS

3.4 TOXICOKINETICS

3.4.1 Absorption

3.4.1.1 Inhalation Exposure

No studies regarding absorption in humans after inhalation exposure to di-n-butyl phthalate were located. 

The relatively low concentration of di-n-butyl phthalate found in the lungs of rats exposed to 50 mg/m3

 of

di-n-butyl phthalate for up to 6 months was suggested to indicate rapid absorption (Kawano 1980b). 

However, no metabolites were measured in this study, and so the lack of accumulation could be due to

lung metabolism rather than absorption.

3.4.1.2 Oral Exposure

No studies regarding absorption in humans after oral exposure to di-n-butyl phthalate were located.

Studies in laboratory animals indicate that di-n-butyl phthalate is rapidly and extensively absorbed by the

oral route. Extensive absorption is indicated by the fact that, in rats, 63–97% of an orally administered

dose was accounted for in the urine within 24 hours after dosing (Foster et al. 1982; Tanaka et al. 1978;

Williams and Blanchfield 1975). Forty-eight hours after dosing, 85–100% of an oral dose of

14C-di-n-butyl phthalate was excreted in the urine (Tanaka et al. 1978; Williams and Blanchfield 1975). 

Similar results were obtained in hamsters, where 73% of an orally administered dose of 14C-di-n-butyl

phthalate was excreted in the urine within 24 hours (Foster et al. 1982). In vitro studies indicate that a

metabolite of di-n-butyl phthalate, mono-n-butyl phthalate, is probably the main form absorbed through

the intestine (Lake et al. 1977; Takahashi and Tanaka 1989).

3.4.1.3 Dermal Exposure

No studies regarding absorption in humans after dermal exposure to di-n-butyl phthalate were located,

although in vitro studies using human skin indicate that slow absorption by this route might occur (Scott

et al. 1987). 
DI-n-BUTYL PHTHALATE 52

3. HEALTH EFFECTS

In rats, approximately 60% of a single dermal dose of 157 μmol/kg was excreted in the urine during a

7-day period (the di-n-butyl phthalate remained on the skin for 7 days). The rate of di-n-butyl phthalate

excretion (percentage of dose in 24 hours) remained constant over 7 days at 10–12% (Elsisi et al. 1989).

The in vitro rate of dermal absorption in rats has been shown to be much greater than in humans (human

skin absorption was 0.8% that of rat skin) (Scott et al. 1987).

3.4.2 Distribution

There are no data on the distribution of di-n-butyl phthalate in humans. Animal data suggest that

following inhalation, oral, or dermal exposure, di-n-butyl phthalate is widely distributed throughout the

body and does not accumulate in the body. There are no data on transplacental transfer or transfer via

maternal milk. There is some evidence to suggest that di-n-butyl phthalate and its metabolites are rapidly

cleared from the body (Foster et al. 1982; Tanaka et al. 1978; Williams and Blanchfield 1975). Thus, it is

unlikely that di-n-butyl phthalate will be stored in maternal tissues and released during pregnancy or

lactation.

3.4.2.1 Inhalation Exposure

No studies regarding distribution in humans after inhalation exposure to di-n-butyl phthalate were

located.

In rats exposed to di-n-butyl phthalate by inhalation for 3 or 6 months, di-n-butyl phthalate was detected

in all organs examined from rats exposed at 50 mg/m3

 (Kawano 1980b). After 6 months of exposure, the

highest concentrations were found in brain, followed by lung, kidney, liver, and testicles (Kawano

1980b). Organ concentrations varied considerably between rats. At exposure to 0.5 mg/m3

, di-n-butyl

phthalate was consistently detected only in brains of exposed rats (Kawano 1980b).

3.4.2.2 Oral Exposure

No studies regarding distribution in humans after oral exposure to di-n-butyl phthalate were located.

Studies in rats on the distribution of 14C-labeled di-n-butyl phthalate indicate that it is distributed

throughout the body and that no significant retention occurs in any organ (Tanaka et al. 1978; Williams
DI-n-BUTYL PHTHALATE 53

3. HEALTH EFFECTS

and Blanchfield 1975). Evaluation of tissues for 14C at intervals 4–48 hours after dosing showed no

accumulation. At all of the time points evaluated, no organ contained >0.7% of the administered dose

(Williams and Blanchfield 1975). Even when rats were fed 0.1% di-n-butyl phthalate in the diet for up to

12 weeks, no accumulation in any organs was observed (Williams and Blanchfield 1975).

Following a single oral dose of 1,500 mg/kg [14C]-di-n-butyl phthalate to pregnant rats on gestational

day 14, the amount of radioactivity in the embryo peaked at 0.12% of the total administered dose at

6 hours postdosing, and thereafter rapidly declined to undetectable levels (Saillenfait et al. 1998).

3.4.2.3 Dermal Exposure

No studies regarding distribution in humans following dermal exposure to di-n-butyl phthalate were

located.

A study in rats indicated that there was little or no accumulation of di-n-butyl phthalate in the body 7 days

after a single dermal application of 43.6 mg/kg of 14C-labeled di-n-butyl phthalate (Elsisi et al. 1989). 

Though approximately 65% of the dose had been absorbed and eliminated, only small amounts were

found in tissues. Of the administered dose, 1.4% was in the skin, 1.1% was in muscle, and 0.41% was in

adipose tissue. All other tissues combined contained <0.5% of the dose. About 33% of the dose

remained at the site of application.

3.4.3 Metabolism

There is no direct evidence in humans or animals that the metabolism of di-n-butyl phthalate differs

between adults and children. However, the activity of glucuronosyltransferase, a phase II enzyme

involved in the biotransformation of mono-n-butyl phthalate to mono-n-butyl phthalate glucuronide,

differs between adults and infants; adult activity is achieved at 6–18 months of age (Leeder and Kearns

1997). 
DI-n-BUTYL PHTHALATE 54

3. HEALTH EFFECTS

3.4.3.1 Inhalation Exposure.

No studies regarding metabolism in humans or animals following inhalation exposure to di-n-butyl

phthalate were located.

3.4.3.2 Oral Exposure

No studies regarding di-n-butyl phthalate metabolism in humans were located. Studies in animals

indicate that metabolism of di-n-butyl phthalate proceeds mainly by hydrolysis of one butyl ester bond to

yield mono-n-butyl phthalate. The product that appears in the urine is mainly mono-n-butyl phthalate

conjugated with glucuronic acid, with lower levels of unconjugated mono-n-butyl phthalate, various

oxidation products of mono-n-butyl phthalate (see Figure 3-2), and a small amount of the free phthalic

acid (Figure 3-2) (Albro and Moore 1974; Foster et al. 1982; Kawano 1980b; Tanaka et al. 1978;

Williams and Blanchfield 1975).

Species differences in the excretion of conjugated and unconjugated di-n-butyl phthalate in the urine of

rats and hamsters have been identified by Foster et al. (1982). Rats excreted a larger proportion (14%) of

the administered dose as unconjugated mono-n-butyl phthalate than hamsters, in which only 3.5% was

excreted unconjugated. The authors indicated that this difference might explain why exposure to

di-n-butyl phthalate causes greater testicular damage in rats than in hamsters (see Section 3.2.2.6

Developmental Effects). 

3.4.3.3 Dermal Exposure

No studies regarding metabolism in humans and animals following dermal exposure to di-n-butyl

phthalate were located.
DI-n-BUTYL PHTHALATE 55

3. HEALTH EFFECTS

COO(CH2)3CH3

COO(CH2)3CH3

COOH

COO(CH2)3CH3

COOH

COOH

COOH

Phthalic Acid Monobutyl Phthalate (MBP)

COOGlucuronate

COO(CH2)3CH3

MBP Glucuronide

-Hydroxybutyl Phthalate

-Carboxypropyl Phthalate

-Hydroxybutyl Phthalate

COOH

COO(CH2)2COCH3 COO(CH2)3COOH

COO(CH2)2CHOHCH3 COO(CH2)3CH3OH

COOH COOH

-Ketobutyl Phthalate

3

3 4

4

Di Butyl Phthalate -nFigure 3-2. Metabolic Scheme for Di-n-butyl Phthalate in Animals

Source: Adapted from Albro and Moore 1974; Foster et al. 1982; Tanaka et al. 1978
DI-n-BUTYL PHTHALATE 56

3. HEALTH EFFECTS

3.4.4 Elimination and Excretion

3.4.4.1 Inhalation Exposure

No studies regarding excretion in humans or animals following inhalation exposure to di-n-butyl

phthalate were located.

3.4.4.2 Oral Exposure

No studies regarding excretion in humans following oral exposure to di-n-butyl phthalate were located. 

Studies in laboratory animals (rats, hamsters, and guinea pigs) indicate that 63–97% of an oral dose of

di-n-butyl phthalate is eliminated in the urine within 24 hours, with 85–100% recovered by 48 hours

(Foster et al. 1982; Tanaka et al. 1978; Williams and Blanchfield 1975). The fraction of the dose that was

not accounted for in the urine was present in the feces. Excretion was essentially complete by 48 hours

after administration of a single oral dose (Tanaka et al. 1978)

3.4.4.3 Dermal Exposure

No studies were located regarding excretion in humans following dermal exposure to di-n-butyl phthalate.

In rats, following a single dermal application of 14C-labeled di-n-butyl phthalate, 10–12% of the

administered dose was excreted in urine and 1% was excreted in the feces (Elsisi et al. 1989). Seven days

after application, 60% of the applied dose had been excreted.

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 
DI-n-BUTYL PHTHALATE 57

3. HEALTH EFFECTS

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 et al.

1987; Andersen and Krishnan 1994). 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 parametrization, (3) model simulation, and (4) model validation (Krishnan and

Andersen 1994). In the early 1990s, validated PBPK models were developed for a number of

toxicologically important chemical substances, both volatile and nonvolatile (Krishnan and Andersen

1994; Leung 1993). PBPK models for a particular substance require estimates of the chemical substancespecific physicochemical parameters, and species-specific physiological and biological parameters. The

numerical estimates of these model parameters are incorporated within a set of differential and algebraic

equations that describe the pharmacokinetic processes. Solving these differential and algebraic equations

provides the predictions of tissue dose. Computers then provide process simulations based on these

solutions. 

The structure and mathematical expressions used in PBPK models significantly simplify the true

complexities of biological systems. If the uptake and disposition of the chemical substance(s) is

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). 
DI-n-BUTYL PHTHALATE 58

3. HEALTH EFFECTS

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 3-3 shows a conceptualized representation of a PBPK model.

Keys et al. (2000) describe a PBPK model of di-n-butyl phthalate in rats that simulates the

pharmacokinetics of both di-n-butyl phthalate and its major metabolite, mono-n-butyl phthalate. The

model is intended for use in simulating doses of mono-n-butyl phthalate to the testes resulting from oral

exposures to di-n-butyl phthalate. It is based on a earlier model developed for simulating the

pharmacokinetics of di(2-ethylhexyl) phthalate and mono(2-ethylhexyl) phthalate (Keys et al. 1999).

Description of the Model. The Keys et al. (2000) model simulates seven tissue compartments: 

small intestine, blood, liver, fat, testis, slowly perfused tissues, and rapidly perfused tissues. The model

simulates the absorption of mono-n-butyl phthalate formed from di-n-butyl phthalate in the small

intestine; absorption of intact di-n-butyl phthalate is assumed not to occur. Conversion of di-n-butyl

phthalate to mono-n-butyl phthalate in the small intestine is simulated with a first order rate constant. 

Absorption of mono-n-butyl phthalate from the small intestine is simulated with a first order rate constant

for uptake into the liver. Elimination of absorbed mono-n-butyl phthalate is assumed to be entirely by

metabolism in the liver. Metabolism of mono-n-butyl phthalate is simulated with a single MichaelisMenten-type function (i.e., km and Vmax), which represents all pathways combined.

Keys et al. (2000) explored five approaches to modeling the pharmacokinetics of di-n-butyl phthalate and

mono-n-butyl phthalate. In a flow-limited version of the model, transfers between blood and tissues are

simulated as functions of blood flow, tissue concentrations of di-n-butyl phthalate or mono-n-butyl 

phthalate, and tissue:blood partition coefficients, assuming instantaneous partitioning of the compounds

between tissue and blood (Ramsey and Anderson 1984). In an enterohepatic circulation version of the 

model, the transfer of mono-n-butyl phthalate from the liver to the small intestine is represented with a first

order rate constant (diffusion-limited) and a time delay constant for the subsequent reabsorption of monon-butyl phthalate from the small intestine. In a diffusion-limited version of the model, the tissue transfers

include a first order rate term (referred to as the permeation constant) that relates the intracellular-toextracellular concentration gradient to the rates of transfer. This model requires estimates of extracellular

tissue volume (ECV) and intracellular volume (ICV); ECV is assumed to be equal to tissue blood volume

and ICV is assumed to be equal to the difference between tissue blood volume and 
DI-n-BUTYL PHTHALATE 59

3. HEALTH EFFECTS

Skin

Kidney

Richly

perfused

tissues

Slowly 

perfused

tissues

Fat

Liver

Lungs

A

R

T

E

R

I

A

L

B

L

O

O

D

V

E

N

O

U

S

B

L

O

O

D

GI

Tract

Vmax Km

Urine

Chemicals in air

contacting skin

Inhaled chemical Exhaled chemical

Ingestion

Feces

Figure 3-3. Conceptual Representation of a Physiologically 

Based Pharmacokinetic (PBPK) Model for a 

Hypothetical Chemical Substance

Source: adapted from Krishnan et al. 1994

Note: This is a conceptual representation of a physiologically based pharmacokinetic (PBPK) model for a

hypothetical chemical substance. The chemical substance is shown to be absorbed via the skin, by inhalation, or by

ingestion, metabolized in the liver, and excreted in the urine or by exhalation.
DI-n-BUTYL PHTHALATE 60

3. HEALTH EFFECTS

total tissue volume. This approach would be expected to underestimate the true ECV of most tissues,

which is approximately 45% of tissue mass (Edelman and Leibman 1959), and overestimate the true ICF;

the significance of these potential differences are not discussed by Keys et al. (2000). In a pH-trapping

version of the model, instantaneous partitioning (i.e., flow-limited) of only the nonionized species of

mono-n-butyl phthalate between the intracellular and extracellular compartments of tissues is assumed,

and the respective concentrations of the nonionized and ionized species in each compartment are

predicted by the pKa for the carboxylic acid moiety of mono-n-butyl phthalate (pKa is assumed to be 3.79,

and intracellular pH is assumed to be approximately 7.0). In a diffusion-limited, pH-trapping version of

the model, mono-n-butyl phthalate is assumed to ionize and reach equilibrium with its nonionized form,

as in the pH trapping version; however, the rate of partitioning of the nonionized mono-n-butyl phthalate

from the extracellular to the intracellular compartment of the tissue is controlled by the permeation

coefficient-surface area-cross product (diffusion-limited). In the intracellular compartment, mono-n-butyl

phthalate is assumed to equilibrate, where it was mostly ionized. The permeation coefficient-surface

area-cross product combined with the nonionized mono-n-butyl phthalate tissue:blood partition

coefficients control the rate at which nonionized mono-n-butyl phthalate is predicted to leave the

intracellular compartment.

Tissue:blood partition coefficients for total and nonionized mono-n-butyl phthalate were estimated from

their n-octanol:water partition coefficients (Kow), using the approach reported by Poulin and Krishnan

(1995). Tissue:blood partition coefficients for total mono-n-butyl phthalate (ionized and nonionized)

were determined experimentally using a vial-equilibration method with correction for pH (Table 3-4).

Keys et al. (2000) note that certain model parameter values were estimated by applying a step-wise

parameter optimization routine to data on blood or tissue levels following oral or intravenous exposure to

di-n-butyl phthalate and mono-n-butyl phthalate. The parameters estimated included the km and Vmax

values for metabolism of mono-n-butyl phthalate in the liver, the first order rate constant for the

metabolism of di-n-butyl phthalate in the intestine, the first-order rate constant for absorption of

mono-n-butyl phthalate from the small intestine, intracellular-to-extracellular transfer constants (e.g.,

permeation coefficient-surface-area-cross product) of nonionized mono-n-butyl phthalate, and biliary

transfer of mono-n-butyl phthalate from liver to small intestine (these values are not provided in the

profile because they are derived from optimization procedures and may not be directly useful for other

models). Keys et al. (2000) do not explicitly cite or describe the data sets used to optimize model 
DI-n-BUTYL PHTHALATE 61

3. HEALTH EFFECTS

Table 3-4. Tissue:Blood Partition Coefficients Used in the 

Keys et al. (2000) Model

Tissue

Nonionized

mono-n-butyl phthalate

(estimated)a

Total

mono-n-butyl phthalate

(experimental)b

Total

mono-n-butyl phthalate

(estimated)c

Liver 15.8 1.22 ± 0.25 0.9

Fat 313.0 0.05 ± 0.5 0.9

Muscle 4.6 Negative 1.9

Testes 4.9 1.9 ± 0.21 4.9

a

from Kow based on algorithms from Poulin and Krishnan (1995); used for the pH trapping and combined diffusion

limited-pH trapping models

b

vial equilibration study with pH correction

c

from Kow at physiological pH (largely ionized) based on algorithms from Poulin and Krishnan (1995); used for the

flow limited, enterohepatic circulation, and diffusion limited models
DI-n-BUTYL PHTHALATE 62

3. HEALTH EFFECTS

parameter values. Based on Table 4 of their report, it appears that at least some data from National

Institute of Environmental Health Sciences (NIEHS) (1994, 1995) were used to optimize the model.

Validation of the Model. Outputs from the various models were compared to observations of blood

concentrations reported from studies of oral gavage or intravenous exposures of rats to di-n-butyl

phthalate (NIEHS 1994, 1995). Based on the comparisons of model outputs to observed time courses for

blood mono-n-butyl phthalate concentrations from NIEHS (1994, 1995), Keys et al. (2000) concluded

that the diffusion-limited, pH-trapping model more closely represents the empirical data. However, it is

difficult to interpret this finding if the same data were used in the model optimization (see Table 4 of

Keys et al. 2000). The diffusion-limited, pH-trapping model simulated reasonably well the time courses

for blood concentrations of mono-n-butyl phthalate reported by NIEHS (1994, 1995). A log-likelihood

ratio test was used to compare the fit of the various augmented models to that of the flow-limited model. 

The diffusion-limited, pH-trapping model gave a better statistical fit to the empirical data than the other

four models, with the next best fit achieved with enterohepatic circulation model. However, the latter

model appeared to underestimate peak mono-n-butyl phthalate plasma concentrations, which would be an

important limitation for its use in risk assessment.

Risk Assessment. The model provides an approach to estimating doses of mono-n-butyl phthalate to

the testes of the rat following oral doses of di-n-butyl phthalate and may be useful for internal doseresponse assessment of rat bioassay data in which the toxicity end point of interest is testicular toxicity. 

However, such uses of the model, or other potential uses in risk assessment, have not been evaluated.

Target Tissues. Output from the model, for which validation exercises were conducted, are

predictions of blood and testes concentrations of mono-n-butyl phthalate.

Species Extrapolation. The model is designed to predict the blood and testes concentrations of

mono-n-butyl phthalate following oral doses of di-n-butyl phthalate to rats. Extrapolation to other species

would require modification of the model to account for different tissue masses, blood flows, and possibly

other kinetic variables.
DI-n-BUTYL PHTHALATE 63

3. HEALTH EFFECTS

Interroute Extrapolation. The model is designed to simulate the pharmacokinetics of di-n-butyl

phthalate and its metabolite, mono-n-butyl phthalate, when exposure is by the oral route. The

pharmacokinetics of di-n-butyl phthalate would be expected to be different for other routes of exposure;

therefore, the output of the model cannot be extrapolated to other routes (e.g., dermal, inhalation) without

modification of the model. Calibration and validation studies utilized gavage exposures for oral dosing,

and therefore, the model may not be applicable to other oral exposure pathways (e.g., dietary, drinking

water) without modification.

3.5 MECHANISMS OF ACTION

3.5.1 Pharmacokinetic Mechanisms

There is good evidence that following oral exposure, di-n-butyl phthalate is metabolized to mono-n-butyl

phthalate and butanol by nonspecific esterases in the gastrointestinal tract (Cater et al. 1977; Lake et

al.1977; Takahashi and Tanaka 1989). The results of studies by Fukuoka et al. (1995) and Zhou et al.

(1990) suggest that mono-n-butyl phthalate may be the chemical responsible for the testicular toxicity of

di-n-butyl phthalate. 

3.5.2 Mechanisms of Toxicity

The most characteristic effect of di-n-butyl phthalate in animal models is the effect on the testes, in

particular the testicular atrophy observed following acute- (Cater et al. 1977; Fukuoka et al. 1989, 1990;

Gray and Gangolli 1986; Oishi and Hiragi 1980b) or intermediate- (Gray et al. 1999; NTP 1995;

Srivastava et al. 1990) duration exposure or in utero/lactational exposure (IRDC 1984; Mylchreest et al.

1998b, 2000; NTP 1995). The testicular atrophy is characterized by sloughing of germ cells as early as

6-hours post exposure (Fukuoka et al. 1990), ultimately resulting in seminiferous tubules with only

Sertoli cells. 

Fukuoka and associates have conducted a series of studies to elucidate the mechanism of testicular

toxicity (Fukuoka et al. 1989, 1990, 1993, 1994, 1995; Zhou et al. 1990). One proposed mechanism of

toxicity involves a disturbance in the interaction between germ cells and Sertoli cells. The Sertoli cellgerm cell interaction is generally considered to be required for the differentiation of male germ cells and

their progression through the seminiferous epithelium and release as mature spermatozoa. Exposure to 
DI-n-BUTYL PHTHALATE 64

3. HEALTH EFFECTS

di-n-butyl phthalate is associated with both the release of iron from hemoglobin and/or transferrin in the

liver and spleen, and the subsequent depletion of iron in the blood and testes. The decreased amount of

available iron results in a decrease in succinate dehydrogenase activity in the Sertoli cells, resulting in

disturbances in the energy transfer system between Sertoli cells and germ cells; anoxia due to iron

depletion and/or disturbances in the energy supply may induce the sloughing of germ cells. Decreases in

testicular sorbitol, fructose, and glucose levels have been observed in the testes 3–12 hours post exposure. 

Two days after exposure, there were significant decreases in sorbitol dehydrogenase and succinate

dehydrogenase activities and decreases in testicular iron and zinc levels. Another mechanism of toxicity

proposed for all phthalate esters that cause testicular toxicity involves interference with the interaction of

follicle stimulating hormone (FSH) with the FSH receptor on Sertoli cells (NTP 2000). This mechanism

may be applicable to di-n-butyl phthalate, but no studies regarding this mechanism and di-n-butyl

phthalate were located. It is likely that mono-n-butyl phthalate, the primary metabolite of di-n-butyl

phthalate, is responsible for the testicular toxicity. 

3.5.3 Animal-to-Human Extrapolations

Species differences in the testicular toxicity of di-n-butyl phthalate have been observed. Severe testicular

atrophy has been observed in rats and guinea pigs orally exposed to di-n-butyl phthalate. In mice exposed

to the same oral dose, focal testicular atrophy was observed, and no testicular effects were observed in

hamsters (Gray et al. 1982). The basis for the species differences is not known, but could be related to

species differences in the free concentration of the primary metabolite of di-n-butyl phthalate,

mono-n-butyl phthalate (Foster et al. 1982). In rats, the levels of mono-n-butyl phthalate and di-n-butyl

phthalate and β-glucuronidase activity in the testes were markedly higher than in hamsters. Foster et al.

(1982) suggested that the rate of mono-n-butyl phthalate glucuronide hydrolysis in rats is higher than in

hamsters resulting in increased mono-n-butyl phthalate levels in the rat testes. There are insufficient data

to assess whether rats, mice, or hamsters would be an appropriate animal model for testicular toxicity in

humans. 

Studies in nonhuman primates with phthalate esters (primarily di-isononyl phthalate and di-2-ethylhexyl

phthalate) have shown no hepatic effects similar to those seen in rodents, including peroxisome

proliferation (Astill 1989; Pugh et al. 2000; Rhodes et al. 1986; Short et al. 1987); this suggests that

primates, including humans, are probably not sensitive to the hepatic effects of peroxisome proliferators. 
DI-n-BUTYL PHTHALATE 65

3. HEALTH EFFECTS

3.6 ENDOCRINE DISRUPTION

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, or otherwise

interfere with the normal function of the endocrine system. Chemicals with this type of activity are most

commonly referred to as endocrine disruptors. Some scientists believe that chemicals with the ability to

disrupt the endocrine system are a potential threat to the health of humans, aquatic animals, and wildlife. 

Others believe that endocrine disrupting chemicals do not pose a significant health risk, particularly in

light 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

compounds are derived from plants and are similar in structure and action as endogenous estrogen. While

there is some controversy over the public health significance of endocrine disrupting chemicals, it is

agreed that the potential exists for these compounds to affect the synthesis, secretion, transport, binding,

action, or elimination of natural hormones in the body that are responsible for the maintenance of

homeostasis, reproduction, development, and/or behavior (EPA 1997). As a result, endocrine disruptors

may play a role in the disruption of sexual function, immune suppression, and neurobehavioral function. 

Endocrine disruption is also thought to be involved in the induction of breast, testicular, and prostate

cancers, as well as endometriosis (Berger 1994; Giwercman et al. 1993; Hoel et al. 1992).

Phthalates are a class of chemicals that have been implicated as having estrogenic properties. There is

both in vitro and in vivo evidence of the weak estrogenic behavior of di-n-butyl phthalate. The results of

three in vitro assays provide evidence of weak estrogenic activity. The first study used the recombinant

yeast screening test to assess estrogenic activity (Harris et al. 1997). In this test, a gene for human

estrogen receptor is integrated into the main yeast genome and is expressed in a form capable of binding

to estrogen response elements and controlling the expression of the reporter gene lac-Z; when the lac-Z

gene is expressed, β-galactoside is produced. Harris et al. (1997) found a dose-dependent increase in

β-galactosidase production suggesting that di-n-butyl phthalate had some estrogenic activity. However,

the di-n-butyl phthalate was approximately 10-million-fold less potent than estradiol. Di-n-butyl

phthalate also induced proliferation of MCF-7 and ZR-75 human breast cancer cell lines (Harris et al.

1997). Zacharewski et al. (1998) found that di-n-butyl phthalate induced reporter gene (luciferase)

activity in MCF-7 human breast cancer cells, but not HeLa human cervical carcinoma cells, transfected

with human estrogen receptor, although approximately 3,000-fold less potent than 17β-estradiol. 

Additionally, Zacharewski et al. (1998) found that di-n-butyl phthalate was capable of supporting a very
DI-n-BUTYL PHTHALATE 66

3. HEALTH EFFECTS

modest amount of growth in an estrogen-dependent recombinant yeast strain. Jobling et al. (1995) found

that di-n-butyl phthalate reduced the binding of 17β-estradiol to the fish estrogen receptor and stimulated

the transcriptional activity of the estrogen receptor. Zacharewski et al. (1998) found that di-n-butyl

phthalate was also capable of competing weakly with 17β-estradiol for binding to Sprague-Dawley rat

uterine estrogen receptor in vitro, although over 36,000 times weaker than 17β-estradiol. However,

differences in the kinetics of displacement of estrogen from the fish and rat estrogen receptors by

di-n-butyl phthalate may indicate significant species differences between estrogen receptors for binding

di-n-butyl phthalate (Jobling et al. 1995; Zacharewski et al. 1998). Although the results of the in vitro

studies consistently suggest that di-n-butyl phthalate has estrogenic properties, the in vivo data do not

provide supportive evidence for di-n-butyl phthalate estrogenicity. This may be due, at least in part, to

the presence in vivo of esterases that metabolize di-n-butyl phthalate to mono-n-butyl phthalate, which

has been reported not to interact with the estrogen receptor (Mylchreest et al. 1998b). An acute in vivo

assay by Milligan et al. (1998) did not find a significant increase in uterine vascular permeability in

ovariectomized mice 4 hours after subcutaneous administration of 927 mg/kg di-n-butyl phthalate. In

contrast to 17β-estradiol, di-n-butyl phthalate did not affect body weight, induce an increase in uterine

wet weight, or induce vaginal cornification in ovariectomized rats treated orally with up to

2,000 mg/kg/day di-n-butyl phthalate for 4 days (Zacharewski et al. 1998). Likewise, di-n-butyl phthalate

did not induce lordosis behavior or increased uterine weight in ovariectomized rats after exposure for

2 days, followed by 0.5 mg progesterone (Gray et al. 1999). Ema et al. (2000a) found that di-n-butyl

phthalate failed to induce a decidual cell response in rats. Pseudopregnant rats (females bred to

vasectomized males) treated di-n-butyl phthalate on days 0–8 of pseudopregnancy, followed by surgical

induction of the decidual cell response had lower ovarian weights, uterine weights, and serum

progesterone levels on day 9 of pseudopregnancy, compared to controls, indicating a lack of estrogenic

activity. However, the results of the NTP (1995) multigeneration study, particularly the finding that the

reproductive effects in the first generation males appeared more adverse than those in the parental

generation (see Sections 2.2.2.5 Reproductive Effects and 3.2.2.6 Developmental Effects for a description

of these effects), are suggestive that di-n-butyl phthalate can disrupt normal male development. 

Additionally, the decreases in anogenital distance observed in rat fetuses (Ema et al. 1998, 2000b;

Mylchreest et al. 1999, 2000) suggest that di-n-butyl phthalate has anti-androgenic properties. This is

further supported by the findings of Gray et al. (1999), showing similar, but not identical, effects from

di-n-butyl phthalate exposure as from exposure to linuron, a known androgen receptor ligand. These

effects included delayed preputial separation, reduced fertility, testicular atrophy, and reduced sperm

production in treated males, and reduced anogenital distance, increased number of retained nipples, and
DI-n-BUTYL PHTHALATE 67

3. HEALTH EFFECTS

decreased androgendependent tissue weights in male offspring (exposed in utero and via lactation only)

of treated rats. However, these androgen-related effects do not appear to be mediated by interaction of

di-n-butyl phthalate or its primary metabolite, mono-n-butyl phthalate, with the androgen receptor

(Mylchreest et al. 1998b, 1999) (see Section 3.5.2 Mechanisms of Toxicity for a discussion of the

possible mechanism of androgen disruption). Di-n-butyl phthalate is known to be a testicular toxicant. 

One mechanism of toxicity proposed for all phthalate esters that cause testicular toxicity involves

interference with the interaction of follicle stimulating hormone (FSH) with the FSH receptor on Sertoli

cells (NTP 2000). This mechanism may be applicable to di-n-butyl phthalate, but no studies regarding

this mechanism and di-n-butyl phthalate were located. 

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 5.6 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,
DI-n-BUTYL PHTHALATE 68

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infants have a larger proportion of their bodies as extracellular water and their brains and livers are

proportionately larger (Altman and Dittmer 1974; Fomon 1966; Fomon et al. 1982; Owen and Brozek

1966; Widdowson and Dickerson 1964). The infant also has an immature blood-brain barrier (Adinolfi

1985; Johanson 1980) and probably an immature blood-testis barrier (Setchell and Waites 1975). Many

xenobiotic metabolizing enzymes have distinctive developmental patterns. At various stages of growth

and development, levels of particular enzymes may be higher or lower than those of adults, and

sometimes unique enzymes may exist at particular developmental stages (Komori et al. 1990; Leeder and

Kearns 1997; NRC 1993; Vieira et al. 1996). Whether differences in xenobiotic metabolism make the

child more or less susceptible also depends on whether the relevant enzymes are involved in activation of

the parent compound to its toxic form or in detoxification. There may also be differences in excretion,

particularly in newborns who all have a low glomerular filtration rate and have not developed efficient

tubular secretion and resorption capacities (Altman and Dittmer 1974; NRC 1993; West et al. 1948). 

Children and adults may differ in their capacity to repair damage from chemical insults. Children also

have a longer remaining lifetime in which to express damage from chemicals; this potential is particularly

relevant to cancer.

Certain characteristics of the developing human may increase exposure or susceptibility while 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 information on the toxicity of di-n-butyl phthalate in children was located, and there is a limited

amount of data in adults. The available oral-exposure animal studies clearly demonstrate that the

developing organism is sensitive to the toxicity of di-n-butyl phthalate. Postimplantation losses and

decreases in the number of live fetuses have been observed in a number of acute-duration studies in which

rats received gavage doses of 630 mg/kg/day and higher on gestational days 0–8, 7–15, 7–9, 10–12,

13–15, or 6, 8, 10, 12, 13, 14, 15, or 16 (Ema et al. 1993, 1994, 1995, 1997a, 2000a) or in mice receiving

gavage doses of 2,500 mg/kg/day on gestational days 6–13 (Hardin et al. 1987). Decreases in the number

of live pups per litter have also been observed in intermediate-duration studies in which rats or mice were

exposed to 80 or 1,950 mg/kg/day, respectively, throughout gestation, lactation, and postweaning (NTP

1995), or rats were exposed to 250–500 mg/kg/day in utero and during lactation (Gray et al. 1999). 

Decreases in fetal/pup body weight have been observed in rats receiving gavage doses of 500 mg/kg/day
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or higher di-n-butyl phthalate on gestational days 0–8 (Ema et al. 2000a), 630 or 750 mg/kg/day on

gestational days 7–15, 7–9, 10–12, 13–15, 6, 7, 8, 9, 10, 11, or 16 (Ema et al. 1994, 1995, 1997a), and in

rats and mice exposed to 240 or 460 mg/kg/day, respectively, in the diet throughout gestation, lactation,

and postnatal days 28–56 (NTP 1995). Skeletal (primarily fusion of cervical vertebrae) and external

(cleft palate) malformations have been observed in rats receiving gavage doses of 750 mg/kg/day on

gestational days 7–9 or 13–15 (Ema et al. 1994, 1995). Impaired development of the reproductive system

has also been observed in an acute-duration study (Ema et al. 1998) and in several intermediate-duration

studies (IRDC 1984; Mylchreest et al. 1998b; NTP 1995). Ema et al. (1998) reported an increased

incidence of undescended testes and decreased anogenital distance in the offspring of rats receiving

gavage doses of 555 mg/kg/day and higher on gestational days 11–21. The reproductive effects observed

in the intermediate-duration studies are similar to the effects observed in adult animals exposed to

di-n-butyl phthalate. Decreases in reproductive organ weights, testicular degeneration/ atrophy, and

hypospermia have been observed in the offspring of rats exposed throughout gestation, lactation, and

postnatally to 250 mg/kg/day and higher di-n-butyl phthalate (Gray et al. 1999; IRDC 1984; Mylchreest

et al. 1998b, 2000; NTP 1995). More details about these studies can be found in Section 3.2.2.6

Developmental Effects.

NTP (1995) conducted two studies to assess the impact of perinatal exposure on the subchronic toxicity

of di-n-butyl phthalate. In the first study, weanling rats and mice were exposed to dietary di-n-butyl

phthalate for 13 weeks. In the second study, the 13-week dietary exposure was immediately preceded by

gestational and lactational exposure. Similar effects, particularly decreases in body weight gain,

hepatomegaly, and testicular degeneration/atrophy were observed in both studies; suggesting that the

perinatal rat is neither resistant nor hypersensitive to the short-term toxic effects of di-n-butyl phthalate as

compared to rats only exposed postnatally (NTP 1995). 

No human or animal data were located that examined possible age-related differences in the

toxicokinetics of di-n-butyl phthalate. However, it is known that one of the enzymes involved in phase II

biotransformation of mono-n-butyl phthalate, the primary di-n-butyl phthalate metabolite, is influenced

by age. Glucoronsyltransferase activity differs in adults and children under the age of 6–18 months

(Leeder and Kearns 1997). Di-n-butyl phthalate and its primary metabolite, mono-n-butyl phthalate, have

been detected in placental and embryonic tissues of treated pregnant rats (Saillenfait et al. 1998), with

mono-n-butyl phthalate accounting for 50–95% of the total amount recovered. In the embryo,

approximately 1% of the recovered mono-n-butyl phthalate was conjugated with glucuronic acid, but
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approximately 10% was conjugated in maternal plasma and placenta; this may indicate limited transfer of

conjugated mono-n-butyl phthalate to the embryo or an inability of embryonic tissues to conjugate

mono-n-butyl phthalate. There are no data on the toxicokinetic properties of di-n-butyl phthalate in

children or immature animals, or on transfer via maternal milk. Toxicokinetic information on di-n-butyl

phthalate is sparse, but existing oral studies (Foster et al. 1982; Tanaka et al. 1978; Williams and

Blanchfield 1975) indicate that di-n-butyl phthalate and its metabolites are rapidly cleared from the body. 

