Aggregate

Exposures to

Phthalates in

Humans

July 2002
ACKNOWLEDGMENTS

Contributors 

Joseph DiGangi, PhD, USA, 

Ted Schettler MD, MPH, USA

Madeleine Cobbing, UK

Mark Rossi, MA, USA

Reviewers

HCWH thanks the following individuals for reviewing an earlier draft of this report. Their comments and suggestions were invaluable and substantially improved the manuscript. We are grateful for their contribution.

Their review, however, does not constitute endorsement of the report or its conclusions. Two additional

reviewers chose to remain anonymous.

Earl Gray PhD

Michael McCally MD, PhD

The contributing authors would also like to thank Cecilia DeLoach, Tracey Easthope, Per Rosander, Jamie

Harvie and Charlotte Brody for their editing and proofreading of this report.

Health Care Without Harm

1755 S St. NW, Suite 6B • Washington, DC 20009 • www.noharm.org • 202-234-0091
Aggregate Exposures to Phthalates in Humans iii

Contents

Acknowledgements......................................................................................ii

Executive Summary.....................................................................................1

Abbreviations..............................................................................................4

Preface......................................................................................................5

Introduction................................................................................................6

Phthalates in Consumer Products.................................................................9

Phthalate Toxicity ......................................................................................14

Exposures Resulting from Medical Procedures .............................................17

Aggregate Exposures in the General Population............................................20

A Legacy of Inadequate Responses ............................................................28

Safer Alternatives......................................................................................31

Conclusions .............................................................................................33

Appendix I. MEHP Exposures in the Hospital................................................36

Appendix II. Phthalate Toxicity ....................................................................39

References...............................................................................................43

Aggregate Exposures to Phthalates in Humans 1

Executive Summary

Phthalates are a family of chemicals that are produced in the millions of tons annually worldwide,

and are a principal component of many diverse products that consumers come into contact with at

home, at work, and in hospitals. They include products made of flexible polyvinyl chloride plastic

(PVC), cosmetics and other personal care goods, pesticides, building materials, lubricants, adhesives, and

film, among other items. Phthalates are released into

the environment by manufacturers and escape from

consumer products in which they are used.

Worldwide ecosystem contamination and direct contact with phthalate-containing products result in virtually ubiquitous human exposures. 

Health effects that may be caused by exposure to

phthalates differ among the various individual compounds and depend on the timing and the size of the

dose. Young, developing organisms are more vulnerable to exposure to phthalates than adults. In particular, the developing male reproductive tract appears to

be the most sensitive endpoint, although effects on

the liver, kidneys, lungs, and blood clotting are also

of concern. In animal tests considered relevant to

humans, several of the phthalates, including di-(2-

ethylhexyl) phthalate (DEHP), di-butyl phthalate

(DBP), benzyl butyl phthalate (BBP), and perhaps

di-isononyl phthalate (DINP), interfere with male

reproductive tract development and are toxic to cells

in the testes responsible for assuring normal sperm

and hormone production. 

Human exposure to DEHP from PVC medical

devices used in patient care has been known for

some time. Expert panels of the US National

Toxicology Program (NTP) and Health Canada, as

well as the US Food and Drug Administration

(FDA), however, have recently reviewed the toxicology of DEHP and considered exposures to patients

that may result from the use of DEHP-containing

equipment. Each review concluded that some

patients are likely to be exposed to potentially unsafe

amounts of DEHP while receiving medical care. 

Testing by the US Centers for Disease Control and

Prevention (CDC) recently showed that phthalate

exposures are virtually ubiquitous in the general population. Women of reproductive age experience some of

the highest exposure levels to phthalates that can interfere with normal male reproductive tract development. 

In this report, we summarize what is known about

human exposures to phthalates and consider the

potential health impacts of exposure to real-world

mixtures of these chemicals. Using a relative potency

approach, based on what is known about mechanisms of action and available experimental data, it

becomes clear that, for a large number of women of

reproductive age, their aggregate exposure to phthalates is sufficient to significantly increase the risk of

abnormal development in male fetuses and baby

boys. Women of reproductive age who require medical care may be exposed to additional phthalates,

largely DEHP, in the medical setting, that, depending

on the procedure, can add significantly to their existing levels.

According to sample data from the CDC, an estimated 5% of women of reproductive age from the general

population are contaminated with 75% or more of the

level of just one of the phthalates, DBP, that may

begin to impair normal reproductive tract development in their baby boys. Many of these women are

also regularly exposed to significant amounts of BBP

and DEHP, so that their aggregate exposures pose

even greater risks. When any of these women requires

medical care that exposes them to additional DEHP

from PVC medical devices, even more is added. 
Where are these phthalates coming from in the general population? No one knows for certain, but perhaps the high exposures to DBP in women of

reproductive age provide a clue, at least for that

phthalate. DBP is used in a variety of cosmetic and

personal care products. Recent testing identified

DBP in some hair spray, fragrances, and deodorants.

Many nail polishes also have large quantities of DBP.

Unfortunately, labeling requirements are sufficiently

lax so that it is extraordinarily difficult to identify

phthalate-containing products and to begin to narrow down the search for the sources of widespread

general population exposures. 

Chemical policy in the US is severely “Balkanized”161

and requires major revisions. For example, the Food

and Drug Administration is responsible for food contaminants (including phthalates), drug ingredients

(including phthalates), medical devices (including

phthalate-containing PVC products), and cosmetics

(including phthalates). Unfortunately, each of these

activities is a responsibility of a different division

within FDA, each of which carries out its work in isolation from the others. As a consequence, when the

medical device division considers the safety of exposure to DEHP, they consider only medical devices and

not the real world of population-wide exposures to

multiple phthalates from multiple sources. And, when

the cosmetics division considers phthalates in personal care products, not only do they limit their concerns

to products in their domain, but they must prove the

likelihood of harm with no requirement that manufacturers will supply safety data. 

When the Consumer Products Safety Commission

(CPSC) considers the safety of phthalates in, for

example, children’s toys, they consider only the

phthalate that may leach out of the toy when a child

chews on it, and not the other phthalates that the

same child may be exposed to from contaminated

food, contaminated air, or medical care. 

And when the Environmental Protection Agency

(EPA) considers whether or not to allow phthalates

in a pesticide formulation, they examine those proposals one at a time, failing to consider aggregate

exposures to multiple phthalates from multiple

sources. 

As a result, phthalates permeate the environment

and contaminate large populations of people

throughout the world. Phthalates are in the blood of

pregnant women at levels of concern, particularly

when the contaminants are considered in the aggregate. Phthalates cross the placenta and also contaminate breast milk. Relevant animal tests show that

phthalates interfere with normal fetal and infant

development. 

Manufacturers of phthalates continue to produce

large amounts and sell them to product manufacturers who use them in thousands of products.

Manufacturers consistently argue that there is no

evidence that anyone has been harmed by phthalates. As we note, however, and as confirmed by the

NTP panel and FDA, no study has ever examined

the impacts of phthalate exposure on the developing

male reproductive tract in people. Not one. 

Lack of evidence can hardly be used as evidence of

safety when no one has ever looked. The increasing

incidence of hypospadias, undescended testes, testicular cancer, and declining sperm counts in the US

and many other parts of the world suggests that a

closer look at many reproductive tract toxicants and

endocrine disruptors is urgently needed in people.

With respect to phthalates, however, evidence from

relevant animal studies and from limited studies of

non-reproductive tract impacts in hospitalized

patients is sufficient to require phasing out the use of

many of the phthalates. As the Health Canada panel

concluded, “the status quo is not an acceptable

option.”

Regulatory agencies charged with protecting medical

patients, public health, and the environment must

substantially revise procedures and protocols to consider the potential impacts of phthalate exposures in

the aggregate, rather than as single chemical exposures. In Europe, vigorous debate is underway regarding the phase-out of the general use of many

phthalates in consumer products. Alternatives to

phthalates that perform well are currently on the

market for nearly every use.

Phthalates also serve as a case-study that demonstrates the failure of current chemical policy in the

US. Regulatory authority is spread among agencies

that compete with one another rather than cooperate. Lines of communication are limited and infrequently used. No one agency is authorized to look at

the “big picture”. 

2 Health Care Without Harm
Public health and the environment can only be truly

protected when safer materials are substituted far

upstream in the manufacturing process. Humans

have demonstrated the capacity to contaminate

every nook and cranny of every ecosystem and every

developing fetus with synthetic chemicals that can

impair normal development. Now we need to

demonstrate that we can change. 

First, we need to recognize that a major overhaul of

current regulatory policy is long overdue. Under the

current framework, government approval simply does

not provide adequate real-world protection from

chemical exposures. The FDA, the EPA, the CPSC,

and other government agencies, with necessary

authorization, must begin to transform their makebelieve regulatory framework into a new, sciencebased system that properly considers the reality of

aggregate exposures to toxic chemicals and that

requires meaningful pre-market testing of

commercial chemicals. Second, consumers must

insist on the right to know about chemicals in commercial products and must have unhindered access

to toxicity and exposure data. Third, manufacturers

can and must shift to cleaner production practices

and materials that produce cleaner, sustainable products more suited to the contemporary world and the

one we will leave to future generations. 

Aggregate Exposures to Phthalates in Humans 3
Abbreviations

μg Microgram 

ATBC O-acetyl tributyl citrate

BEP Butyl A-ethylhexyl phthalate

BBP Butyl benzyl phthalate

CABG Coronary artery bypass graft

CDC US Centers for Disease Control and

Prevention

CPB Cardiopulmonary bypass

CPSC US Consumer Product Safety Commission

DBGP Di-butylglycol phthalate

DBP Di-(n-butyl) phthalate

DCHP Dicyclohexyl phthalate

DEHA Di-(2-ethylhexyl) adipate

DEHP Di-(2-ethylhexyl) phthalate

DEHPA Di-(2-ethylhexyl) phosphate

DEP Diethyl phthalate

DHP Dihexyl phthalate

DHP Di-n-hexyl phthalate

DIBE Di-isobutylhexahydro phthalate

DIBP Di-isobutyl phthalate

DIDP Di-isodecyl phthalate

DIHP Di-isoheptyl phthalate

DINP Di-isononyl phthalate

DIOP Di-isooctyl phthalate

DMP Di-methyl phthalate

DOP Di-n-octyl phthalate

DPHP Di-(2-propylheptyl) phthalate

DPOP Diphenyl 2-ethylhexyl phosphate

DPP Di-n-pentyl phthalate

DTDP Di-tridecyl phthalate

ECMO Extracorporeal membrane oxygenation

FDA US Food and Drug Administration

KEMI Swedish National Chemicals Inspectorate

Kg Kilogram 

L Liter 

L11 Di-L-undecyl phthalate

L7-11 Di-L-heptyl, undecyl phthalate

L7-9 Di-L-heptyl, nonyl phthalate

L9 Di-L-nonyl phthalate

L9-11 Di-L-nonyl, undecyl phthalate

MBP Mono-n-butyl phthalate

MEHP Mono-(ethylhexyl) phthalate

MPP Monopentyl phthalate

NTP US National Toxicology Program

PVC Polyvinyl chloride plastic

RPF Relative potency factor

TETM Tri-2-ethylhexyl trimellitate

TI Tolerable intake

TPN Total parenteral nutrition

UDP Undecyl dodecyl phthalate

US EPA US Environmental Protection Agency

4 Health Care Without Harm
Aggregate Exposures to Phthalates in Humans 5

Preface

Health Care Without Harm (HCWH), the campaign

for environmentally responsible health care, works to

help reduce the public health and environmental

impacts of activities associated with medical institutions, without compromising the quality of care. To a

large extent, the materials used in medical facilities

influence those impacts. Metals, solvents, plastics,

pharmaceuticals, radioactive materials, and other

toxic compounds can pose threats to public health

and the environment, as well as to patients and hospital workers, if they are not carefully chosen and

manufactured, used, and disposed of properly. 

Polyvinyl chloride (PVC) is one of the predominant

plastics used in medical care. Initially, HCWH was

concerned with the public health and environmental

impacts of the manufacture and disposal of PVC

medical products. These concerns centered primarily

on the generation of dioxins, furans, and other toxic

organochlorine compounds during the manufacture

and incineration of PVC. PVC also requires additives

to impart certain qualities like stability and flexibility.

Medical products made of PVC are usually softened

with a plasticizer from the family of chemicals known

as phthalates. Under certain circumstances, a considerable amount of the phthalate most commonly used

in these devices, di-(2-ethylhexyl) phthalate

(DEHP), can leach out of medical devices causing

direct patient exposures. A closer look at DEHP

leaching led to additional concerns about patient

safety. Consequently, HCWH petitioned the US

Food and Drug Administration (FDA) to examine

the safety of DEHP-containing products more closely. The results of the FDA safety assessment, as well

as those of other government-sponsored expert panels are discussed in this report. 

HCWH became even more concerned about phthalates when the US Centers for Disease Control and

Prevention (CDC) published data about general population exposures. Not only are medical devices only

one of a number of sources of phthalate exposures,

but the levels of phthalate exposure in the general

population are high enough to raise serious questions

about their safe use in hundreds of consumer products to which we are regularly exposed. Many people

from the general population are contaminated with a

significant body burden of phthalates. Some kinds of

medical care add more. As these exposures add up, it

becomes clear that aggregate phthalate exposures,

from multiple sources, raise a significant public

health concern. 

Where are human exposures to phthalates coming

from? We have only partial answers. The search cannot be confined to only one business sector, since

phthalates are so widely used in so many products. In

addition to medical devices, HCWH looked at information about phthalates in food, air, cosmetics, children’s toys, and many other consumer products to

help identify other exposure sources. This investigation leads to serious concerns about the adequacy of

current regulatory policies and manufacturing practices for protecting public health and the environment. It is a cautionary tale about the risks

associated with divided responsibilities and failure to

connect the dots. 
People and wildlife are regularly exposed to industrial chemicals through food, water, air, or from direct

contact with a variety of consumer products. Many

of these chemicals are toxic at some dose and under

certain conditions of exposure. Attempts to estimate

the risks from contact with industrial chemicals rely

heavily on understanding their toxicity and the

nature of exposures. The route of exposure, whether

through ingestion, inhalation, absorption through

the skin, or intravenous administration, can significantly influence a chemical’s toxicity. The magnitude of exposure is also important, but the timing,

duration, and pattern of exposure are also critical

factors that determine toxic impacts. We know, for

example, that low-level exposures to industrial

chemicals that have no discernable effects on adults

can have profound and lifelong impacts if the exposure occurs during developmental windows of vulnerability, as, for example, during fetal life, infancy,

or childhood. 

Chemicals, or their metabolic byproducts with long

half-lives, may build up to toxic concentrations in

the environment and in people and wildlife. Even

those chemicals that do not persist for long periods

of time may pose a problem if they are so widely used

that we are repeatedly and continuously exposed to

them. This report is about such a class of chemicals.

They are the phthalates—a family of chemicals that

are produced in the millions of tons annually worldwide and used in hundreds of consumer and industrial products. Phthalates are ubiquitous environmental

contaminants and are nearly always found at some

concentration in virtually all people and wildlife. 