Thus, di-n-butyl phthalate from maternal preconception exposure is highly unlikely to be stored in

maternal tissues and released during pregnancy or lactation. 

Subsequent sections of this chapter (Sections 3.8, 3.9, 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).

Due to a nascent understanding of the use and interpretation of biomarkers, implementation of biomarkers

as tools of exposure in the general population is very limited. A biomarker of exposure is a xenobiotic

substance or its metabolite(s) or the product of an interaction between a xenobiotic agent and some target

molecule(s) or cell(s) that is measured within a compartment of an organism (NAS/NRC 1989). The

preferred biomarkers of exposure are generally the substance itself or substance-specific metabolites in

readily obtainable body fluid(s), or excreta. However, several factors can confound the use and

interpretation of biomarkers of exposure. The body burden of a substance may be the result of exposures

from more than one source. The substance being measured may be a metabolite of another xenobiotic

substance (e.g., high urinary levels of phenol can result from exposure to several different aromatic

compounds). Depending on the properties of the substance (e.g., biologic half-life) and environmental

conditions (e.g., duration and route of exposure), the substance and all of its metabolites may have left the

body by the time samples can be taken. It may be difficult to identify individuals exposed to hazardous

substances that are commonly found in body tissues and fluids (e.g., essential mineral nutrients such as
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copper, zinc, and selenium). Biomarkers of exposure to di-n-butyl phthalate are discussed in Section 3.8.1.

Biomarkers of effect are defined as any measurable biochemical, physiologic, or other alteration within an

organism that, depending on magnitude, can be recognized as an established or potential health

impairment or disease (NAS/NRC 1989). This definition encompasses biochemical or cellular signals of

tissue dysfunction (e.g., increased liver enzyme activity or pathologic changes in female genital epithelial

cells), as well as physiologic signs of dysfunction such as increased blood pressure or decreased lung

capacity. Note that these markers are not often substance specific. They also may not be directly

adverse, but can indicate potential health impairment (e.g., DNA adducts). Biomarkers of effects caused

by di-n-butyl phthalate 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 Di-n-butyl Phthalate

The presence of di-n-butyl phthalate has been reported in a number of human tissues and fluids. 

Di-n-butyl phthalate has been found in adipose tissue obtained from surgical procedures or autopsies

(Mes et al. 1974; EPA 1986g), in lipid-rich atherosclerotic plaques (Ferrario et al. 1985), in seminal fluid

(Murature et al. 1987), and in blood serum (Ching et al. 1981a; EPA 1986g). No study identified the

source, amount, or duration of exposure to di-n-butyl phthalate associated with levels in the body. A

study comparing surgical patients having known plasticizer exposure from intravenous bags and tubing

with controls without known exposure found no correlation between exposure and serum levels of

di-n-butyl phthalate (Ching et al. 1981a). There was no quantitative relationship between the

concentration of di-n-butyl phthalate in seminal fluid and sperm count (Murature et al. 1987). Thus,

measurements of di-n-butyl phthalate in body tissues and fluids can indicate that exposure has taken

place, but not the amount or duration of exposure. No data were found on the concentration of the

primary metabolite, mono-n-butyl phthalate, in human body tissues or fluids.
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3.8.2 Biomarkers Used to Characterize Effects Caused by Di-n-butyl Phthalate

Effects caused by di-n-butyl phthalate exposure in animals include liver changes and effects on

development and reproduction. None of these effects appear to be specific to di-n-butyl phthalate

exposure. Liver changes, such as altered enzymatic activity and peroxisome proliferation, are induced by

many other chemicals (Moody et al. 1991; Popp et al. 1989). These and other effects associated with

di-n-butyl phthalate exposure do not appear to be sufficiently specific to serve as biomarkers of effects.

3.9 INTERACTIONS WITH OTHER CHEMICALS

Administration of zinc provides some protection against the testicular toxicity of di-n-butyl phthalate

exposure in rats (Cater et al. 1977). No other studies were located regarding the interaction of di-n-butyl

phthalate with other chemicals. Schulsinger and Mullgaard (1980) reported that humans exposed to a

mixture of three phthalate esters, including di-n-butyl phthalate, did not develop dermal sensitization, but

since di-n-butyl phthalate is negative for skin sensitization, these results shed little light on possible

interactions.

3.10 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE

A susceptible population will exhibit a different or enhanced response to di-n-butyl phthalate than will

most persons exposed to the same level of di-n-butyl phthalate 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 di-n-butyl phthalate, or

compromised function of organs affected by di-n-butyl phthalate. Populations who are at greater risk due

to their unusually high exposure to di-n-butyl phthalate are discussed in Section 6.7 Populations with

Potentially High Exposures.

There are no data in humans to suggest that any segment of the human population is unusually susceptible

to the effects of di-n-butyl phthalate. However, in animal studies, a number of developmental effects were

reported, including postimplantation losses, decreases in the number of live fetuses, decreases in fetal/pup

body weight, increases in the incidence of external and skeletal malformations, and impaired development

of the reproductive system (Ema et al. 1993, 1994, 1995a, 1997a, 1998, 2000a, 2000b; Gray et al. 1999;

IRDC 1984; Mylchreest et al. 1998b, 1999, 2000; NTP 1995). In most of these studies, the developmental
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effects were at dietary or gavage levels which were not associated with maternal toxicity. This suggests

that the fetus may be somewhat more susceptible to di-n-butyl phthalate than the adult, and that it may be

prudent to consider pregnant females more susceptible to di-n-butyl phthalate than other adults. Some

studies suggested that pregnant rats may be more susceptible to the lethal effects of di-n-butyl phthalate. A

more detailed discussion of children’s susceptibility can be found in Section 3.7.

3.11 METHODS FOR REDUCING TOXIC EFFECTS

This section will describe clinical practice and research concerning methods for reducing toxic effects of

exposure to di-n-butyl phthalate. 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

di-n-butyl phthalate. When specific exposures have occurred, poison control centers and medical

toxicologists should be consulted for medical advice. 

No texts were found that provided specific information about treatment following exposures to di-n-butyl

phthalate

3.11.1 Reducing Peak Absorption Following Exposure

Methods for reducing peak absorption of di-n-butyl phthalate include gut dilution, eye irrigation, and

washing with soap (Ellenhorn 1997). No information regarding ways to reduce absorption following

inhalation exposure was located. 

3.11.2 Reducing Body Burden

No experimental data regarding methods for reducing the di-n-butyl phthalate body burden were located. 

The available toxicokinetic data suggest that di-n-butyl phthalate is rapidly cleared from the body. 

Twenty-four hours after dosing, 63–97% of an oral dose is excreted in the urine (Foster et al. 1982;

Tanaka et al. 1978; Williams and Blanchfield 1975). 
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3. HEALTH EFFECTS

3.11.3 Interfering with the Mechanism of Action for Toxic Effects

No methods which would interfere with mechanism of di-n-butyl phthalate toxic were identified.

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 di-n-butyl phthalate 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 di-n-butyl phthalate.

The following categories of possible data needs have been identified by a joint team of scientists from

ATSDR, NTP, and EPA. They are defined as substance-specific informational needs that if met would

reduce the uncertainties of human health assessment. This definition should not be interpreted to mean

that all data needs discussed in this section must be filled. In the future, the identified data needs will be

evaluated and prioritized, and a substance-specific research agenda will be proposed.

3.12.1 Existing Information on Health Effects of Di-n-butyl Phthalate

The existing data on health effects of inhalation, oral, and dermal exposure of humans and animals to

di-n-butyl phthalate are summarized in Figure 3-4. The purpose of this figure is to illustrate the existing

information concerning the health effects of di-n-butyl phthalate. 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 (ATSDR 1989), is substance-specific

information necessary to conduct comprehensive public health assessments. Generally, ATSDR defines a

data gap more broadly as any substance-specific information missing from the scientific literature.
DI-n-BUTYL PHTHALATE 75

3. HEALTH EFFECTS

Figure 3-4. Existing Information on Health Effects of Di-n-butyl Phthalate
DI-n-BUTYL PHTHALATE 76

3. HEALTH EFFECTS

Limited data are available on effects in humans, consisting of an occupational study of workers exposed

to mixtures of plasticizers and dermal sensitization studies conducted to evaluate the effects of di-n-butyl

phthalate in cosmetic products. Data from animal studies are more extensive. As a result of early

findings on testicular effects of di-n-butyl phthalate, most studies have tended to concentrate mainly on

developmental and reproductive effects. A few studies provide data on systemic effects, but since these

appear to be minor, research in this area has not been extensive. No data are available on the chronic

effects of di-n-butyl phthalate, or on its carcinogenic potential.

3.12.2 Identification of Data Needs

Acute-Duration Exposure. No information regarding health effects of di-n-butyl phthalate in

humans was located. Animal studies that have examined the acute toxicity of orally administered

di-n-butyl phthalate have primarily focused on reproductive (Cater et al. 1977; Fukuoka et al. 1989, 1990;

Gray et al. 1982; Oishi and Hiraga 1980b; Tanino et al. 1987) and developmental (Ema et al. 1993, 1994,

1995a, 1997b, 1998; Saillenfait et al. 1998) end points. An acute-duration oral MRL was derived from a

NOAEL for developmental effects (Mylchreest et al. 2000). The systemic toxicity of di-n-butyl phthalate

has not been adequately assessed. No information concerning target organs following acute-duration

inhalation or dermal exposure to di-n-butyl phthalate in animals or humans was located, and no acute

inhalation MRL could be derived. Additional information concerning the target organs and mechanism of

toxicity of di-n-butyl phthalate exposure by the inhalation, oral, and dermal routes are needed to assess

the risks to populations surrounding hazardous waste sites that might be exposed to di-n-butyl phthalate

for brief periods.

Intermediate-Duration. No human data on the toxicity of di-n-butyl phthalate following

intermediate-duration exposure were identified. Systemic, reproductive, and developmental effects have

been observed in animals following oral exposure. The liver appears to be the most sensitive systemic

target in rats and mice exposed to di-n-butyl phthalate in the diet for 13 weeks (NTP 1995; Schilling et al.

1992). The reproductive effects consist of testicular atrophy with decreases in spermatogenesis

(Murakami et al. 1986a, 1986b; NTP 1995; Srivastava et al. 1990), and the developmental effects

included decreases in the number of pups per litter in rats and impaired reproductive development in male

offspring (NTP 1995). An intermediate-duration oral MRL was not derived because the lowest LOAEL

was identified for a serious effect and the study did not identify a NOAEL. A toxicity study
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3. HEALTH EFFECTS

identifying a NOAEL for developmental effects are needed for assessing risk for populations living near

hazardous waste sites. 

No intermediate-duration inhalation studies were identified. These data are needed for assessing risk

associated with exposure to inhaled di-n-butyl phthalate. The only intermediate-duration dermal study

(Lehman 1955) examined a very limited number of end points and would have limited usefulness for

assessing hazard and risk following dermal exposure to di-n-butyl phthalate. 

Chronic-Duration Exposure and Cancer. No information concerning the toxic effects of chronicduration exposure to di-n-butyl phthalate in humans or animals by any route of exposure was located. 

Studies to establish the target organs and levels causing effects following chronic-duration exposure to

di-n-butyl phthalate by inhalation, oral, and dermal exposure are needed to assess the risks to populations

surrounding hazardous waste sites that might be exposed to di-n-butyl phthalate for long periods of time.

No information regarding the carcinogenicity of di-n-butyl phthalate in humans or animals was located. 

Genotoxicity. A limited number of in vitro tests for genotoxicity suggest that di-n-butyl phthalate

may have weak genotoxic potential. No in vivo studies have been conducted. In vivo genotoxicity

studies are needed to determine whether di-n-butyl phthalate has mutagenic potential and, if so, what the

possible mechanism of genotoxicity might be.

Reproductive Toxicity. No data on the reproductive toxicity of di-n-butyl phthalate in humans were

located. Testicular atrophy and decreased fertility have been observed in orally-exposed animals (Cater et

al. 1977; Fukuoka et al. 1989, 1990; Gray et al. 1982; Oishi and Hiraga 1980b; Tanino et al. 1987). 

Species differences are apparent, with rats and guinea pigs being more sensitive than mice, and hamsters

being relatively insensitive to this effect (Gray et al. 1982). The species differences may be related to an

increased ability to hydrolyze mono-n-butyl phthalate glucuronide resulting in increased levels of free

mono-n-butyl phthalate and testicular toxicity. Information that could be used to determine which animal

species would be a good model for testicular toxicity in humans would be useful in assessing risk in

humans exposed to di-n-butyl phthalate. Further, studies administering chronic low levels of di-n-butyl

phthalate are needed to determine whether or not any reproductive impairment or endocrine 
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disruption occurs at background levels. Additionally, it is not known if testicular effects would also be a

sensitive end point following inhalation or dermal exposure. 

Developmental Toxicity. No human developmental toxicity studies were located. Studies in rats

and mice have shown that oral exposure to di-n-butyl phthalate can result in a number of developmental

effects including postimplantation loss, decreases in the number of live births/litter, external, internal, and

skeletal malformations, and impaired development of the reproductive system in male offspring (Ema et

al. 1993, 1994, 1995a, 1997b, 1998, 2000a, 2000b; Gray et al. 1999; IRDC 1984; Mylchreest et al.

1998b, 1999, 2000; NTP 1995; Saillenfait et al. 1998). Although a number of studies have examined the

developmental toxicity of di-n-butyl phthalate, NOAELs have not been identified for some of the more

sensitive developmental effects, such as decreases in the number of live births and impaired development

of the reproductive system, following intermediate-duration oral exposure. Identification of NOAELs for

these effects are needed to establish an intermediate-duration oral MRL for di-n-butyl phthalate. NTP

(1995) conducted two studies to assess whether perinatal exposure increased the toxicity of di-n-butyl

phthalate. The studies did not find any difference in terms of critical effects and doses; however,

reproductive performance was not evaluated, and it is also not known if there would be any second

generation developmental effects. Developmental end points have not been assessed in animals following

inhalation or dermal exposure. Such studies are needed for extrapolating the possible risk to human

populations exposed environmentally by these routes. 

Immunotoxicity. The results from the available human and animal studies indicate that di-n-butyl

phthalate is not a skin-sensitizing agent following dermal exposure (Lehman 1955; Schulsinger and

Mollgaard 1980). These studies did not assess other aspects of immunotoxicity. Additionally,

immunotoxicity has not been adequately assessed following inhalation or oral exposure. Tests of several

additional end points of humoral and cell-mediated immune function are needed to assess the sensitivity

of this system to di-n-butyl phthalate.

Neurotoxicity. The neurotoxic potential of di-n-butyl phthalate has not been adequately evaluated in

human or animal studies. Neurotoxicity studies are needed to determine the hazards associated with

human exposure to di-n-butyl phthalate. 
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Epidemiological and Human Dosimetry Studies. Very limited epidemiological studies have

been performed and generally involved exposure to a mixture of plasticizers at poorly-characterized

levels; blood and tissue levels were the primary end points examined (Ferrario et al. 1985; Mes et al.

1974; Schulsinger and Mollgaard 1980). 

Studies of people occupationally exposed to di-n-butyl phthalate are needed to assess the effects of

di-n-butyl phthalate on human health. Since one of the most significant effects in animals is testicular

atrophy, epidemiology studies of reproductive parameters in humans exposed to di-n-butyl phthalate

would be particularly relevant. Such studies would be most valuable if dosimetry methods could be

developed to provide reliable exposure data to accompany health effects data. This would assist in

establishing cause/effect relationships and developing methods to monitor individuals living near

hazardous waste sites.

Biomarkers of Exposure and Effect. 

Exposure. The presence and concentration of di-n-butyl phthalate can be measured in a variety of

biological tissues and fluids, but no information that would allow correlation of body levels with source,

route, amount, or duration of exposure to di-n-butyl phthalate was located. The primary metabolite of

di-n-butyl phthalate in several species is mono-n-butyl phthalate, and so mono-n-butyl phthalate or its

glucuronide conjugate could possibly serve as a biomarker of exposure to di-n-butyl phthalate. However,

because mono-n-butyl phthalate is also a metabolite of butyl benzyl phthalate (Nativelle et al. 1999), it is

not a specific biomarker for di-n-butyl phthalate. Therefore, studies that identify specific markers of

exposure and determine the relationship between body levels of di-n-butyl phthalate and exposure are

needed to develop methods for identifying and monitoring populations with high exposure to di-n-butyl

phthalate.

Effect. No known biomarkers of effect of di-n-butyl phthalate were identified. Studies to identify some

early indication of impending injury to the male and female reproductive systems, perhaps based on the

interference of zinc metabolism, would be valuable in assessing likely health consequences in people with

above-average exposure to di-n-butyl phthalate.
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Absorption, Distribution, Metabolism, and Excretion. Studies in laboratory animals indicate

that di-n-butyl phthalate given orally is readily absorbed, mainly as the metabolite mono-n-butyl

phthalate, and subsequently, is rapidly excreted. Limited data exist regarding inhalation and dermal

absorption. Studies on the absorption and metabolism of di-n-butyl phthalate by the inhalation and

dermal routes are needed to evaluate human health risk by these routes of exposure. 

Comparative Toxicokinetics. Syrian hamsters appear to be relatively resistant to the testicular

effects of di-n-butyl phthalate compared to the rat. A comparative metabolic study with rats and hamsters

indicated some quantitative differences between the two species with respect to the excretion of

metabolites in the urine. Additional comparative studies, perhaps with other species, may add to our

understanding of the mechanisms of toxicity to the male reproductive organs. Since it is well known that

there are a wide variety of esterases with varying affinity for different substrates, further information on

the substrate specificities of the esterases in various species, and on the enzymes involved in

detoxification of di-n-butyl phthalate, especially glucuronosyltransferase, could help to understand the

biological mechanisms behind the species differences in response to di-n-butyl phthalate.

Methods of Reducing Toxic Effects. Di-n-butyl phthalate is metabolized in the gastrointestinal

tract by nonspecific esterases to form mono-n-butyl phthalate. Identification of substances that could

inhibit this biotransformation and possibly reduce absorption or that would induce glucuronidation of

mono-n-butyl phthalate would be valuable. There are no methods to block the toxic response due to

exposure to di-n-butyl phthalate or to mitigate the observed health effects. 

Children’s Susceptibility. No information on the toxicity of di-n-butyl phthalate in children has been

located. Studies that examine sensitive end points such as reproductive, hematological, or hepatic effects

in young animals would be useful for assessing whether children will be unusually susceptible to

di-n-butyl phthalate toxicity. It is particularly important to conduct studies on chronic low level exposure

of di-n-butyl phthalate because of its ubiquitous nature in many everyday items. Further, research suggests

di-n-butyl phthalate may have the capability to disrupt the endocrine system; such potential is especially

critical in developing and prepubescent children. The available animal data suggest that the developing

organism is sensitive to di-n-butyl phthalate toxicity. As discussed in Section 3.2.2.6, the observed

developmental effects include postimplantation losses, decreases in the number of live fetuses per litter,

decreases in fetal/pup body weights, increases in the incidences of external and skeletal malformations,

and altered reproductive development in the offspring. Data needs relating to development are discussed
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in detail in the Developmental Toxicity subsection above. There are no data on whether di-n-butyl

phthalate can cross the placenta or be transferred to an infant via breast milk. Although there are no data

on whether di-n-butyl phthalate is stored in maternal tissues and whether these stores can be mobilized

during pregnancy or lactation, the rapid clearance of di-n-butyl phthalate in animals receiving a single oral

dose suggests that di-n-butyl phthalate would not be stored in maternal tissues. 

The available toxicokinetic data did not evaluate the potential differences between adults and children,

although there is some evidence that there are age-related differences in the activity of at least one

enzyme, UDP-glucoronsyltransferase, that is involved in the metabolism of di-n-butyl phthalate. 

Toxicokinetic studies examining how aging can influence the absorption, distribution, and excretion of

di-n-butyl phthalate would be useful in assessing children’s susceptibility to di-n-butyl phthalate toxicity. 

The mechanism of action for a number of toxic effects have not been elucidated. There are no data to

determine whether there are age-specific biomarkers of exposure or effects or any interactions with other

chemicals that would be specific for children. There is very little available information on methods for

reducing di-n-butyl phthalate toxic effects or body burdens; it is likely that research in adults would also

be applicable to children. 

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

Ongoing studies pertaining to di-n-butyl phthalate have been identified and are shown in Table 3-5.
DI-n-BUTYL PHTHALATE 82

3. HEALTH EFFECTS

Table 3-5. Ongoing Studies on Di-n-butyl Phthalate

Investigator Affiliation Research description Sponsor

Cunningham, ML NIEHS, NIH Evaluation of peroxisome proliferationinterspecies differences, induction of

carcinogenicity

NIEHS

Pereira, MM Medical College of

Ohio

Effect of peroxisome proliferators on

methylation of genes

NIEHS

Thomas, R Florida A&M University Genotoxicity of di-n-butyl phthalate ATSDR

ATSDR = Agency for Toxic Substances and Disease Registry; NIEHS = National Institute of Environmental Health
DI-n-BUTYL PHTHALATE 83

4. CHEMICAL AND PHYSICAL INFORMATION

4.1 CHEMICAL IDENTITY

Information regarding the chemical identity of di-n-butyl phthalate is located in Table 4-1. Table 4-1 lists

common synonyms, trade names, and other pertinent identification information for di-n-butyl phthalate.

4.2 PHYSICAL AND CHEMICAL PROPERTIES

Information regarding the physical and chemical properties of di-n-butyl phthalate is located in Table 4-2. 

Table 4-2 lists important physical and chemical properties of di-n-butyl phthalate, but is not intended to

be all inclusive.
DI-n-BUTYL PHTHALATE 84

4. CHEMICAL AND PHYSICAL INFORMATION

COO(CH2)3CH3

COO(CH2)3CH3

Table 4-1. Chemical Identity of Di-n-butyl Phthalate

Characteristic Information Reference

Chemical name Di-n-butyl phthalate HSDB 2000

Synonym(s) 1,2-Benzenedicarboxylic acid, dibutyl

ester; Butyl phthalate; DBP; Dibutyl-ophthalate; Dibutyl phthalate; Phthalic

acid butyl ester

HSDB 2000;

Budavari 1996

Registered trade name(s) Caswell No. 292; Celluflex DBP;

Palatinol C; Polycizer DBP; PX 104;

Staflex DBP; Uniflex DB

HSDB 2000

Chemical formula C16H22O4 Budavari 1996

Chemical structure Metcalf 1994

Identification numbers:

CAS Registry

NIOSH RTECS

EPA Hazardous Waste

OHM/TADS

DOT/UN/NA/IMCO

HSDB

NCI

84-74-2

TI0875000

U069

7216617 

UN 2810/NA 9095

922

5804

Lewis 1993

HSDB 2000

EPA 1992

CIS 1999

DOT 1998

HSDB 2000

NIH 1999

CAS = Chemical Abstracts Services; CIS = Chemical Information System; DOT/UN/NA/IMCO = Department of

Transportation/United Nations/North America/International Maritime Dangerous Goods Code; EPA =

Environmental Protection Agency; HSDB = Hazardous Substance 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
DI-n-BUTYL PHTHALATE 85

4. CHEMICAL AND PHYSICAL INFORMATION

Table 4-2. Physical and Chemical Properties of Di-n-butyl Phthalate

Property Information Reference

Molecular weight 278.34 Budavari 1996

Color Colorless to faint yellow HSDB 1999

Physical state Oily liquid Lewis 1993

Melting point -35 EC Verschueren 1996

Boiling point 340 EC Budavari 1996

Density at 20 EC 1.04 kg/L Ashford 1994

Odor Slight ester-like EPA 1993

Odor threshold:

Water

Air

No data

0.26–1.47 mg/m3 EPA 1980b

Taste Strong and bitter taste HSDB 1999

Solubility:

Water

Freshwater at 20 EC

Organic solvent (s)

11.2 mg/L

10.1–11.1 mg/L

Very soluble in alcohol, ether, acetone,

and benzene

Staples et al. 1997

Shiu et al. 1990

Budavari 1996

Partition coefficients:

Log Kow

Log Koc

4.72

4.45

3.7

3.14

4.17

Hansch et al. 1995

Staples et al. 1997

de Bruijn et al. 1989

Russell and McDuffie 1986

Sullivan et al. 1982

Vapor pressure at 25 EC 2.01x10-5 mmHg

2.7x10-5 mm Hg

Donovan 1996

Staples et al. 1997

Polymerization No data

Photolysis No data

Henry's law constant at 25 EC 4.5x10-6 atm-m3

/mole

8.83x10-7 atm-m3

/mole

Roy 1994

Staples et al. 1997

Autoignition temperature 403 EC Weiss 1986

Flashpoint 157 EC NIOSH 1997

Flammability limits at 25 EC No data

Incompatibilities Reacts explosively with liquid chlorine Bisesi 1994

Conversion factors (25 EC) 11.36 mg/m3

=approximately 1 ppm

1 mg/m3

=0.088 ppm

Bisesi 1994

Explosive limits Lower explosive limit: 0.5% at 236 EC NIOSH 1997

HSDB = Hazardous Substance Data Bank; NIOSH = National Institute for Occupational Safety and Health

DI-n-BUTYL PHTHALATE 87

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

5.1 PRODUCTION

Di-n-butyl phthalate is a member of a class of compounds called phthalate esters. During the 1980s, there

was an increase in the production of phthalate esters with a world-wide production volume of 2 million

tons per year (Thuren and Larsson 1990).

Di-n-butyl phthalate can be manufactured via the esterification of phthalic acid with n-butyl alcohol in the

presence of a catalyst such as sulfuric acid or p-toluene sulfonic acid (Bisesi 1994; Cadogan and Howick

1996; EPA 1981). This reaction is generally performed at a temperature of 150 EC along with agitation

(EPA 1981). Water from this process is either recovered for other operations or treated and discharged as

waste water. Di-n-butyl phthalate is finally purified by vacuum distillation and/or with activated

charcoal. The majority of phthalate esters are produced in Europe with the United States and Asia and

Pacific rim countries producing similar amounts each (Cadogan and Howick 1996). 

Production volume records for di-n-butyl phthalate could only be located combined with the production

volume for di-iso-butyl phthalate. The production volume of di-n-butyl phthalate with di-iso-butyl

phthalate in the United States from 1979 to 1994 can be found on Table 5-1 (USITC 1980, 1981, 1982,

1983, 1984, 1985, 1986a, 1986b, 1987, 1988, 1989, 1990, 1991, 1992, 1993, 1994, 1995).

Di-n-butyl phthalate is produced at two locations in the United States (SRI 2000). These locations

include: Eastman Chemical Company (Kingsport, Tennessee) and Unitex Chemical Corporation

(Greensboro, North Carolina). 

5.2 IMPORT/EXPORT

Di-n-butyl phthalate is imported to the United States from various countries including Japan, Canada,

Mexico, Belgium, and Germany (Deyrup 1999). The total amount of di-n-butyl phthalate imported in

1997 was 358,600 pounds (162,700 kg), while for 1998, it was 567,600 pounds (257,500 kg). No

quantitative data were located on exports of di-n-butyl phthalate. Total phthalate ester exports from the

United States in 1977, however, was 42,500 kg (93,700 pounds), and di-n-butyl phthalate were estimated 
DI-n-BUTYL PHTHALATE 88

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

Table 5-1. U.S. Production Volumes of Di-n-butyl Phthalatea

Year Production volume (x1,000 kg)

1980 8,226

1981 9,029

1982 7,790

1983 9,187

1984 10,964

1985 9,878

1986 10,858

1987 11,440

1988 11,573

1989 9,725

1990 7,917

1991 8,506

1992 6,555

1993 6,662

1994 7,752

Source: USITC 1980, 1981, 1982, 1983, 1984, 1985, 1986a, 1986b, 1987, 1988, 1989, 1990, 1991, 1992, 1993,

1994, 1995

a

with di-iso-butyl phthalate
DI-n-BUTYL PHTHALATE 89

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

to be about 1% of total phthalate production (EPA 1981). On that basis, about 425 kg (937 pounds) of

di-n-butyl phthalate was probably exported in 1977. More current data could not be located.

5.3 USE

The most important use of di-n-butyl phthalate is as a plasticizer (Cadogan and Howick 1992, 1996). 

Plasticizers are compounds that are added to other substances in order to make them softer and more

flexible (Cadogan and Howick 1996). Di-n-butyl phthalate appears to be primarily used as a plasticizer in

polyvinyl acetate emulsion adhesives (white glues and carpenter’s glues, see Pocius 1991); as a solvent

for oil-soluble dyes, insecticides, peroxides, and other organics; as an antifoam agent; as a fiber lubricant

in the textile industry; as a solvent/plasticizer for nitrocellulose lacquers (Eastman Chemical Company

1999a); and as epoxy resins (EPA 1981, see also Cadogan and Howick 1992, 1996; Towae et al. 1992). 

Although there was limited use of di-n-butyl phthalate in polyvinyl chloride (PVC) plastics during the

1970s and 1980s, it is not currently used as a plasticizer in PVC (NTP 2000). Di-n-butyl phthalate is also

used as a fragrance fixative (Eastman Chemical Company 1999b; EPA 1981), and as a plasticizer in

polysulfides and polyurethanes, and as an alcohol denaturant (EPA 1981). Due to the higher volatility of

di-n-butyl phthalate compared to other phthalate esters, it is unsuitable as a plasticizer in products that

will be exposed to high temperature conditions on a continual basis. It is, however, very suitable in

imparting high flexibility, especially at lower temperatures (Cadogan and Howick 1996). Di-n-butyl

phthalate is often used in conjunction with higher molecular weight esters to improve the flexibility of

plasticizer combinations (Cadogan and Howick 1992).

Di-n-butyl phthalate has also been used in a number of other applications throughout the world. It has

been used in cosmetics, lubricants, floor carpets, tapestry, nail polish (Fishbein 1992), clothing treatments

for chiggers (Metcalf 1994), and rubber settings in dentistry (Tesk et al. 1993), for measurement of pore

space in carbon black (Dannenberg et al. 1992), and dehydration of maleic acid (Felthouse et al. 1995), as

a fuel stabilizer/plasticizer in propellents (Lindner 1993b), in nitroglycerin explosives as a desensitizer

(Lindner 1993a), as a solvent for chlorinated rubber, in leather varnishes and lacquers (Bisesi 1994), as an

adjusting agent for lead chromate pigments, as a concrete additive to impart work ability, and in polyvinyl

acetate emulsions (EPA 1981). Di-n-butyl phthalate is listed by EPA as an inert ingredient in some

pesticides (EPA 1999a) and an active ingredient in others (EPA 1999b).
DI-n-BUTYL PHTHALATE 90

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

A more current break down of usage data for di-n-butyl phthalate could not be located. Table 5-2

presents facilities that manufacture or use di-n-butyl phthalate according to Toxics Release Inventory

(TRI) data.

5.4 DISPOSAL

Currently, a number of different disposal operations may occur for di-n-butyl phthalate. During the

manufacturing of plasticizers, aerosols containing di-n-butyl phthalate can reach concentrations of

500 mg/m3

 (Cadogan and Howick 1996). Many facilities have begun using incineration equipment to

reduce aerosol concentrations to practically zero. Also, after transportation or storage operations have

ceased, di-n-butyl phthalate is generally washed out from its storage containers. This wash water is

passed through a series of separators to remove residuals, which are then incinerated. 

Some products containing phthalate ester plasticizers (e.g., flooring) may lose plasticizer through

extraction by soapy water during cleaning operations (Cadogan and Howick 1996). This waste water

could then flow into municipal sewage systems, where it will be later treated and discharged into the

environment.

Finally, since di-n-butyl phthalate is found in many household products, it may ultimately be disposed of

into municipal landfills (Cadogan and Howick 1996).
Table 5-2. Facilities that Produce, Process, or Use Di-n-butyl Phthalate

Statea

Number of

facilities

Range of maximum amounts

on site in poundsb Activities and usesc

AR 3 100–99,999 9, 10, 13

AZ 1 1,000–9,999 10

CA 7 0–99,999 8, 10, 12, 13

CO 1 10,000–99,999 8

FL 3 100,000–999,999 8, 11

GA 2 1,000–99,999 8, 9

IA 2 10,000–99,999 9, 10

IL 6 0–99,999 8, 9, 10

IN 4 100–99,999 2, 3, 8, 13

KS 2 10000–999,999 8, 10

KY 2 100–99,999 8, 12

LA 1 10,000–99,999 13

MA 4 1,000–999,999 8, 9, 10

MD 1 10,000–99,999 8

MI 3 100–99,999 10, 12, 13

MO 2 1,000–9,999 8, 9

NC 7 100–999,999 1, 4, 8, 10, 11, 12

NE 1 1,000–9,999 8, 9

NJ 7 1,000–99,999 2,3,4,8,10,11, 13

NY 8 1,000–99,999 2,3,8,10,11, 13

OH 3 1,000–99,999 8, 13

OK 1 100,000–999,999 7

PA 3 1,000–99,999 8, 13

RI 1 1,000–9,999 2, 3, 8

TN 3 1,000–999,999 1, 3, 4, 8, 12

TX 4 1,000–999,999 8, 10, 13

UT 1 10,000–99,999 13

VA 2 1,000–999,999 8

WA 2 1,000–99,999 10, 11, 13

WI 2 1,000–9,999 8, 10

Source: TRI99 2001

a

Post office state abbreviations used

b

Range represents maximum amounts on site reported by facilities in each state c

Activities/Uses:

1. Produce

2. Import

3. Onsite use/processing

4. Sale/Distribution

5. Byproduct

6. Impurity

7. Reactant

8. Formulation Component

9. Article Component

10. Repackaging

11. Chemical Processing Aid

12. Manufacturing Aid 

13. Ancillary/Other Uses

DI-n-BUTYL PHTHALATE 93

6. POTENTIAL FOR HUMAN EXPOSURE

6.1 OVERVIEW

Di-n-butyl phthalate has been identified in at least 471 of the 1,585 hazardous waste sites that have been

proposed for inclusion on the EPA National Priorities List (NPL) (HazDat 2001). However, the number

of sites evaluated for di-n-butyl phthalate is not known. The frequency of these sites can be seen in

Figure 6-1. Of these sites, 469 are located within the United States and 2 are located in the

Commonwealth of Puerto Rico (not shown). 

Di-n-butyl phthalate is one of several phthalate esters that are widely used as a plasticizers in a range of

polymers (e.g., polyvinyl acetate, nitrocellulose) that are found in many common consumer products

including home furnishings, paints, clothing, and cosmetic products. Because of its many uses, di-n-butyl

phthalate is widespread in the environment and has been identified at low levels in all environmental

media. Therefore, humans may be exposed to di-n-butyl phthalate by inhalation, by ingestion of water or

food containing di-n-butyl phthalate, and by dermal contact with plastics, cosmetics, or other materials

containing di-n-butyl phthalate.

In air, di-n-butyl phthalate may be adsorbed to particulate matter or occur as a vapor. Di-n-butyl

phthalate is expected to decompose in the air, or be transported to water and/or soil by wet (snow or rain)

or dry (wind and settling) deposition. Di-n-butyl phthalate is taken up from water by a variety of aquatic

organisms. In water and soil, di-n-butyl phthalate is subject to microbial degradation; degradation in the

presence (aerobic) and absence (anaerobic) of oxygen has been reported. Exposure of the general

population to di-n-butyl phthalate may occur through contact with contaminated air, water, food, soil,

and/or products in which di-n-butyl phthalate is intentionally incorporated.

6.2 RELEASES TO THE ENVIRONMENT

The TRI data should be used with caution because only certain types of facilities are required to report. 