This report discusses three parallel lines of research.

First, we review the toxicity of members of the

phthalate family, with an emphasis on health effects

relevant to people. Second, we describe relatively

recent data concerning general population exposures

to phthalates and consider the sources of those

exposures. We discuss those exposures in light of the

current understanding of the toxicity of phthalates,

and focus our concerns on exposures to women of

reproductive age, developing children, and young

medical patients. Finally, using studies that shed

light on the mechanisms by which phthalates exert

their toxicity, particularly with respect to reproduction and development, we conclude that phthalate

exposures should be considered in the aggregate

when estimating the potential harm that may result

from human exposures. Unfortunately, product

manufacturers and regulatory agencies responsible

for protecting public health and the environment

each fail to consider total exposures to this family of

chemicals. As a result, a substantial number of people are at risk of harm. 

A combination of limited human data and a wealth

of animal studies show that phthalates can impair

reproduction and development, alter liver and kidney function, damage the heart and lungs, and affect

blood clotting. Studies that have focused on cancer

as a phthalate-related health concern show that

phthalates cause liver cancer in rodents, but many

investigators have concluded that the cancer seen in

animal tests is not relevant to people because of

species differences in response. 

Early studies looked largely at impacts in adults,

where phthalates seemed to have relatively low acute

toxicity. It also seemed that, in adult animals, fairly

large doses were necessary to cause impacts on the

testes, ovaries, and liver. Scientific reports then

showed, however, that some medical patients

exposed to DEHP, a phthalate that leaches from

PVC, or polyvinyl chloride plastic medical devices,

receive doses that are similar to those causing health

effects in laboratory animals. 

Reports in the scientific literature over the past 10-

15 years have raised additional concerns. Developing

organisms are uniquely vulnerable to phthalate exposures, and, in particular, the developing male reproductive tract appears to be the most sensitive organ

system. Abnormal development of the testes, penis,

6 Health Care Without Harm

Introduction 
and other components of the male reproductive tract

occurs at levels of exposure that are hundreds or

thousands of times lower than those necessary to

cause damage in adults. Several expert panels,

including those assembled by the US Food and Drug

Administration (FDA), the National Toxicology

Program’s Center for the Evaluation of Risks to

Human Reproduction (NTP), and Health Canada

(HC) have recently independently concluded that

those animal studies are relevant for predicting

health impacts in people. 

The second line of research addresses human exposures to phthalates. One of the phthalates, di-(2-ethylhexyl) phthalate (DEHP) is added to polyvinyl

chloride (PVC) plastic to soften and make flexible

this inherently rigid material. DEHP-containing PVC

is used for many purposes, and one application is in a

variety of medical products. Under certain circumstances, depending on the product and the purpose

for which it is used, DEHP leaches out of these

devices causing direct patient exposures. The FDA,

NTP, and HC have each determined that the level of

exposure can, in some instances, rise to a level of

serious concern, particularly in vulnerable individuals, such as fetuses and infants, and even in adults

who are repeatedly exposed. 

Beyond health care institutions, however, the CDC

studied phthalate exposures in the general population. The results were surprising. Virtually all people

studied had some level of various phthalate by-products in their urine, indicating widespread exposures.

But some people had far higher concentrations than

others. When the investigators looked more closely

at highly exposed subgroups, they found that women

of reproductive age were among them. This is a particularly troubling finding, in light of the particular

vulnerability of the fetus to phthalate toxicity. 

A third line of research has examined the mechanisms of phthalate toxicity and considered the cumulative or aggregate impacts of members of the

phthalate family in experimental animals. Studies

show that some industrial chemicals act as antiandrogens, interfering with male development in at

least two ways. They can decrease testosterone synthesis in the fetal testes or they can block the androgen receptor through which testosterone initiates its

control over male development. In either case,

testosterone-dependent gene activation is reduced.

Several phthalates interfere with testosterone synthesis in the developing organism, including DEHP, BBP,

DBP, and perhaps DINP. 6 63 107 109 It follows that exposures to these phthalates should be considered in the

aggregate for the purposes of estimating risks from

exposure. Moreover, exposure to these phthalates

should be considered in the aggregate with exposures

to other chemicals that are also anti-androgenic

through androgen receptor blockade or interference

with testosterone synthesis.

The problem is that regulatory agencies generally do

not estimate risks from chemical exposure by considering aggregate exposures. They assess safety as if we

are exposed to single chemicals, despite real world

evidence of multiple exposures to multiple chemicals

from multiple sources. There are two notable exceptions. The EPA has been directed by Congressional

legislation to consider cumulative exposures to pesticides used on food when the chemicals act through a

common mechanism of action. The other is in the

pharmaceutical division of the FDA where there is

some recognition that biologically active drugs often

interact with each other and may have additive

effects. Physicians, nurses, and pharmacists are routinely expected to consider drug interactions and

cumulative impacts when prescribing, administering,

or providing medications. Most patients also understand this concern and have learned to ask about it

when new medications are considered. 

In the medical products division of the FDA, however, their 2001 Safety Assessment of DEHP Released

from PVC Medical Devices compares an estimated

safe exposure level (tolerable intake) to individual

kinds of therapy. They acknowledge that patients are

exposed to DEHP from multiple medical sources, but

focus their safety analysis on single sources. The

FDA safety assessment also concentrates entirely on

sources of phthalate exposure in the medical care

setting and fails to consider exposures to phthalates

in individuals from the general population who also

happen to require medical care. Data from the CDC

show that pregnant women come to the hospital

already significantly contaminated with phthalates,

and medical exposures add more. And, when the

FDA assesses the safety of phthalates used in cosmetics, they typically consider only exposures to one

kind of phthalate from individual cosmetic products.

No regulatory agency is adding up all the exposures

to all of the phthalates from all of the sources and

assessing the safety of that real world mixture. Yet,

many people in the general population are currently

exposed to various phthalates at levels of concern. 

In this report we outline an approach that attempts

to address the reality of multiple sources of phthalate

Aggregate Exposures to Phthalates in Humans 7
exposures. We know far less than we ought to about

the consequences of exposure to real world complex

mixtures of industrial chemicals. For the phthalates,

however, available exposure and toxicity data make it

clear that the world in which people and wildlife live

is not the make-believe world of the FDA, the EPA,

and the Consumer Product Safety Commission.

People are exposed to phthalates at levels of significant concern. As we will see, however, people are

not being protected by product manufacturers or regulatory agencies, and are hard-pressed to find ways to

protect themselves. 

8 Health Care Without Harm
Aggregate Exposures to Phthalates in Humans 9

Phthalates in 

Consumer Products 

Phthalates are a principal component of flexible PVC

products, cosmetics, pesticides, building maintenance

products, lubricants, and personal care goods that

surround consumers at home, work, and in hospitals.

PVC without additives is inherently a rigid and brittle material, requiring large amounts of plasticizers to

make flexible products. In fact, approximately 90% of

global plasticizer production is destined for use in

polyvinyl chloride plastic (PVC). 14 The remaining

10% is used in adhesives, caulks, skin creams, detergents, electrical capacitors, hairsprays, inks, solvents,

lubricating oils, lotions, nail polish, paints, fragrances, and pharmaceuticals.23 74 120 In personal care

products, phthalates provide flexibility, impart an

oily “moisturizing” film, and help dissolve and fix

other cosmetic ingredients. 15 The film forming and

flexibility properties imparted by phthalates are also

useful in paints, inks, fillers, adhesives and caulks

and insulating properties in electrical cabling and

capacitors. 25

Phthalate structure 

The oily, plasticizing properties of phthalates come

from their chemical structures. Phthalates represent

a broad chemical family containing a benzene ring,

two carbonyl groups, and two alcohol groups to generate a diester structure. Common branched phthalates such as DEHP, DBP, BBP, and DINP feature

branched-chain alcohol moieties of 6 to 13 carbons.