This is not an exhaustive list.
1-56-111193163

Frequency of

NPL Sites

Derived from HazDat 2001

Figure 6-1. Frequency of NPL Sites with Di-n-butyl Phthalate Contamination
DI-n-BUTYL PHTHALATE 95

6. POTENTIAL FOR HUMAN EXPOSURE

Di-n-butyl Phthalate has been identified in a variety of environmental media (air, surface water, leachate,

groundwater, soil, and sediment) collected at 471 of 1,585 current or former NPL hazardous waste sites

(HazDat 2001).

6.2.1 Air

As presented in Chapter 4, di-n-butyl phthalate has a relatively low vapor pressure and Henry’s law

constant, as well as a relatively high octanol/water partition coefficient and soil sorption coefficient. This

combination of properties is consistent with a chemical that is found to only a limited extent in air 

(see Staples et al. 1997). However, di-n-butyl phthalate appears to be ubiquitous in air at very low levels

(see Section 6.4), apparently from the widespread distribution and use of plastics and other products

containing di-n-butyl phthalate. In Sweden, Thurén and Larsson (1990) could not correlate di-n-butyl

phthalate fallout rates with specific sources or transport routes on a nationwide basis. They found no

“distributional patterns or gradient,” which suggests that any local patterns were obscured by di-n-butyl

phthalate contribution from other sources or that emission sources of roughly equal magnitude were

diffuse. In contrast, monitoring data show that elevated fallout concentrations of bis(2-ethylhexyl)

phthalate (a similar molecule) are associated with industrial activity (Thurén and Larsson 1990). Elevated

fallout concentrations of bis(2-ethylhexyl) phthalate were only seen near a stack, and no elevated

concentrations could be seen 2 km away from the stack. No pattern associating distance from sources and

concentration was seen with di-n-butyl phthalate by Ritsema et al. (1989) in Lake Yssel in the

Netherlands, while for other higher-molecular-weight phthalate esters, a pattern was evident. The authors

suggested that atmospheric fallout from diffuse sources may be the dominant mechanism by which

di-n-butyl phthalate enters the lake.

The possibility of many diffuse sources of di-n-butyl phthalate is supported by some of the uses. For

example, some of the products that contain di-n-butyl phthalate include thin sheets and coatings

(including such products as floor wax [Weschler et al. 1990] and paint [Crump 1995]). These products

characteristically have large surface area-to-volume ratios, which may allow di-n-butyl phthalate to

volatilize more readily relative to other products with smaller surface area-to-volume ratios. For example,

Crump (1995) reported that 0.04 mg/m3

 of di-n-butyl phthalate, which had volatilized from paint, was

detected in indoor air. Cadogan and Howick (1996) reported an indoor overall emission rate of

2.3x10-4 mg/second-m3

 at 25 EC for all phthalate plasticizers in products such as wall coverings, flooring,

upholstery, and wire insulation. 
DI-n-BUTYL PHTHALATE 96

6. POTENTIAL FOR HUMAN EXPOSURE

Di-n-butyl phthalate is a component of cigarette and wood smoke (Otson et al. 1991) and waste

incinerator stacks (Jay and Stieglitz 1995; Nishikawa et al. 1992). Di-n-butyl phthalate is listed by EPA

as an inert ingredient in some pesticides (EPA 1999a) and an active ingredient in others (EPA 1999b). 

Releases to the atmosphere have been reported in EPA Toxic Release Inventory (TRI99 2001), and the

quantities are presented in Table 6-1. The TRI data should be used with caution because only certain

types of facilities are required to report. This is not an exhaustive list. Nonetheless, according to TRI99

(2001), manufacturing and processing facilities in 32 states emitted an estimated 36,477 pounds (ca.

17 metric tons) to the air, or approximately 9% of the total environmental release. 

Di-n-butyl phthalate has also been identified in the condensed water (Jay and Stieglitz 1995) and exhaust

gas (Nishikawa et al. 1992) from waste incinerators. In addition, Jones et al. (1996) used the CORAL+

model to estimate that a large U.S. city would emit approximately 200 g/year from all manholes, based on

sewage concentrations of 7 μg di-n-butyl phthalate/L of sewage. The model was very sensitive to

manhole ventilation rates and the authors noted that the estimate was probably very conservative. 

Di-n-butyl phthalate has been identified in 2 air samples collected from the 471 NPL hazardous waste

sites where it was detected in some environmental media (HazDat 2001). 

6.2.2 Water

Bauer and Herrmann (1997) reported the concentration of di-n-butyl phthalate in the leachate from

various fractions of household wastes from the regions of Bayreuth and Straubling in Germany. The

wastes included food waste, paper for recycling, unusable paper, cardboard, plastic films, other plastics,

textiles, 8–40 mm screened fraction, <8 mm screened fraction, compound packing waste, compound

materials, and disposable diapers. It is anticipated that household waste from continental Europe is

similar to that in the United States, so the same profile would be expected in both places. Further

information on this study is presented in Section 6.4.

According to TRI99 (2001), releases to water amount to approximately 279 pounds (0.13 metric tons) or

approximately 0.07% of the total amount released to all compartments (see Table 6-1). Releases to

underground injection wells amount to approximately 290,000 pounds (132 metric tons) or approximately

74% of the total amount released to all compartments. These releases occurred only in the 
Table 6-1. Releases to the Environment from Facilities that Produce, Process, or Use Di-n-

Reported amounts released in pounds per yeara

Stateb

Number offacilities Airc Water

Undergroundinjection Land

Total on-sitereleased

Total off-sitereleasee 

AL 1 No data No data No data No data No data No data AZ 1 192 No data No data No data 192 No data AR 4 751 0 No data No data 751 No data CA 14 568 0 No data No data 568 1,324 CO 2 0 0 No data No data 0 No data FL 4 910 0 290,000 No data 290,910 250 GA 5 575 No data No data No data 575 No data IL 16 4,070 0 No data No data 4,070 20,722 IN 6 34 No data No data No data 34 1,127 IA 4 1 No data No data No data 1 171 KS 2 2,360 No data No data No data 2,360 2,069 KY 2 0 No data No data No data 0 No data LA 2 0 0 No data No data 0 No data MD 1 0 No data No data No data 0 No data MA 8 251 No data No data No data 251 No data MI 6 43 0 No data 9,421 9,464 9,718 MN 2 No data No data No data No data No data No data MO 6 501 No data No data No data 501 318 NE 1 10 No data No data No data 10 1,014 NJ 18 415 0 No data 0 415 4 NY 10 267 92 No data 0 359 1,031 NC 12 3,862 0 No data 4,224 8,086 8,662 OH 13 22 1 No data No data 23 1,390 OK 2 5 No data No data No data 5 No data PA 6 260 No data No data No data 260 No data 
Table 6-1. Releases to the Environment from Facilities that Produce, Process, or Use Di-n-

(continued)

Reported amounts released in pounds per yeara

Stateb

Number offacilities Airc Water

Undergroundinjection Land

Total on-sitereleased

Total off-sitereleasee

RI 1 365 No data No data No data 365 1,800 TN 4 14,211 160 No data No data 14,371 No data TX 14 436 0 No data 0 436 No data UT 1 13 No data No data No data 13 No data VA 5 851 21 No data No data 872 No data WA 2 5,498 5 No data 0 5,503 250 WI 5 6 No data No data No data 6 500 Total 184 36,477 279 290,000 13,645 340,401 50,350 Source: TRI99 2001aData in TRI are maximum amounts released by each facility.bPost office state abbreviations are used.cThe sum of fugitive and stack releases are included in releases to air by a given facility. dThe sum of all releases of the chemical to air, land, water, and underground injection wells. eTotal amount of chemical transferred off-site, including to publicly owned treatment works (POTW).
DI-n-BUTYL PHTHALATE 99

6. POTENTIAL FOR HUMAN EXPOSURE

state of Florida. The TRI data should be used with caution because only certain types of facilities are

required to report. This is not an exhaustive list. Di-n-butyl phthalate has been identified in

217 groundwater and 78 surface water samples collected form the 471 NPL hazardous waste sites, where

it was detected in some environmental media (HazDat 2001).

Di-n-butyl phthalate may also be released into surface waters from industrial sources (Sheldon and Hites

1979), municipal waste water (Stubin et al. 1996), and leachate from sanitary landfills (EPA 1990a;

Kinman et al. 1995). Di-n-butyl phthalate has also been reportedly released to groundwater from a

hazardous waste site (Eckel et al. 1993).

Di-n-butyl phthalate has been detected in 5% of the urban runoff samples from 2 of the 19 cities tested by

EPA (Howard 1989). Concentrations in this urban waste water ranged from 0.5 to 11 μg/L. Sewage

sludge has been shown to concentrate di-n-butyl phthalate from water by about 25-fold. A concentration

of 966 μg/L sludge was reported by Feiler et al. (1980). It is believed that di-n-butyl phthalate in waste

water comes from a variety of sources including wash water used on vinyl flooring (Cadogan and Howick

1996). Disposal of secondary sewage effluent by rapid infiltration into the subsurface has been reported

to produce a plume over 3,500 m long of groundwater contaminated with di-n-butyl phthalate at

concentrations up to 450 mg/L (Barber 1992; Barber et al. 1988). Di-n-butyl phthalate has been

identified in river and ocean sediments at points of sewage outflow from urban areas (Fallon and Horvath

1985; Swartz et al. 1983). 

6.2.3 Soil

According to TRI99 (2001), releases to land amount to approximately 13,645 pounds (6.2 metric tons) or

approximately 3.5% of the total (see Table 6-1). Based on this analysis of TRI data alone, soil does not

appear to be a medium that commonly receives industrial releases. The TRI data should be used with

caution because only certain types of facilities are required to report. This is not an exhaustive list. 

Di-n-butyl phthalate has been identified in 280 soil and 126 sediment samples collected from the

471 NPL hazardous waste sited where it was detected in some environmental media (HazDat 2001).

No other release of di-n-butyl phthalate to soils has been reported; however, di-n-butyl phthalate has been

reported in leachate from sanitary landfills (EPA 1990a; Kinman et al. 1995) and in groundwater from a

hazardous waste site (Eckel et al. 1993). These monitoring data indicate release to soil. Thurén and 
DI-n-BUTYL PHTHALATE 100

6. POTENTIAL FOR HUMAN EXPOSURE

Larsson (1990) also noted that the average yearly atmospheric input to soil in Sweden was 202 μg/m2 for

di-n-butyl phthalate. Also, di-n-butyl phthalate may seep into soil from di-n-butyl phthalate containing

sewage sludge that is deposited on land.

6.3 ENVIRONMENTAL FATE

6.3.1 Transport and Partitioning

Di-n-butyl phthalate appears to be ubiquitous in air at low levels, is in both the vapor phase and

associated with particulates, and is subject to both wet (rain and snow) and dry (wind and settling)

deposition on the Earth's surface. Eisenreich et al. (1981) calculated that wet and dry deposition of

di-n-butyl phthalate into the five Great Lakes amounted to 47.7 metric tons per year, which corresponds

to an average fallout rate of 16.2 μg/m2

 per month. Thurén and Larsson (1990) reported that the average

fallout rate in Sweden for di-n-butyl phthalate was 16.8 μg/m2

 per month (the range was

1.98–335.5 μg/m2

 per month). Thurén and Larsson (1990) also estimated the median fallout

concentration to be 36 ng/L. The authors also noted that for a related phthalate ester, bis(2-ethylhexyl)

phthalate, fallout rate decreased with increasing distance (but only up to 2 km away) from a stack at a

facility that used bis(2-ethylhexyl) phthalate (see Section 6.2). A similar behavior is likely for di-n-butyl

phthalate. Nonetheless, the authors noted that no specific overall fallout patterns were observed. This is

consistent with a diffuse source of di-n-butyl phthalate in the atmosphere. In addition, di-n-butyl

phthalate has been found in 2 m deep Antarctic snow (Desideri et al. 1994) and in the snow in the

Austrian Alps (Gröllert et al. 1997), suggesting that di-n-butyl phthalate can be transported for long

distances so that di-n-butyl phthalate measured in one part of the world may have originated elsewhere. 

This transport is likely particle sorbed di-n-butyl phthalate because vapor phase di-n-butyl phthalate

reacts rapidly with hydroxyl radicals in the atmosphere (see Section 6.3.2.1), while the particle-sorbed

chemical does not react rapidly with hydroxyl radicals (di-n-butyl phthalate is associated with particulates

at low temperatures). Atmospheric fallout is negatively correlated with temperature so that less di-n-butyl

phthalate is subject to fallout in the summer than in the winter (Staples et al. 1997; Thurén and Larsson

1990). This is in keeping with a higher proportion of the atmospheric di-n-butyl phthalate in the vapor

state in the warm summer and less in the cold winter.

In water, di-n-butyl phthalate adsorbs to suspended particles, but, in many cases, the majority remains

dissolved. Based on log Koc values of 3.14 (Russell and McDuffie 1986) and 4.17 (Sullivan et al. 1982),
DI-n-BUTYL PHTHALATE 101

6. POTENTIAL FOR HUMAN EXPOSURE

di-n-butyl phthalate is anticipated to sorb relatively strongly to suspended particulates and sediments (see

Swann et al. 1983); however, this is not always observed. Dissolved di-n-butyl phthalate is more readily

advected and may be more available for biodegradation than particle-bound material. When dissolved in

water, di-n-butyl phthalate may be associated with dissolved humic materials, potentially increasing the

apparent water solubility by a small amount. Based on Henry’s law constants of 4.5x10-6 (Roy 1994)

and 8.83x10-7 (Staples et al. 1997) atm-m3

/mole, di-n-butyl phthalate is not expected to volatilize

significantly from water to the atmosphere (Lyman 1982). Germain and Langlois (1988) and Staples et

al. (1997) reported that 83.5–86% of the di-n-butyl phthalate was dissolved and 14–16.5% was bound to

suspended material (the concentrations of suspended material were 3.0–7.83 mg/L) in Niagara and St.

Lawrence Rivers. By contrast, Ritsema et al. (1989) reported that 29–57% of the di-n-butyl phthalate in

Lake Yssel water (the Netherlands) was dissolved, while 43–71% was associated with suspended

material. Matsuda and Schnitzer (1971) reported that di-n-butyl phthalate was slightly more soluble in

water containing fulvic acids extracted from soil than in pure water, and that solubility increased with

increasing fulvic acid concentration. Therefore, di-n-butyl phthalate may be present in higher dissolved

concentrations in waters with high concentrations of humic materials than in waters with low

concentrations of humic materials. Finally, in an estuary in the United Kingdom, Preston and Al-Omran

(1986, 1989) and Al-Omran and Preston (1987) reported that 66–86% of the di-n-butyl phthalate was

dissolved, while 14–34% was bound to suspended material, and that more adsorption occurs at higher salt

concentration. The authors reported that suspended material averaged 1,524 mg/L.

No reports were located that detailed the sorption of di-n-butyl phthalate specifically to freshwater

sediments; however, it is anticipated that the sorption to these sediments will be similar to that of

suspended materials. Sullivan et al. (1982) reported that di-n-butyl phthalate is rapidly adsorbed from

seawater onto marine sediment, but they did not report a Koc so that comparison with other reports is

difficult.

In soil, di-n-butyl phthalate is expected to have limited mobility based on its log Koc (see Table 4-2).

However, some migration to groundwater occurs, but may be limited to soils with low organic content

soils or sites with high water tables. Russell and McDuffie (1986) reported a log Koc of 3.14 in a soil in

Broome County, New York. According to Swann et al. (1983), this Koc is indicative of relatively low

mobility, suggesting that di-n-butyl phthalate will have limited migration to groundwater. Nonetheless,

Eckel et al. (1993) reported finding di-n-butyl phthalate in the groundwater under the Hipps Road landfill

NPL site in Florida. This site was developed at a location with unconsolidated medium- to fine-grained
DI-n-BUTYL PHTHALATE 102

6. POTENTIAL FOR HUMAN EXPOSURE

sand that allowed rapid movement of percolating water. Similarly, Barber (1992) reported finding

di-n-butyl phthalate in the groundwater near rapid infiltration beds where secondary sewage effluent was

disposed for over 50 years, and Kinman et al. (1995) reported the presence of di-n-butyl phthalate in

sanitary landfill leachate.

In addition to the cases noted above, the presence of organic solvents in hazardous waste sites may

increase the solubility of compounds such as di-n-butyl phthalate, thus increasing the amounts that may

leach from the site into the subsoil and into groundwater. For example, 1-octanol-saturated water

increases the solubility of di-n-butyl phthalate approximately six times its normal water solubility

(Nyssen et al. 1987).

Finally, data indicate that di-n-butyl phthalate can partition from food and water into a variety of

organisms. Studies using radioactively labeled di-n-butyl phthalate have shown accumulation of

radioactivity in aquatic invertebrates (Sanders et al. 1973) and fish (Wofford et al. 1981). Most of the

accumulated radioactivity is apparently in the form of the primary metabolite, mono-n-butyl phthalate

(Howard 1989). Numerous experiments have shown that the accumulation of di-n-butyl phthalate in the

aquatic and terrestrial food chain is limited by biotransformation (i.e., transformation of chemical

compounds within a living system), which progressively increases with trophic level (Staples et al. 1997). 

In general, bioconcentration factors decrease for organisms that possess more advanced metabolic

systems (Stalling et al. 1973). For example, the mean bioconcentration factors for algae, crustaceans,

insects, and fish are 3,399, 662±229, 624±144, and 167 mg/g (wet weight), respectively (Staples et al.

1997).

In greenhouse studies, Shea et al. (1982) demonstrated dose-dependent partitioning of di-n-butyl

phthalate from soils into corn, soybean, and wheat seedlings. For example, plant to soil bioconcentration

factors (defined as the ratio of wet weight concentrations in plant and soil, respectively) were <0.002 for

corn, indicating the limited bioaccumulation potential of di-n-butyl phthalate by terrestrial plants.

6.3.2 Transformation and Degradation

It should be noted that many of the studies reporting di-n-butyl phthalate biodegradation use radiolabeled

material as the substrate and measure 14CO2 as an indication of the extent of biodegradation. The reported

percentage of evolved 14CO2 indicates the amount of mineralization, but is not necessarily an indication of
DI-n-BUTYL PHTHALATE 103

6. POTENTIAL FOR HUMAN EXPOSURE

the extent of degradation. In addition to oxidation to CO2, microbial communities can also, for example,

incorporate organic substrates into cellular materials, or produce simple degradation products or high

molecular-weight materials. All of these processes contribute to the overall removal of the substrate, but

are not indicated by the percentage of 14CO2 reported.

6.3.2.1 Air

In air, di-n-butyl phthalate in vapor form would be expected to react with hydroxyl radicals since it has

extractable hydrogens. An overall hydroxyl radical reaction rate of 9.28x10-12 cm3

/molecule-second was

calculated using the AOPWin program (version 1.88, Meylan and Howard 1993). Assuming 1.5x106

•OH

molecules/cm3

, the half-life of di-n-butyl phthalate vapor in air can be calculated to be approximately

14 daylight hours. For di-n-butyl phthalate adsorbed to airborne particles, the half-life may be

considerably longer and may account for the long range transport of di-n-butyl phthalate, but this has not

been studied.

6.3.2.2 Water

Many papers describing the biodegradation of di-n-butyl phthalate in environmental waters and waste

water are available in the literature (Scholz et al. 1997; Staples et al. 1997). Di-n-butyl phthalate is

frequently reported to degrade 50–100% aerobically within 1–28 days in both fresh and marine water, and

anaerobically over 90% within 30 days in fresh water (Staples et al. 1997). In a river die-away test using

water from three rivers in the Netherlands, Schouten et al. (1979) reported that 90% of the initial 50 μg/L

di-n-butyl phthalate was removed in 3 days, while only 10% was lost in the sterile controls. Johnson et

al. (1984) found that di-n-butyl phthalate was degraded aerobically in water and sediment from Little

Dixie Lake in Columbia, Missouri. Approximately 63% degradation was observed in 7 days and 70%

degradation was observed in 14 days as measured by 14CO2 evolution using initial di-n-butyl phthalate

concentrations of 0.082–8.2 mg/L. In fresh and estuarine waters from U.S. sources, EPA (1984a)

reported that the range of time for one-half of the initial di-n-butyl phthalate (500 μg/L) to disappear was

1.7–13 days. The authors reported a 0–7 day lag period, and no degradation was seen in sterile controls. 

Johnson and Lulves (1975) reported that di-n-butyl phthalate (initial concentration of 1 mg/L) incubated

anaerobically in sediment degraded 61% in 7 days and 98% in 30 days as measured by recovery of

di-n-butyl phthalate.
DI-n-BUTYL PHTHALATE 104

6. POTENTIAL FOR HUMAN EXPOSURE

In contrast to biodegradation, abiotic hydrolysis appears to be a slow process. EPA (1989d) reported that

the hydrolysis half-life for di-n-butyl phthalate was approximately 22 years.

In screening tests using activated sludge, removal of >90% of the initial di-n-butyl phthalate is reported. 

For example, Kodama and Takai (1974) reported that 97–99.5% of the di-n-butyl phthalate at

0.1–1.0 mg/L degraded in a 3-day test. Using acclimated sludge in a semi-continuous activated sludge

test, O’Grady et al. (1985) reported that >90% of the initial of 3 mg/L concentration of di-n-butyl

phthalate degraded in 1 day. Under anaerobic conditions in activated sludge, di-n-butyl phthalate was

completely degraded to carbon dioxide and methane over a period of 20 days (Hannah et al. 1986). 

Shelton and Tiedje (1984) reported that 75–100% of the theoretical yield of methane was evolved in

56 days.

6.3.2.3 Sediment and Soil

Di-n-butyl phthalate also rapidly degrades in soil and sediments (Staples et al. 1997). For example,

500 μg/L of di-n-butyl phthalate in river and estuarine sediment samples degraded to one-half the initial

concentration in 1–5 days (EPA 1984a), and 92% (by 14CO2 evolution) of the di-n-butyl phthalate was

degraded in lake sediment in 14 days at 28 EC (Johnson et al. 1984). Inman et al. (1984) reported that

1 mg/L di-n-butyl phthalate in four soils was degraded to >80% (determined by 14CO2 evolution) within

80 days in almost every case. Silica sand and a sterile control showed almost no degradation. One of the

soils, Plainfield, required 200 days to reach 89.6% 14CO2 evolution. In four samples of Little Popo Agie

River (Wyoming) sediment, Heitkamp and Johnson (1984) reported that di-n-butyl phthalate, at a

concentration of 25.6 μg/L, was degraded aerobically to 71–75% (measured by 14CO2 evolution) in

14 days. In one sample, degradation was reported to be only 2.2%. Samples were taken from both upand downstream of an oil field waste water discharge point; the sediment that degraded only 2.2% of the

initial di-n-butyl phthalate was taken at the discharge point, which suggests that toxic substances may

have retarded the degradation.
DI-n-BUTYL PHTHALATE 105

6. POTENTIAL FOR HUMAN EXPOSURE

6.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT

6.4.1 Air

As presented in Chapter 4, di-n-butyl phthalate has a relatively low vapor pressure and Henry’s law

constant, as well as a relatively high octanol/water partition coefficient and soil sorption coefficient. This

combination of properties is consistent with a chemical that is found to only a limited extent in air. 

Nonetheless, di-n-butyl phthalate appears to be widespread in air at low levels, with urban air having

somewhat higher concentrations than air in rural or uninhabited areas. It should be noted that because

phthalates are widespread, they appear in the laboratory environment, and considerable effort must be

exercised by analysts to ensure that external contamination has not influenced the results. The monitoring

studies reported here appear to have taken reasonable efforts to eliminate contamination from their

analyses. Di-n-butyl phthalate has been reported over the Pacific and Atlantic Oceans at levels of

approximately 1x10-6 mg/m3

 (1 ng/m3) (Atlas and Giam 1981; Giam et al. 1980), in outdoor air in

Sweden, the United States (Thurén and Larsson 1990), and Canada (Otson et al. 1991) at

2.3x10–7–4.99x10-5 mg/m3

 (0.23–49.9 ng/m3), over New York City at levels of 3.3x10-6–5.7x10-6 mg/m3

(3.3–5.7 ng/m3) (Bove et al. 1978), in industrialized areas along the Niagara River at levels of

4.5x10-6 mg/m3

 (4.5 ng/m3) as vapor and at 6.2x10-6 mg/m3 (6.2 ng/m3) in particulate matter (Hoff and

Chan 1987), in indoor air in a “sick” building at levels of 1.2x10-3–5.9x10-3 μg/m3

 (1,200–5,900 ng/m3)

(but not in the air on the roof of the building) (Weschler et al. 1990), in residences in Canada at

>1.0x10-5 mg/m3

 (>10 ng/m3) (Otson et al. 1991), cigarette and wood smoke (Otson et al. 1991), and

waste incinerator stacks at 7.7x10-3 mg/m3

 (7,700 ng/m3) (Jay and Stieglitz 1995; Nishikawa et al. 1992). 

Crump (1995) reported that 0.04 mg/m3

 of di-n-butyl phthalate from paint was detected in indoor air. As

noted in Section 6.2.1, Cadogan and Howick (1996) reported that an indoor overall emission rate of

2.3x10-4 mg/second-m3

 at 25 EC has been calculated for all phthalate plasticizers in products such as wall

coverings, flooring, upholstery, and wire insulation.

6.4.2 Water

Overall there appears to be considerable uniformity in the concentration of di-n-butyl phthalate in the

surface waters of the United States, if locally contaminated areas are excluded. The National Drinking

Water Contaminant Occurrence Database (NDOD), which contains data from ambient water samples, lists

the number of detections of di-n-butyl phthalate in groundwater and surface water at several locations
DI-n-BUTYL PHTHALATE 106

6. POTENTIAL FOR HUMAN EXPOSURE

around the United States. Di-n-butyl phthalate was detected in groundwater at 1 of 363 sites (0.3% of

sites) with a concentration of 57 μg/L (EPA 2000a). In lakes/reservoirs, di-n-butyl phthalate was detected

at 2 of 15 sites (13.3% of sites) with a range and average concentration of 2.5–10.7 and 6.6 μg/L,

respectively (EPA 2000a). In other surface waters, di-n-butyl phthalate was detected at 9 of 253 sites

(3.6% of sites) with a range and average concentration of 0.2–150 and 17.1 μg/L, respectively (EPA

2000a). Water samples taken along the Mississippi River at the origin of the river in Minnesota, at the

junction of the Ohio River, below Memphis, Tennessee, and just below New Orleans had di-n-butyl

phthalate concentration of 0.15, 0.14, 0.15, and 0.14 μg/L, respectively (DeLeon et al. 1986). There was

no apparent effect of input from cities, industrial sources, or tributaries along the length of the river. 

These data suggest that transport mechanisms rather than source factors play a major role in the

distribution of di-n-butyl phthalate. This observation is consistent with the continuous extensive wet and

dry deposition from air (see Section 6.3.1). At one site, Delaware River water contained 0.6 μg/L of

di-n-butyl phthalate that could be traced to industrial sources (Sheldon and Hites 1979); lower average

concentrations were noted downstream (range, 0.1–10.4 μg/L). The difference between upstream and

downstream average concentrations was not large and may reflect analytical variability. Concentrations

of di-n-butyl phthalate in water from the Inner Harbor Navigation Canal (which connects Lake

Ponchartrain to the Mississippi River near New Orleans) were 0.5–0.7 μg/L (McFall et al. 1985b).

The results of a 10-city drinking water survey reported the presence of di-n-butyl phthalate in 6 of 10 city

water supplies. Levels ranged from 0.1 to 0.2 μg/L for five cities; the level was 5.0 μg/L for one city

(Keith et al. 1976).

Bauer and Herrmann (1997) reported that di-n-butyl phthalate was present in the leachate from various

fractions of household wastes from the regions of Bayreuth and Straubling in Germany. The wastes

included food waste, paper for recycling, unusable paper, cardboard, plastic films, other plastics, textiles,

8–40 mm screened fraction, <8 mm screened fraction, compound packing waste, compound materials,

and disposable diapers. Leachate from a mixture of all waste categories except food waste contained a

maximum of 34 μg/L of di-n-butyl phthalate, while leachate from a mixture of waste categories limited to

plastic films, other plastics, textiles, 8–40 mm screened fraction, <8 mm screened fraction, and compound

materials contained a maximum of 63 μg/kg di-n-butyl phthalate. The authors were careful to exclude

inadvertent sources of phthalate esters. This report indicates that di-n-butyl phthalate is present in

European household waste and that it leaches from that waste to percolating water. The extent to which
DI-n-BUTYL PHTHALATE 107

6. POTENTIAL FOR HUMAN EXPOSURE

this occurs in a landfill is unclear as is whether or not the dissolved di-n-butyl phthalate leaches to

groundwater after leaving landfills.

6.4.3 Sediment and Soil

Considerable variability is encountered in the available data on sediments and soils. In a study of

sediments from Los Angeles Sanitation District's sewage outfalls, di-n-butyl phthalate was reported at

5 sites with concentrations ranging from 118 to 355 μg/kg dry weight (Swartz et al. 1983). Similar values

were obtained along the Detroit River. Detectable di-n-butyl phthalate concentrations were reported in

4 of 13 samples, with values ranging from 190 to 650 μg/kg dry weight. Marine sediment from San Luis

Pass, Texas had approximately 15–93 μg/kg dry weight of di-n-butyl phthalate (Murray et al. 1981). 

Bauer and Herrmann (1997) reported that di-n-butyl phthalate was present in household waste in Europe

(see Sections 6.4.2 and 6.4.4) and leached from waste. It is anticipated that this leaching will occur in a

municipal waste landfill and that di-n-butyl phthalate will enter the soil surrounding these landfills. It is

further anticipated that this European waste is not considerably different from waste generated in the

United States.

6.4.4 Other Environmental Media

Very little recent information on di-n-butyl phthalate concentrations in other environmental media in the

United States is available. Recent information, however, is available for some European countries and for

Canada, and these studies show the presence of di-n-butyl phthalate in a range of foods and textiles. It

should be noted that di-n-butyl phthalate is approved by the U.S. Food and Drug Administration (FDA)

for use as an indirect food additive in adhesives (21 CFR 175.105), in paper and paperboard in contact

with aqueous and fatty foods (21 CFR 176.170), in cellophane (not to exceed 5%) (21 CFR 177.1200),

and in rubber articles intended for multiple use (21 CFR 177.2600), and thus, di-n-butyl phthalate may

enter food products indirectly in the United States. Some of the European studies show migration from

adhesives into foodstuffs. In addition, di-n-butyl phthalate is used as a lubricant in the manufacture of

textiles and has been found in clothing in Europe. Mean concentrations of di-n-butyl phthalate in food

group samples, from 1993 Total Diet Study conducted by the Ministry of Agriculture, Fisheries & Food

(MAFF) in Great Britain, were 0.003, 0.09, 0.1, and 0.2 μg/g (wet weight) for milk, carcass meat, eggs,

and poultry, respectively (MAFF 1996a). In a market basket survey of 98 different food types obtained

from Halifax, Canada in 1986, di-n-butyl phthalate was detected in butter (1.5 μg/g), freshwater fish
DI-n-BUTYL PHTHALATE 108

6. POTENTIAL FOR HUMAN EXPOSURE

(0.5 μg/g), cereal products (ranged from not detected up to 0.62 μg/g), baked potatoes (0.63 μg/g),

coleslaw (0.11 μg/g), bananas (0.12 μg/g), blueberries (0.09 μg/g), pineapples (0.05 μg/g), margarine

(0.64 μg/g), white sugar (0.2 μg/g), and gelatin dessert (0.09 μg/g) (Health Canada 1994). In Germany,

the concentration of di-n-butyl phthalate in milk and milk products ranged from not detected (i.e.,

<0.01 mg/kg) to 0.07 mg/kg (Bruns-Weller and Pfordt 2000a, 2000b). The authors noted that di-n-butyl

phthalate concentrations in milk purchased at the retail level were no higher than raw milk. The

concentration of di-n-butyl phthalate in retail infant formula from Great Britain ranged from <0.05 to

0.09 μg/g (dry weight basis) (MAFF 1998). In Germany, levels of di-n-butyl phthalate in baby food

ranged from not detected (i.e., <0.01 mg/kg) to 0.03 mg/kg (Bruns-Weller and Pfordt 2000a, 2000b).

Di-n-butyl phthalate may enter food materials by uptake from the environment. For example, reported

concentrations of di-n-butyl phthalate in fish ranged from 78 to 200 μg/kg (Giam and Wong 1987;

Stalling et al. 1973; Williams 1973). Concentrations of di-n-butyl phthalate in fish from various Great

Lakes (United States) harbors and tributary mouths ranged from <2x10-5 to 3.5x10-2 μg/kg wet weight

(de Vault 1985). Oyster and clam concentrations of di-n-butyl phthalate ranged from 40 to 570 μg/kg

(McFall et al. 1985a; Ray et al. 1983). Ishida et al. (1981) reported the presence of di-n-butyl phthalate in

egg white (but not in yolk) collected from six regions of Japan. Concentrations of di-n-butyl phthalate

ranged from 50 to 150 μg/kg. 

Table 6-2 summarizes the concentration of di-n-butyl phthalate found in food packaged in paper and

board packing materials (range, <0.02–62 μg/g food), and the concentration of di-n-butyl phthalate in the

packaging materials used to contain the foods (range, <5–5,860 μg/g packaging material) (MAFF 1995). 

In another study, Aurela et al. (1999) found that di-n-butyl phthalate could migrate into sugar from

adhesives used in the joints of paper packaging materials. After storage in a package for 4 months, the

sugar contained 0.5–1.0 mg/kg of di-n-butyl phthalate; unpackaged sugar did not contain any phthalates. 

Higher concentrations were reported for that portion of the sugar that touched the seams of the packaging

material. Di-n-butyl phthalate found in coffee filter paper may contaminate coffee beverages during the

brewing process. For example, two of nine samples of coffee filters contained 8,200 and 15,000 μg/kg

di-n-butyl phthalate (Fricker and Hardy 1990). 

Table 6-3 summarizes the concentration of di-n-butyl phthalate detected in various categories of waste

from European sources (Bauer and Hermann 1997). The authors also calculated that 11.4–106.7 mg/kg

di-n-butyl phthalate was present in the waste on a dry-weight basis and constituted the second most 
DI-n-BUTYL PHTHALATE 109

6. POTENTIAL FOR HUMAN EXPOSURE

Table 6-2. Concentration of Di-n-butyl Phthalate in Paper and Board Packaging and

Food Packaged in Paper and Board

Food types

Number of

samples

Concentration in

packaging (mg/kg)a

Number of

samples

Concentration in

food (mg/kg)b

Bakery productsc and

snacks

20 <5–2,560 5 <0.02–0.9

Confectionery 17 20–550 7 <0.02–5.8

Meat and fish products 7 40–1,380 2 0.05, 4.4

Fats 21 20–2,500 5 outer, 1.5–8.4

core, 1.4–8.7

Pasta and cereals 11 16–110 2 <0.02, 0.5

Dried fruits 2 10–16 1 <0.02

Flour and sugar 9 <5–450 2 0.2, 1.6

Gravy granules and

parmesan cheesed

7 150–3,160 5 0.8–62

Miscellaneous 6e 29–5,860 2f 0.04, 10

Source: MAFF (1995)

a

Limit of detection was 5 mg/kg packaging.

b

Limit of detection was 0.02 mg/kg food.

c

”Backey products” in original source.

d

These products have been grouped together as they have the same type of packaging. e

This group consists of samples of short crust pastry mix, Yorkshire pudding, an ice lolly, waffles, eggs, and

vegetable burger mix.

f

This group consists of one sample of an ice lolly and vegetable burger mix.
DI-n-BUTYL PHTHALATE 110

6. POTENTIAL FOR HUMAN EXPOSURE

Table 6-3. Concentration of Di-n-butyl Phthalate in Categories of 

Household Waste

Waste fraction

Concentration of di-n-butyl phthalate (mg/kg)a,b

 Minimum Maximum Mean 

Food waste 1.8 10.2 5.6

8–40 mm fraction 5.1 67.1 38.1

<8 mm fraction 10.3 17.6 15.0

Paper for recycling 9.6 22.0 15.2

Unusable paper 6.8 22.3 11.6

Cardboard 14.4 121.7 45.6

Plastic films 13.5 105.0 36.2

Other plastics 36.1 762.6 181.2

Textiles 6.0 18.9 10.9

Compound packing waste 60.1 115.3 82.4

Compound materials 609.7 2,160.0 1,473.0

Disposable diapersc 3.2 43.0 11.0

Source: Bauer and Herrmann (1997)

a

Results are from six extractions except “compound materials”, for which the results are for nine extractions. b

The listing of the precision of the values presented in this table is the same as the original paper. c

Described as “nappies” in the original paper.
DI-n-BUTYL PHTHALATE 111

6. POTENTIAL FOR HUMAN EXPOSURE

commonly found phthalate ester, constituting 6.0–6.7% of the total phthalates found in the waste

(bis-2-ethylhexyl phthalate was the most common phthalate ester, constituting 91.9–93.3% of the total

phthalates found).