The linear phthalates contain linear alcohol groups

and include short chain phthalates such as DEP and

DMP, and other phthalates with chain lengths of

seven to 11 carbons that are use to impart increased

flexibility at low temperatures. 48 The benzene ringbased structure of phthalates helps reduce their viscosity but also makes them harder to degrade. 68

Phthalates move freely through the PVC polymer to

impart flexibility and other characteristics.144 Since

they are not covalently bound to the polymer, they

are fairly easily released to air, water, saliva, blood, IV

solutions, nutritional formulas, and other extracting

materials. 46 86 110 153 Since phthalates tend to be fat soluble, they leach more readily into lipid-containing

solutions. Depending on the circumstances of use,

2% - 50% of the phthalate content can emerge from

products over their service life. 86

Phthalates in personal care and

other consumer products

Many personal care products, building materials,

clothing, toys, adhesives, inks, pesticides, films, food

wraps, food containers, and other consumer items

contain phthalates. Phthalate concentrations in personal care products can approach and sometimes

exceed 200 gm/kg (20%). 5 Other consumer products

can contain levels of phthalates ranging from 60 -

800 gm/kg (6-80%). 36 86 116 141 Four of the principal

phthalates used in commerce are BBP, DBP, DEHP,

and DINP. Butyl benzyl phthalate (BBP) is added to

cosmetic products, flooring, paints, coatings, adhesives, and printing inks. 45 113 Di-n-butyl phthalate

(DBP) is used in cosmetics, toys, flooring, adhesives,

wallpaper, furniture, raincoats, plastic cling wrap, and

shower curtains. 1 4 Di-(2-ethylhexyl) phthalate

(DEHP) is the principal phthalate used in a variety

of products including medical devices, cabling, flooring, and auto parts and interiors. 86 Di-isononyl

phthalate (DINP) is widely used in children’s toys,

flooring, fabrics, gloves, tarps, garden hoses, shoes,

autos, paper packaging materials used for food contact, and sealing gaskets for food containers. 24 114 See

Table 1 for examples of phthalates in commerce. 
A recent study by the Danish EPA tested PVC shower curtains, flooring, gloves, carpet tiles, wallpaper,

and bags and found at least one type of phthalate in

all products at levels that varied from 24 - 630

gm/kg.30 Combined levels of DIDP-DINP were found

at 88 gm/kg in shower curtains, 110 gm/kg in bags,

260 gm/kg in wallpaper, 290 gm/kg in carpet tiles,

310 gm/kg in flooring, and 600 gm/kg in gloves. A

recent Greenpeace study found phthalates at levels

up to 390 gm/kg in a variety of PVC consumer products made for children including diaper pants

(DINP), diaper-changing mats (DINP), rain covers

for strollers (DEHP), drinking straws (DINP), cribrail teethers (DINP), and hats (DEHP). 67

Phthalates in PVC 

medical products

PVC medical products also contain phthalates.

Levels of DEHP, the most commonly used, range

from 200-800 gm/kg (20-80%). 36 116 PVC products

that release DEHP in the clinical setting include IV

storage bags, ventilator tubing, IV infusion sets,

endotracheal tubes, IV infusion catheters, nasogastric tubes, blood storage bags, enteral and parenteral

nutrition storage bags and tubing, blood administration sets, urinary catheters, exam gloves, suction

catheters, chest tubes, nasal cannula tubing,

hemodialysis tubing, syringes, extracorporeal membrane oxygenation (ECMO), and cardiopulmonary

bypass (CPB) tubing. 153

10 Health Care Without Harm

Table 1. Types of products containing phthalates

Product Type Examples Phthalates

Automotive PVC auto floor mats DEHP

Auto sheeting L11

PVC underbody DINP

PVC upholstery DEHP

Beauty Aftershaves DEP

Deodorants DBP, DEP

Skin Creams DEP

Hair preparations BBP, DMP, DBP, DEP

Nail polishes DBP

Fragrances DEHP, BBP, DBP, DEP

Powders DEP

Building -Home Adhesives BBP, DHP, DIOP, DIDP

PVC carpet covers DEHP

Caulks /grouting unspecified

Paint unspecified

PVC drawer liners DEHP, DINP

PVC flooring BBP, DEHP, DBP

PVC furniture covers DEHP

PVC garden hoses DIBP

PVC gaskets BBP, DEHP, DINP, L7-9, L7-11

PVC inflatable furniture DEHP

PVC inflatable pools DEHP

PVC insulation DEHP

PVC mattress pads DEHP

PVC roofing film DEHP

PVC shades DEHP, DINP

PVC shower curtains DEHP, DBP

PVC tarps DEHP

PVC tubing BBP, DEHP, DINP, L7-11

PVC wall coverings L7-9, DINP, DEHP, DBP

PVC water beds DEHP

PVC-coated fabrics L7-9

PVC-covered cables DEHP, DIDP, L11, L7-11
Lack of consumer notification

This widespread use of phthalates in consumer products is largely invisible to the public because most

products do not require labels to identify their presence. PVC building products, PVC toys, PVC auto

parts, PVC clothing, PVC baby products and other

common PVC consumer products do not require

labeling that reveals their phthalate content or even

identifies the plastic as PVC. The US Food and Drug

Administration (FDA) requires some labeling of cosmetic ingredients, but the law does not require listing

of phthalates or other ingredients considered fragrance components nor does the law require labeling

of products sold to professional salons. 152

Aggregate Exposures to Phthalates in Humans 11

Table 1. Types of products containing phthalates (continued)

Product Type Examples Phthalates

Consumer PVC aprons DEHP

PVC backpacks DEHP

PVC balls DEHP

PVC bibs DEHP

PVC changing pads DEHP

PVC clothing DEHP, DINP

PVC crib rail teether DINP

PVC diaper pants DEHP

PVC luggage DEHP, DBP

PVC notebook covers DEHP

PVC packaging DEHP

PVC purses DEHP

PVC shoes DIBP, DEHP, DINP

PVC stroller covers DEHP

PVC tablecloths DEHP

PVC toys DEHP, DINP

PVC umbrellas DEHP

PVC weight covers DEHP

Food Packaging PVC squeeze bottles unspecified

PVC packaging unspecified

PVC straws DINP, DEHP

PVC tubing unspecified

Cling Wrap unspecified

Industrial/Agriculture Electric capacitors DEHP

Fillers unspecified

Pesticides DEHP

Printing ink BBP, DBP

PVC conveyer belts DINP, L7-11

Vacuum pump oil DEHP

Medical PVC blood bags DEHP

PVC catheters DEHP

PVC colostomy bags DEHP

PVC dentures DBP

PVC enteral feeding bags DEHP

PVC gloves DEHP

PVC IV bags DEHP

PVC mattress covers DEHP

PVC oxygen tents DEHP

PVC pillow case covers DEHP

PVC syringes DEHP

PVC tubing DEHP

PVC urine bags DEHP

Pharmaceutical Coating ingredient DBP

Stabilizer DBP

Sources: 4 5 24 49 74 86 98 114 127 144 

See the Health Care Without Harm website for updates to this table: http://www.noharm.org
According to a voluntary reporting system used by

the FDA, DEP-containing products include 42

colognes, 7 powders, 8 aftershaves and 8 skin

creams.151 The Agency also lists DMP in 11 hair

preparations and DBP in 120 nail basecoats, polishes

and enamels and 27 other manicuring preparations.

Since this is a voluntary system and manufacturers

have no obligation to report, a comprehensive analysis of the use of phthalates in personal care products

is not publicly available. 

Labeling requirements on medical products vary considerably, and the agency does not require manufacturers to note the presence of PVC or phthalates

specifically. Some products warn against the use of

DEHP-containing IV bags to administer certain

drugs that can accelerate DEHP leaching.76 77 The

FDA is currently drafting a risk management strategy

as a follow up to their September, 2001 safety assessment of DEHP in PVC medical devices. That strategy may include labeling recommendations. 

Phthalates in the environment 

The manufacture, use, and disposal of PVC and

other phthalate-containing products have resulted in

extensive environmental releases of phthalates.

Consequently, phthalates are now one of the most

abundant industrial pollutants in the environment,

and are widely present in air, water, soils, and sediments. 29 140

Available data underestimate the release of phthalates from manufacturing facilities since companies

are not required to report releases of many commonly produced chemicals. In the US, for example, companies are not currently required to report releases of

DINP, DEP, or BBP, despite their high production volume. However, large US industries are required to

report environmental releases of DBP and DEHP to

the US EPA as part of the Toxic Release Inventory

when annual releases exceed 25,000 pounds or when

the facility otherwise uses in excess of 10,000

pounds.32 In 1999, the top 100 US companies reported total DBP releases of more than 390,000 pounds.

The same year, the top US 100 companies emitting

DEHP reported nearly 1.2 million pounds of releases.

In Germany, total DEHP emissions during processing

were estimated at over 1.5 million pounds per year in

1998 and the overall annual environmental releases

of DEHP in Germany are estimated to be considerably in excess of 3.3 million pounds. These reports,

however, do not include phthalates released to the

environment from the use or disposal of finished

consumer products. 

Phthalates such as DEHP have been measured in virtually all fresh water and marine environments and

in lake sediments, storm water runoff, sewage treatment plants, and sewage sludge. DEHP, DBP, and

DEP were found at levels exceeding 700 μg/kg in

sediments from Lake Mead, a national park in the

US.13 DEHP is in ocean sediments at sewage outfall

points (25 mg/kg) and all the sediments in rivers

near sewage outflows in New Jersey, USA.3 DEHP is

also the most prominent toxic organic chemical in

sewage sludge.57 DEHP levels in sludge have been

measured at 55 – 300 mg/kg. More than five billion

pounds of sludge are spread onto US land each year. 3

Buried PVC products in landfills release phthalates

into landfill leachates. 31 DEHP levels in these liquids

have been measured at 34-7,900 μg/kg.3 In the US,

DEHP, DEP, and DBP have been found in 18%, 44%,

and 30% respectively, of the hazardous waste sites

designated as national priorities for clean-up

(Superfund sites.) 3 4 5 In Sweden, Italy, Germany and

the UK, various phthalates and their metabolites

have also been detected in landfill leachates.

Phthalate concentrations for phthalic acid, DEP, and

DMP were 18,900 μg/kg, 540 μg/kg, and 300 μg/kg

respectively. 9

DEHP has been measured in indoor air at concentrations ranging from 8 ng/cm3 to 3 mg/cm3

. 99 156

A Health Canada Expert Panel evaluation of the

risks associated with DEHP exposures concluded

that inhalation exposure to DEHP is second only to

ingestion of DEHP-contaminated food. 35 Presumably

DEHP air contamination is the result of its being

released from PVC in the indoor environment.

Even remote areas contain phthalates. DEHP has

been found in the Antarctic pack ice, the Antarctic

sub-surface snow at depths up to three meters, and

in deep-sea jellyfish from more than 3000 feet below

the surface of the Atlantic Ocean. 3 100

12 Health Care Without Harm
Phthalates in people

Given the multiple uses of phthalates in hundreds of

consumer products and worldwide environmental

contamination with phthalates, it comes as no surprise that people and wildlife are virtually universally

exposed to phthalates. The general population is

exposed to phthalates through food, water, air, and

the use of phthalate-containing consumer products

that may be eaten, inhaled, or applied directly to the

skin and absorbed. Whatever the sources, most people are regularly exposed to phthalates so that some

combination of these chemicals or their byproducts

can be detected in the blood or urine of virtually

everyone in the general population. 

Unlike some chemicals, like dioxin, lead, or mercury,

that tend to persist and build up in various tissues,

phthalates are generally not persistent, though under

some circumstances, phthalates do tend to accumulate in certain organs. 80 But because exposures are

so frequent and common, some level or body burden

of the phthalate family of chemicals can regularly be

detected. The potential health impacts of these universal exposures are discussed in the following sections of this report with special attention paid to

groups of people who are disproportionately exposed. 

Aggregate Exposures to Phthalates in Humans 13
14 Health Care Without Harm

Phthalate Toxicity

Phthalates display a variety of toxic effects in animal

studies following chronic exposure or even after

short-term exposures in particularly vulnerable

organisms. These effects include damage to the liver,

kidney, heart, and lungs as well as adverse effects on

reproduction, development, and blood clotting. The

effects of human exposures to phthalates have not

been well studied. Long latency periods between relevant exposures and health impacts, unquantified

exposures, and subtle effects that are difficult to

detect complicate and limit the few existing epidemiological studies of phthalate impacts in humans. But

these limitations do not fully explain why the

impacts of phthalates on humans have not been

thoroughly investigated. 

The testicular toxicity of DEHP in experimental animals, for example, was described in 1972, but no one

has investigated its effect on human male reproductive capacity.10 116 Even the consequences of potentially high exposures to DEHP from, for example,

total parenteral nutrition or hemodialysis of breastfeeding mothers have not been the subject of scientific review. Although most toxicity data come from

studies in laboratory animals, human correlates to

some effects seen in animal studies have also been

described. This body of data collectively has generated concern in the medical and public health communities as well as government regulatory agencies. 

Reproductive and

developmental effects

In general, the monoester metabolite of the parent

phthalate compound is thought to be responsible for

adverse reproductive and developmental effects of

phthalates. In animal testing, impacts include

decreased fertility in females, fetal defects, reduced

survival of offspring, birth defects, altered hormone

levels, and uterine damage. Phthalates that display

one or more of these effects include BBP39 40 41 44 64 109 121,

DBP40 92 131, DEP52 92, DHP92, DIDP75 155, DINP64 114 150,

MBP38 130, MDP43, and MEHP97 129. 

In males, phthalates cause prostate damage, femalelike areolas/nipples, and reproductive malformations

in infants, including altered hormone levels, testicular atrophy, reduced sperm production and motility,

undescended testes, hypospadias, Sertoli cell damage,

and Leydig cell tumors. Phthalates that display one

or more of these effects include BBP2 64 109 121 134,

DBP42 54 56 106 108 157, DEHP8 12 56 64 65 94 124, DEP19 82 92,

DHP 92, DINP64 114 150, DPP55, MEHP71, MBP71, and

MPP71. 