Bruns-Weller and Pfordt (2000b) reported that a variety of clothing sampled in Germany contained levels

of di-n-butyl phthalate ranging from 0.66 to 30.43 mg/kg. Di-n-butyl phthalate is used as a lubricant for

textiles (see Section 5.3).

6.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE

Di-n-butyl phthalate is present in both urban and rural air (1–6 ng/m3

), some drinking waters

(0.1–0.5 μg/L; the data are >20 years old), and some foods (3–1,500 μg/kg) (see above). Thus, the

general population is likely to be exposed to di-n-butyl phthalate at levels that are generally in the low

ppb range or below. It should be noted that some of the U.S. data presented above are 10 or more years

old, so current exposure levels might be different. Based on these data, the highest exposure to di-n-butyl

phthalate is most likely to come from some dairy products, fish, and seafood, if these foods comprise a

large part of the diet. Di-n-butyl phthalate is also an indirect food additive that is present in food

containers and may be transferred to foods. There is evidence of this in European and Canadian studies,

but not in U.S. studies. It may be more likely that, for the general population, air is the main source of

di-n-butyl phthalate exposure if dairy products and seafood are not important in the diet. No data were

available that could be used to estimate doses from dermal exposure to di-n-butyl phthalate.

Chan and Meek (1994) estimated the daily intake of di-n-butyl phthalate by the population of Canada (see

Table 6-4). Based on the medium-specific intakes, it is estimated that the average daily intake of

di-n-butyl phthalate for the various age groups in the general population in Canada range from 1.9 to

5.0 μg/kg body weight/day. It should be noted that these estimates do not include intake from consumer

products (e.g., nail polish). Based on the percentage of di-n-butyl phthalate in some cosmetics (from

0.1 to between 10 and 25%), these products could contribute significantly to the exposure of some

members of the general population. 

The National Institute for Occupational Safety and Health (NIOSH) conducted the National Occupational

Exposure Survey (NOES) from 1981 to 1983 (NIOSH 1988a). Data from the survey show that an

estimated 31,502 facilities use di-n-butyl phthalate in 199 industries involving 138 occupations (RTECS 
DI-n-BUTYL PHTHALATE 112

6. POTENTIAL FOR HUMAN EXPOSURE

Table 6-4. Estimated Daily Intake of Di-n-butyl Phthalate by the 

Population of Canada

Substrate/

mediuma

Estimated intake by age groups of di-n-butyl phthalate (μg/kg body weight/day)

0–0.5 yearsb 0.5–4 yearsc 5–11 yearsd 5–19 yearse 20–70 yearsf

Ambient air 0.00021–

0.00030

0.00033–

0.00040

0.00033–

0.00041

0.00028–

0.00038

0.00025–

0.00034

Indoor air 0.68 0.91 1.1 0.87 0.78

Drinking

water

0.11 0.062 0.033 0.022 0.021

Food 1.6 4.1 3.2 1.4 1.1

Soil <0.0005–

0.0070

<0.00038–

0.0054

<0.00013–

0.00049

<0.000035–

0.00049

<0.000028–

0.00040

Total

estimated

intake

2.4 5.0 2.3 2.3 1.9

Source: Chan and Meek 1994

a

Mean concentrations in ambient air based on a small study in a limited region of Ontario were 4.5–6.2 ng/m3; the

maximum concentration in indoor air was 2.85 μg/m3

 based on a small and possibly unrepresentative number

(n=9) of homes in Montreal; mean values were not specified. It is assumed that people generally spend 4 hours

outdoors and 20 hours indoors. Di-n-butyl phthalate was not detected in drinking water in a regional study in

Ontario (limit of detection, 1.0 μg/L); mean values in surface water and groundwater supplies in Alberta were

1.0 μg/L. Di-n-butyl phthalate was detected in butter (1.5 μ/g), fresh water fish (0.5 μg/g), cereal products (ranged

from not detected up to 0.62 μg/g), baked potatoes (0.63 μg/g), coleslaw (0.11 μg/g), bananas (0.12 μg/g),

blueberries (0.09 μg/g), and pineapples (0.05 μg/g), margarine (0.64 μg/g), white sugar (0.2 μg/g), and gelatin

dessert (0.09 μg/g). The detection limits, which were not specified for individual foodstuffs, varied depending on

the reagent blank values, interferences arising from coextracted food components, and the fat content of the food

(range, 0.01–0.5 μg/g); the content in food stuffs in which di-n-butyl phthalate was not detected was considered to

be 0. Calculated intakes are based upon consumptions of individual food composites for each age group in the

population. The di-n-butyl phthalate content in the soil in urban areas of Port Credit, Oakville, and Burlington,

Ontario, ranged from <0.1 to 1.4 μg/g. Available data were insufficient to estimate intake from consumer products,

though cosmetics may contribute significantly to the exposure of some members of the general population in

certain age groups, based on the percentage content of some products (0.1 to between 10 and 25%). b

Assumed to weigh 7 kg, breathe 2 m3 air, drink 0.75 L water, and ingest 35 mg soil. c

Assumed to weigh 13 kg, breathe 5 m3 air, drink 0.8 L water, and ingest 50 mg soil. d

Assumed to weigh 27 kg, breathe 12 m3 air, drink 0.9 L water, and ingest 35 mg soil. e

Assumed to weigh 57 kg, breathe 21 m3 air, drink 1.3 L water, and ingest 20 mg soil. f

Assumed to weigh 70 kg, breathe 23 m3 air, drink 1.5 L water, and ingest 20 mg soil.
DI-n-BUTYL PHTHALATE 113

6. POTENTIAL FOR HUMAN EXPOSURE

1999). Exposed populations are estimated to be 512,631 employees, of whom 198,249 are female. 

Exposures in occupational settings can occur through skin contact and by inhalation of vapors and dust. 

Phthalates are manufactured within closed systems, but workers can be exposed during filtering or

loading/unloading of tank cars (NTP 2000). Higher exposures to phthalates can occur during

incorporation of the phthalate in the final product (e.g., plastics) if the process runs at a high temperature. 

In a limited number of surveys, di-n-butyl phthalate levels in production facilities in the United States

have ranged from concentrations below the detection limit (0.01–0.02 mg/m3

) to 0.08 mg/m3 (NTP 2000). 

Following a review of six studies, the American Chemistry Council has estimated exposure to di-n-butyl

phthalate in the workplace based upon an assumed level of 1 mg/m3

 in the air during the production of

phthalates (NTP 2000). Exposure levels during incorporation of di-n-butyl phthalate into plastic are not

known. An exposure level was estimated by using assumptions of a 10 m3/day inhalation and a 70 kg

body weight. The resulting exposure estimate was 143 μg/kg body weight/workday for workers

employed in phthalate manufacturing (NTP 2000).

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).

Studies from Europe and Canada suggest that children may be exposed to di-n-butyl phthalate from food.

However, little information is available that would allow an estimation of exposures from food and the

differences between adult and child diets from U.S. studies. Infant food from Germany had only traces of

di-n-butyl phthalate at levels ranging from not detected (i.e., <0.01 mg/kg) to 0.03 mg/kg (Bruns-Weller

and Pfordt 2000a, 2000b). Mother’s milk samples from German women also contained low amounts of
DI-n-BUTYL PHTHALATE 114

6. POTENTIAL FOR HUMAN EXPOSURE

di-n-butyl phthalate at concentrations in the range of 0.01–0.05 mg/kg. Di-n-butyl phthalate was detected

in infant formula from Great Britain at concentrations ranging from 0.08 to 0.40 mg/kg (dry weight basis)

in 1996 and <0.05–0.09 mg/kg (dry weight basis) in 1998 (MAFF 1996b, 1998). While di-n-butyl

phthalate has been found in food in the United States, mainly fish, it is difficult to determine how

widespread contamination of food is, based on the available information, some of which is >20 years old.

Chan and Meek (1994) estimated the daily intake of di-n-butyl phthalate by children in Canada (see

Table 6-4). Based on the medium-specific intakes, it is estimated that the average daily intake of

di-n-butyl phthalate for age groups from 0–11 years in the general population in Canada range from 2.4 to

5.0 μg/kg body weight/day. In Great Britain, the range of average exposure from infant formula was 2.4

and 1.4 μg/kg body weight/day at birth and 6 months, respectively, in 1998 (MAFF 1998). In 1996, the

average exposures from infant formula were 14 and 9.3 μg/kg body weight/day at birth and 6 months,

respectively. 

Children, and especially small children, may be exposed to elevated levels of di-n-butyl phthalate from

chewing on soft plastic material if it contains this chemical as a plasticizer; however, it is unclear exactly

what products may contain di-n-butyl phthalate. Di-n-butyl phthalate can migrate from plastics into

surrounding media, including saliva and air. For example, Lygre et al. (1993) reported that di-n-butyl

phthalate in denture material (polymethyl methacrylate) leached into saliva in the mouths of adult patients

with new dentures. The concentration range was not detected–7.5 mg/L with a mean concentration of

0.1 mg/L. Out of 11 adult patients, 7 had detectable levels of di-n-butyl phthalate. No di-n-butyl

phthalate was detected in the saliva of adult patients with old dentures or in the controls (the detection

limit was 0.1 mg/L). In addition, 0.04 mg/m3 of di-n-butyl phthalate, which had volatilized from paint,

was detected in indoor air (Crump 1995). Cadogan and Howick (1996) reported that an indoor overall

emission rate of 2.3x10-4 mg/second-m3

 at 25 EC has been calculated for all phthalate plasticizers in

products such as wall coverings, flooring, upholstery, and wire insulation. Since the physical processes

associated with the leaching of plasticizers from plastics should be the same for all plastics, it is

anticipated that di-n-butyl phthalate will also migrate from other plastics to whatever medium is present at

the plastic interface. Di-n-butyl phthalate is used in vinyl flooring and floor wax, and children, especially

young children, often crawl and play on floors. No data are available that allow a quantification of the

number or types of plastic products that contain di-n-butyl phthalate as a plasticizer; however, latest

public production figures show that approximately 6,662 metric tons (1.5x107

 pounds) of di-n-butyl 
DI-n-BUTYL PHTHALATE 115

6. POTENTIAL FOR HUMAN EXPOSURE

phthalate were produced in the United States in 1993 (see Chapter 5). Some plastics can contain >50%

plasticizer (Cadogan and Howick 1996) and, based on the presence of di-n-butyl phthalate in the air and

water, at least some of this is likely to escape either by volatilization or other transfer process to the

surrounding material (e.g., saliva, skin, water). Thus, it appears that children may be more highly

exposed to di-n-butyl phthalate than adults because they are potentially exposed dermally while lying on

floors and carpets, and by inhalation by playing near potential sources such as flooring and carpeting. 

Mouthing of toys is another potential source of oral phthalate exposure in children. However, use of

di-n-butyl phthalate in toys appears to be rare. In an analysis of 17 plastic toys, di-n-butyl phthalate was

detected in one polyvinyl chloride doll’s head at 0.01% by weight (Rastogi 1998). No information,

however, is available that would allow the confirmation of this possibility or the quantification of the

potential exposures.

There are no specific examples of di-n-butyl phthalate contamination in homes resulting from inadvertent

transport to the home from workplace exposures.

Young children sometimes ingest soil either intentionally through pica (the desire to eat substances, such

as soil or chalk, not normally eaten) or unintentionally through hand-to-mouth activity. While no

childhood exposures to di-n-butyl phthalate from soil ingestion or dermal soil exposure have been

documented, this phthalate has been detected in soil. In addition, di-n-butyl phthalate has also been

detected in atmospheric fallout in both urban and rural areas, and is not expected to migrate rapidly to

groundwater or to volatilize rapidly from soil surfaces. Nonetheless, di-n-butyl phthalate is anticipated to

degrade rapidly, and exposures to this chemical from other sources are anticipated to be much greater. 

Therefore, exposures of children to di-n-butyl phthalate from soil would likely be slight. No information

is available on the absorption in the stomach (bioavailability) of di-n-butyl phthalate in soil to children.

6.7 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES

Individuals who manufacture or use plasticizers probably would have the highest potential for exposure to

di-n-butyl phthalate. People living near chemical factories or hazardous waste sites where di-n-butyl

phthalate is present could also have higher than average exposure. Certain cosmetics, such as nail polish,

contain di-n-butyl phthalate, and higher exposures may result to consumers of these products. In addition,

since many plastic articles contain di-n-butyl phthalate and many of these are used in homes and

businesses, indoor concentrations may be higher than outdoor concentrations, as has been reported (see 
DI-n-BUTYL PHTHALATE 116

6. POTENTIAL FOR HUMAN EXPOSURE

Section 6.4.1 above). Therefore, populations that work indoors may be exposed to higher concentrations

than those who work outdoors. Insufficient information is available to quantify any differences.

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 di-n-butyl phthalate 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 di-n-butyl phthalate. 

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. Data are available on the physical and chemical properties of

di-n-butyl phthalate (see Chapter 4), and further research in this area does not appear to be required. 

Nonetheless, measurements of properties such as water solubility, vapor pressure, and octanol/water

partition coefficient are technically difficult because di-n-butyl phthalate and other phthalates are

ubiquitous contaminants in the environment and are contaminates of laboratory air and surfaces, making

accurate measurements difficult. Hence, a set of data that are very carefully determined are needed.

Production, Import/Export, Use, Release, and Disposal. Available data indicate that di-n-butyl

phthalate is produced in substantial amounts at several locations in the United States, is widely used in a

variety of consumer products, and is subject to regulations concerning disposal; however, no publicly

available current production data are available. In addition, in the specialty plasticizer market, the amount

of specific plasticizers used in various applications are not available and data may change over time. 

Authoritative sources of current data on production, imports, exports, specific uses, releases 
DI-n-BUTYL PHTHALATE 117

6. POTENTIAL FOR HUMAN EXPOSURE

to environmental media, and disposal methods were not located. Collecting such data would be valuable

in estimating human exposure to di-n-butyl phthalate. 

Environmental Fate. Biodegradation is well described in the literature, and the importance of

hydrolysis reactions can be inferred from sterile controls reported with biodegradation studies. Major

gaps are present in the understanding of partitioning and transport of di-n-butyl phthalate in water. For

example, the log Koc of di-n-butyl phthalate is reported to be 3.14 (see Chapter 4), which indicates that the

majority of di-n-butyl phthalate in water will be sorbed to sediments or suspended particles. Many

reports, however, have measured the dissolved/sorbed concentration of di-n-butyl phthalate in

environmental samples and have found that, in some cases, in excess of 70% of the di-n-butyl phthalate is

in the dissolved state. A greater knowledge of this process would allow a more comprehensive

understanding of the exposure potential for aquatic organisms to di-n-butyl phthalate. Similarly, a better

understanding of the partitioning of di-n-butyl phthalate on atmospheric particles and their washout/

fallout characteristics would also allow better exposure assessments.

Bioavailability from Environmental Media. Exposure of the general public occurs via air, water,

food supply, cosmetics, and soils. However, the bioavailability of di-n-butyl phthalate in each of these

media has not been investigated. Data of this type, especially on the availability of di-n-butyl phthalate

that is bound to soils, sediments, and air particulates by the inhalation, oral, and dermal routes, are needed

to assess the relative importance of these media to human exposure. 

Food Chain Bioaccumulation. Available data indicate that di-n-butyl phthalate tends to be taken

up and metabolized by invertebrates and fish. Numerous studies have shown that the accumulation of

di-n-butyl phthalate in the aquatic and terrestrial food chain is limited by biotransformation, which

progressively increases with trophic level (Staples et al. 1997). Therefore, di-n-butyl phthalate will not

biomagnify through the food chain. 

Exposure Levels in Environmental Media. Information on exposure levels in the environment is

relatively sparse. Although a number of atmospheric air levels have been reported, it would be useful to

know more specifics about urban air levels. More extensive data on food and drinking water levels of

di-n-butyl phthalate would also be useful in assessing total human exposure.
DI-n-BUTYL PHTHALATE 118

6. POTENTIAL FOR HUMAN EXPOSURE

Exposure Levels in Humans. No data are available showing the concentration of di-n-butyl

phthalate in common plastic consumer products. A list of the composition of common plastic consumer

products and the amount of di-n-butyl phthalate that they contain would allow a much better estimation of

exposures from these products. Di-n-butyl phthalate has been extensively monitored in food in Europe

and Canada, but very little information is available about the U.S. food supply. This type of information,

especially information about infant foods and mother’s milk, would permit an estimation of the

importance of food in di-n-butyl phthalate exposures. In addition, di-n-butyl phthalate is an indirect food

additive present in food containers, and the extent to which it migrates into food would allow a better

estimation of exposures from food. While some information about migration is available from European

studies, information on migration from packaging meeting U.S. standards would allow better assessments

of exposures from food. In addition, few data are available on human tissue levels of di-n-butyl

phthalate, so it is not possible at this time to assess the total impact of di-n-butyl phthalate on the human

population. Moreover, information relating exposure levels to levels in humans are needed to assess risks

to populations surrounding hazardous waste sites.

Exposures of Children. A number of studies are available that report di-n-butyl phthalate

concentrations in infant foods and mother’s milk in Europe. Similar studies are not available for U.S.

sources, and this information could be used to better estimate the importance of food as a source of

di-n-butyl phthalate exposures to children. No data are available that allow the estimation of exposures

resulting from mouthing and/or chewing on plastics or other compounds containing di-n-butyl phthalate. It

is possible that the majority of plastic toys used by children contain plasticizers, and the extent to which

these contain di-n-butyl phthalate is not known. A complete study of the migration of di-n-butyl phthalate

from plastics and other compounds into saliva, including the effects of chewing, also has not been

performed. This information would allow a much better estimation of children’s exposure to di-n-butyl

phthalate. It is known that di-n-butyl phthalate migrates from polymethyl methacrylate denture material

into saliva (see Lygre et al. 1993); however, dentures are present in the mouth for long periods, and the

applicability of this study to di-n-butyl phthalate migration from plastic and other materials to saliva in

children’s mouths is unclear. In addition to the potential migration of di-n-butyl phthalate from plastic and

other materials to saliva, the potential also exists for dermal and inhalation exposures. Di-n-butyl phthalate

is also used in cosmetics, such as nail polish, and children may play with some of these products. The

extent to which these products contain di-n-butyl phthalate is not known. While it is much more likely that

exposures will occur from plastics and other materials, no data are available on childhood exposures to

di-n-butyl phthalate from soil either from ingestion or from dermal exposure. 
DI-n-BUTYL PHTHALATE 119

6. POTENTIAL FOR HUMAN EXPOSURE

Child health data needs relating to susceptibility are discussed in Section 3.12.2 Identification of Data

Needs: Children’s Susceptibility.

Exposure Registries. No exposure registries for di-n-butyl phthalate were located. This compound

is not currently one of the compounds for which a subregistry has been established in the National

Exposure Registry. The compound 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

the exposure to this compound.

6.8.2 Ongoing Studies

The Federal Research in Progress (FEDRIP 2000) database provides information on ongoing studies;

however, none were found that fill any of the data needs identified in Section 6.8.1.

No information was located regarding ongoing studies on the environmental fate and transport of

di-n-butyl phthalate or on levels of human exposure to di-n-butyl phthalate.

DI-n-BUTYL PHTHALATE 121

7. ANALYTICAL METHODS

The purpose of this chapter is to describe the analytical methods that are available for detecting, 

measuring, and/or monitoring di-n-butyl phthalate, its metabolites, and other biomarkers of exposure and

effect to di-n-butyl phthalate. 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.

Di-n-butyl phthalate may be determined by high resolution gas chromatography with an electron capture

detector (HRGC/ECD) (EPA 1984b), gas chromatography/mass spectrometry (GC/MS) (EPA 1994a), gas

chromatography with a flame ionization detector (GC/FID) (NIOSH 1994), gas chromatography/Fourier

transform infrared spectrometry (GC/FTIR) (EPA 1994b), high performance liquid chromatography/mass

spectrometry (HPLC/MS) (Coldham et al. 1998), or high performance liquid chromatography/ion-trap

mass spectrometry (HPLC/Ion Trap-MS) (Coldham et al. 1998). Prior to analysis, di-n-butyl phthalate

must be separated from the biological or environmental sample matrix and prepared in a form suitable for

introduction into the analytical instrument. Methods for extracting di-n-butyl phthalate from biological

materials and environmental samples are discussed in Sections 7.1 and 7.2. 

Phthalates are common environmental contaminants that frequently contaminate laboratory glassware, 

sampling equipment, and solvents used to extract di-n-butyl phthalate from various media for analysis

(Staples et al. 1997). As a result, it is difficult to make accurate measurements at low levels (<10 ppb). 

Care must be taken to preclude environmental and other samples from contamination with di-n-butyl

phthalate.
DI-n-BUTYL PHTHALATE 122

7. ANALYTICAL METHODS

7.1 BIOLOGICAL SAMPLES

Since di-n-butyl phthalate is relatively nonvolatile and lipophilic, most methods for separating it from

biological materials involve extraction into an organic solvent such as ether, heptane, or acetonitrile. In

most cases, the material is homogenized in the solvent to improve extraction efficiency. Additional

sample cleanup steps may be required to separate fats and other endogenous lipophilic materials in the

samples that co-extract from the biological material (Walters 1986). Several analytical methods for the

determination of di-n-butyl phthalate in biological materials are listed in Table 7-1.

Recently, Blount et al. (2000) summarized a methodology to detect di-n-butyl phthalate metabolites in

urine. In humans or animals, di-n-butyl phthalate is metabolized to mono-n-butyl phthalate and oxidative

products, which are excreted through the urine and feces. Human urine samples are processed by

β-glucuronidase hydrolysis (to release the mono phthalate ester) followed by solid-phase extraction. The

eluate is concentrated; mono-n-butyl phthalate is chromatographically resolved by reverse-phase HPLC,

detected by negative ion atmospheric pressure chemical ionization (APCI) tandem mass spectrometry,

and quantified by isotope dilution.

7.2 ENVIRONMENTAL SAMPLES

Separation of di-n-butyl phthalate from environmental samples such as water, soil, sediment, or wastes is

also usually accomplished through extraction with an organic solvent. In some cases, di-n-butyl phthalate

in water may be separated without solvents by adsorption onto a suitable polymer such as Tenax (Pankow

et al. 1988). Analytical methods for the determination of di-n-butyl phthalate in environmental samples

are given 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 di-n-butyl phthalate 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 di-n-butyl phthalate. 
Table 7-1. Analytical Methods for Determining Din-butyl Phthalate in Biological Sa

Sample matrix Preparation method

Analyticalmethod

Sample detectionlimit Recovery 

Aquatic organisms Extract with acetonitrile and

petroleum ether

HRGC/ECD 0.1 ng/g 68% 

Adipose tissue Extraction, bulk lipid removal, Florisil

fractionation

HRGC/MS 10 ng/g No data 

Bile (cattle) Extraction, fractionation by cation and

anion exchange chromatography,β-glucuronidase/sulphatasehydrolysis

HPLC/IonTrap-MS;HPLC/MS

No data 93.5±4.4% 

Blood plasma(cattle)

Extraction, fractionation by cation andanion exchange chromatography,β-glucuronidase/sulphatasehydrolysis

HPLC/IonTrap-MS;HPLC/MS

No data 89.6±1.6% 

Blood serum Extraction, bulk lipid removal, Florisil

fractionation

HRGC/MS 10 ng/g No data 

Blood serum Extraction with organic solvents

(propanol, heptane)

GC/MS No data No data 

Cooked meat Removal with nitrogen gas trap,

extraction with diethyl ether

GC/MS No data No data 

Urine (cattle) Extraction, fractionation by cation and

anion exchange chromatography,β-glucuronidase/sulphatasehydrolysis

HPLC/IonTrap-MS;HPLC/MS

No data 76.2±2.3% 

Urine

β-glucuronidase hydrolysis, solidphase extraction HPLC/APCI-MS 0.6 ng/mL >90% 

APCI = negative ion atmospheric pressure chemical ionization; ECD = electron capture detector; GC = gas chromatography; HPLC = hchromatography; HRGC = high resolution gas chromatography; MS = mass spectrometry
Table 7-2. Analytical Methods for Determining Din-butyl Phthalate in Environmental 

Sample matrix Preparation method

Analyticalmethod

Sample detection limit Recovery 

Air Adsorption/solvent extraction with

cellulose ester membrane

NIOSH 5020GC/FID

1–20 mg/m3

20 L air sample

No data 

Water Extract with dichloromethane,

exchange to hexane, concentrate

EPA 625HRGC/ECD

2.5 μg/L 80±6%a 

Water Extract with dichloromethane,

exchange to hexane, concentrate

EPA 606HRGC/ECD

0.36 μg/L 80±6%a 

Liquid EPA Extraction Method 3510 using

dichloromethane followed by cleanup

EPA 8061GC/ECD

0.33 μg/L 76.5–108% 

Groundwater EPA Extraction Methods 3510 or

3520 using dichloromethane followedby cleanup

EPA 8250AGC/MS

2.5 μg/La 76% 

Wastes, non-watermiscible

Extract with dichloromethane followedby cleanup

EPA 8410GC/FT-IR

10 μg/L No data 

Wastes, non-watermiscible

Extract with dichloromethane,cleanup, exchange to hexane

EPA 8060GC/ECD or FID

36 mg/kg 96% 

Wastes, non-watermiscible

EPA Extraction Methods 3510 or3520 using dichloromethane followedby cleanup

EPA 8270GC/FT-IR

50 mg/kg 76% 

Soil Extraction using 

dichloromethane/acetone(1:1),followed by cleanup

EPA 8061GC/ECD

0.33 μg/L 90–95% 

Soil Extract with dichloromethane,

cleanup, exchange to hexanefollowed by cleanup

EPA 8060GC/ECD or FID

2.4x10-4 mg/kg 96% 
Table 7-2. Analytical Methods for Determining Din-butyl Phthalate in Environmental Samp

Sample matrix Preparation method

Analyticalmethod

Sample detection limit Recovery 

Soil EPA Extraction Methods 3510 or

3520 using dichloromethane followedby cleanup

EPA 8250AGC/MS

1.7 mg/kg 96% 

Soil/sediment Extract with dichloromethane followed

by cleanup

EPA 8410GC/FT-IR

10 μg/Lb No data 

Soil/sediment EPA Extraction Methods 3510 or

3520 using dichloromethane followedby cleanup

EPA 8270GC/FT-IR

0.66 mg/kg 76% 

aRelative recovery, percent, ±standard deviationbDetection limits for some samples may be several orders of magnitude higher depending upon the sample characteristics and extractio

ECD = electron capture detector; FID = flame ionization detector; FT-IR = Fourier transform-infrared spectrometer; GC = gas chromatogspectrometry
DI-n-BUTYL PHTHALATE 126

7. ANALYTICAL METHODS

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. Sensitive and selective

methods using high resolution GC or HPLC are available for the qualitative and quantitative measurement

of di-n-butyl phthalate after it is separated from the biological matrix of tissue or fluid. However,

methods for recovery of di-n-butyl phthalate from such samples have not been extensively developed, and

additional work to improve and standardize sample extraction and preparation methods for biological

fluids and tissues would be valuable in providing quantitative information concerning human exposure. 

The sensitivity of existing methods may not be high enough to measure background levels in the

population, since an existing study failed to detect di-n-butyl phthalate in several samples (EPA 1986g). 

Because of the widespread use of di-n-butyl phthalate in laboratory equipment, cosmetics, and other

consumer products, studies to determine background levels in the population must be done with care to

avoid false positives from inadvertent contamination (see Staples et al. 1997). Since health effects appear

to occur only after high levels of exposure, existing methods are probably capable of measuring body

levels at which effects would be expected to occur in humans. HPLC/MS has been adapted to measure

body levels of metabolites of di-n-butyl phthalate, primarily mono-n-butyl phthalate, which have the

potential to be biomarkers of exposure (Blount et al. 2000).

No information was located concerning biomarkers of effect of di-n-butyl phthalate. Precise, accurate,

reliable, and specific methods for measuring background levels of biomarkers of effect in the population,

as well as the levels at which health effects may occur, are needed.

Methods for Determining Parent Compounds and Degradation Products in Environmental

Media. Good methods with adequate sensitivity and selectivity are available for detecting and

quantifying di-n-butyl phthalate contamination in water, air, soil, and waste samples. Soil, water, and

food are the media of most concern for human exposure to di-n-butyl phthalate. The basic methods of

extraction followed by high resolution GC (with derivatization of sample) or HPLC-MS have 
DI-n-BUTYL PHTHALATE 127

7. ANALYTICAL METHODS

the potential to be sensitive enough to measure background levels of di-n-butyl phthalate and its

degradation products in the environment, but care must taken to ensure that samples are representative,

volumes are sufficient, contamination is avoided, preservation is adequate, and extraction and purification

are complete. In measuring background levels in environmental media, contamination can pose a

particular problem because of the extensive use of di-n-butyl phthalate in products found in laboratories. 

Existing methods should be sufficiently sensitive to measure levels of di-n-butyl phthalate at which health

effects might occur. 

7.3.2 Ongoing Studies

Examination of the literature suggests that studies are underway to improve means for determining

di-n-butyl phthalate in biological samples and environmental media. Improvements continue to be made

in chromatographic separation and detection. Current high level activity in the areas of supercritical fluid

extraction and supercritical fluid chromatography (Smith 1988) includes di-n-butyl phthalate in biological

samples and environmental media as an analyte. Fourier transform infrared flow cell detectors are

promising for this application (Wieboldt et al. 1988). 

A search of Federal Research in Progress reported no ongoing studies relating to analytical methods

development (FEDRIP 2000).

DI-n-BUTYL PHTHALATE 129

8. REGULATIONS AND ADVISORIES

The international, national, and state regulations and guidelines regarding di-n-butyl phthalate in air,

water, and other media are summarized in Table 8-1.

An MRL of 0.5 mg/kg/day has been derived for acute-duration oral exposure to di-n-butyl phthalate

based on a NOAEL of 50 mg/kg/day for developmental effects in the offspring of rats orally exposed by

gavage to di-n-butyl phthalate on gestational days 12–21 (Mylchreest et al. 2000). 

A chronic MRL for DNB was not derived. There were no adequate chronic-duration oral studies

identified for humans or animals. EPA verified an RfD of 0.1 mg/kg/day based on a study by Smith

(1953)(IRIS 1999). In this study, 10 rats were fed diets containing 0.01-1.25 % dibutyl phthalate. Half of

the high dose group died within the first week of exposure. ATSDR did not have confidence in this study

to derive an MRL due to the lack of detail and apparent conflict in the reported results. EPA also had low

confidence in the study; the RfD received a low rating.

The health effects data for di-n-butyl phthalate were evaluated by EPA and determined to be inadequate

for derivation of an inhalation RfC; the RfC is considered not verifiable (IRIS 1999).
DI-n-BUTYL PHTHALATE 130

8. REGULATIONS AND ADVISORIES

Table 8-1. Regulations and Guidelines Applicable to Di-n-butyl Phthalate

Agency Description Information References

INTERNATIONAL

Guidelines:

IARC Carcinogenic classification No data

NATIONAL

Regulations and

Guidelines:

a. Air

ACGIH TLV-TWA 5 mg/m3 ACGIH 2000

EPA RAC 100 μg/m3 EPA 2001p

40CFR266

Appendix IV

NIOSH REL (TWA)

IDLH

5 mg/m3

4,000 mg/m3

NIOSH 2001

OSHA PEL (8-hour TWA)

General industry 5 mg/m3

OSHA 2001c

29CFR1910.1000

Table Z-1

PEL (8-hour TWA)

Construction industry 5 mg/m3

OSHA 2001b

29CFR1926.55

Appendix A

PEL (8-hour TWA)

Shipyard industry 5 mg/m3

OSHA 2001a

29CFR1915.1000

USC HAP USC 2001

42USC7412

b. Water

DOT Marine pollutant DOT 2001b

49CFR172.101

Appendix B

EPA Effluent guidelines—aluminum

forming point source category

TTO >0.01 mg/L

EPA 2001h

40CFR467.02

Effluent guidelines—coil coating

point source category

TTO >0.01 mg/L

EPA 2001g

40CFR465.02

Effluent guidelines—metal

finishing point source category

TTO >0.01 mg/L

EPA 2001q

40CFR433.11
DI-n-BUTYL PHTHALATE 131

8. REGULATIONS AND ADVISORIES

Table 8-1. Regulations and Guidelines Applicable to Di-n-butyl Phthalate

(continued)

Agency Description Information References

NATIONAL (cont.)

EPA Effluent guidelines; steam

electric power generating point

source category—priority

pollutants

EPA 2001o

40CFR423

Appendix A

Human health consumption

Water and organism

Organism only

2.7 mg/L

12 mg/L

EPA 1999c

NPDES—permit application

testing requirements

Organic toxic

pollutants in each of

four fractions in

analysis by GC/MS

volatiles

EPA 2001l

40CFR122

Appendix D

Table II

NPDES—permit testing

requirements for publicly owned

treatment works

EPA 2001m

40CFR122

Appendix J

Table 2

Process waste water discharges

resulting from the manufacture

of bulk organic chemicals

EPA 2001a

40CFR414.70

Standards for owners/operators

of hazardous waste TSD

facilities— groundwater

monitoring (PQL)

5 μg/L EPA 2001i

40CFR264

Appendix IX

Toxic pollutant effluent

limitations and standards for

direct discharge point sources

that use end-of-pipe biological

treatments—effluent limitations

Maximum for any 1-day

Maximum for any monthly 

average

57 μg/L

27 μg/L

EPA 2001u

40CFR414.91(b)

Toxic pollutant effluent

limitations and standards for

direct discharge point sources

that do not use end-of-pipe

biological treatments—effluent

limitations

Maximum for any 1-day

Maximum for any monthly 

average

43 μg/L

20 μg/L

EPA 2001v

40CFR414.101(b)
DI-n-BUTYL PHTHALATE 132

8. REGULATIONS AND ADVISORIES

Table 8-1. Regulations and Guidelines Applicable to Di-n-butyl Phthalate

(continued)

Agency Description Information References

NATIONAL (cont.)

EPA Toxic pollutant standards for

indirect discharge point

sources—effluent limitations

Maximum for any 1-day

Maximum for any monthly 

average

43 μg/L

20 μg/L

EPA 2001w

40CFR414.111(b)

Water quality standards—toxics

criteria for those states not

complying with Clean Water Act

Section 303(c)(2)(B)

No data EPA 2001t

40CFR131.36

c. Food

FDA Indirect food additive—

adhesives and components of

coating

FDA 2000a

21CFR175.105

Indirect food additive—

adhesives and components of

coatings; catalysts and crosslinking agents for epoxy resins

For use only in

coatings for

containers having a

capacity of 

1,000 gallons or

more when intended

for repeated use in

contact with alcoholic

beverages containing

up to 8% of alcohol

by volume

FDA 2000f

21CFR175.300(b)

Indirect food additive—

limitations on cellophane for

food packaging

Alone or in

combination with

other phthalates—

total phthalates do

not exceed 5%

FDA 2000b

21 CFR 177.1200

Indirect food additive—paper

and paperboard components

FDA 2000d

21CFR176.170

Indirect food additive—paper

and paperboard components

Adjuvant substances

permitted to be used

in the preparation of

slimicides

FDA 2000g

21CFR176.300(d)
DI-n-BUTYL PHTHALATE 133

8. REGULATIONS AND ADVISORIES

Table 8-1. Regulations and Guidelines Applicable to Di-n-butyl Phthalate

(continued)

Agency Description Information References

NATIONAL (cont.)