Some of the effects caused by DEHP in males

include altered zinc concentrations, testicular atrophy and infertility. 153 The FDA notes that these same

symptoms are seen in male hemodialysis patients. In

fact, the Agency called the similarity between the

testicular damage observed in animals and male

hemodialysis patients “strikingly similar” and concluded that the effects seen in rodents “may have a

clinical correlate in humans.” 153

Several other government agencies have concluded

that the reproductive effects caused by DEHP are

relevant to humans. The US NTP’s Center for the

Evaluation of Risks to Human Reproduction

(CERHR) Expert Panel concluded in its review of

DEHP toxicity that the “rodent data are assumed

relevant to predicting that DEHP has the potential

to produce adverse reproductive system effects in
humans.” 116 In 2001, the Swedish National

Chemicals Inspectorate concluded in its review of

DEHP for the EU that, “The effects on testis, fertility, and development, observed in different animal

species and at relatively low levels, are considered to

be relevant to humans.” 86 Finally, in 2002, Health

Canada’s Expert Advisory Panel on DEHP in

Medical Devices concluded that, “the mechanism by

which developmental and testicular toxicity in particular occur in rodents appears relevant to

humans.”69

Altered liver and kidney function

Phthalates such as DBP, DEHP, and DINP cause a

variety of alterations in kidney function in animals

including renal cysts, reduction in creatinine clearance, and transitional cell carcinoma. 20 27 158

Phthalates also increase liver weight, affect liver

function, and alter liver enzymes in rodents. These

effects have been observed after exposure to DBP,

DEHP, DMP, DEP, DINP, and DIDP. 4 17 52 87 133 150 Some,

but not all, of the liver changes seen in rodents are

thought by many researchers not to be relevant to

humans (see below). However, certain effects due to

phthalate exposure have been observed in both primates and humans. In a small study of monkeys, for

example, DEHP caused adverse effects in the liver

after leaching from PVC blood bags during blood

transfusions. 79 In contrast, transfusions given to two

monkeys from polyethylene containers without

DEHP did not cause liver damage. Human patients

undergoing hemodialysis are also exposed to large

doses of DEHP from PVC tubing. Changes in liver

enzymes similar to those observed in animal studies

are also seen in these patients. 153 In the US alone,

approximately 250,000 people require dialysis treatment. 111

Other human liver effects that have been reported to

occur following DEHP exposure include cholestasis,

in which bile excretion is impaired. One prospective

study found cholestasis in infants undergoing extracorporeal membrane oxygenation (ECMO). 135 These

infants received large doses of DEHP, which leached

from PVC tubing. Another study failed to find

ECMO-related cholestasis when exposure to DEHP

was lower.83 Cholestasis and other liver abnormalities

are also observed in neonatal infants receiving total

parenteral nutrition.59 The cause(s) of these liver

abnormalities are not fully understood, and the

potential role of DEHP has never been fully investigated. The high lipid content of the nutrition solution facilitates phthalate leaching from DEHP-containing products, and these patients likely receive

even larger DEHP doses than dialysis patients.96 A

recent Health Canada Expert Advisory Panel recommended that “total parenteral nutrition solutions be

administered to newborns and infants only via products which do not contain DEHP.” 69 

DEHP and DINP cause liver carcinoma and adenomas in rodents.20 89 105 These tumors are linked to the

proliferation of small cellular organelles known as

peroxisomes. In humans, peroxisome proliferation in

the liver after exposure to phthalates and other peroxisome proliferators is generally not found to an

appreciable degree. Therefore, one possibility is that

phthalates do not have the potential to cause liver

cancer in humans. However, phthalates cause peroxisome proliferation by interacting with a nuclear

steroid hormone receptor that governs gene expression. This receptor is also found in humans but at

1-10% of the amount observed in rodents. 86 Since

the difference between the human and rodent receptor is quantitative, the potential for human response

may vary with the receptor content in different individuals. In fact, a 10-fold difference in receptor transcription has been observed in different individuals.146

These observations led a researcher in the field to

conclude that, “the potential human carcinogenicity

of these chemicals cannot be summarily ignored.”154

Heart, lung, and

hematologic effects

Phthalates can also adversely impact the heart and

blood pressure, though many animal studies have

used fairly high exposure levels. One study, however,

using intravenous injection of MEHP in rats, reported a slowing of the heart rate beginning at a total

dose of 57 mg/kg and a drop in blood pressure beginning at 157 mg/kg.126 Patients undergoing coronary

artery bypass grafting can be exposed to 2.2-80 mg

MEHP/operation and patients undergoing heart

transplants 0.5-2.5 mg/operation.11 Neonates undergoing exchange transfusion can be exposed to MEHP

at levels up to 0.68 mg/kg.138 Little is known about

species differences in susceptibility to cardiac effects

of phthalates.

The effects of phthalates on the lung are not well

known. DIDP increases the width of alveolar septa

and causes inflammatory reactions in animal studies.60 In humans, lung disorders similar to hyaline

Aggregate Exposures to Phthalates in Humans 15
membrane disease occurred in several pre-term

infants ventilated with PVC tubing containing

DEHP. 128 The symptoms diminished when the PVC

tubing was replaced with ethylene vinyl acetate tubing that does not contain plasticizers. A 1999 study

found that phthalates such as DEHP and BBP

migrate from PVC flooring to house dust.117 The

authors reported a higher frequency of children with

bronchial obstruction, characteristic of asthma

attacks, in homes with PVC flooring.78 They proposed that the structural similarity between phthalates and prostaglandins might provide a mechanistic

explanation for the observed association. 

The FDA cites numerous studies that indicate that

DEHP stimulates complement activation and platelet

aggregation and that these effects are significantly

reduced when non-PVC/non-DEHP alternatives are

used.153 According to the FDA, complement activation appears to be involved in the inflammatory

response observed in cardiopulmonary bypass

patients. Platelet aggregation can lead to the formation of small blood clots that are thought to cause

neurological complications in cardiopulmonary

bypass patients and infarcts of the brain, lung, and

kidney in patients that receive extracorporeal membrane oxygenation.53

Potential role of isomeric

mixtures in phthalate toxicity 

Phthalate toxicity can be further complicated by the

presence of large numbers of isomers or chemical

variants. In a study of DINP, the US Consumer

Product Safety Commission (CPSC) noted that DINP

is a mixture of up to 100 isomers and that only five

have been even minimally studied.149 One type of

DINP was carcinogenic, but the CPSC claimed that it

was never commercialized. However, the agency did

warn that, “It is conceivable that one or more existing types of DINP for which data are unavailable

could also be more toxic and/or carcinogenic.”149

16 Health Care Without Harm
Aggregate Exposures to Phthalates in Humans 17

Exposures Resulting 

from Medical Procedures 

The deposition of DEHP in human tissues resulting

from the use of DEHP-containing PVC medical

products has been documented for thirty years. In

1972, DEHP released from PVC blood-bags was

detected in the lungs, liver, spleen, and abdominal

fat.80 In the mid-1970s, investigators found significant levels of DEHP in the heart and gastrointestinal

tract of neonatal infants treated with PVC umbilical

catheters.72 Higher levels of DEHP were correlated

with more extensive transfusion, catheter use, and

death. In 1976, DEHP was found in human serum

following hemodialysis.62 93 In 1985, DEHP and its

more toxic metabolite, MEHP, were found in

hemodialysis patients.123 Both the parent compound

and its metabolite were also found in newborn

infants who had received exchange transfusions.137 138

Sjoberg et al., (1985) measured post-exchange transfusion levels of MEHP in plasma of newborn infants

at 2.4-15.1 μg/mL. In 1989, DEHP was also found in

the blood, liver, heart, and testes of neonatal infants

undergoing extracorporeal membrane oxygenation.132

Ventilation with PVC tubing also deposits DEHP in

the lungs.128 In the 1990s, further evidence accumulated of DEHP deposition due to exchange transfusions and dialysis and its high exposure potential

from infusion lines used in total parenteral nutrition.50 96 122

FDA Safety Assessment of DEHP

In 2001, the FDA released its Safety Assessment of

DEHP Released from PVC Medical Devices.153 The

Agency estimated DEHP exposures from a variety of

medical procedures and compared the results to their

calculated tolerable intake for DEHP. Table 2 shows

that a variety of medical procedures result in DEHP

exposures close to the tolerable intake established by

the Agency. These procedures include IV infusion

with drugs requiring pharmaceutical vehicles for solubilization, adult total parenteral nutrition, adult

coronary artery bypass graft (CABG) replacement

transfusion, neonatal replacement transfusion, adult

orthotopic heart transplant, and adult hemodialysis.