FDA Indirect food additive—polyester

resins, cross-linked; solvents for

inhibitors, accelerators, and

catalysts

Quantity used does

not exceed that

reasonably required

to accomplish

intended physical or

technical effect

FDA 2000e

21CFR177.2420(b)

Indirect food additives—rubber

articles intended for repeated

use

Total not to exceed

30% by weight of

rubber product

FDA 2000c

21CFR177.2600

d. Other

ACGIH BEI

Carcinogenic classification

No data ACGIH 2000

CPSC Consumer product limits No data

DOT Reportable quantity 10 pounds DOT 2001a

49CFR172.101

Appendix A

Table 1

EPA Carcinogenic classification

RfD

Group Da

0.1 mg/kg/day

IRIS 2001

Designated hazardous

substance

EPA 2001c

40CFR116.4

Health and environmental

protection standards for uranium

and thorium mill tailings—listed

constituent

EPA 2001k

40CFR192

Appendix I

Identification and listing of

hazardous waste

U069 EPA 2001f

40CFR261.33

Land disposal restrictions—

universal treatment standards

Wastewater standard

Nonwastewater standard

0.057 mg/L2

28 mg/kg3

EPA 2001x

40CFR268.48(a)

Municipal solid waste landfills—

hazardous inorganic and

organic constituents

Suggested method

PQL

8060 8270

5 μg/L 10 μg/L

EPA 2001j

40CFR258

Appendix II
DI-n-BUTYL PHTHALATE 134

8. REGULATIONS AND ADVISORIES

Table 8-1. Regulations and Guidelines Applicable to Di-n-butyl Phthalate

(continued)

Agency Description Information References

NATIONAL (cont.)

EPA Pollutants eligible for a removal

credit

If requirements for

total hydrocarbons

are met when

sewage sludge is

fired in a sewage

sludge incinerator

EPA 2001n

40CFR403

Appendix G

Reportable quantity 100 pounds EPA 2001d

40CFR302.4

Toxic chemical release

reporting; Community Right-toKnow—effective date

01/01/87 EPA 2001b

40CFR372.65

TSCA—health and safety data

reporting; studies not subject to

the reporting requirements

EPA 2001r

40CFR716.120(c)

TSCA—testing consent order for

environmental effects

01/09/89 EPA 2001s

40CFR799.5000

STATE

Regulations and

Guidelines:

a. Air

Arkansas RAC 100 μg/m3 BNA 2001

California RAC 100 μg/m3 BNA 2001

Delaware RAC 100 μg/m3 BNA 2001

Idaho Toxic air pollutants

OEL

EL

AAC

5.0 mg/m3

0.333 pounds/hour

0.25 mg/m3

BNA 2001

Illinois RAC 100 μg/m3 BNA 2001

Kansas Ambient air quality standards 10 tons/year CDC 1999

Kentucky RAC 100 μg/m3 BNA 2001

Minnesota HAP threshold 10 tons/year BNA 2001

New Hampshire Regulated toxic air pollutant

OEL 5 mg/m3

BNA 2001

Rhode Island HAP BNA 2001

STATE (cont.)
DI-n-BUTYL PHTHALATE 135

8. REGULATIONS AND ADVISORIES

Table 8-1. Regulations and Guidelines Applicable to Di-n-butyl Phthalate

(continued)

Agency Description Information References

South Carolina RAC 100 μg/m3 BNA 2001

Toxic air emissions—maximum

allowable concentration

25 μg/m3 BNA 2001

Tennessee RAC 100 μg/m3 BNA 2001

Vermont Hazardous ambient air standard

Averaging time

Action level (8-hours)

500 μg/m3

8 hours

21 pounds

BNA 2001

Wisconsin <25 ft

$25 ft <75 ft

$75 ft

Ambient air concentrations

0.269 pounds/hour

1.04 pounds/hour

8.11 pounds/hour

120 μg/m3

Wisconsin DNR

2001

Wyoming RAC 100 μg/m3 BNA 2001

b. Water

Alaska Groundwater clean-up level 3.65 mg/L BNA 2001

Arkansas Goundwater monitoring (PQL) 5 μg/L BNA 2001

Delaware Freshwater 

Fish ingestion only

Fish and water ingestion

Marine/Estuarine

Fish and shellfish ingestion

13 mg/L

2.8 mg/L

2.1 mg/L

BNA 2001

Florida Drinking water guideline 0.7 mg/L HSDB 2001

Georgia Instream concentration 12.1 mg/L BNA 2001

Illinois Groundwater monitoring (PQL) 5 μg/L BNA 2001

Kentucky Hazardous constituents for

groundwater monitoring (PQL)

5 μg/L BNA 2001

Maximum allowable instream

concentration

2.7 mg/L BNA 2001

Louisiana Groundwater monitoring (PQL) 5 μg/L BNA 2001

Maine Drinking water guideline 0.22 mg/L HSDB 2001

Massachusetts Groundwater monitoring (PQL) 5 μg/L BNA 2001

Michigan Groundwater quality treatment

technology standard

35 μg/L BNA 2001

Minnesota Drinking water guideline 0.7 mg/L HSDB 2001

STATE (cont.)
DI-n-BUTYL PHTHALATE 136

8. REGULATIONS AND ADVISORIES

Table 8-1. Regulations and Guidelines Applicable to Di-n-butyl Phthalate

(continued)

Agency Description Information References

Nebraska Aquatic life criteria

Acute

Chronic

No data

12 mg/L

BNA 2001

New Hampshire Drinking water guideline 0.8 mg/L HSDB 2001

Water quality criteria

Water and fish ingestion

Fish consumption only

2.7 mg/L

12 mg/L

BNA 2001

Ambient groundwater quality

standard

34 mg/L BNA 2001

New Jersey Groundwater quality criteria

PQL

900 μg/L

20 μg/L

BNA 2001

New Mexico Groundwater parameter (PQL) 0.01 mg/L BNA 2001

New York Groundwater monitoring (PQL) 5 μg/L BNA 2001

Oklahoma Hazardous constituent (PQL) 5 μg/L BNA 2001

South Carolina Water quality criteria

Organism consumption

Groundwater monitoring (PQL)

12 mg/L

5 μg/L

BNA 2001

Vermont Consumption of water and

organism

Consumption of organism only

2.7 mg/L

12 mg/L

BNA 2001

Virginia Hazardous constituent (PQL) 5 μg/L BNA 2001

Public water supply

All other surface waters

2.7 mg/L

12 mg/L

BNA 2001

Wisconsin Drinking water guideline 0.1 mg/L HSDB 2001

Groundwater standard

Enforcement standard

Preventive action limit

100 mg/L

20 mg/L

BNA 2001

c. Food No data

d. Other

Alabama RfD 0.1 mg/kg/day BNA 2001

Delaware Direct exposure criteria for soil

Residential

Industrial/commercial

1,000 ppm

2,500 ppm

BNA 2001

Massachusetts RfD 0.1 mg/kg/day BNA 2001

STATE (cont.)

Minnesota RfD

Health risk limit

0.1 mg/kg/day

700 μg/L

BNA 2001
DI-n-BUTYL PHTHALATE 137

8. REGULATIONS AND ADVISORIES

Table 8-1. Regulations and Guidelines Applicable to Di-n-butyl Phthalate

(continued)

Agency Description Information References

Missouri Hazardous constituents BNA 2001

New York Reportable quantity

Air

Land/water

10 pounds

1 pound

BNA 2001

a

Group D: inadequate or no human and animal evidence of carcinogenicity

AAC = acceptable ambient concentrations; ACGIH = American Conference of Governmental Industrial Hygienists;

BEI = biological exposure index; BNA = Bureau of National Affairs; CDC = Center for Disease Control;

CFR = Code of Federal Regulations; CPSC = Consumer Product Safety Commission; DNR = Department of

Natural Resources; DOT = Department of Transportation; EL = emissions level; EPA = Environmental Protection

Agency; FDA = Food and Drug Administration; GC/MS = gas chromatography/mass spectroscopy;

HAP = hazardous air pollutant; HSDB = Hazardous Substances Data Bank; IARC = International Agency for

Research on Cancer; IDLH = immediately dangerous to life and health; IRIS = Integrated Risk Information System;

NIOSH = National Institute of Occupational Safety and Health; NPDES = National Pollutant Discharge Elimination

System; OEL = occupational exposure level; OSHA = Occupational Safety and Health Administration;

PEL = permissible exposure limit; PQL = practical quantitation limit; RAC = reference air concentration;

REL = recommended exposure limit; RfD = oral reference dose; TLV = threshold limit value; TSCA = Toxic

Substances Control Act; TSD = treatment, storage, and disposal; TTO = total toxic organics; TWA = time-weighted

average; USC = United States Code

DI-n-BUTYL PHTHALATE 139

9. REFERENCES

Acey R, Healy P, Unger TF, et al. 1987. Growth and aggregation behavior of representative

phytoplankton as affected by the environmental contaminant di-n-butyl phthalate. Bull Environ Contam

Toxicol 39:1-6.

ACGIH. 1986. Documentation of the threshold limit values and biological exposure indices. 5th ed. 

American Conference of Governmental Industrial Hygienists. Cincinnati, OH.

ACGIH. 1998. Documentation of the threshold limit values and biological exposure indices. 6th ed. 

American Conference of Governmental Industrial Hygienists. Cincinnati, OH.

*ACGIH. 2000. Documentation of the threshold limit values and biological exposure indices. American

Conference of Governmental Industrial Hygienists. Cincinnati, OH.

*Adinolfi M. 1985. The development of the human blood-CSF-brain barrier. Dev Med Child Neurol 

27:532-537.

*Adlercreutz H. 1995. Phytoestrogens: Epidemiology and a possible role in cancer protection. Environ

Health Perspect Suppl 103(7):103-112.

*Agarwal DK, Lawrence WH, Nunez LJ, et al. 1985. Mutagenicity evaluation of phthalic acid esters and

metabolites in Salmonella typhimurium cultures. J Toxicol Environ Health 16:61-69.

Albaiges J, Casado F, Ventura F. 1986. Organic indicators of groundwater pollution by a sanitary

landfill. Water Res 20:1153-1159.

 *Albro PW, Moore B. 1974. Identification of the metabolites of simple phthalate diesters in rat urine. J

Chromatogr 94:209-218. 

Albro PW, Jordan S, Corbett JT, et al. 1984. Determination of total phthalate in urine by gas

chromatography. Anal Chem 56:247-250.

Albro PW, Thomas R, Fishbein L. 1973. Metabolism of diethylhexyl phthalate by rats isolation and

characterization of the urinary metabolites. J Chromatogr 76:321-330.

*Allsopp M, Vianello G. 1992. Poly(vinyl chloride). In: Elvers B, Hawkins S, Schultz G, eds. 

Ullman's Encyclopedia of Industrial Chemistry vol. A21. Weinheim, Germany: VCH Vergsgesellschaft,

717-742.

*Al-Omran LA, Preston MR. 1987. The interactions of phthalate esters with suspended particulate

material in fresh and marine waters. Environ Pollut 46:177-186.

*Altman PL, Dittmer DS, eds. 1974. Biological handbooks: Biology data book. Vol. III, 2nd ed. 

Bethesda, MD: Federation of American Societies for Experimental Biology, 1987-2008.

*Cited in text
DI-n-BUTYL PHTHALATE 140

9. REFERENCES

Amacher DE, Schomaker SJ, Burkhardt JE. 1998. The relationship among microsomal enzyme

induction, liver weight and histological change in rat toxicology studies. Food Chem Toxicol 36:831-

839.

*Andersen ME, Kirshnan 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 3rd, Gargas ML, et al. 1987. Physiologically based pharmacokinetics and

the risk assessment process for methylene chloride. Toxicol Appl Pharmacol 87:185-205.

*Ashford R. 1994. Dibutyltin dichloride. In: Ashford R, ed. Ashford's Dictionary of Industrial

Chemicals. London, England: Wavelength Publications Ltd., 279.

*Astill BD. 1989. Metabolism of DEHP: Effects of prefeeding and dose variation, and comparative

studies in rodents and the cynomolgus monkey (CMA studies). Drug Metab Rev 21(1):35-53.

*Atlas E, Giam CS. 1981. Global transport of organic pollutants: Ambient concentrations in the remote

marine atmosphere. Science 211:163-165.

Atlas E, Velasco A, Sullivan K, et al. 1983. A radio tracer study of air-water exchange of synthetic

organic compounds. Chemosphere 12:1251-1258.

*ATSDR. 1989. Decision guide for identifying substance-specific data needs related to toxicological

profiles. Atlanta, GA: Agency for Toxic Substances and Disease Registry, Division of Toxicology. 

*Aurela B, Kulmala H, Söderhjelm L. 1999. Phthalates in paper and board packaging and their

migration into Tenax and sugar. Food Addit Contam 16(12):571-577.

Bakale G, McCreary RD. 1987. A physico-chemical screening test for chemical carcinogens: The ke

test. Carcinogenesis 8:253-264.

*Barber ED, Astill BD, Moran EJ, et al. 1987. Peroxisome induction studies on seven phthalate esters. 

Toxicol Ind Health 3(2):7-22.

*Barber ED, Cifone M, Rundell J, et al. 2000. Results of the L5178Y mouse lymphoma assay and the

Balb/3T3 cell in vitro transformation assay for eight phthalate esters. J Anal Toxicol 20:69-80.

*Barber L. 1992. Hierarchical analytical approach to evaluating the transport and biogeochemical fate of

organic compounds in sewage-contaminated groundwater, Cape Cod, MA. In: Lesage S, Jackson R, eds. 

Groundwater contamination and analysis at hazardous waste sites. New York, NY: Marcel Dekker, Inc.,

73-120.

*Barber LB, Thurman EM, Schroeder MP, et al. 1988. Long-term fate of organic micro pollutants in

sewage-contaminated groundwater. Environ Sci Technol 22:205-211.

*Barnes DG, Dourson M. 1988. Reference dose (RfD) Description and use in health risk assessments. 

Regul Toxicol Pharmacol 8:471-486. 
DI-n-BUTYL PHTHALATE 141

9. REFERENCES

*Baue MJ, Herrmann R. 1997. Estimation of the environmental contamination by phthalic acid esters

leaching from household wastes. Sci. Total Environ. 208:49-57.

Bedding ND, McIntyre AE, Perry R, et al. 1982. Organic contaminants in the aquatic environment: 1. 

Sources and occurrence. Sci Total Environ 25:143-167.

*Bell FP. 1982. Effects of phthalate esters on lipid metabolism in various tissues, cells and organelles in

mammals. Environ Health Perspect 45:41-50.

*Berger G. 1994. Epidemiology of endometriosis. In: Nezhat CR, Berger GS, Nezhat CH, et al., eds. 

Modern surgical management of endometriosis. New York, NY: Springer-Verlag. 

Bernstein ME. 1984. Agents affecting the male reproductive system: Effects of structure on activity. 

Drug Metab Rev 15:941-996.

*BIBRA. 1986. A 21 day feeding study of di-n-butyl phthalate to rats: Effects on the liver and liver

lipids. Report to Chemical Manufacturers Association, Washington, DC. Carshalton, Surrey, UK: The

British Industrial Biological Research Association. CMA Reference PE 28.0-BT-BIB.

*Bisesi MS. 1994. Esters. In: Clayton GD, Clayton FE, eds. Patty's industrial hygiene and toxicology. 

New York, NY: John Wiley & Sons, Inc., 2967-3118.

*Blount BC, Milgram KE, Silva MJ, et al. 2000. Quantitative detection of eight phthalate metabolites in

human urine using HPLC-APCI-MS/MS. Anal Chem 72:4127-4134.

*BNA. 2001. Environment and safety: States and territories. Bureau of National Affairs. 

http://www.bna.com/. February 13, 2001.

Bove JL, Dalven P. 1981. A GC/MS method of determining airborne di-n-butyl- and di-(2-ethylhexyl)

phthalates. Int J Environ Anal Chem 10:189-196.

*Bove JL, Dalven P, Kukreja VP. 1978. Airborne di-butyl and di-(2-ethylhexyl)-phthalate at three New

York, NY: City air sampling stations. Int J Environ Anal Chem 5:189-194.

Bower RK, Haberman S, Minton PD. 1970. Teratogenic effects in the chick embryo caused by esters of

phthalic acid. J Pharmacol Exp Ther 171:314-324.

*Bruns-Weller E, Pfordt J. 2000a. [Determination of phthalic acid esters in foodstuffs and mother's

milk]. Z Ernahrungswiss 1(1):25-28. (German)

*Bruns-Weller E, Pfordt J. 2000b. [Determination of phthalic acid esters in foodstuffs, mother's milk,

dust, and textiles]. UmweltwissSchadst-Forsch 12(3):125-130. (German)

*Budavari S. 1996. n-Butyramide. In: Budavari S, O'Neil M, Smith S, et al., eds. The Merck index. 

Whitehouse Station, NJ: Merck & Co., Inc., 1628.

Burmaster DE. 1982. The new pollution: Groundwater contamination. Environment 24:7-13, 33-36.
DI-n-BUTYL PHTHALATE 142

9. REFERENCES

*Cadogan D, Howick C. 1992. Plasticizers. In: Elvers B, Hawkins S, Schultz G, eds. Ullmann's

encyclopedia of industrial chemistry. 5th ed. Vol A20: Photography to plastics, processing. Weinheim,

Germany: VCH Verlagsgesellschaft, 439-457.

*Cadogan D, Howick C. 1996. Plasticizers. In: Kroschwitz J, Howe-Grant, eds. Kirk-Othmer

encyclopedia of chemical technology. Vol 19. New York, NY: John Wiley & Sons Inc., 258-290.

Cagianut B. 1954. Keratitis erosiva and nephritis toxica nach einnahme von dibutylphthalat. Schweiz

Med Wochenschr 35:1243-1244. 

Calnan CD. 1975. Dibutyl phthalate. Contact Dermatitis 1:388.

Cater BR, Cook MW, Gangolli SD. 1976. Zinc metabolism and dibutyl phthalate-induced testicular

atrophy in the rat. Biochem Soc Trans 4:652-653.

*Cater BR, Cook MW, Gangolli SD, et al. 1977. Studies on dibutyl phthalate-induced testicular atrophy

in the rat: Effect on zinc metabolism. Toxicol Appl Pharmacol 41:609-618.

CCTTE. 1988. Computerized Listing of Chemicals Being Tested for Toxic Effects. Geneva,

Switzerland: United Nations Environment Programme, International Programme on Chemical Safety,

International Register of Potentially Toxic Chemicals. .

*CDC. 1999. Kansas. Center for Disease Control & Prevention. http://search.cdc.gov/shd/search2.html. 

May 25, 1999.

*Chan PKL, Meek ME. 1994. Di-n-butyl phthalate: Evaluation of risks to health from environmental

exposure in Canada. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev 12(2):257-268.

Chapin RE, Gulati D, Barnes L. 1997. Di-n-butyl phthalate, rats. Environ Health Perspect Suppl

105:249-250.

Chapin RE, Sloane RA, Haseman JK. 1998. Reproductive endpoints in general toxicity studies: Are

they predictive? Reprod Toxicol 12:489-494.

*Ching NP, Jham GN, Subbarayan C, et al. 1981a. Gas chromatographic-mass spectrometric detection

of circulating plasticizers in surgical patients. J Chromatogr 222:171-177.

Ching NP, Jham GN, Subbarayan C, et al. 1981b. Gas chromatographic quantitation of two plasticizers

contaminating IV fluids stored in plastic containers. J Chromatogr B Biomed Sci Appl 225:196-201.

Chrostek WJ, Moshell AN. 1984. Health hazard evaluation report no. HETA 81-275-1122, General

Telephone Company, York, Pennsylvania. Cincinnati, OH: U.S. Department of Health and Human

Services, Public Health Service, Centers for Disease Control, National Institute for Occupational Safety

and Health.

Chung HY. 1999. Volatile components in crabmeats of charybdis feriatus. J Agric Food Chem 47:2280-

2287.

*CIS. 1999. The Chemical Information System. http://www.oxmol.com/prods/cis. May 24,1999.
DI-n-BUTYL PHTHALATE 143

9. REFERENCES

Clansky KB, ed. 1986. Chemical guide to the OSHA hazard communication standard. Burlingame, CA: 

Roytech Publications, Inc., 57, 653-656.

Clark JR, Patrick JM Jr, Moore JC, et al. 1987. Waterborne and sediment-source toxicities of six organic

chemicals to grass shrimp (Palaemonetes pugio) and amphioxus (Branchiostoma caribaeum). Arch

Environ Contam Toxicol 16:401-407.

Clayton GD, Clayton FE, eds. 1981. Patty's industrial hygiene and toxicology, third revised edition,

volume 2A, toxicology. New York, NY: John Wiley and Sons, 2344-2347.

*Clewell HJ III, Andersen ME. 1985. Risk assessment extrapolations and physiological modeling. 

Toxicol Ind Health 1(4):111-113.

CLPSD. 1988. Contract Laboratory Program Statistical Database. Viar and Company, Management

Services Division. Alexandria, VA. December 22, 1988.

*Coldham NG, Dave M, Sauer MJ. 1998. Analysis of di-n-butyl phthalate biotransformation in cattle by

liquid chromatography/ion trap mass spectrometry/mass spectrometry. J Mass Spectrom 33:803-810.

*Colón I, Caro D, Bourdony CJ, et al. 2000. Identification of phthalate esters in the serum of young

Puerto Rican girls with premature breast development. Environ Health Perspect 108(9):895-900.

Cook JC, Klinefelter GR, Hardisty JF, et al. 1999. Rodent leydig cell tumorigenisis: A review of the

physiology, pathology, mechanisms, and relevance to humans. Crit Rev Toxicol 29(2):169-261.

*Cosmetic Ingredient Review Committee. 1985. Final report on the safety assessment of dibutyl

phthalate, dimethyl phthalate, and diethyl phthalate. J Am Coll Toxicol 4(3):267-303.

Cote MG, Plaa GL, Valli VE, et al. 1985. Subchronic effects of a mixture of "persistent" chemicals

found in the Great Lakes. Bull Environ Contam Toxicol 34:285-290.

Cripe CR, Walker WW, Pritchard PH, et al. 1987. A shake-flask test for estimation of biodegradability

of toxic organic substances in the aquatic environment. Ecotoxicol Environ Saf 14:239-251.

*Crump DR. 1995. Volatile organic compounds in indoor air. In: Hester RE, Harrison RM, ed. 

Volatile organic compounds in the atmosphere. Issues in environmental science and technology 4th ed.

Cambridge: Royal Society of Chemistry, 109-124.

Cummings A, Gray LE Jr. 1987. Dibutyl phthalate: Maternal effects versus fetotoxicity. Toxicol Lett

39:43-50.

Cummings A, Harris S. 1990. Identifying sites of maternally mediated early pregnancy loss in the rat. 

Toxicologist 10:224.

Daniel JW. 1978. Toxicity and metabolism of phthalate esters. Clin Toxicol 13:257-268.

Daniel JW. 1979. Toxicity and metabolism of phthalate esters. In: Winek L, Shanor SP, eds. 

Toxicology annual: Vol. 3. New York, NY: Marcel Dekker, Inc., 257-268.
DI-n-BUTYL PHTHALATE 144

9. REFERENCES

*Dannenberg E, Paquin L, Gwinnell H. 1992. Carbon (carbon black). In: Kroschwitz J, Howe-Grant

M, eds. Kirk-Othmer encyclopedia of chemical technology. New York, NY: John Wiley & Sons Inc.,

1044-1045, 1072-1074.

David RM, Moore MR, Cifone MA, et al. 1999. Chronic peroxisome proliferation and hepatomegaly

associated with the hepatocellular tumorigenesis of di(2-ethylhexyl)phthalate and the effects of recovery. 

Toxicol Sci 50:195-205.

*de Bruijn J, Busser F, Seinen W, et al. 1989. Determination of octanol/water partition coefficients for

hydrophobic organic chemicals with the "slow-stirring" method. Environ Toxicol Chem 8:499-512.

DeFoe DL, Holcombe GW, Hammermeister DE, et al. 1990. Solubility and toxicity of eight phthalate

esters to four aquatic organisms. Environ Toxicol Chem 9:623-636. 

*DeLeon IR, Byrne CJ, Peuler EA, et al. 1986. Trace organic and heavy metal pollutants in the

Mississippi River. Chemosphere 15(6):795-805.

*Desideri P, Lepri L, Checchini L, et al. 1994. Organic compounds in surface and deep antarctic snow. 

Int J Environ Anal Chem 55:33-46.

Desideri PG, Lepri L, Udisti R, et al. 1998. Analysis of organic compounds in Antarctic snow and their

origin. Int J Environ Anal Chem 71(3-4):331-351.

*DeVault DS. 1985. Contaminants in fish from Great Lakes harbors and tributary mouths. Arch

Environ Contam Toxicol 14:587-594.

*Deyrup C. 1999. Chemical imports. Chemical Market Reporter 255(1):38-39. 

Di Bella G, Saitta M, Pellegrino M, et al. 1999. Contamination of Italian citrus essential oils: Presence of

phthalate esters. J Agric Food Chem 47:1009-1012.

*Donovan S. 1996. New method for estimating vapor pressure by the use of gas chromatography. J

Chromatogr A 749:123-129.

DOT. 1998. Department of Transportation. Code of Federal Regulations. Title 49, vol. 2, parts 100-

185.

*DOT. 2001a. List of hazardous substances and reportable quantities. U.S. Department of

Transportation. Code of Federal Regulations 49 CFR 171.101, Appendix A. http://www.dot.gov. April

3, 2001.

*DOT. 2001b. List of marine pollutants. U.S. Department of Transportation. Code of Federal

Regulations. 49 CFR 171.101. Appendix B. http://www.dot.gov. April 3, 2001.

*Eastman Chemical Company. 1999a. Kingsport, TN: Eastman Chemical Company,

http://www.eastman.com/ProductCat/producthome.asp?Product=60&EastmanDotCom=True. August 5,

1999.
DI-n-BUTYL PHTHALATE 145

9. REFERENCES

*Eastman Chemical Company. 1999b. Kingsport, TN: Eastman Chemical Company,

http://www.eastman.com/ProductCat/ListApplications.asp?productid=60&EastmanDotCom=True. July

30, 1999.

Eaton RW, Ribbons DW. 1982. Metabolism of dibutyl phthalate and phthalate by Micrococcus sp. 

strain 12B. J Bacteriol 151:48-57.

*Eckel W, Ross B, Isensee R. 1993. Pentobarbitol found in ground water. Ground Water 31(5):801-

803.

Eckel W, Ross B, Isensee R. 1994. Reply to the preceding discussion by Douglas C. Bailey of

“pentobarbitol found in ground water”. Ground Water 32:150-151.

*Edelman IS, Leibman J. 1959. Anatomy of body water and electrolytes. Am J Med 27:256-277.

*Eisenreich SJ, Looney BB, Thornton JD. 1981. Airborne organic contaminants in the Great Lakes

ecosystem. Environ Sci Technol 15(1):30-38.

Ekwall B, Nordensten C, Albanus L. 1982. Toxicity of 29 plasticizers to HeLa cells in the MIT-24

system. Toxicology 24:199-210.

*Ellenhorn MJ, ed. 1997. Plastics, plasticizers, and epoxy resins. In: Ellenhorn's medical toxicology: 

Diagnosis and treatment of human poisoning. Baltimore, Maryland: Williams & Wilkins, 1677-1680.

*Elsisi AE, Carter DE, Sipes IG. 1989. Dermal absorption of phthalate diesters in rats. Fundam Appl

Toxicol 12:70-77.

*Ema M, Amano H, Itami T, et al. 1993. Teratogenic evaluation of di-n-butyl phthalate in rats. Toxicol

Lett 69:197-203.

*Ema M, Amano H, Ogawa Y. 1994. Characterization of the developmental toxicity of di-n-butyl

phthalate in rats. Toxicology 86:163-174.

*Ema M, Harazono A, Miyawaki E, et al. 1997a. Developmental effects of di-n-butyl phthalate after a

single administration in rats. J Appl Toxicol 17(4):223-229.

*Ema M, Harazono A, Miyawaki E, et al. 1997b. Embryo lethality following maternal exposure to

dibutyl phthalate during early pregnancy in rats. Bull Environ Contam Toxicol 58:636-643.

*Ema M, Kurosaka R, Amano H, et al. 1995a. Comparative developmental toxicity of n-butyl benzyl

phthalate and di-n-butyl phthalate in rats. Arch Environ Contam Toxicol 28:223-228.

Ema M, Kurosaka R, Amano H, et al. 1995b. Developmental toxicity evaluation of mono-n-butyl

phthalate in rats. Toxicol Lett 78:101-106.

*Ema M, Kurosaka R, Harazono A, et al. 1996. Phase specificity of developmental toxicity after oral

administration of mono-n-butyl phthalate in rats. Arch Environ Contam Toxicol 31:170-176.

*Ema M, Miyawaki E, Kawashima K. 1998. Further evaluation of developmental toxicity of di-n-butyl

phthalate following administration during late pregnancy in rats. Toxicol Lett 98:87-93.
DI-n-BUTYL PHTHALATE 146

9. REFERENCES

*Ema M, Miyawaki E, Kawashima K. 2000a. Critical period for adverse effects on development of

reproductive system in male offspring of rats given di-n-butyl phthalate during late pregnancy. Toxicol

Lett 111:271-278.

*Ema M, Miyawaki E, Kawashima K. 2000b. Effects of dibutyl phthalate on reproductive function in

pregnant and pseudopregnant rats. Reprod Toxicol 14:13-19.

EMMI. 1999. EPA environmental monitoring methods index: Detail analyte. Version I. PC no. 4082. 

Rockland, MD: Government Institutes.

Engelhardt G, Wallnofer PR. 1978. Metabolism of di- and mono-n-butyl phthalate by soil bacteria. 

Appl Environ Microbiol 35:243-246.

Engelhardt G, Wallnöfer PR, Hutzinger O. 1975. The microbial metabolism of di- n-butyl phthalate and

related dialkyl phthalates. Bull Environ Contam Toxicol 13(3):342-347.

EPA. 1979. Water-related environmental fate of 129 priority pollutants: Volume I: Introduction and

technical background, metals and inorganics, pesticides and PCBs. Washington, DC: U.S.

Environmental Protection Agency, Office of Water Planning and Standards. EPA-440/4-79-029a. NTIS

No. PB 80-204373.

EPA. 1980a. U.S. Environmental Protection Agency. Federal Register. 45:33084-33133.

*EPA. 1980b. Ambient water quality criteria for: Phthalate esters. Washington, DC: U.S.

Environmental Protection Agency, Environmental Criteria and Assessment Office. EPA-440/5-80-067. 

NTIS No. PB81-117780.

*EPA. 1981. An exposure and risk assessment for phthalate esters: Washington, DC: U.S.

Environmental Protection Agency, Office of Water Regulations and Standards. EPA-440/4-81-020. 

NTIS No. PB85-211936.

EPA. 1982a. Aquatic fate process data for organic priority pollutants. Washington, DC: U.S.

Environmental Protection Agency, Office of Water Regulations and Standards. EPA 440/4-81-014.

EPA. 1982b. Test method: Phthalate esters-method 606. In: Longbottom JE, Lichtenberg JJ, eds. Test

methods: Methods for organic chemical analysis of municipal and industrial wastewater. Cincinnati,

OH: U.S. Environmental Protection Agency, Environmental Monitoring and Support Laboratory. EPA600/4-82-057. 

EPA. 1982c. Test method: Base/neutrals and acids-method 625. In: Longbottom JE, Lichtenberg JJ,

eds. Test methods: Methods for organic chemical analysis of municipal and industrial wastewater. 

Cincinnati, OH: U.S. Environmental Protection Agency, Environmental Monitoring and Support

Laboratory. EPA-600/4-82-057. 

EPA. 1982d. U.S. Environmental Protection Agency. Federal Register. 47:26992-27008.

EPA. 1983a. Reportable quantity document for 1,2-benzene dicarboxylic acid, dibutyl ester (dibutyl

phthalate). Washington, DC: U.S. Environmental Protection Agency, Office of Solid Waste and

Emergency Response. External Review Draft. ECAO-CIN-R039.
DI-n-BUTYL PHTHALATE 147

9. REFERENCES

EPA. 1983b. Treatability manual: Volume I. Treatability data. Washington, DC: U.S. Environmental

Protection Agency, Office of Research and Development. EPA-600/2-82-001a.

*EPA. 1984a. Development of a fate/toxicity screening test. Gulf Breeze, FL: U.S. Environmental

Protection Agency, Office of Research and Development. EPA-600/4-84-074. NTIS No. PB84-246370.

*EPA. 1984b. U.S. Environmental Protection Agency. Federal Register. 49:209.

EPA. 1984c. GC/MS analysis of organics in drinking water concentrates and advanced waste treatment

concentrates: Volume I: Analysis results for 17 drinking water, 16 advanced waste treatment and 3

process blank concentrates. Research Triangle Park, NC: U.S. Environmental Protection Agency, Office

of Research and Development. EPA-600/1-84-020a. NTIS No. PB85-128221.

EPA. 1985. U.S. Environmental Protection Agency: Part II. Federal Register 50:13456-13522.

*EPA. 1986a. Method 8060: Phthalate esters. 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. 1986b. Method 8250: Gas chromatography/mass spectrometry for semivolatile organics: Packed

column technique. 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. 1986c. Method 8270: Gas chromatography/mass spectrometry for semivolatile organics: capillary

column technique. 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. Method 8410: Capillary column analysis of semivolatile organic compounds by gas

chromatography/fourier transform infrared (GC/FT-IR) spectrometry. 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. 1986e. Method 8060: Gas chromatography/ mass spectrometry for semivolatile organics:

Capillary column technique. 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. 1986f. Toxic and priority organics in municipal sludge land treatment systems. Cincinnati OH: 

U.S. Environmental Protection Agency, Office of Research and Development. EPA/600/2-86/010. NTIS

No. PB86-150208.

*EPA. 1986g. Broad scan analysis of the FY82 national human adipose tissue survey specimens: 

Volume I-Executive summary. Washington, DC: U.S. Environmental Protection Agency, Office of

Toxic Substances. EPA 560/5-86-035.

EPA. 1987a. U.S. Environmental Protection Agency: Part II. Federal Register. 52:13378-13410.

EPA. 1987b. U.S. Environmental Protection Agency: Part II. Federal Register. 52:25942-25953.
DI-n-BUTYL PHTHALATE 148

9. REFERENCES

*EPA. 1987c. Health effects assessment for selected phthalic acid esters. Cincinnati, OH: U.S.

Environmental Protection Agency, Environmental Criteria and Assessment Office. EPA/600/8-88/053. 

NTIS No. PB88-178934.

EPA. 1987d. U.S. Environmental Protection Agency. Federal Register. 52:48073-48074. 

EPA. 1987e. Reference dose (RfD): Description and use in health risk assessments. Volume I,

Appendix A: Integrated Risk Information System supportive documentation. Washington, DC: U.S.

Environmental Protection Agency, Office of Health and Environmental Assessment. EPA/600/8-

86/032a.

EPA. 1988a. U.S. Environmental Protection Agency: Part II. Federal Register. 53:31138-31222.

EPA. 1988b. U.S. Environmental Protection Agency: Part II. Federal Register. 53:4500-4539.

EPA. 1988c. U.S. Environmental Protection Agency: Part V. Federal Register. 53:38642-38654.

EPA. 1989a. Interim Methods for Development of Inhalation References Doses. Washington, DC: U.S.

Environmental Protection Agency, Office of Health and Environmental Assessment. EPA 600/8-

88/066F.

EPA. 1989b. U.S. Environmental Protection Agency: Part II. Federal Register. 54:1056-1120.

EPA. 1989c. U.S. Environmental Protection Agency. Federal Register. 54:618-621.

*EPA. 1989d. Hydrolysis rate constants for enhancing property-reactivity relationships. Athens, GA: 

U.S. Environmental Protection Agency, Office of Research and Development. PB 89-220479.

*EPA. 1990a. Characterization of municipal waste combustion ash, ash extracts, and leachates.

Washington, DC: U.S. Environmental Protection Agency. EPA530-SW-90-029A.

*EPA. 1990b. Interim methods for the development of inhalation reference concentrations. Washington,

DC: U.S. Environmental Protection Agency, Office of Health and Environmental Assessment. EPA

600/8-90/066A.

*EPA. 1992. U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR260-299.

*EPA. 1993. Reference guide to odor thresholds for hazardous air pollutants listed in the clean air act

amendments of 1990. Washington, DC: U.S. Environmental Protection Agency. PB92-239516.

*EPA. 1994a. Method 8250A: Semivolatile organic compounds by gas chromatography/mass

spectrometry (GS/MS). Washington, DC: U.S. Environmental Protection Agency. 

*EPA. 1994b. Method 8410: Gas chromatography/fourier transform infrared (GC/FT-IR) spectrometry

for semivolatile organics: Capillary column. Washington, DC: U.S. Environmental Protection Agency.

*EPA. 1996a. Drinking Water Regulations and Health Advisories. Washington, DC: U.S.

Environmental Protection Agency, Office of Water. EPA 822-B-96-002.
DI-n-BUTYL PHTHALATE 149

9. REFERENCES

*EPA. 1996b. Method 8061A: Phthalate esters by gas chromatography with electron capture detection

(GC/ECD). Washington, DC: U.S. Environmental Protection Agency. 

*EPA. 1997. Special report on environmental endocrine disruption: An effects assessment and analysis. 

Washington, DC: U.S. Environmental Protection Agency. EPA/630/R-96/012.

EPA. 1998a U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 372.65.

EPA. 1998b. U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 266.

EPA. 1998c. U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 116.4.

EPA. 1998d. U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 264.

EPA. 1998e. U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 302.4.

EPA. 1998f. U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 467.2.

EPA. 1998g. U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 465.02.

EPA. 1998h. U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 433.11.

EPA. 1998i. U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 413.02.

EPA. 1998j. U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 469.12.

EPA. 1998k. U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 414.101.

EPA. 1998l. U.S. Method 8270: Semivolatile organic compounds by gas chromatography/mass

spectrometry (GS/MS). Washington, DC: U.S. Environmental Protection Agency. 

*EPA. 1999a. Washington, DC: U.S. Environmental Protection Agency, Office of Pesticide Programs

http://www.epa.gov/opprd001/inerts/list2inerts.html. August 5, 1999.

*EPA. 1999b. Washington, DC: U.S. Environmental Protection Agency, Office of Pesticide Programs

http://www.epa.gov/opppmsd1/DataSubmittersList/dslchem.htm. August 5, 1999.

*EPA. 1999c. National recommended water quality criteria-correction. Washington, DC: U.S.

Environmental Protection Agency, Office of Water. EPA 822-Z-99-001.

EPA. 1999d. Toxic chemical release reporting: Community right-to-know: Chemicals and chemical

categories to which this part applies. U.S. Environmental Protection Agency. Code of Federal

Regulations. http://www.access.gpo.gov/nara/cfr/waisidx_99/40cfr372_99.html. February 8, 2001.

*EPA. 1999e. Identification of specific chemical substance and mixture testing requirements: Testing

consent orders for substances and mixtures with chemical abstract service registry numbers. U.S.

Environmental Protection Agency. Code of Federal Regulations. 

http://www.access.gpo.gov/nara/cfr/waisidx_99/40cfr799_99.html. February 8, 2001.
DI-n-BUTYL PHTHALATE 150

9. REFERENCES

EPA. 2000a. Designation of hazardous substances. U.S. Environmental Protection Agency. Code of

Federal Regulations. http://www.access.gpo.gov/nara/cfr/waisidx_00/40cfr14_00.html. October 25,

2000.

EPA. 2000b. Identification and listing of hazardous waste: Discarded commercial chemical products,

off-specification species, container residues and spill residues thereof. U.S. Environmental Protection

Agency. Code of Federal Regulations. 

http://www.access.gpo.gov/nara/cfr/waisidx_00/40cfr261_00.html. February 8, 2001.

EPA. 2000c. National drinking water contaminant occurrence database. Envirofacts Warehouse. U.S.

Environmental Protection Agency. http://www.epa.gov:9966.

*EPA. 2001a. Applicability: description of the bulk organic chemicals subcategory. U.S. Environmental

Protection Agency. Code of Federal Regulations. 40 CFR 414.70, Appendix C. 

http://www.access.gpo.gov/nara/cfr/...1_00/Title_40/40cfr414_main_00.html. April 3, 2001.

*EPA. 2001b. Chemicals and chemical categories to which this part applies. U.S. Environmental

Protection Agency. Code of Federal Regulations. 40 CFR 372.65. 

http://www.access.gpo.gov/nara/cfr/...1 00/Title_40/40cfr372main_00.html. April 5, 2001.

*EPA. 2001c. Designation of hazardous substances. U.S. Environmental Protection Agency. Code of

Federal Regulations. 40 CFR 116.4. 

http://www.access.gpo.gov/nara/cfr/...100/Title_40/40cfr116_main_00.html. April 5, 2001.

*EPA. 2001d. Designation of hazardous substances. U.S. Environmental Protection Agency. Code of

Federal Regulations. 40 CFR 302.4. 

http://www.access.gpo.gov/nara/cfr/...1 00/Title 40/40cfr302 main 00.html. April 5, 2001.

*EPA. 2001e. Di-n-butyl phthalate: 84-74-2. U.S. Environmental Protection Agency. Office of Air

Quality Planning and Standards. http://www.epa.gov/ttnuatwl/hlthef/di-n-but.html. January 8, 2001.

*EPA. 2001f. Discarded commercial chemical products, off-specification species, container residues,

and spill residues thereof. U.S. Environmental Protection Agency. Code of Federal Regulations. 40

CFR 261.33. http://www.access.gpo.gov/nara/cfr/...1 00/Title 40/40cfr261 main 00.html. April 5, 2001.

*EPA. 2001g. General definitions. U.S. Environmental Protection Agency. Code of Federal

Regulations. 40 CFR 264, Appendix IX.

http://www.access.gpo.gov/nara/cfr/...1 00/Title 40/40cfr465 main 00.html. April 5, 2001.

*EPA. 2001h. General definitions. U.S. Environmental Protection Agency. Code of Federal

Regulations. 40 CFR 467.02. 

http://www.access.gpo.gov/nara/cfr/...1 00/Title 40/40cfr467 main00.html. April 5, 2001.

*EPA. 2001i. General definitions. U.S. Environmental Protection Agency. Code of Federal

Regulations. 40 CFR 264, Appendix IX. 

http://www.access gpo.gov/nara/cfr/...1 00/Title 40/40cfr264 main 00.html. April 5, 2001.

*EPA. 2001j. List of hazardous inorganic and organic constituents 1. U.S. Environmental Protection

Agency. Code of Federal Regulations. 40 CFR 258, Appendix II. http://www.access.gpo.gov/nara/cfr/...

1 00/Title 40/40cfr258 main 00.html. April 3, 2001.
DI-n-BUTYL PHTHALATE 151

9. REFERENCES

*EPA. 2001k. Listed constituents. U.S. Environmental Protection Agency. Code of Federal

Regulations. 40 CFR 192, Appendix I. 

http://www.access.gpo/gov/nara/cfr/...1_00/Title_40/40cfr192_main_00.html. April 3, 2001.

EPA. 2001l. NPDES permit testing requirements. U.S. Environmental Protection Agency. Code of

Federal Regulations. 40 CFR 122.21, Appendix D. 

http://www.access.gpo.gov/nara/cfr/...1 00/Title40/40cfr122 main 00.html. April 3, 2001.

EPA. 2001m. NPDES permit testing requirements for publicly owned treatment works. U.S.

Environmental Protection Agency. Code of Federal Regulations. 40 CFR 122.21, Appendix J. 

http://www.access.gpo.gov/nara/cfr/...1 00/Title 40/40cfr403 main 00.html. April 3, 2001.

*EPA. 2001n. Pollutants eligible for a removal credit. U.S. Environmental Protection Agency. Code of

Federal Regulations. 40 CFR 403, Appendix G. 

http://www.access.gpo/nara/cfr/...1 00/Title 4/40cfr403 main 00.html. April 3, 2001.

*EPA. 2001o. Priority pollutants. U.S. Environmental Protection Agency. Code of Federal

Regulations. 40 CFR 423, Appendix A. 

http://www.access.gpo.gov/nara/cfr/...1 00/Title 40/40cfr266 main 00.html. April 4, 2001.

*EPA. 2001p. Reference air concentrations. U.S. Environmental Protection Agency. Code of Federal

Regulations. 40 CFR 266, Appendix IV. 

http://www.access.gpo.gov/nara/cfr/...1 00/Title 40/40cfr266 main 00.html. April 3, 2001.

*EPA. 2001q. Specialized definitions. U.S. Environmental Protection Agency. Code of Federal

Regulations. 40 CFR 433.11. 

http://www.access.gpo.gov/nara/cfr/...1 00/Title 40/40cfr433.11 main00.html. April 3, 2001.

*EPA. 2001r. Substances and listed mixtures with chemical abstract service registry numbers. U.S.

Environmental Protection Agency. Code of Federal Regulations. 40 CFR 716.120. 

http://www.access.gpo.gov/nara/cfr/...1 00/Title 40/40cfr716.120 main 00.html. April 5, 2001.

*EPA. 2001s. Testing consent orders for substances and mixtures with chemical abstract service registry

numbers. U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 799.5000. 

http://www.access.gpo.gov/nara/cfr/...1 00/Title 40/40cfr799.5000 main 00.html. April 5, 2001.

*EPA. 2001t. Toxic criteria for those states not complying with Clean Water Act section 303(c)(2)(B). 

U.S. Environmental Protection Agency. Code of Federal Regulations 40 CFR 131.36. 

http://www.access.gpo.gov/nara/cfr/..1 00/Title 40/40cfr131.36 main 00.html. April 3, 2001.

*EPA. 2001u. Toxic pollutants effluent limitations and standards for direct discharge point sources that

use end-of-pipe biological treatment. U.S. Environmental Protection Agency. Code of Federal

Regulations. 40 CFR 414.91. 

http://www.access.gpo.gov/nara/cfr/...1 00/Title 40/40cfr414.91 main 00.html. April 3, 2001.

*EPA. 2001v. Toxic pollutant effluent limitations and standards for direct discharge point sources that

do not use end-of-pipe biological treatment. U.S. Environmental Protection Agency. Code of Federal

Regulations. 40 CFR 414.101. 

http://www.access.gpo.gov/nara/cfr/..1 00/Title 40/40cfr414.101 main 00.html. April 3, 2001.
DI-n-BUTYL PHTHALATE 152

9. REFERENCES

*EPA. 2001w. Toxic pollutant standards for indirect discharge point sources. U.S. Environmental

Protection Agency. Code of Federal Regulations. 40 CFR 414.111. 

http://www.access.gpo.gov/nara/cfr/...1 00/Title 40/40cfr414.111 main 00.html. April 3, 2001.

*EPA. 2001x. Universal treatment standards. U.S. Environmental Protection Agency. Code of Federal

Regulations. 40 CFR 268.48. 

http://www.access.gpo.gov/nara/cfr/...1 00/Title 40/40cfr268.48 main 00.html. April 3, 2001.

*Fallon ME, Horvath FJ. 1985. Preliminary assessment of contaminants in soft sediments of the Detroit

River. J Great Lakes Res 11(3):373-378. 

FDA. 1998a. Food and Drug Administration. Code of Federal Regulations. 21 CFR 177.2600.

FDA. 1998b. Food and Drug Administration. Code of Federal Regulations. 21 CFR 177.1200.

FDA. 1998c. Food and Drug Administration. Code of Federal Regulations. 21 CFR 175.105.

FDA. 1998d. Food and Drug Administration. Code of Federal Regulations. 21 CFR 176.170.

*FDA. 1999. Indirect food additives: Paper and paperboard components: Components of paper and

paperboard in contact with aqueous and fatty foods. Food and Drug Administration. Code of Federal

Regulations. 21 CFR 176.170. http://www.access.gpo.gov/nara/cfr/waisidx_99/21cfr176_99.html. 

February 2, 2001.

*FDA. 2000a. Indirect food additives: Adhesives and components of coatings: Adhesives. Food and

Drug Administration. Code of Federal Regulations. 21 CFR 175.105.

http://www.access.gpo.gov/nara/cfr/waisidx_00/21cfr175_00.html. February 2, 2001.

*FDA. 2000b. Indirect food additives: Polymers: Cellophane. Food and Drug Administration. Code of

Federal Regulations. 21 CFR 177.1200.

http://www.access.gpo.gov/nara/cfr/waisidx_00/21cfr177_00.html. February 2, 2001.

*FDA. 2000c. Indirect food additives: Polymers: Substances for use only as components of articles

intended for repeated use: Rubber articles intended for repeated use. Food and Drug Administration. 

Code of Federal Regulations. 21 CFR 177.2600. 

http://www.access.gpo.gov/nara/cfr/waisidx_00/21cfr177_00.html. February 2, 2001.

*FDA. 2000d. Components of paper and paperboard in contact with aqueous and fatty food. National

Archives and Records Administration. Code of Federal Regulations. 21 CFR 176.170. 

http://www.access.gpo.gov/nara/cfr/waisidx 00/21cfr176.00.html. April 5, 2001.

*FDA. 2000e. Polyester resins, cross-linked. National Archives and Records Administration. Code of

Federal Regulations. 21 CFR 177.2420, Appendix B. 

http://www.access.gpo.gov/nara/cfr/waisidx_00/21cfr175_00.html. April 3, 2001.

*FDA. 2000f. Resinous and polymeric coatings. National Archives and Records Administration. Code

of Federal Regulations. 21 CFR 175.300. 

http://www.access.gpo.gov/nara/cfr/waisidx_00/21cfr175_00.html. April 3, 2001.
DI-n-BUTYL PHTHALATE 153

9. REFERENCES

*FDA. 2000g. Slimicides. National Archives and Records Administration. Code of Federal Regulations

21 CFR 176.300, Appendix D. http://www.access.gpo.gov/nara/cfr/waisidx 00/21cfr176 00.html. April

3, 2001.

*FEDRIP. 1999. Federal Research in Progress: Di-n-butyl Phthalate. Dialog Information Services, Inc. 

Palo Alto, CA. February 1992. 

*FEDRIP. 2000. Federal Research in Progress: Di-n-butyl Phthalate. Dialog Information Services, Inc. 

Palo Alto, CA.

*Feiler HD, Storch PJ, Southworth R. 1980. Organics in municipal sludges survey of forty cities. Natl

Conf Munic Ind Sludge Util Disposal [pap.], 53-57.

*Felthouse TR, Burnett JC, Mitchell SF, et al. 1995. Maleic anhydride, maleic and fumaric acid. In: 

Kroschwitz JI, Howe-Grant M, eds. Kirk-Othmer encyclopedia of chemical technology. New York, NY: 

John Wiley & Sons, 902-928.

*Ferrario JB, DeLeon IR, Tracy RE. 1985. Evidence for toxic anthropogenic chemicals in human

thrombogenic coronary plaques. Arch Environ Contam Toxicol 14:529-534.

Fishbein L. 1984. Toxicity of the components of styrene polymers: Polystyrene, acrylonitrile-butadienestyrene (ABS) and styrene-butadiene-rubber (SBR). Reactants and additives. In: Jarvisalo J, Pfaffli P,

Vainio H, eds. Industrial hazards of plastics and synthetic elastomers. New York, NY: Alan R. Liss,

Inc., 239-262.

*Fishbein L. 1992. Exposure from occupational versus other sources. Scand J Work Environ Health

18(suppl 1):5-16.

*Florin I, Rutberg L, Curvall M, et al. 1980. Screening of tobacco smoke constituents for mutagenicity

using the Ames' test. Toxicology 18:219-232.

*Fomon SJ. 1966. Body composition of the infant. Part I: The male “reference infant”. In: Falkner F,

ed. 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 35:1169-1175.

*Foster PM, Cook MW, Thomas LV, et al. 1982. Differences in urinary metabolic profile from di-nbutyl phthalate-treated rats and hamsters: A possible explanation for species differences in susceptibility

to testicular atrophy. Drug Metab Dispos 11(1):59-61.

Foster PM, Lake BG, Cook MW, et al. 1981. Structure-activity requirements for the induction of

testicular atrophy by butyl phthalates in immature rats: Effect on testicular zinc content. In: Snyder R, 

Parke DV, Kocsis JJ, et al., eds. Biological reactive intermediates-II: Chemical mechanisms and

biological effects, Part A. New York, NY: Plenum Press, 445-452.

Foster PM, Thomas LV, Cook MW, et al. 1980. Study of the testicular effects and changes in zinc

excretion produced by some n-alkyl phthalates in the rat. Toxicol Appl Pharmacol 54:392-398.
DI-n-BUTYL PHTHALATE 154

9. REFERENCES

*Fricker C, Hardy J. 1990. Characterization of commercially available coffee filter papers. J Environ

Sci Health Part A 25(8):927-936.

FSTRAC. 1988. Summary of state and federal drinking water standards and guidelines. Washington,

DC: Federal-State Toxicology and Regulatory Alliance Committee, Chemical Communication

Subcommittee.

*Fukuoka M, Kobayashi T, Hayakawa T. 1994. Mechanism of testicular atrophy induced by di-n-butyl

phthalate in rats. VI. A possible origin of testicular iron depletion. Biol Pharm Bull 17(12):1609-1612.

*Fukuoka M, Kobayashi T, Hayakawa T. 1995. Mechanism of testicular atrophy induced by di-n-butyl

phthalate in rats. Part 5. Testicular iron depletion and levels of ferritin, hemoglobin and transferrin in the

bone marrow, liver and spleen. J Appl Toxicol 15(5):379-386.

*Fukuoka M, Kobayashi T, Zhou Y, et al. 1993. Mechanism of testicular atrophy induced by di-n-butyl

phthalate in rats. Part 4. Changes in the activity of succinate dehydrogenase and the levels of transferring

and ferritin in the sertoli and germ cells. J Appl Toxicol 13(4):241-246.

*Fukuoka M, Tanimoto T, Zhou Y, et al. 1989. Mechanism of testicular atrophy induced by di-n- butyl

phthalate in rats. Part 1. J Appl Toxicol 9(4):277-283.

*Fukuoka M, Zhou Y, Tanaka A, et al. 1990. Mechanism of testicular atrophy induced by di-n-butyl

phthalate in rats. Part 2. The effects on some testicular enzymes. J Appl Toxicol 10(4):285-293.

Gangolli SD. 1982. Testicular effects of phthalate esters. Environ Health Perspect 45:77-84.

Geissert JO. 1977. Technical assistance report no. TA-76-66. Cincinnati, OH: National Institute for

Occupational Safety and Health. NTIS No. PB82-189747.

*Germain A, Langlois C. 1988. Contamination des eaux et des sediments en suspension du fleuve saintlaurent par les pesticides organochlores, les biphenyles polychlores et d'autres contaminants organiques

prioritaires. Water Pollut Res J Can 23(4):602-614.

Gesler RM. 1973. Toxicology of di-2-ethylhexyl phthalate and other phthalic-acid ester plasticizers. 

Environ Health Perspect 3:73-79.

*Giam CS, Wong MK. 1987. Plasticizers in food. J Food Prot 50(9):769-782.

*Giam CS, Atlas E, Chan HS, et al. 1980. Phthalate esters, PCB and DDT residues in the Gulf of

Mexico atmosphere. Atmos Environ 14:65-69.

Giam CS, Chan HS, Neff GS. 1978a. Phthalate ester plasticizers, DDT, DDE and polychlorinated

biphenyls in biota from the Gulf of Mexico. Mar Pollut Bull 9:249-251.

Giam CS, Chan HS, Neff GS, et al. 1978b. Phthalate ester plasticizers: A new class of marine pollutant. 

Science 199:419-421.

*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.
DI-n-BUTYL PHTHALATE 155

9. REFERENCES

Goncharuk EI, Sidorenko GI, Golubchikov MV. 1990. [Use of the mother-fetus-newborn infant system

of combined effects of pesticides and other chemicals]. Gig Sanit Jun(6):4-7. (Russian) 

Gosselin RE, Smith RP, Hodge HC, et al, eds. 1984. Clinical toxicology of commercial products. 5th

ed. Baltimore, MD: Williams and Wilkins, II-204.

Gothe R. 1974. Oxidation with tetrabutylammonium permanganate for quantitation of DDT residues in

GLC determination of chlorinated hydrocarbons. Bull Environ Contam Toxicol 11:451-455.

Gray LE, Ostby JS, Mylchreest E, et al. 1998. Dibutyl phthalate (DBP) induces antiandrogenic but not

estrogenic in vivo effects in LE Hooded rats. Toxicologist 42(1-S):176.

Gray LE, Ostby J, Sigmon R J, et al. 1988. The development of a protocol to assess reproductive effects

of toxicants in the rat. Reprod Toxicol 2:281-287.

*Gray LE, Wolf C, Lambright C, et al. 1999. Administration of potentially antiandrogenic pesticides

(procymidone, linuron, iprodione, chlozolinate, p,p'-DDE, and ketoconazole) and toxic substances

(dibutyl- and diethylhexyl phthalate, PCB 169, and ethane dimethane sulphonate) during sexual

differentiation produces diverse profiles of reproductive malformations in the male rat. Toxicol Ind

Health 15(1-2):94-118.

*Gray TJ, Gangolli SD. 1986. Aspects of the testicular toxicity of phthalate esters. Environ Health

Perspect 65:229-235.

*Gray TJ, Rowland IR, Foster PM, et al. 1982. Species differences in the testicular toxicity of phthalate

esters. Toxicol Lett 11:141-147.

Green DR, Le Pape D. 1987. Stability of hydrocarbon samples on solid-phase extraction columns. Anal

Chem 59:699-703.

*Grollert C, Kasper A, Puxbaum H. 1997. Organic compounds in high alpine snow. Int J Environ Anal

Chem 67:213-222.

Gulati DK, Hope E, Teague J, et al. 1991. Reproductive toxicity assessment by continuous breeding in

Sprague-Dawley rats: A comparison of two study designs. Fundam Appl Toxicol 17:270-279.

*Guzelian PS, Henry CJ, Olin SS. 1992. Similarities and Differences between children and adults:

Implications for risk assessment. Washington, DC: International Life Sciences Institute Press. 

Haley TJ. 1975. Vinyl chloride: How many unknown problems? J Toxicol Environ Health 1:47-73.

Hall DE, Austin P, Fairweather FA. 1966. Acute (mouse and rat) and short-term (rat) toxicity studies on

dibutyl(diethylene glycol bisphthalate). Food Cosmet Toxicol 4:383-388.

*Hannah SA, Austern BM, Eralp AE, et al. 1986. Comparative removal of toxic pollutants by six

wastewater treatment processes. J Water Pollut Control Fed 58(1):27-34. 

Hannah SA, Austern BM, Eralp AE, et al. 1988. Removal of organic toxic pollutants by trickling filter

and activated sludge. J Water Pollut Control Fed 60:1281-1283.
DI-n-BUTYL PHTHALATE 156

9. REFERENCES

*Hansch C, Leo A, Hoekman D, eds. 1995. Exploring QSAR; Hydrophobic, electronic, and steric

constants. Washington, DC: American Chemical Society, 144.

*Hardin BD. 1987. A recommended protocol for the Chernoff/Kavlock preliminary developmental

toxicity test and a proposed method for assigning priority scores based on results of that test. Teratog

Carcinog Mutagen 7:85-94.

*Hardin BD, Schuler RL, Burg JR, et al. 1987. Evaluation of 60 chemicals in a preliminary

developmental toxicity test. Teratog Carcinog Mutagen 7:29-48. 

*Harris CA, Henttu P, Parker MG, et al. 1997. The estrogenic activity of phthalate esters in vitro.

Environ Health Perspect 105(8):802-811.

Harsanyi BB, Foong WC, Jones DW. 1988. Implantation of denture soft polymers into hamster cheek

pouch [Abstract]. J Dent Res 67:263.

Hauser TR, Bromberg SM. 1982. EPA's monitoring program at Love Canal 1980. Environ Monit

Assess 2:249-271.

Hawker DW, Connell DW. 1986. Bioconcentration of lipophilic compounds by some aquatic organisms. 

Ecotoxicol Environ Saf 11:184-197.

Hawthorne SB. 1988. 1988 workshop on supercritical fluid chromatography. American Laboratory

(August 1988):6-8.

*HazDat. 1999. Agency for Toxic Substances and Disease Registry(ATSDR). Results of HazDat

searches for group 13 chemicals. Atlanta, GA.

*HazDat. 2001. Agency for Toxic Substances and Disease Registry(ATSDR). Results of HazDat

searches for group 13 chemicals. Atlanta, GA.

*Hazleton Biotechnologies. 1986. Mutagenicity of IC in a mouse lymphoma mutation assay: Final

report. Hazleton Biotechnologies Company, Kensington, MD. HB Project No. 20989.

*Heitkamp MA, Johnson B. 1984. Impact of an oil field effluent on microbial activities in a Wyoming

river. Can J Microbiol 30:786-792.

*Ho C-T, Lee KN, Jin QZ. 1983. Isolation and identification of volatile flavor compounds in fried

bacon. J Agric Food Chem 31:336-342.

*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. 

*Hoff RM, Chan K-W. 1987. Measurement of polycyclic aromatic hydrocarbons in the air along the

Niagara River. Environ Sci Technol 21:556-561.

Horton R. 2000. Retraction: Interferon alfa-2b... in Behçet's disease. Lancet 356:1292-1299.
DI-n-BUTYL PHTHALATE 157

9. REFERENCES

*Howard PH, ed. 1989. Handbook of environmental fate and exposure data of environmental chemicals. 

Vol. 1. Large production and priority pollutants. Chelsea, MA: Lewis Publishing Inc., 217-228.

Howard PH, Banerjee S, Robillard KH. 1985. Measurement of water solubilities, octanol/water partition

coefficients and vapor pressures of commercial phthalate esters. Environ Toxicol Chem 4:653-661.

Howarth JA, Price SC, Dobrota M, et al. 2001. Effects on male rats of di-(2-ethylhexyl) phthalate and din-hexylphthalate administered alone or in combination. Toxicol Lett 121:35-43.

HSDB. 1988. Hazardous Substances Data Bank. National Library of Medicine, National Toxicology

Information Program, Bethesda, MD. December 1988.

HSDB. 1999. Hazardous Substances Data Bank. National Library of Medicine, National Toxicology

Information Program, Bethesda, MD. May 17, 1999.

HSDB. 2000. Hazardous Substances Data Bank. National Library of Medicine, National Toxicology

Information Program, Bethesda, MD. December 2000.

*HSDB. 2001. Hazardous Substances Data Bank. National Library of Medicine, National Toxicology

Information Program, Bethesda, MD. http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?HSDB. February

2001.

Hudson RA, Austerberry CF, Bagshaw JC. 1981. Phthalate ester hydrolases and phthalate ester toxicity

in synchronously developing larvae of the brine shrimp (Artemia). Life Sci 29:1865-1872.

Hudson VW. 1982. TSCA interagency testing committee actions related to phthalates. Environ Health

Perspect 45:135-136.

Husain SL. 1975. Dibutyl phthalate sensitivity. Contact Dermatitis 1:395.

Hutchins SR, Tomson MB, Ward CH. 1983. Trace organic contamination of ground water from a rapid

infiltration site: A laboratory-field coordinated study. Environ Toxicol Chem 2:195-216.

Imajima T, Shono T, Zakari O, et al. 1997. Prenatal phthalate causes crytorchidism postnatally by

inducing transabdominal ascent of testis in fetal rats. J Pediatr Surg 32(1):18-21.

*Inman JC, Strachan SD, Sommers LE, et al. 1984. The decomposition of phthalate esters in soil. J

Environ Sci Health B19(2):245-257.

*Inouye B, Ogino Y, Ishida T, et al. 1978. Effects of phthalate esters on mitochondrial oxidative

phosphorylation in the rat. Toxicol Appl Pharmacol 43:189-198. 

IRIS. 1999. Dibutyl phthalate. Integrated Risk Information System, U.S. Environmental Protection

Agency. http://www.epa.gov./IRIS/subst/0038.htm. April 19, 1999.

*IRIS. 2001. Dibutyl phthalate. Integrated Risk Information System, U.S. Environmental Protection

Agency. http://www.epa.gov./IRIS/subst/0038.htm. January 8, 2001.

*IRDC. 1984. Study of fertility and general reproductive performance in rats (IR-83-145). International

Research and Development Corporation: Mattawan, MI.

IRPTC. 1989. IRPTC data profile on: Dibutyl phthalate. International Register of Potentially Toxic

Chemicals, United Nations Environment Programme, Geneva, Switzerland. January 1989.
DI-n-BUTYL PHTHALATE 158

9. REFERENCES

*Ishida M, Suyama K, Adachi S. 1981. Occurrence of dibutyl and di(2-ethylhexyl) phthalate in chicken

eggs. J Agric Food Chem 29:72-74.

*Ishidate M Jr, Odashima S. 1977. Chromosome tests with 134 compounds on Chinese hamster cells in

vitro—a screening for chemical carcinogens. Mutat Res 48:337-353.

Jansson B, Jensen S, Olsson M, et al. 1975. Identification by GC-MS of phenolic metabolites of PCB and

p,p'

-DDE isolated from Baltic guillemot and seal. Ambio 4:93-97.

*Jay K, Steiglitz L. 1995. Identification and quantification of volatile organic components in emissions of

waste incineration plants. Chemosphere 30(7):1249-1260

Jianlong W, Lujun C, Hanchang S, et al. 2000. Microbial degradation of phthalic acid esters under

anaerobic digestion of sludge. Chemosphere 41:1245-1248.

Jianlong W, Ping L, Hanchang S, et al. 1997. Biodegradation of phthalic acid ester in soil by indigenous

and introduced microorganisms. Chemosphere 35(8):1747-1754.

*Jobling S, Reynolds T, White R, et al. 1995. A variety of environmentally persistent chemicals,

including some phthalate plasticizers, are weakly estrogenic . Environ Health Perspect 103(6):582-587.

*Johanson CE. 1980. Permeability and vascularity of the developing brain: cerebellum vs cerebral

cortex. Brain Res 190:3-16.

John JA, Wroblewski DJ, Schwetz BA. 1984. Teratogenicity of experimental and occupational exposure

to industrial chemicals. Issues Rev Terat 2:267-324.

*Johnson BT, Lulves W. 1975. Biodegradation of di-n-butyl phthalate and di-2-ethylhexyl phthalate in

fresh water hydrosoil. J Fisher Res Board Can 32(3):333-339.

*Johnson BT, Heitkamp MA, Jones JR. 1984. Environmental and chemical factors influencing the

biodegradation of phthalic acid esters in freshwater sediments. Environ Pollut (Series B) 8:101-118.

Johnson BT, Stalling DL, Hogan JW, et al. 1977. Dynamics of phthalic acid esters in aquatic organisms. 

In: Suffet IH, ed. Fate of pollutants in the air and water environments: Part 2. Chemical and biological

fate of pollutants in the environment. New York, NY: John Wiley and Sons, 283-300.

Johnson EM, Gabel BE. 1983. An artificial embryo for detection of abnormal developmental biology. 

Fundam Appl Toxicol 3:243-249.

Johnson EM, Newman LM, Gabel BE, et al. 1988. An analysis of the Hydra assay's applicability and

reliability as a developmental toxicity prescreen. J Am Coll Toxicol 7:111-126.

Jones AE, Kahn RH, Groves JT, et al. 1975. Phthalate ester toxicity in human cell cultures. Toxicol Appl

Pharmacol 31:283-289.

*Jones D, Burklin C, Seaman J. 1996. Models to estimate volatile organic hazardous air pollutant

emissions from municipal sewer systems. J Air Waste Manag Assoc 46:657-666.
DI-n-BUTYL PHTHALATE 159

9. REFERENCES

Jury WA, Winer AM, Spencer WF, et al. 1987. Transport and transformations of organic chemicals in the

soil-air-water ecosystem. Rev Environ Contam Toxicol 99:119-164.

Kamiya A, Ose Y. 1987. Mutagenic activity and PAH analysis in municipal incinerators. Sci Total

Environ 61:37-49.

Kaneshima H, Yamaguchi T, Itoh K. 1978a. Studies on the effects of phthalate esters on the biological

system: (Part 3). The in vitro metabolism of dibutyl phthalate in the small intestines of rats. Bull Environ

Contam Toxicol 20:725-728.

*Keys DA, Wallace DG, Kepler TB, et al. 1999. Quantitative evaluation of alternative mechanisms of

blood and testes disposition of di(2-ethylhexyl0 phthalate and mono(2-ethylhexyl) phthalate in rats. 

Toxicol Sci 49:172-185.

Kaneshima H, Yamaguchi T, Okui T, et al. 1978b. Studies on the effects of phthalate esters on the

biological system (Part 2) In vitro metabolism and biliary excretion of phthalate esters in rats. Bull

Environ Contam Toxicol 19:502-509.

*Kaplan W, ed. 1998. Trade names and designations of plasticizers. Modern Plastics Encyclopedia 1999. 

75(12):c111, c115.

Kawamura K, Kaplan IR. 1983. Organic compounds in the rainwater of Los Angeles. Environ Sci

Technol 17:497-501.

*Kawano M. 1980a. [Toxicological studies on phthalate esters. 1. Inhalation effects of dibutyl phthalate

(DBP) on rats.] Nippon Eiseigaku Zasshi (Jpn J Hyg) 35:684-692. (Japanese).

*Kawano M. 1980b. [Toxicological studies on phthalate esters. 2. Metabolism, accumulation and

excretion of phthalate esters in rats.] Nippon Eiseigaku Zasshi (Jpn J Hyg) 35:693-701. (Japanese)

*Kawashima Y, Hanioka N, Matsumura M, et al. 1983. Induction of microsomal stearoyl-CoA

desaturation by the administration of various peroxisome proliferators. Biochim Biophys Acta 752:259-

264.

*Keith LH, Garrison AW, Allen FR, et al. 1976. Identification of organic compounds in drinking water

from thirteen U.S. cities. In: Keith LH, ed. Identification and analysis of organic pollutants in water. 

Ann Arbor, MI: Ann Arbor Science Publishers, Inc., 329-362.

Kerster HW, Schaeffer DJ. 1983. Brine shrimp (Artemia salina) Nauplii as a teratogen test system. 

Ecotoxicol Environ Saf 7:342-349.

*Keys DA, Wallace DG, Kepler TB, et al. 2000. Quantitative evaluation of alternative mechanisms of

blood disposition of di(n-butyl) phthalate and mono(n-butyl) phthalate in rats. Toxicol Sci 53:173-184.

Killinger JM, Basaran AH, Mezza LE, et al. 1988a. Prechronic dosed feed study of dibutyl phthalate

(CAS No. 84-74-2) in B6C3F, mice (phase I - maximum perinatal dose). Report to National Toxicology

Program, Research Triangle Park, NC, by Battelle, Columbus, OH. 

Killinger J, Basaran A, Mezza L, et al. 1989. Perinatal dose study of dibutyl phthalate in rats and mice. 

Toxicologist 9(1):273.
DI-n-BUTYL PHTHALATE 160

9. REFERENCES

Killinger LM, Basaran AH, Persing RL, et al. 1988b. Maximum perinatal dose feed study of dibutyl

phthalate (CAS No. 84-74-2) in Fischer 344 rats. Research Triangle Park: National Toxicology Program. 

Killinger JM, Melnick R, Basaran A, et al. 1991. Effect of dibutyl phthalate on the F344 rat with and

without in utero exposure. Toxicologist 11:341.

*Kinman R, Nutini D, Carson D. 1995. Evaluation of leachate and gas from sanitary landfills with and

without HHW components. Proc Ind Waste Conf 49:263-269.

*Kleisasser NH, Kastenbauer ER, Weissacher H, et al. 2000. Phthalates demonstrate genotoxicity on

human mucosa of the upper aerodigestive tract. Environ Mol Mutagen 35:9-12.