In addition, the FDA estimates indicate that several

procedures exceed the Agency’s tolerable intake of

DEHP. These include total parenteral nutrition with

lipids in neonates, transfusions to trauma patients

and ECMO in adults, neonatal exchange transfusions, adult coronary artery bypass graft, adult and

neonatal artificial heart transplant, and adult and

neonatal enteral nutrition. 

The FDA concluded that DEHP exposures may not

be safe for patients receiving medical treatments that

exceed the tolerable intake as shown in Table 2. The

Agency also expressed concern over the risk to children and cited three main findings: 

1) Children receive a greater DEHP dose than

adults from some procedures; 

2) Metabolic differences may cause children to

absorb more DEHP, create more of its toxic

metabolite, MEHP, and excrete less MEHP; and

3) Children may be more sensitive to the toxic

effects of DEHP than adults. 

The FDA safety assessment of DEHP is consistent

with the conclusions of the National Toxicology

Program’s Center for the Evaluation of Risks to

Human Reproduction. In 2000, the NTP Expert

Panel concluded in its review of DEHP that: 

“The available reproductive and developmental toxicity data and the limited but suggestive human

exposure data indicate that exposures of intensivelytreated infants/children can approach toxic doses in

rodents, which causes the Panel serious concern

that exposure may adversely affect male reproductive tract development.”116
18 Health Care Without Harm

Table 2. Estimated DEHP doses from PVC medical products for various medical

procedures calculated by the US FDA compared to tolerable intakes (mg/kg/day) 

Procedure DEHP Dose Tolerable Intake Ratio Tolerable 

Intake/Dose*

IV infusion

Crystalloid solutions 0.005 0.6 120

Drugs requiring solubilization 0.15 0.6 4

TPN

Adult; added lipid 0.13 0.6 5

Neonatal; added lipid 2.5 0.6 0.2

Transfusion

Adult; trauma patient 8.5 0.6 0.1

Adult; ECMO 3.0 0.6 0.2

Adult; CABG replacement 0.28 0.6 2

Neonate; exchange 22.6 0.6 0.02

Neonate; replacement 0.3 0.6 2

Cardiopulmonary bypass

Adult; CABG 1.0 0.6 0.6

Adult; orthotopic heart transplant 0.3 0.6 2

Adult; artificial heart transplant 2.4 0.6 0.3

ECMO

Neonate 14 0.6 0.04

Dialysis

Adult hemodialysis 0.36 0.6 2

Adult peritoneal dialysis <0.01 0.6 >60

Enteral nutrition

Adult 0.14 0.04 0.3

Neonate 0.14 0.04 0.3

Data source: 153 

Abbreviations: IV: intravenous; TPN: total parenteral nutrition; ECMO: extracorporeal membrane oxygenation; CABG: coronary artery bypass graft. 

See the Health Care Without Harm website for updates to this table: http://www.noharm.org

*a ratio of <1 means that the dose exceeds the tolerable intake
Aggregate Exposures to Phthalates in Humans 19

Limits of the FDA

Safety Assessment 

The FDA failed to consider two significant issues

when comparing the tolerable intake for DEHP to

exposures from various medical procedures: 

1) Although the agency mentioned the problem of

aggregate exposures to DEHP from multiple

medical sources, they did not take this reality

into account when listing medical procedures

that might result in exposures in excess of the

tolerable intake.

2) When calculating the tolerable intake for DEHP,

the FDA attempted to factor in exposures to

other phthalates in the hospital setting. But,

they failed to consider exposures to all phthalates in the general population that result in a

pre-existing body burden in patients entering

the health care system. 

Aggregate exposures

in the hospital

DEHP is not the only phthalate to which patients

are exposed in the hospital. The FDA cites studies

that identified DBP, DEP, DMP, or BEP in PVC medical devices including nasogastric tubing, microfilters,

butterfly catheters, denture base material, infusion

tubing, infusion bags, and intestinal tubing. Levels of

these additional phthalates varied from 1% to 20% in

the medical products.153

The FDA derived a tolerable intake for DEHP, which

included a safety factor of 3 that is intended to

account for both “increased sensitivity to DEHPinduced testicular effects during pre- and post-natal

exposure and the possibility that humans can be

exposed to phthalates other than DEHP and MEHP

that exert their effect via a similar mechanism of

action.” Based on relevant animal studies, an

increased sensitivity to DEHP-induced testicular

effects in very young developing organisms seems

clear. Whether or not a safety factor of 3 is sufficient

protection for that population is a matter of conjecture. Beyond that, however, the Agency limited

their consideration of concurrent exposures to multiple phthalates to those resulting only from medical

care. If one considers concurrent exposure to multiple phthalates from multiple sources, including those

that result in a body burden of phthalates before a

patient enters a medical facility, a different picture

emerges. A safety factor of 3, intended to account for

both increased prenatal/postnatal sensitivity and

multiple phthalate exposures from all sources,

appears to be inadequate. 

In addition, the FDA notes that, in some instances,

DEHP metabolizes to its toxic metabolite MEHP

prior to the initiation of medical therapies. This

transformation is facilitated by lipases present in

stored blood and plasma, but can also occur by

hydrolysis in stored IV solutions. The FDA cites

studies that measured MEHP in hospital patients

undergoing coronary bypass, hemodialysis, and peritoneal dialysis. The Agency also acknowledged that

nursing infants could receive significant doses of

MEHP in breast milk from mothers undergoing

hemodialysis. The FDA performed some calculations

to estimate the impact of MEHP that are described

further in Appendix I. However, in the end, the

Agency focused only on DEHP when listing procedures that might result in exposures exceeding the

tolerable intake. 

In conclusion, although the FDA acknowledges that

individual patients can be exposed to DEHP from

multiple sources in the medical setting and to multiple phthalates from medical devices, they fail to integrate that information into the real world in which

patients live—a world where people are exposed to

multiple phthalates from non-medical and medical

sources at levels that, for many prospective patients,

are close to or exceed FDA’s tolerable intake. 
20 Health Care Without Harm

Aggregate Exposures 

in the General Population

Human exposure to phthalates in the general population has been recognized for over 30 years, but the

levels of contemporary exposures were demonstrated

in a study recently conducted by the US Centers for

Disease Control and Prevention (CDC). The results

suggest that some of the highest exposures to phthalates occur in women of childbearing age, a population that is most vulnerable to phthalates’ ability to

damage the developing child. Previous attempts to

measure phthalates in human tissue have been complicated by their ubiquitous presence that contaminates samples and prevents accurate measurement.

A new analytical method developed by the CDC

permitted estimates of phthalate exposure by determining levels of their monoester metabolites in urine.

The CDC study

In 1999, investigators from the CDC measured the

levels of various chemicals in blood and urine samples from 1,029 people, six years or older, as part of

the National Health and Nutrition Examination

Survey (NHANES).23 Among the chemicals of interest were seven common phthalates. Investigators

measured metabolites of these phthalate parent compounds in urine samples of the participants. The

study revealed evidence of population-wide exposures to multiple phthalates with DEP, DBP, and BBP

present at the highest levels. Breakdown metabolites

of DEHP, DOP, and DINP were also observed.