Kluwe WM. 1982. Overview of phthalate ester pharmacokinetics in mammalian species. Environ Health

Perspect 45:3-9.

Knudsen FR, Pottinger TG. 1999. Interaction of endocrine disrupting chemicals, singly and in

combination, with estrogen-, androgen-, and corticosteroid-binding sites in rainbow trout (oncorhynchus

mykiss). Aquat Toxicol 44:159-170.

*Kodama T, Takai Y. 1974. [Determination of phthalate esters.] Kogai lo saroaku 10:977-980. 

(Japanese).

*Komori M, Nishio K, Kitada M, et al. 1990. Fetus-specific expression of a form of cytochrome P-450 in

human livers. Biochemistry 29:4430-4433.

Kool HJ, van Kreijl CF, Zoeteman BC. 1982. Toxicology assessment of organic compounds in drinking

water. CRC Crit Rev Environ Control 12:307-357.

Korhonen A, Hemminki K, Vainio H. 1983. Embryotoxic effects of phthalic acid derivatives, phosphates

and aromatic oils used in the manufacturing of rubber on 3 day chicken embryos. Drug Chem Toxicol

6:191-208.

*Krauskopf LG. 1973. Studies of the toxicity of phthalates via ingestion. Environ Health Perspect 3:61-

72.

*Krishnan K, Andersen ME. 1994. Physiologically based pharmacokinetic modeling in toxicology. In:

Hayes AW, ed. Principles and methods of toxicology 3rd ed. New York, NY: Academic Press, 399-437. 

*Krishnan K, Andersen ME, Clewell H 3rd, et al. 1994. Physiologically based pharmacokinetic modeling

of chemical mixtures. In: Yang R, ed. Toxicology of chemical mixtures. New York, NY: Raven Press,

149-188. 

Kurane R. 1986. Microbial degradation of phthalate esters. Microbiol Sci 3:92-95.

Kurane R, Suzuki T, Takahara Y. 1979. Microbial population and identification of phthalate esterutilizing microorganisms. Agric Biol Chem 43:907-917.
DI-n-BUTYL PHTHALATE 161

9. REFERENCES

Lake BG, Cook WM, Worrell NR, et al. 1991. Dose-response relationships for induction of hepatic

peroxisome proliferation and testicular atrophy by phthalate esters in the rat [Abstract]. Hum Exp Toxicol

10:67-68.

*Lake BG, Phillips JC, Linnell JC, et al. 1977. The in vitro hydrolysis of some phthalate deters by hepatic

and intestinal preparations from various species. Toxicol Appl Pharmacol 39:239-248.

*Lamb JC, Chapin RE, Teague J, et al. 1987. Reproductive effects of four phthalic acid esters in the

mouse. Toxicol Appl Pharmacol 88:255-269.

Lamb JC, Reel J, Lawton AD, et al. 1997. Di-n-butyl phthalate, mice. Environ Health Perspect Suppl

105:247-248.

Lao RC, Oja H, Thomas RS, et al. 1973. Assessment of environmental problems using the combination of

gas chromatography and quadruple mass spectrometry. Sci Total Environ 2:223-233.

Lawrence WH, Malik M, Turner JE, et al. 1975. A toxicological investigation of some acute, short-term,

and chronic effects of administering di-2-ethylhexyl phthalate (DEHP) and other phthalate esters. Environ

Res 9:1-11.

Layton DW, Mallon BJ, Rosenblatt DH, et al. 1987. Deriving allowable daily intakes for systemic

toxicants lacking chronic toxicity data. Regul Toxicol Pharmacol 7:96-112.

Layton DW, McKone TE, Hall CH, et al. 1986. Demilitarization of conventional ordinance: Priorities for

data-base assessments of environmental contaminants. Fort Detrick, Federick, MD: U.S. Army Medical

Research and Development Command. ADA 182922.

*LBI. 1985a. Evaluation of 1C in the in vitro transformation of BALB/3T3 cells assay: Final Report. 

Litton Bionetics, Inc. Chemical Manufacturers Association, Washington, DC. LBI Project No. 20992.

LBI. 1985b. Evaluation of IC in the mouse lymphoma toxicity assay: Final report. Litton Bionetics, Inc. 

Chemical Manufacturers Association, Washington, DC. LBI Project No. 20989.

*Leeder JS, Kearns GL. 1997. Pharmacogenetics in pediatrics: Implications for practice. Pediatr Clin

North Am 44(1):55-77.

LeFaux R, ed. 1968. Practical toxicology of plastics. Cleveland, OH: The Chemical Rubber Co., 137-

138, 346-349, 412-419.

*Lehman AJ. 1955. Insect repellents. Assoc of Food and Drug Officials. Quarterly Bulletin 19:87-99.

*Leung H-W. 1993. Physiologically-based pharmacokinetic modelling. In: Ballentine B, Marro T,

Turner P, eds. General and applied toxicology. New York, NY: Stockton Press, 153-164.

*Lewis R. 1993. Dibutylphenyl phosphate. In: Lewis R, ed. Hawley's condensed chemical dictionary. 

New York, NY: Van Nostrand Reinhold Company, 374.

Ligocki MP, Pankow JF. 1985. Assessment of absorption/solvent extraction with polyurethane foam and

adsorption/thermal desorption with Tenax-GC for the collection and analysis of ambient organic vapors. 

Anal Chem 57:1138-1144.
DI-n-BUTYL PHTHALATE 162

9. REFERENCES

Ligocki MP, Leuenberger C, Pankow JF. 1985. Trace organic compounds in rain-II. Gas scavenging of

neutral organic compounds. Atmos Environ 19:1609-1617.

Lindner V. 1991a. Explosives and propellants (explosives). In: Kroschwitz JI, Howe-Grant M, eds. 

Kirk-Othmer encyclopedia of chemical technology. New York, NY: John Wiley & Sons, 21, 56.

Lindner V. 1991b. Explosives and propellants (propellants). In: Kroschwitz JI, Howe-Grant M, eds. 

Kirk-Othmer encyclopedia of chemical technology. New York, NY: John Wiley & Sons, 69, 115.

*Lindner V. 1993a. Explosives and propellants (explosives). In: Kroschwitz J, Howe-Grant M, eds. 

Kirk-Othmer encyclopedia of chemical technology 4th ed. New York, NY: John Wiley & Sons, Inc., 21,

56-68.

*Lindner V. 1993b. Explosives and propellants (propellants). In: Krowschwitz J, Howe-Grant, eds. 

Kirk-Othmer encyclopedia of chemical technology 4th ed. New York, NY: John Wiley & Sons Inc., 69,

115-125.

*Livingston, AL. 1978. Forage plant estrogens. J Toxicol Environ Health 4:301-324. 

Lock EA, Mitchell AM, Elcombe CR. 1989. Biochemical mechanisms of induction of hepatic

peroxisome proliferation. Ann Rev Pharmacol Toxicol 29:145-163.

*Lygre H, Solheim E, Gjerdet N, et al. 1993. Leaching of organic additives from dentures in vivo. Acta

Odontol Scand 51:45-51.

*Lyman WJ. 1982. Adsorption coefficient for soils and sediments. In: Lyman WJ, Reehl WF,

Rosenblatt DH, eds. Handbook of chemical property estimation methods; Environmental behavior of

organic compounds. New York, NY: McGraw-Hill Book Co., 4-1 - 4-3.

*MAFF. 1995. Food surveillance information sheet. MAFF-UK - Phthalates in paper and board

packaging. Ministry of Agriculture, Fisheries, and Food. http://www.foodstandards.gov.uk/maff. October

16, 2000.

*MAFF. 1996a. Food surveillance information sheet. MAFF-UK - Phthalates in food. Ministry of

Agriculture, Fisheries, and Food. http://www.foodstandards.gov.uk/maff. October 16, 2000.

*MAFF. 1996b. Food surveillance information sheet. MAFF-UK - Phthalates in infant formula. 

Ministry of Agriculture, Fisheries, and Food. http://www.foodstandards.gov.uk/maff.. October 16, 2000.

*MAFF. 1998. Food surveillance information sheet. MAFF-UK - Phthalates in infant formula - followup survey. Ministry of Agriculture, Fisheries, and Food. http://www.foodstandards.gov.uk/maff. October

16, 2000.

*Matsuda K, Schnitzer M. 1971. Reactions between fulvic acid, a soil humic material and dialkyl

phthalates. Bull Environ Contam Toxicol 6(3):200-204.

*Mayr U, Butsch A, Schneider S. 1992. Validation of two in vitro test systems for estrogenic activities

with zearalenone, phytoestrogens and cereal extracts. Toxicology 74:135-149.
DI-n-BUTYL PHTHALATE 163

9. REFERENCES

*McFall JA, Antoine, SR, DeLeon IR. 1985a. Base-neutral extractable organic pollutants in biota and

sediments from Lake Pontchartrain. Chemosphere 14(10):1561-1569.

*McFall JA, Antoine SR, DeLeon IR. 1985b. Organics in the water column of Lake Pontchartrain. 

Chemosphere 14(9):1253-1265.

*Melnick RL, Schiller CM. 1985. Effect of phthalate esters on energy coupling and succinate oxidation

in rat liver mitochondria. Toxicology 34:13-27. 

*Mes J, Coffin DE, Campbell DS. 1974. Di-n-butyl and di-2-ethylhexyl phthalate in human adipose

tissue. Bull Environ Contam Toxicol 12(6):721-725.

Metcalf RL. 1991. Insect control technology. In: Kroschwitz JI, Howe-Grant M, eds. Kirk-Othmer

encyclopedia of chemical technology. New York, NY: John Wiley & Sons, 590, 600.

*Meylan W, Howard P. 1993. Computer estimation of the atmospheric gas-phase reaction rate of organic

compounds with hydroxyl radicals and ozone. Chemosphere 26(12):2293-2299.

Michael LC, Pellizari ED. 1988. Development and evaluation of a procedure for determining volatile

organics in water. Environ Sci Technol 22:565-570.

*Milkov LE, Aldyreva MV, Popova TB, et al. 1973. Health status of workers exposed to phthalate

plasticizers in the manufacture of artificial leather and films based on PVC resins. Environ Health

Perspect 3:175-178.

*Milligan SR, Balasubramanian AV, Kalita JC. 1998. Relative potency of xenobiotic estrogens in an

acute in vivo mammalian assay. Environ Health Perspect 106(1):23-26.

*Moody DE, Reddy JK, Lake BG, et al. 1991. Peroxisome proliferation and nongenotoxic

carcinogenesis: Commentary on a symposium. Fund Appl Toxicol 16(2):233-248.

Morrissey RE, Lamb JC, Schwetz BA, et al. 1988. Association of sperm, vaginal cytology, and

reproductive organ weight data with results of continuous breeding reproduction studies in Swiss (CD-1)

mice. Fundam Appl Toxicol 11:359-371.

*Morselli PL, Franco-Morselli R, Bossi L. 1980. Clinical pharmacokinetics in newborns and infants:

Age-related differences and therapeutic implications. Clin Pharmacokin 5:485-527.

*Murakami K, Nishiyama K, Higuti T. 1986a. Toxicity of dibutyl phthalate and its metabolites in rats. 

Nippon Eiseigaku Zasshi (Jpn J Hyg) 41(4):775-781.

*Murakami K, Nishiyama K, Higuti T. 1986b. Mitochondrial effect of orally administered dibutyl

phthalate in rats. Nippon Eiseigaku Zasshi (Jpn J Hyg) 41(4):769-774.

*Murature DA, Tang SY, Steinhardt G, et al. 1987. Phthalate esters and semen quality parameters. 

Biomed Environ Mass Spectrom 14:473-477. 

*Murray HE, Ray LE, Giam CS. 1981. Analysis of marine sediment, water and biota for selected organic

pollutants. Chemosphere 10(11/12):1327-1334.
DI-n-BUTYL PHTHALATE 164

9. REFERENCES

Mylchreest E, Cattley RC, Foster PMD. 1998a. Di(n-butyl) phthalate disrupts prenatal androgenregulated male reproductive development in a manner different from flutamide. Toxicologist 42(1-S):176.

*Mylchreest E, Cattley RC, Foster PMD. 1998b. Male reproductive tract malformations in rats following

gestational and lactational exposure to di(n-butyl) phthalate: An antiandrogenic mechanism? Toxicol Sci

43:47-60.

*Mylchreest E, Sar M, Cattley RC, et al. 1999. Disruption of androgen-related male reproductive

development by di(n-butyl) phthalate during late gestation in rats is different from flutamide. Toxicol

Appl Pharm 156:81-95.

*Mylchreest E, Wallace DG, Cattley RC, et al. 2000. Dose-dependent alterations in androgen-regulated

male reproductive development in rats exposed to di(n-butyl) phthalate during late gestation. Toxicol Sci

55:143-151.

NAS. 1977. Drinking water and health. Washington, DC: National Academy of Sciences.

*NAS/NRC. 1989. Report of the oversight committee. In: Biologic markers in reproductive toxicology. 

National Academy of Sciences/National Research Council. Washington, DC: National Academy Press,

15-35.

NATICH. 1988. NATICH data base report on state, local and EPA air toxics activities. Research

Triangle Park, NC: U.S. Environmental Protection Agency, Office of Air Quality Planning and Standards,

National Air Toxics Information Clearinghouse. EPA-450/5-88-007. NTIS No. PB 89-106983.

Natusch DF, Tomkins BA. 1978. Isolation of polycyclic organic compounds by solvent extraction with

dimethyl sulfoxide. Anal Chem 50:1429-1434.

Nematollahi J, Guess WL, Autian J. 1967. Plasticizers in medical application. I. Analysis and toxicity

evaluation of dialkyl benzenedicarboxylates. J Pharm Sci 56:1446-1453.

Nerín C, Cacho J, Gancedo P. 1993. Platicizers from printing inks in a selection of food packagings and

their migration to food. Food Addit Contam 10(4):453-460.

*NIEHS. 1994. Prestart toxicokinetic study report: Di-n-butyl phthalate (DBP) in rodent plasma. 

Research Triangle Park, NC: National Institute of Environmental Health Sciences. NIH contract no. N01-

ES-15307. 

*NIEHS. 1995. Toxicokinetic study report: The Toxicokinetics and metabolism of di-n-butyl phthalate. 

Research Triangle Park, NC: National Institute of Environmental Health Sciences. NIH contract no. NIH

contract no. N01-ES-15307.

*NIH. 1999. Toxicology and environmental health information. National Institute of Health, National

Library of Medicine. http://chem.sis.nlm.nih.gov. May 23, 1999. 

*Nikonorow M, Mazur H, Piekacz H. 1973. Effect of orally administered plasticizers and polyvinyl

chloride stabilizers in the rat. Toxicol Appl Pharmacol 26:253-259.
DI-n-BUTYL PHTHALATE 165

9. REFERENCES

NIOSH. 1977. Health hazard evaluation/toxicity determination report 76-92-363, Jeffery Bigelow Design

Group, Inc., Washington, DC. Cincinnati, OH: National Institute for Occupational Safety and Health. 

NIOSH-TR-HHE-76-92-36. NTIS No. PB-273913.

NIOSH. 1985a. NIOSH pocket guide to chemical hazards. Washington, DC: U.S. Department of Health

and Human Services, Public Health Service, Centers for Disease Control, National Institute for

Occupational Safety and Health.

NIOSH. 1985b. Dibutyl phthalate and di(2-ethylhexyl) phthalate - method 5020. In: NIOSH manual of

analytical methods. 3rd ed. Cincinnati, OH: National Institute for Occupational Safety and Health. 

*NIOSH. 1988a. National occupational exposure survey. Cincinnati, OH: National Institute for

Occupational Safety and Health.

NIOSH. 1988b. National occupational hazard survey. Cincinnati, OH: National Institute for

Occupational Safety and Health.

*NIOSH. 1994. National occupational exposure survey. Cincinnati, OH: National Institute for

Occupational Safety and Health.

NIOSH. 1995. National occupational exposure survey. Cincinnati, OH: National Institute for

Occupational Safety and Health.

*NIOSH. 1997. National occupational exposure survey. Cincinnati, OH: National Institute for

Occupational Safety and Health.

NIOSH. 1999a. Acute toxicity data. Cincinnati, OH. National Institute for Occupational Safety and

Health.

NIOSH. 1999b. Pocket guide to chemical hazards. Washington DC: National Institute for Occupational

Safety and Health, U.S. Department of Health and Human Services. 

*NIOSH. 2001. Pocket guide to chemical hazards. National Institute for Occupational Safety and Health. 

http://www.cdc.gov/niosh/npg/npgd0187.html. January 8, 2001.

*Nishikawa H, Katami T, Takahara Y, et al. 1992. Emission of organic compounds by combustion of

waste plastics involving chloride polymer. Chemosphere 25(12):1953-1960.

NLM. 1988. Chemline. National Library of Medicine, Bethesda, MD. December 1988. 

Norpoth K. 1983. Phthalates. In: Parmeggiani L, ed. Encyclopedia of occupational health and safety. 

3rd ed. Vol. 2. Geneva, Switzerland: International Labour Office, 1690-1693.

*NRC. 1993. Pesticides in the diets of infants and children. National Research Council. Washington,

DC: National Academy Press.

*NTP. 1984. Di(n-butyl) phthalate: Reproduction and fertility assessment in CD-1 mice when

administered in the feed. Research Triangle Park, NC: National Institute of Environmental Health

Science, National Toxicology Program. NTP 84-411. NTIS No. PB85-144798. 
DI-n-BUTYL PHTHALATE 166

9. REFERENCES

*NTP. 1995. Toxicity studies of dibutyl phthalate (CAS no. 84-74-2) administered in feed to F344/N and

B6C3F1 mice. National Toxicology Program Toxicity Report Series, 30. Research Triangle Park, NC: 

National Toxicology Program/National Institutes of Health. 

*NTP. 2000. NTP-CERHR expert panel report on dinbutyl phthalate. Alexandria, VA: Center for the

Evaluation of Risks to Human Reproduction, U.S. Department of Health and Human Services, National

Toxicology Program. NTP-CERHR-DBP-00.

*Nyssen GA, Miller ET, Glass TF, et al. 1987. Solubilities of hydrophobic compounds in aqueousorganic solvent mixtures. Environ Monit Assess 9:1-11.

Oehme M. 1985. Negative ion chemical ionization mass spectrometry—a useful technique for the

selective detection of polar substituted polycyclic aromatic hydrocarbons with mutagenic properties. 

Chemosphere 14:1285-1297.

*O'Grady DP, Howard PH, Werner AF. 1985. Activated sludge biodegradation of 12 commercial

phthalate esters. Appl Environ Microbiol 49(2):443-445.

Ohta Y, Nakamoto M. 1979. Metabolism of di-n-butyl phthalate by Aeromonas sp. Hakko Kogaku

Kaishi 57:50-53.

*Oishi S, Hiraga K. 1980a. Effect of phthalic acid esters on mouse testes. Toxicol Lett 5:413-416.

*Oishi S, Hiraga K. 1980b. Testicular atrophy induced by phthalic acid esters: Effect on testosterone and

zinc concentrations. Toxicol Appl Pharmacol 53:35-41.

Okada S, Tamemasa O. 1978. [Distribution and metabolism of di-(n-butyl)-phthalate in mice and its

interaction with nucleic acids and proteins.] Yakugaku Zasshi 98:1229-1235. (Japanese)

OSHA. 1989. U.S. Department of Labor. Occupational Safety and Health Administration: Part III. 

Federal Register. 54:2332-2983.

OSHA. 1998a. Occupational Safety and Health Administration. Code of Federal Regulations. 29 CFR

1910.1000.

OSHA. 1998b. Occupational Safety and Health Administration. Code of Federal Regulations. 29 CFR

1926.55.

OSHA. 1998c. Occupational Safety and Health Administration. Code of Federal Regulations. 29 CFR

1915.1000.

OSHA. 1999. Safety and health regulations for construction: Gases, vapors, fumes, dusts, and mists. 

Occupational Safety and Health Administration. Code of Federal Regulations. 

http://www.access.gpo.gov/nara/cfr/waisidx_99/29cfr1926_99.html. February 2, 2001.

OSHA. 2000a. Occupational safety and health standards: Air contaminants. Occupational Safety and

Health Administration. Code of Federal Regulations. 

http://www.access.gpo.gov/nara/cfr/waisidx_99/29cfr1910a_99.html. February 2, 2001.
DI-n-BUTYL PHTHALATE 167

9. REFERENCES

OSHA. 2000b. Occupational safety and health standards for shipyard employment: Air contaminants. 

Occupational Safety and Health Administration. Code of Federal Regulations. 

http://www.access.gpo.gov/nara/cfr/waisidx_00/29cfr1915_00.html. February 7, 2001.

*OSHA. 2001a. Air contaminants. Occupational and Safety & Health Administration. U.S. Department

of Labor. Code of Federal Regulations. 29 CFR 1915.1000. 

http://www.osha.slc.gov/OshStd_data/1915_1000.html. April 5, 2001.

*OSHA. 2001b. Gases, vapors, fumes, dusts, and mists. Occupational Safety & Health Administration. 

U.S. Department of Labor. Code of Federal Regulations. 29 CFR 1926.55, Appendix A. 

http://www.osha:slc.gov/OshStd_toc/OSHA_Std_toc_1926.html. April 5, 2001.

*OSHA. 2001c. Limits for air contaminants. Occupational and Safety & Health Administration. U.S.

Department of Labor. Code of Federal Regulations. 29 CFR 1910.1000, (Table Z-1). http://www.oshaslc.gov/OshStd_data/1910_1000_TABLE Z-1.html. April 5, 2001.

*Otson R, Davis C, Fellin P, et al. 1991. Source apportionment for PAH in indoor air (northern climates). 

In: Cooke M, et al., eds. Polynuclear aromatic hydrocarbons: Measurement, means, and metabolism,

International Symposium, 11th ed. Columbus, OH: Battelle Press, 667-685.

Overcash MR, Weber JB, Miles ML. 1982. Behavior of organic priority pollutants in the terrestrial

system: Di-n-butyl phthalate ester, toluene, and 2,4-dinitrophenol. Raleigh, NC: North Carolina State

University, Water Resources Research Institute. UNC-WRRI-82-171.

Overturf ML, Druilhet RE, Liehr JG, et al. 1979. Phthalate esters in normal and pathological human

kidneys. Bull Environ Contam Toxicol 22:536-542.

*Owen GM, Brozek J. 1966. Influence of age, sex, and nutrition on body composition during childhood

and adolescence. In: Falkner F, ed. Human Development. Philadelphia, PA: WB Saunders, 222-238.

Packham RF, Beresford SA, Fielding M. 1981. Health related studies of organic compounds in relation to

re-use in the United Kingdom. Sci Total Environ 18:167-186.

Pancorbo OC, Varney TC. 1986. Fate of synthetic organic chemicals in soil-groundwater systems. Vet

Hum Toxicol 28:127-143. 

*Pankow JF, Ligocki MP, Rosen ME, et al. 1988. Adsorption/thermal desorption with small cartridges

for the determination of trace aqueous semivolatile organic compounds. Anal Chem 60:40-47.

Petrasek AC, Kugelman IJ, Austern BM, et al. 1983. Fate of toxic organic compounds in wastewater

treatment plants. J Water Pollut Control Fed 55(10):1286-1296.

PHRED. 1988. Public Health Risk Evaluation Database. U.S. Environmental Protection Agency,

Washington, DC. March 1988.

Pizzoli M, Scandola M, Ceccorulli G, et al. 1985. Rate of absorption of di-n-butyl phthalate in glassy

poly(vinylchloride). Polym Comm 26:107-109. 

*Pocius AV. 1991. Adhesives. In: Kroschwitz JI, Howe-Grant M, eds. Kirk-Othmer encyclopedia of

chemical technology. Vol 1. New York, NY: John Wiley & Sons, 445-466.
DI-n-BUTYL PHTHALATE 168

9. REFERENCES

*Popp JA, Marsman DS, Cattley RC, et al. 1989. Hepatocarcinogenicity and peroxisome proliferation. 

CIIT Activities 9(3):1-7. 

*Preston MR, Al-Omaran LA. 1986. Dissolved and particulate phthalate esters in the River Mersey

Estuary. Marine Pollut Bull 17(12):548-553.

*Preston MR, Al-Omaran LA. 1989. Phthalate ester speciation in estuarine water, suspended particulates

and sediments. Environ Pollut 48:183-193.

*Poulin P, Krishnan K. 1995. An algorithm for predicting tissue: Blood partition coefficients of organic

chemicals from n-octanol: water partition coefficient data. J Toxicol Environ Health 46:117-129.

*Pugh GJ, Isenberg JS, Kamendulis LM, et al. 2000. Effects of di-isononyl phthalate, di-2-ethylhexyl

phthalate, and clofibrate in cynomolgus monkeys. Toxicol Sci 2000:181-188.

*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.

Rao MS, Reddy JK. 1987. Peroxisome proliferation and hepatocarcinogenesis. Carcinogenesis 8:631-

636.

*Rastogi SC. 1998. Gas chromatographic analysis of phthalate esters in plastic toys. Chromatographia

47(784):724-726.

*Ray LE, Murray HE, Giam CS. 1983. Organic pollutants in marine samples from Portland, Maine. 

Chemosphere 12(7/8):1031-1038.

Reddy JK, Rao MS, Lalwani ND, et al. 1987. Induction of hepatic peroxisome proliferation by

xenobiotics. In: Fahimi HD, Sies H, eds. Peroxisomes in biology and medicine. Heidelberg, West

Germany: Springer-Verlag, 255-262.

*Rhodes C, Orton TC, Pratt IS, et al. 1986. Comparative pharmacokinetics and subacute toxicity of di(2-

ethylhexyl) phthalate (DEHP) in rats and marmosets: Extrapolation of effects in rodents to man. Environ

Health Perspect 65:299-308.

Rieger MM. 1991. Cosmetics. In: Kroschwitz JI, Howe-Grant M, eds. Kirk-Othmer encyclopedia of

chemical technology. New York, NY: John Wiley & Sons, 607, 616.

*Ritsema R, Cofino WP, Frintrop PLM, et al. 1989. Trace-level analysis of phthalate esters in surface

water and suspended particulate matter by means of capillary gas chromatography with electron- capture

and mass-selective detection. Chemosphere 18(11/12):2161-2175.

Rosenbaum AS, Axelrad DA, Woodruff TJ, et al. 1999. National estimates of outdoor air toxics

concentrations. J Air Waste Manage Assoc 49:1138-1152.

Rowland IR, Cottrell RC, Phillips JC. 1977. Hydrolysis of phthalate esters by the gastro-intestinal

contents of the rat. Food Cosmet Toxicol 15:17-21.

*Roy WR. 1994. Groundwater contamination from municipal landfills in the U.S.A.. In: Adriano DC,

ed. Contaminated groundwaters . Northwood, UK: Sci Rev, 411-446. 
DI-n-BUTYL PHTHALATE 169

9. REFERENCES

*RTECS. 1999. Registry of Toxic Effects of Chemical Substances. National Institute for Occupational

Safety and Health. April 19, 1999.

*Rubin RJ, Kozumbo W, Kroll R. 1979. Ames mutagenic assay of a series of phthalic acid esters: 

Positive response of the dimethyl and diethyl esters in TA 100 [Abstract]. Toxicol Appl Pharmacol

48:A133.

*Russell DJ, McDuffie B. 1986. Chemodynamic properties of phthalate esters: partitioning and soil

migration. Chemosphere 15(8):1003-1021. 

Saido K, Motohashi S, Kuroki T. 1980. Studies on the thermal decomposition of phthalic acid esters. 

Thermal decomposition of di-n-butyl phthalate and analysis of its decomposed products. Nihon Daigaku

Yakugaku Kenkyu Hokoku 20:1-10.

*Saillenfait AM, Payan JP, Fabry JP, et al. 1998. Assessment of developmental toxicity, metabolism, and

placental transfer of di-n-butyl phthalate administered to pregnant rats. Toxicol Sci 45:212-224.

Salthouse TN, Matlaga BF, O'Leary RK. 1973. Microspectrophotometry of macrophage lysosomal

enzyme activity: A measure of polymer implant tissue toxicity. Toxicol Appl Pharmacol 25:201-211.

*Sanders HO, Mayer FL, Jr, Walsh DF. 1973. Toxicity, residue dynamics, and reproduction effects of

phthalate esters in aquatic invertebrates. Environ Res 6:84-90.

Sandmeyer EE. Kirwin CJ Jr. 1981. Esters. In: Clayton GD, Clayton FE, eds. Patty's industrial hygiene

and toxicology. 3rd ed. Volume 2A: Toxicology. New York, NY: John Wiley and Sons, 2344-2412.

Sax NI, Lewis RJ Sr, eds. 1987. Hawley's condensed chemical dictionary. 11th ed. New York, NY: Van

Nostrand Reinhold Company, 372.

*Schilling K, Kaufman W, Hildebrand B. 1992. Study on the oral toxicity of dibutyl phthalate in Wistar

rats—administration via the diet over 3 months. BASF Corporation. Ludwigshafen, Germany. 

Microfiche No. OTS0535640; Document ID 86-920000903.

Schmid P, Schlatter C. 1985. Excretion and metabolism of di(2-ethylhexyl)-phthalate in man. 

Xenobiotica 15(3):251-256.

*Scholz N, Diefenbach R, Rademacher I, et al. 1997. Biodegradation of DEHP, DBP, and DINP: Poorly

water soluble and widely used phthalate plasticizers. Bull Environ Contam Toxicol 58:527-534.

*Schouten MJ, Peereboom JW, Brinkman U. 1979. Liquid chromatographic analysis of phthalate esters

in Dutch river water. Int J Environ Anal Chem 7:13-23.

*Schulsinger C, Mollgaard K. 1980. Polyvinyl chloride dermatitis not caused by phthalates. Contact

Dermatitis 6:477-480.

*Scott RC, Dugard PH, Ramsey JD, et al. 1987. In vitro absorption of some o-phthalate deters through

human and rat skin. Environ Health Perspect 74:223-227.
DI-n-BUTYL PHTHALATE 170

9. REFERENCES

*Seed JL. 1982. Mutagenic activity of phthalate esters in bacterial liquid suspension assays. Environ

Health Perspect 45:111-114.

*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.

Seth PK. 1982. Hepatic effects of phthalate esters. Environ Health Perspect 45:27-34.

Shafer KH, Cooke M, DeRoos F, et al. 1981. WCOT capillary column GC/FT-IR and GC/MS for

identifying toxic organic pollutants. Appl Spectrosc 35:469-472.

*Shahin MM, Von Borstel RC. 1977. Mutagenic and lethal effects of alpha-benzene hexachloride,

dibutyl phthalate and trichloroethylene in Saccharomyces cerevisiae. Mutat Res 48:173-180.

Shanker R, Ramakrishna C, Seth PK. 1985. Degradation of some phthalic acid esters in soil. Environ

Pollut (Series A) 39:1-7.

*Shea PJ, Weber JB, Overcash MR. 1982. Uptake and phytotoxicity of di-n-butyl phthalate in corn (Zea

mays). Bull Environ Contam Toxicol 29:153-158.

*Sheldon LS, Hites RA. 1979. Sources and movement of organic chemicals in the Delaware River. 

Environ Sci Technol 13(5):574-579.

*Shelton DR, Tiedje JM. 1984. General method for determining anaerobic biodegradation potential. 

Appl Environ Microbiol 47(4):850-857.

*Shibata K, Motooka K, Murata K, et al. 1982. Increase in growth rate and activity of the trytophan-NAD

pathway caused by di-n-butyl phthalate in rats fed on a tryptophan-limited diet. J Nutr Sci Vitaminol

28:173-177.

Shibko SI, Blumenthal H. 1973. Toxicology of phthalic acid esters used in food-packaging material. 

Environ Health Perspect 3:131-137.

*Shiota K, Nishimura H. 1982. Teratogenicity of di(2-ethylhexyl) phthalate (DEHP) and di-n-butyl

phthalate (DBP) in mice. Environ Health Perspect 45:65-70.

Shiota K, Chou MJ, Nishimura H. 1980. Embryotoxic effects of di-2-ethylhexyl phthalate (DEHP) and

di-n-butyl phthalate (DBP) in mice. Environ Res 22:245-253.

*Shiu WY, Ma KC, Mackay D, et al. 1990. Solubilities of pesticide chemicals in water part II: Data

compilation. Rev Environ Contam Toxicol 116:15-187.

Shono T, Suita S. 2000. Letter to the editor. Toxicol Appl Pharmacol 164:336.

Shono T, Kai H, Suita S, et al. 2000. Time-specific effects of mono-n-butyl phthalate on the

transabdominal descent of the testis in rat fetuses. BJU Int 86(1):121-125.

*Short RD, Robinson EC, Lington AW, et al. 1987. Metabolic and peroxisome proliferation studies wuth

di(2-ethylhexel)phthalate in rats and monkeys. Toxicol Ind Health 3(1):185-195.
DI-n-BUTYL PHTHALATE 171

9. REFERENCES

Singh AR, Lawrence WH, Autian J. 1972. Teratogenicity of phthalate esters in rats. J Pharm Sci 61:51-

55.

Singh AR, Lawrence WH, Autian J. 1973. Embryonic-fetal toxicity and teratogenic effects of adipic acid

esters in rats. J Pharm Sci 62:1596-1600.

Sittig M, ed. 1985. Handbook of toxic and hazardous chemicals and carcinogens. 2nd ed. Park Ridge, NJ: 

 Noyes Publications, 311-312.

*Smith CC. 1953. Toxicity of butyl stearate, dibutyl sebacate, dibutyl phthalate, and methoxyethyl oleate. 

AMA Arch Ind Hyg Occup Med 7:310-318.

*Smith RM. 1988. Supercritical fluid chromatography. Anal Chem 60(24):1394A.

SRI. 1985. Directory of chemical producers. Stanford Research Institute. United States of America. 

Menlo Park, CA: SRI International, 799.

SRI. 1986. Directory of chemical producers. Stanford Research Institute. United States of America. 

Menlo Park, CA: SRI International, 9055.

SRI. 1987. Directory of chemical producers. Stanford Research Institute. United States of America. 

Menlo Park, CA: SRI International, 889.

SRI. 1988. Directory of chemical producers. Stanford Research Institute. United States of America. 

Menlo Park, CA: SRI International, 870.

*SRI. 1998. Directory of chemical producers. Stanford Research Institute. United States of America. 

Menlo Park, CA: SRI International, 870.

*SRI. 2000. Directory of chemical producers. Stanford Research Institute. United States of America. 

Menlo Park, CA: SRI International.

*Srivastava S, Singh GB, Srivastaba SP, et al. 1990. Testicular toxicity of di-n-butyl phthalate in adult

rats: Effect on marker enzymes of spermatogenesis. Indian J Exp Biol 28:67-70.

Stahlschmidt-Allner P, Allner B, Rombke J, et al. 1997. Endocrine disrupters in the aquatic environment. 

Environ Sci Pollut Res Int 4:155-162

*Stalling DL, Hogan JW, Johnson JL. 1973. Phthalate ester residues—their metabolism and analysis in

fish. Environ Health Perspect 3:159-173. 

Staples CA, Parkerton TF, Peterson DR. 2000. A risk assessment of selected phthalate esters in North

American and Western European surface waters. Chemosphere 40:885-891.

*Staples C, Peterson D, Parkerton T, et al. 1997. The environmental fate of phthalate esters: A literature

review. Chemosphere 35(4):667-749.

*STAPPA/ALAPCO. 1999. State and Territorial Air Pollution Program Administrators/Association of

Local Air Pollution Control Officials. Washington, D.C. http://www.4cleanair.org/states.html#NorthC. 

May 6, 1999.
DI-n-BUTYL PHTHALATE 172

9. REFERENCES

Steen WC, Paris DF, Baughman GL. 1980. Effects of sediment sorption on microbial degradation of

toxic substances. Contaminants and Sediments 1:477-482.

Streufert JM, Jones JR, Sanders HO. 1980. Toxicity and biological effects of phthalate esters on midges

(Chironomus plumosus). Trans Mo Acad Sci 14:33-40.

Stott WT. 1988. Chemically induced proliferation of peroxisomes: Implications for risk assessment. 

Regul Toxicol Pharmacol 8:125-159.

*Stubin A, Bronsnan T, Porter K, et al. 1996. Organic priority pollutants in New York City municipal

wastewaters: 1989-1993. Water Environ Res 68(6):1037-1044.

Sugawara N. 1974. Toxic effect of a normal series of phthalate esters on the hatching of shrimp eggs. 

Toxicol Appl Pharmacol 30:87-89.

*Sullivan KF, Atlas EL, Giam C-S. 1982. Adsorption of phthalic acid esters from seawater. Environ Sci

Technol 16:428-432.

*Swann R, Laskowski D, McCall P, et al. 1983. A rapid method for the estimation of the environmental

parameters octanol/water partition coefficient, soil sorption constant, water to air ratio, and water

solubility. Residue Rev 85:18-28.

*Swartz RC, Schults DW, Ditsworth GR, et al. 1983. Sediment toxicity, contamination, and

macrobenthic communities near a large sewage outfall. In: Boyle TP, ed. Validation and predictability of

laboratory methods for assessing the fate and effects of contaminants in aquatic ecosystems. Philadelphia,

PA: ASTM, 152-175.

Tabak HH, Quave SA, Mashni CI, et al. 1981. Biodegradability studies with organic priority pollutant

compounds. J Water Pollut Control Fed 53:1503-1518.

Tagatz ME, Plaia GR, Deans CH. 1986. Toxicity of dibutyl phthalate-contaminated sediment to

laboratory- and field-colonized estuarine benthic communities. Bull Environ Contam Toxicol 37:141-150.

*Takahashi T, Tanaka A. 1989. Biochemical studies on phthalic esters. V. Comparative studies on in

vitro hydrolysis of di-n-butyl phthalate isomers in rats. Arch Toxicol 63:72-74.

*Tanaka A, Matsumoto A, Yamaha T. 1978. Biochemical studies on phthalic esters. III. Metabolism of

dibutyl phthalate (DBP) in animals. Toxicology 9:109-123.

*Tanino M, Ikemoto I, Tanaka A. 1987. Enzyme levels in rat testis damaged experimentally with dibutyl

phthalate. Jikeikai Med J 34:245-252.

Tavares IA, Vine ND. 1985. Phthalic acid esters inhibit arachidonate metabolism by rat peritoneal

leucocytes. J Pharm Pharmacol 37:67-68.

Tavares IA, Bennett A, Gaffen JD, et al. 1984. The biological activities of phthalate esters on rat gastric

muscle. Eur J Pharmacol 106:449-452.

Taylor BF, Curry RW, Corcoran EF. 1981. Potential for biodegradation of phthalic acid esters in marine

regions. Appl Environ Microbiol 42(4):590-595.
DI-n-BUTYL PHTHALATE 173

9. REFERENCES

Tesk JA, Antonucci JM, Eichmiller FC, et al. 1991. Dental materials. In: Kroschwitz JI, Howe-Grant

M, eds. Kirk-Othmer encyclopedia of chemical technology. New York, NY: John Wiley & Sons, 1002,

1014.

*Tesk JA, Antonucci J, Eichmiller F, et al. 1993. Dental materials. In: Kroschwitz, ed. Kirk-Othmer

encyclopedia of chemical technology. New York, NY: John Wiley & Sons Inc., 1002-1022

Thomas JA, Wienckowski DB, Gillies BA, et al. 1986. Effects of phthalic acid esters (PAEs) on the

neonate and aspects of teratogenic actions. Environ Health Perspect 65:243-248.

*Thurén A. 1986. Determination of phthalates in aquatic environments. Bull Environ Contam Toxicol

36:33-40.

*Thurén A, Larsson P. 1990. Phthalate esters in the Swedish atmosphere. Environ Sci Technol 

24:554-559.

Timofievskaya LA, Balynina ES. 1979. [Neurotoxic action of some o-phthalic acid esters.] Toksikol

Nov Prom Khim Veshchestv 15:123-128. (Russian)

*Towae,FK, Enke,W,J, Jäckh,R, Bhargava,N. 1992. Phthalic acid and derivatives. In: Elvers B,

Hawkins S, Schultz G, eds. Ullmann's encyclopedia of industrial chemistry. 5th ed., Volume A20. 

Weinheim, Germany: VCH Verlagsgesellschaft, 439-457.

TRI96. 1999. Toxic Chemical Release Inventory. National Library of Medicine, national Toxicology

Information Program, Bethesda, MD.

*TRI98. 2000. TRI Explorer: Providing access to EPA’s toxics release inventory data. Washington,

DC: Office of Information Analysis and Access. Offices of Environmental Information. U.S.

Environmental Protection Agency. Toxic Release Inventory. http://www.epa.gov/triexplorer/. May 16,

1999.

*TRI99. 2001. TRI Explorer: Providing access to EPA’s toxics release inventory data. Washington,

DC: Office of Information Analysis and Access, Offices of Environmental Information, U.S.

Environmental Protection Agency. Toxic Release Inventory. http://www.epa.gov/triexplorer/. May 15,

2001.

*UATW. 1999. Unified Air Toxics Website. U.S. Environmental Protection Agency, Office of Air

Quality Planning and Standards. http://www.epa.gov/ttnuatw1/uatwn.html. May 6, 1999.

Urushigawa Y, Yonezawa Y. 1979. Chemico-biological interactions in biological purification systems: 

VI. Relation between biodegradation rate constants of di-n-alkyl phthalate esters and their retention times

in reverse phase partition chromatography. Chemosphere 8:317-320.

*USC. 2001. Hazardous air pollutants. U.S. Code. 42USC4712. 

http://www.4law.cornell.edu/uscode/42/7412.text.html. April 4, 2001.

USDC. 1994. United States Department of Commerce. U.S. merchandise trade: exports, general

imports, and imports for consumption: January 1994. FT925/94-1.
DI-n-BUTYL PHTHALATE 174

9. REFERENCES

*USITC. 1980. Synthetic organic chemicals- United States production and sales, 1979. Washington,

DC: U.S. International Trade Commission. USITC Pub. No. 1099.

*USITC. 1981. Synthetic organic chemicals- United States production and sales, 1980. Washington,

DC: U.S. International Trade Commission. USITC Pub. No. 1183.

*USITC. 1982. Synthetic organic chemicals- United States production and sales, 1981. Washington,

DC: U.S. International Trade Commission. USITC Pub. No. 1292.

*USITC. 1983. Synthetic organic chemicals- United States production and sales, 1982. Washington,

DC: U.S. International Trade Commission. USITC Pub. No. 1422.

*USITC. 1984. Synthetic organic chemicals- United States production and sales, 1983. Washington,

DC: U.S. International Trade Commission. USITC Pub. No. 1588.

*USITC. 1985. Synthetic organic chemicals- United States production and sales, 1984. Washington,

DC: U.S. International Trade Commission. USITC Pub. No. 1745.

*USITC. 1986a. Synthetic organic chemicals- United States production and sales, 1985. Washington,

DC: U.S. International Trade Commission. USITC Pub. No. 1892.

*USITC. 1986b. Synthetic organic chemicals- United States production and sales, 1986. Washington,

DC: U.S. International Trade Commission. USITC Pub. No. 2009.

*USITC. 1987. Synthetic organic chemicals- United States production and sales, 1987. Washington,

DC: U.S. International Trade Commission. USITC Pub. No. 2118.

*USITC. 1988. Synthetic organic chemicals - United States production and sales, 1987. Washington,

DC: U.S. International Trade Commission. USITC Pub. No. 2219.

*USITC. 1989. Synthetic organic chemicals - United States production and sales, 1989. Washington,

DC: U.S. International Trade Commission. USITC Pub. No. 2338.

*USITC. 1990. Synthetic organic chemicals - United States production and sales, 1990. Washington,

DC: U.S. International Trade Commission. USITC Pub. No. 2470.

*USITC. 1991. Synthetic organic chemicals - United States production and sales, 1991. Washington,

DC: U.S. International Trade Commission. USITC Pub. No. 2607.

*USITC. 1992. Synthetic organic chemicals - United States production and sales, 1992. Washington,

DC: U.S. International Trade Commission. USITC Pub. No. 2720.

*USITC. 1993. Synthetic organic chemicals - United States production and sales, 1993. Washington,

DC: U.S. International Trade Commission. USITC Pub. No. 2810.

*USITC. 1994. Synthetic organic chemicals- United States production and sales, 1994. Washington,

DC: U.S. International Trade Commission. USITC Pub. No. 2810.

*USITC. 1995. Synthetic organic chemicals- United States production and sales, 1994. Washington,

DC: U.S. International Trade Commission. USITC Pub. No. 2810.
DI-n-BUTYL PHTHALATE 175

9. REFERENCES

van Wezel AP, van Vlaardigen P, Posthumus R, et al. 2000. Environmental risk limits for two

phthalates, with special emphasis on endocrine disruptive properties. Ecotoxicol Environ Saf 46:305-321.

Verschueren K, ed. 1983. Handbook of environmental data on organic chemicals. 2nd ed. New York,

NY: Van Nostrand Reinhold Company, 468-471.

*Verschueren K, ed. 1996. Dibutylphenylphosphate. In: Handbook of environmental data on organic

chemicals 3rd ed. New York, NY: Van Nostrand Reinhold, 641-646.

Vicedo JL, Pellin M, Vilanova E. 1985. Phthalates and organophosphorus compounds as cholinesterase

inhibitors in fractions of industrial hexane impurities. Arch Toxicol 57:46-52. 

*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 238:476-483.

VIEW Database. 1989. Agency for Toxic Substances and Disease Registry (ATSDR), Office of External

Affairs, Exposure and Disease Registry Branch, Atlanta, GA. June 20, 1989.

Virgin HI. 1988. Accumulation of di-n-butyl phthalate in plants and its effect on pigment and protein

content. Physiologia Plantarum 72:190-196.

Wahl HG, Hoffmann A, Häring H-U, et al. 1999. Identification of plasticizers in medical products by a

combined direct thermodesorption-cooled injection system and gas chromatography-mass spectrometry. 

J Chromatogr A847:1-7.

Wallace D. 1999. Consumer exposures to plasticizers and other migrants. Organohalogen Compounds

44:285-288.

Walseth F, Nilsen OG. 1981. Reversibility of the effects of dibutyl phthalate (DBP) on rat liver and lung

microsomal enzyme activities and serum protein levels. Acta Pharmacol Toxicol 49(Part 1):90.

*Walseth F, Nilsen OG. 1984. Phthalate esters: II. Effects of inhaled dibutyl phthalate on cytochrome

P-450 mediated metabolism in rat liver and lung. Arch Toxicol 55:132-136.

*Walseth F, Nilsen OG. 1986. Phthalate esters: Effects of orally administered dibutylphthalate on

cytochrome P-450 mediated metabolism in rat liver and lung. Acta Pharmacol Toxicol 59:263-269.

*Walters SM. 1986. Cleanup of samples. In: Zweig G, Sherma J, eds. Analytical methods for

pesticides and plant growth regulators. Vol 15. Principles, statistics, and applications. New York, NY: 

Academic Press, Inc., 67-110.

Wang Z, Zhang Y. 1989. [The study of toxicity of DBP to testis in rats. I. Target cell and time-effect

relation.] Weisheng Dulixue Zazhi 3:25-28. (Chinese).

Ward JA. 1990. Studies of age-related testicular and reproductive endocrine toxicity of di-n-butyl

phthalate in rats (testicular atrophy). [Abstract]. Diss Abstr Int B 52:782.

Weast RC, ed. 1985. CRC handbook of chemistry and physics. Boca Raton, FL: CRC Press Inc., C430.
DI-n-BUTYL PHTHALATE 176

9. REFERENCES

*Weiss G, ed. 1986. Dibutyl phthalate. In: Hazardous Chemicals Data Book 2nd ed. Park Ridge, NJ: 

Noyes Data Corporation, 347.

*Weschler C, Sheilds H, Rainer D. 1990. Concentrations of volatile organic compounds at a building

with health and comfort complaints. Am Ind Hyg Assoc J 51(5):261-268.

*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.

White RD, Carter DE, Earnest D, et al. 1980. Absorption and metabolism of three phthalate deters by the

rat small intestine. Food Cosmet Toxicol 18:383-386.

*White RD, Earnest DL, Carter DE. 1983. The effect of intestinal esterase inhibition on the in vivo

absorption and toxicity of di-n-butyl phthalate. Food Chem Toxicol 21(1):99-101.

*Widdowson EM, Dickerson JWT. 1964. Chapter 17: 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, 1-247.

*Wieboldt RC, Adams GE, Later DW. 1988. Sensitivity improvement in infrared detection for

supercritical fluid chromatography. Anal Chem 60:2422-2427.

Wilbourn J, Montesano R. 1982. An overview of phthalate ester carcinogenicity testing results: The

past. Environ Health Perspect 45:127-128.

Wilkinson SM, Beck MH. 1992. Allergic contact dermatitis from dibutyl phthalate, propyl gallate and

hydrocortisone in Timodine. Contact Dermatitis 27:197.

*Williams DT. 1973. Dibutyl- and di-(2-ethylhexyl) phthalate in fish. J Agric Food Chem 21(6):1128-

1129.

*Williams DT, Blanchfield BJ. 1975. The retention, distribution, excretion and metabolism of dibutyl

phthalate-7-14C in the rat. J Agric Food Chem 23(5):854-858.

Windholz M, Budavari S, eds. 1983. The Merck index: An encyclopedia of chemicals, drugs, and

biologicals. 10th ed. Rahway, NJ: Merck and Company, Inc., 219.

Wine R, Li L, Barnes L, et al. 1997. Reproductive toxicity of di-n-butyl phthalate in a continuous

breeding protocol in Sprague-Dawley rats. Environ Health Perspect 105:102-107.

*Wisconsin DNR. 2001. Draft working list: September 2000 NR 445 chemicals list. Wisconsin

Department of Natural Resources. 

http://www.dnr.state.wi.us/org/aw/air/hot/nr445rev/draftchemlist092000.xls. February 8, 2001.

*Wofford HW, Wilsey CD, Neff GS, et al. 1981. Bioaccumulation and metabolism of phthalate esters

by oysters, brown shrimp, and sheepshead minnows. Ecotoxicol Environ Saf 5:202-210.

Wolfe NL, Burns LA, Steen WC. 1980b. Use of linear free energy relationships and an evaluative model

to assess the fate and transport of phthalate esters in the aquatic environment. Chemosphere 9:393-402.
DI-n-BUTYL PHTHALATE 177

9. REFERENCES

Wolfe NL, Paris DF, Steen WC, et al. 1980a. Correlation of microbial degradation rates with chemical

structure. Environ Sci Technol 14:1143-1146. 

Yamamoto S, Nakadate T, Aizu E, et al. 1990. Anti-tumor promoting action of phthalic acid mono-nbutyl ester cupric salt, a biomimetic superoxide dismutase. Carcinogenesis 11:749-754.

Yanagita T, Enomoto N, Kuzuhara S. 1986. Effects of phthalate esters on liver lysosomal acid lipase and

acid esterase in vitro. Agric Biol Chem 50:1653-1654.

Young LY, O'Connor O, Rivera MD. 1986. Toxic organic chemicals in waste streams: Anaerobic

bioconversion to methane. Washington, DC: U.S. Department of Energy. DOE/CE/40657-1.

*Zacharewski TR, Meek MD, Clemons JH, et al. 1998. Examination of the in Vitro and in Vivo

estrogenic activities of eight commercial phthalate esters. Toxicol Sci 46:282-293.

*Zeiger E, Haworth S, Mortelmans K, et al. 1985. Mutagenicity testing of di (2-ethylhexyl) phthalate

and related chemicals in Salmonella. Environ Mutagen 7:213-232.

Zeiger E, Haworth S, Speck W. 1982. Phthalate ester testing in the National Toxicology Program's

environmental mutagenesis test development program. Environ Health Perspect 45:99-101. 

*Zhou Y, Fukuoka M, Tanaka A. 1990. Mechanisms of testicular atrophy induced by di-n-butyl

phthalate in rats. Part 3. Changes in the activity of some enzymes in the sertoli and germ cells, and in the

levels of metal ions. J Appl Toxicol 10(6):447-453.

*Ziegler E, Edwards BB, Jensen RL et al. 1978. Absorption and retention of lead by infants. Pediatr Res

12:29-34.

Zlatkis A, Kim K. 1976. Column elution and concentration of volatile compounds in biological fluids. J

Chromatogr 126:475-485.

DI-n-BUTYL PHTHALATE 179

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 a 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 which 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.
DI-n-BUTYL PHTHALATE 180

10. GLOSSARY

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.

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 which 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.
DI-n-BUTYL PHTHALATE 181

10. GLOSSARY

Incidence—The ratio of individuals in a population who develop a specified condition to the total number

of individuals in that population who could have developed that condition in a specified time period. 

Intermediate Exposure—Exposure to a chemical for a duration of 15–364 days, as specified in the

Toxicological Profiles.

Immunologic Toxicity—The occurrence of adverse effects on the immune system that may result from

exposure to environmental agents such as chemicals.

Immunological Effects—Functional changes in the immune response.

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 which 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 which 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.
DI-n-BUTYL PHTHALATE 182

10. GLOSSARY

Mortality—Death; mortality rate is a measure of the number of deaths in a population during a specified 

interval of time.

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) which 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 odds ratio of greater than 1 is considered to indicate greater risk

of disease in the exposed group compared to the unexposed.

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 science of quantitatively predicting 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 whereby the

physiologically-based model compartments represent real anatomic regions of the body.

Physiologically Based Pharmacodynamic (PBPD) Model—A type of physiologically-based doseresponse model which 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. 
DI-n-BUTYL PHTHALATE 183

10. GLOSSARY

Physiologically Based Pharmacokinetic (PBPK) Model—Comprised of a series of compartments

representing organs or tissue groups with realistic weights and blood flows. These models require a

variety of physiological information: tissue volumes, blood flow rates to tissues, cardiac output, alveolar

ventilation rates and, possibly membrane permeabilities. The models also utilize biochemical information

such as air/blood partition coefficients, and metabolic parameters. PBPK models are also called

biologically based tissue dosimetry models.

Prevalence—The number of cases of a disease or condition in a population at one point in time. 

Prospective Study—A type of cohort study in which the pertinent observations are made on events

occurring after the start of the study. A group is followed over time.

q1

*—The upper-bound estimate of the low-dose slope of the dose-response curve as determined by the

multistage procedure. The q1* can be used to calculate an estimate of carcinogenic potency, the

incremental excess cancer risk per unit of exposure (usually μg/L for water, mg/kg/day for food, and

μg/m3

 for air).

Recommended Exposure Limit (REL)—A National Institute for Occupational Safety and Health

(NIOSH) time-weighted average (TWA) concentrations 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.
DI-n-BUTYL PHTHALATE 184

10. GLOSSARY

Risk—The possibility or chance that some adverse effect will result from a given exposure to a chemical.

Risk Factor—An aspect of personal behavior or lifestyle, an environmental exposure, or an inborn or

inherited characteristic, that is associated with an increased occurrence of disease or other health-related

event or condition.

Risk Ratio—The ratio of the risk among persons with specific risk factors compared to the risk among

persons without risk factors. A risk ratio greater than 1 indicates greater risk of disease in the exposed

group compared to the unexposed.

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 min continually. No

more than four excursions are allowed per day, and there must be at least 60 min between exposure

periods. The daily Threshold Limit Value - Time Weighted Average (TLV-TWA) may not be exceeded.

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 study of 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 one can be used;

however a reduced UF of three may be used on a case-by-case basis, three being the approximate

logarithmic average of 10 and 1.

Xenobiotic—Any chemical that is foreign to the biological system.

DI-n-BUTYL PHTHALATE A-1

APPENDIX A

ATSDR MINIMAL RISK LEVEL 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.
DI-n-BUTYL PHTHALATE A-2

APPENDIX A

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

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 a hundredfold 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, expert panel peer reviews, and agencywide 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, Agency for Toxic Substances and Disease

Registry, 1600 Clifton Road, Mailstop E-29, Atlanta, Georgia 30333.
DI-n-BUTYL PHTHALATE A-3

APPENDIX A

MINIMAL RISK LEVEL (MRL) WORKSHEET

Chemical Name: Di-n-butyl phthalate

CAS Number: 84-74-2

Date: June 30, 2001

Profile Status: Final 

Route: [ ] Inhalation [X] Oral

Duration: [X] Acute [ ] Intermediate [ ] Chronic

Key to Figure: 21

Species: Rats

Minimal Risk Level: 0.5 [X] mg/kg/day [ ] mg/m3

Reference: Mylchreest E, Wallace DG, Cattley RC, et al. 2000. Dose-dependent alterations in

androgen-regulated male reproductive development in rats exposed to di(n-butyl) phthalate during late

gestation. Toxicol Sci 55:143-151.

Experimental design (human study details or strain, number of animals per exposure/control groups, sex,

dose administration details): Groups of 20 pregnant Sprague-Dawley rats (except 11 in the

500 mg/kg/day group) were treated with 0, 0.5, 5, 50, 100, or 500 mg/kg/day di-n-butyl phthalate by

gavage in corn oil on gestation days 12–21. Dams were examined daily for clinical signs of toxicity,

body weight was recorded daily during treatment, and food intake was recorded twice weekly. Dams

were killed on postpartum day 21, examined grossly, and the weights of liver, kidneys, adrenals, uterus,

and ovaries, and numbers of implantation sites were recorded. On postpartum day 1, numbers of live and

dead pups, clinical signs of toxicity, pup weight, and ano-genital distance were recorded. Additionally,

the location and number of nipples and areolas were recorded for male pups on postpartum day 14. From

postpartum day 30 (females) or 38 (males), pups were examined daily for vaginal opening or preputial

separation, respectively, until occurrence. Pups were killed at sexual maturity (postpartum

day 110±10 days for males; 80±5 days for females), weighed, and internal and external genitalia were

examined for malformations and undescended testes. Organs were weighed, and right testis and

epididymides were examined histologically.

Effects noted in study and corresponding concentrations: No developmental effects or clinical signs of

toxicity were seen in pups exposed to 50 mg/kg/day or less in utero. The only treatment-related effect

seen in the 100 mg/kg/day group was retained areolas and nipples in males (normally seen only in

females) on postpartum day 14. This effect was dose-dependent, being more prominent at

500 mg/kg/day. Permanence of retained areolas and nipples was not assessed. Other statistically

significant effects, seen only in males at 500 mg/kg/day level, were decreased AGD (12% decrease) and

ano-genital distance/body weight at birth; smaller epididymides, dorsolateral prostate, and levator

ani-bulbocavernosus muscle at sexual maturity; and decreased testes weight (when animals with enlarged

testes were excluded). Malformations of the male reproductive tract included absent or malformed

epididymis, absent or malformed vas deferens, hypospadia, and unilaterally absent seminal vesicle. 

Histopathological lesions of the testis seen were seminiferous tubule degeneration, focal interstitial

hyperplasia, and adenoma. In males, no significant changes were seen in age at preputial separation, or

body, kidney, liver, adrenal, ventral prostate, vas deferens, seminal vesicle, or other organ weights (other

than those listed above). In female pups, no significant differences from controls were seen in age of

onset of vaginal opening; body, liver, kidney, adrenal, ovary, or uterus weight; or gross morphology of

the reproductive organs at sexual maturity.
DI-n-BUTYL PHTHALATE A-4

APPENDIX A

Concentration and end point used for MRL derivation: Increased incidence of retained areolas and nipple

in the male offspring of rats exposed to $100 mg//kg/day; no effects were observed at 50 mg/kg/day.

[X] NOAEL [ ] LOAEL

Uncertainty Factors used in MRL derivation:

[ ] 10 for use of a LOAEL

[X] 10 for extrapolation from animals to humans

[X] 10 for human variability

Was a conversion factor used from ppm in food or water to a mg/body weight dose? NA

If an inhalation study in animals, list conversion factors used in determining human equivalent

concentration: NA

Was a conversion used from intermittent to continuous exposure? NA

Other additional studies or pertinent information that lend support to this MRL: A number of

developmental effects involving androgenic-dependent tissues have been observed in acutely or longer

exposed rats; these include decreases in anogenital distance and anogenital distance/body weight ratio,

increased number of retained nipples, and decreased androgen-dependent tissue weights (ventral prostate,

epididymis, cauda epididymis, testes, glans penis, and levator ani-bulbocavernosus) (Ema et al. 1998,

2000b; Gray et al. 1999; Mylchreest et al. 1999, 2000).

Agency Contact (Chemical Manager): Jessilynn Taylor
DI-n-BUTYL PHTHALATE 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,

weight-of-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 they appear within the Discussion of Health Effects by

Route of Exposure section, by route (inhalation, oral, 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. If data are located in the scientific literature, a table of genotoxicity information is

included.

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.
DI-n-BUTYL PHTHALATE B-2

APPENDIX B

Interpretation of Minimal Risk Levels

Where sufficient toxicologic information is available, we have derived minimal risk levels (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. They 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 the Environmental Protection Agency (EPA)

provides (Barnes and Dourson 1988) to determine reference doses for lifetime exposure (RfDs). 

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 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 LSE Tables.

Chapter 3

Health Effects

Tables and Figures for Levels of Significant Exposure (LSE)

Tables (3-1, 3-2, and 3-3) and figures (3-1 and 3-2) 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, minimal risk levels

(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 No-Observed-Adverse-Effect Levels

(NOAELs), Lowest-Observed-Adverse-Effect Levels (LOAELs), or Cancer Effect Levels (CELs).
DI-n-BUTYL PHTHALATE B-3

APPENDIX B

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.

LEGEND

See LSE Table 3-1

(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. When sufficient

data exists, 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

Table 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 2

"18r" data points in 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

regimen 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 1,1,2,2-tetrachloroethane via

inhalation for 6 hours per day, 5 days per week, for 3 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, 1 systemic effect (respiratory) was investigated.
DI-n-BUTYL PHTHALATE B-4

APPENDIX B

(8) NOAEL A No-Observed-Adverse-Effect Level (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").

(9) LOAEL A Lowest-Observed-Adverse-Effect Level (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 Cancer Effect Level (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 the NOAEL of 3 ppm in key number 18 was used to derive an

MRL of 0.005 ppm.

LEGEND

See Figure 3-1

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 intermediate and chronic 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, 18r NOAEL is the critical end point for which an intermediate inhalation

exposure MRL is based. As you can see from the LSE figure key, the open-circle symbol indicates

to a NOAEL for the test species-rat. 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 38r is 1 of 3 studies for which Cancer Effect Levels were derived. The diamond

symbol refers to a Cancer Effect Level for the test species-mouse. The number 38 corresponds to

the entry in the LSE table.
DI-n-BUTYL PHTHALATE B-5

APPENDIX B

(18) Estimated Upper-Bound Human Cancer Risk Levels This is the range associated with the

upper-bound 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 6 Table 3-1. Levels of Significant Exposure to [Chemical x] – Inhalatio

Key tofigurea Species

Exposurefrequency/duration System

NOAEL(ppm)

LOAEL (effect)

Less serious (ppm) Serious (ppm)

2 6 INTERMEDIATE EXPOSURE

5 6 7 8 9 

3 6 Systemic 9 9 9 99 

4 6 18 Rat 13 wk

5 d/wk6 hr/d

Resp 3b 10 (hyperplasia) 

CHRONIC EXPOSURE

11

Cancer 938 Rat 18 mo

5 d/wk7 hr/d

20 (CEL, multiple

organs)

39 Rat 89–104 wk

5 d/wk6 hr/d

10 (CEL, lung tumors

nasal tumors)

40 Mouse 79–103 wk

5 d/wk6 hr/d

10 (CEL, lung tumors

hemangiosarcom

a The number corresponds to entries in Figure 3-1.

12 6 b Used to derive an intermediate inhalation Minimal Risk Level (MRL) of 5 x 10-3 ppm; dose adjusted for intermittent ex

an uncertainty factor of 100 (10 for extrapolation from animal to humans, 10 for human variability).


DI-n-BUTYL PHTHALATE C-1

APPENDIX C

ACRONYMS, ABBREVIATIONS, AND SYMBOLS

ACGIH American Conference of Governmental Industrial Hygienists

ADI Acceptable Daily Intake

ADME Absorption, Distribution, Metabolism, and Excretion

AFID alkali flame ionization detector

AFOSH Air Force Office of Safety and Health

AML acute myeloid leukemia

AOAC Association of Official Analytical Chemists

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

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

CL ceiling limit value

CLP Contract Laboratory Program

cm centimeter

CML chronic myeloid leukemia

CNS central nervous system

CPSC Consumer Products Safety Commission

CWA Clean Water Act

d day

Derm dermal

DHEW Department of Health, Education, and Welfare

DHHS Department of Health and Human Services

DNA deoxyribonucleic acid

DOD Department of Defense

DOE Department of Energy

DOL Department of Labor

DOT Department of Transportation

DOT/UN/ Department of Transportation/United Nations/

NA/IMCO North America/International Maritime Dangerous Goods Code

DWEL Drinking Water Exposure Level

ECD electron capture detection

ECG/EKG electrocardiogram
DI-n-BUTYL PHTHALATE C-2

APPENDIX C

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

ft foot

FR Federal Register

g gram

GC gas chromatography

Gd gestational day

gen generation

GLC gas liquid chromatography

GPC gel permeation chromatography

HPLC high-performance liquid chromatography

hr hour

HRGC high resolution gas chromatography

HSDB Hazardous Substance Data Bank 

IDLH Immediately Dangerous to Life and Health

IARC International Agency for Research on Cancer

ILO International Labor Organization

in inch

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

LCLo lethal concentration, low

LC50 lethal concentration, 50% kill

LDLo lethal dose, low

LD50 lethal dose, 50% kill

LT50 lethal time, 50% kill

LOAEL lowest-observed-adverse-effect level

LSE Levels of Significant Exposure

m meter

MA trans,trans-muconic acid

MAL Maximum Allowable Level

mCi millicurie

MCL Maximum Contaminant Level

MCLG Maximum Contaminant Level Goal

mg milligram

min minute

mL milliliter
DI-n-BUTYL PHTHALATE C-3

APPENDIX C

mm millimeter

mm Hg millimeters of mercury

mmol millimole

mo month

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

NCI National Cancer Institute

NIEHS National Institute of Environmental Health Sciences

NIOSH National Institute for Occupational Safety and Health

NIOSHTIC NIOSH's Computerized Information Retrieval System

NFPA National Fire Protection Association

ng nanogram

NLM National Library of Medicine

nm nanometer

NHANES National Health and Nutrition Examination Survey

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

OPPTS Office of Prevention, Pesticides and Toxic Substances, EPA

OPPT Office of Pollution Prevention and Toxics, EPA

OSHA Occupational Safety and Health Administration

OSW Office of Solid Waste, EPA

OTS Office of Toxic Substances

OW Office of Water

OWRS Office of Water Regulations and Standards, EPA

PAH Polycyclic Aromatic Hydrocarbon

PBPD Physiologically Based Pharmacodynamic 

PBPK Physiologically Based Pharmacokinetic 

PCE polychromatic erythrocytes

PEL permissible exposure limit

PID photo ionization detector
DIn-BUTYL PHTHALATE C-4

APPENDIX C

pg picogram

pmol picomole

PHS Public Health Service

PMR proportionate mortality ratio

ppb parts per billion

ppm parts per million

ppt parts per trillion

PSNS Pretreatment Standards for New Sources

REL recommended exposure level/limit

RfC Reference Concentration

RfD Reference Dose

RNA ribonucleic acid

RTECS Registry of Toxic Effects of Chemical Substances

RQ Reportable Quantity

SARA Superfund Amendments and Reauthorization Act

SCE sister chromatid exchange

sec second

SIC Standard Industrial Classification

SIM selected ion monitoring

SMCL Secondary Maximum Contaminant Level

SMR standard 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 Compound

TPQ Threshold Planning Quantity

TRI Toxics Release Inventory

TSCA Toxic Substances Control Act

TRI Toxics Release Inventory

TWA time-weighted average

U.S. United States

UF uncertainty factor

VOC Volatile Organic Compound

yr year

WHO World Health Organization

wk week

> greater than > greater than or equal to

= equal to

< less than < less than or equal to

% percent α alpha β beta γ gamma δ delta

μm micrometer
DIn-BUTYL PHTHALATE C-5

APPENDIX C

μg microgram q1* cancer slope factor

– negative

+ positive

(+) weakly positive result

(–) weakly negative result

DI-n-BUTYL PHTHALATE D-1

APPENDIX D

INDEX

adipose tissue . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53, 71, 124

adsorption . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102, 123, 125

aerobic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93

ambient air . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10, 113, 135, 136

Antarctic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101

average daily intake . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112, 115

bioaccumulation ................................................................................. 103, 118

bioavailability ................................................................................... 116, 118

bioconcentration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103

biodegradation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102-105, 118

biomagnify . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 118

biomarker . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70, 71, 79

breast milk . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6, 81, 114

cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4, 5, 20, 46, 49, 65, 68, 77, 84, 138

carcinogenic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15, 16, 46, 47, 76, 131, 134

carcinogenicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77, 82, 138

carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65

cardiovascular effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17, 37

Clean Water Act . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133

crustaceans . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103

dermal effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39, 47

disposal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10, 87, 90, 100, 117, 118, 134, 138

DNA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49, 50, 71

endocrine effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18, 39

environment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1-3, 7, 9, 65, 72, 90, 93, 98, 99, 106, 109, 117, 118, 128

estrogenic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39, 65, 66

fetus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67, 73

fish consumption . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137

fruits . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 110

FSH . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64

gastrointestinal effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37

general population . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9, 11, 70, 93, 112, 113, 115

half-life . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9, 70, 104, 105

hematological effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11, 18, 37

Henry’s law . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96, 102, 106

hepatic effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11, 13, 18, 38, 64, 80

hydrolysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54, 64, 105, 118, 123, 124

hydroxyl radical . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104

immunological effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19, 40

kidney . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12, 13, 18, 39, 47, 52

LD50 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20, 47

liver . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10, 11, 13, 18, 38, 39, 52, 58-61, 64, 71, 72, 76

lung . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12, 17, 51, 52, 71

lymphoreticular effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19, 40, 49

milk . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6, 52, 69, 81, 108, 109, 114, 119

Minimal Risk Level (see MRL) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

MRL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11-14, 16, 45, 76, 78, 130

musculoskeletal effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37

National Priorities List (see NPL) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1, 10, 93

neurobehavioral . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65

NOAEL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12-15, 20, 40, 43-47, 76, 77, 130

NOES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112

no-observed-adverse-effect level (see NOAEL) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

NPL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1, 10, 93, 94, 96, 97, 100, 102

ocean . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100
DI-n-BUTYL PHTHALATE D-2

APPENDIX D

ocular effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17, 39

partition coefficients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58, 60, 61, 85

PBPD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57

PBPK . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56-59

pharmacodynamic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56, 57

pharmacokinetic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56, 57, 59, 63

photolysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85

production . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4, 5, 9, 10, 41, 42, 65, 66, 87-89, 114, 115, 117

Public health . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1, 4, 7, 9, 15, 16, 65, 74, 117, 122, 123

reference dose (see RfD) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 138

regulations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7, 8, 117, 130-132, 135, 138

renal effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10, 12, 18, 39, 47

reportable quantity ........................................................................... 134, 135, 138

reproductive system . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10, 41, 69, 72, 78

RfD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 130, 134, 137, 138

sediment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96, 100, 102, 104, 105, 108, 123, 126

soil . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2, 3, 7, 9, 93, 96, 100-103, 105, 106, 108, 113, 116, 119, 123, 125-127, 137

solubility . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9, 85, 102, 103, 117

surface water . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96, 100, 106, 113

time-weighted average (see TWA) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 138

toxicokinetic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15, 69, 73, 81

Toxics Release Inventory (see TRI) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90

transport . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10, 65, 96, 101, 104, 107, 116, 118, 120

TRI . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90, 93, 97, 99, 100

tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46

TWA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131, 138

vapor phase . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101

vapor pressure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85, 96, 106, 117

volatility . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89

volatilization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116