Surprisingly, the concentrations of DEP, DBP, and

BBP metabolites exceeded those of DEHP and DINP,

even though DEHP and DINP are produced in larger

volumes and are more widely used. This may reflect

lower exposures, storage in fat or other tissues, or

metabolism and excretion by a different pathway.15

The results of this study suggest that we know far

less than we should about the sources of human

exposure to these industrial chemicals produced in

high volume and used for so many different purposes.

Perhaps the extensive use of both DEP and DBP in

cosmetic products, including perfumes, nail polishes,

lotions, deodorants, and hairsprays, which result in

skin absorption or inhalation, explains the CDC

findings. Or perhaps other combinations of consumer

products are also responsible. We don’t know.

A closer review of an important subset

CDC scientists examined a subset of the initial population more closely. This sub-group consisted of 289

participants who were 20 – 60 years old. Fifty-six percent were females and the group included Caucasians

(39%), African-Americans (30%), and MexicanAmericans (23%). The study measured breakdown

metabolites of DEP, DEHP, DBP, DCHP, BBP, DOP,

and DINP in random urine samples.15 Phthalate exposures were higher and more common than in the larger study population. More than 75% of the

participants excreted metabolites of DEHP, DEP, BBP,

and DBP. An analysis of demographic factors revealed

the study’s most disturbing finding. The highest levels

of the DBP monoester (MBP) were found in women

of childbearing age. In fact, six of the eight highest

MBP levels for the entire 289-member group were

found in women of reproductive age. 

Given what is known about the pharmacokinetics of

these chemicals, scientists from the CDC and the

National Institute of Environmental Health Sciences

(NIEHS) back-calculated to estimate the oral intake

of individual phthalates that would be expected to

result in the observed urinary residues.90 The calculations were applied to the 289-person sub-group and

a steady-state intake and clearance was assumed.

The 289 participants were further divided into two

demographic groups: 

1) women of reproductive age between 20 and 40

years old (n=97) and 

2) the rest of the adult sample (n=192). 

The authors considered their estimates to be within

an order of magnitude of the true value due to limited understanding of absorption, transformation, and

excretion and its high variability. 
Exceeding previous

intake estimates

Estimates of exposure to phthalates in the two demographic groups, based on actual measurements of urinary metabolic residues, exceeded previous daily

intake estimates, which had been based largely on

contaminated food intake, for almost all of the

phthalates. Table 3 shows exposure estimates for the

two groups. In this sample, women of reproductive

age are exposed to BBP, DBP, and DEP at levels that

are 2 – 45 times higher than previous daily intake

estimates. The rest of the adult group shows BBP,

DBP, and DEP exposures that are 1.7 – 30 times

higher than previous daily intake measurements for

adults. In the 95th percentile and above, women of

reproductive age are exposed to significantly higher

levels of DBP than the population at large (32 vs. 6.5

μg/kg/day). That is, in this study, the upper 5% of

the population of women of reproductive age are

estimated to have oral-equivalent intakes of DBP of

32 μg DBP/kg/day or higher while the upper 5% of

the rest of the population is estimated to have oralequivalent intakes of 6.5 μg DBP/kg/day or higher.

Demographic differences in

phthalate exposures 

Using the NHANES data, CDC and NIEHS scientists also examined other demographic differences in

phthalate exposures.91 They determined that individuals with a high school education or less had higher

levels of DBP than those with an education beyond

high school. Lower income and lower educational

level was associated with higher levels of BBP exposure. DEHP exposures were higher in males, in urban

populations, and in lower income individuals. 

CDC scientists also examined exposure to phthalates

in children using the same methods as prior studies

with adults.18 The study group contained 14 boys and

5 girls between 12 and 18 months old. The children

live in an agricultural area of California, USA.

Metabolites of BBP, DBP, and DEP were detected in

all 19 children. Six children also contained the

breakdown product of DEHP. Median exposure levels

in these children were approximately the same as

adult exposures for DBP and BBP, and somewhat

lower for DEP. For MEHP, the median values were

approximately the same, though the number of children was small. 

A recent study of 46 African-American women 35-

49 years old from the Washington DC area reported

levels of urinary metabolites of several phthalates

and compared them to results from the CDC

NHANES study. The median level of MEHP (the

metabolite of DEHP) in the African-American

women was more than twice as high as adults in the

Aggregate Exposures to Phthalates in Humans 21

Table 3. Estimated phthalate exposures in the 95th percentile 

group of women of reproductive age and general population 

compared to previous estimates of daily intake. (μg/kg/day)90

Phthalate Women of reproductive age Rest of group Daily Intake Estimate

(95th percentile) (95th percentile) (μg/kg/day)

All phthalates 1-11 UK

DEP 90 130 4.0 US

DBP 32 6.5 1.9 Canada

BBP 4.5 3.4 2.0 Canada

DCHP 0.24 0.25

DEHP 3.8 3.5 3.8 - 30 US

5.8 Canada

12 EU

DOP 0.65 1.0 <3.0 US

DINP 3.7 1.4 <3.0 US

References for daily intake estimates for adults: all phthalates: UK103, EU (multiple pathway) 86, DEP: 5, BBP: 46, DBP: 22, DEHP: US 3, DEHP:

Canada 21, DINP: 114 and DOP: 115. 
NHANES study (6.4 vs. 2.8 μg/gm creatinine), and

about twice as high for MBP (the metabolite of DBP;

43.4 vs. 22 μg/gm creatinine).73 MEP levels were

approximately the same. 

Individual adult exposures

and regulatory limits

The CDC calculations of phthalate exposures

demonstrate surprisingly high levels of phthalates in

the bodies of women during their childbearing years.

However, the regulatory systems in the US and

European Union view each phthalate exposure individually instead of collectively. Table 4 compares the

exposure for each phthalate to its regulatory limit.

The data show that none of the phthalate exposures

exceeds exposure limits. In fact, phthalate manufacturers use this data to conclude that exposures to

phthalates are negligible. 33

Assessing aggregate exposures

to multiple phthalates: a relative

potency approach

Actual human exposures to chemicals do not occur

singly, but in aggregate, complex mixtures. In addition, many phthalates display similar toxic effects as

a group.64 These realities require a new approach to

assessing phthalate exposures and impacts that result

from exposure to multiple phthalates in mixtures from

multiple sources in order to protect public health. 

In 1996, the Food Quality Protection Act directed

the US EPA to consider aggregate exposures to pesticides for chemicals that exert their toxicity through a

common mechanism of action. Since then, the FDA

and the Swedish National Chemicals Inspectorate

(KEMI), have also acknowledged the importance of

considering aggregate phthalate exposures.85 153

Estimating the relative potency of individual chemicals

and adding them in order to estimate the total potency

of a mixture is one way to evaluate the impacts associated with aggregate exposures. Two pieces of information are useful for justifying this approach. First, it is

helpful to know something about mechanisms of

action. A relative potency approach is justified when

chemicals exert their toxicity, at least in part, through

a common mechanism of action or a final common

pathway. Second, a common endpoint or related set of

endpoints adds to the evidence that chemicals may

have at least additive effects in an organism. 

22 Health Care Without Harm

Table 4. Estimated exposures in women of reproductive age 

compared to regulatory limits for phthalates. (μg/kg/day)

Phthalate CSTEE US EPA Women of Reproductive Age

Tolerable intake Reference Dose (95th percentile)

DEP 800 90

DBP 100 100 32

BBP 850 200 4.5

DCP 0.24

DEHP 50 22 3.8

DOP 370 0.65

DINP 150 3.7

Abbreviations: CSTEE: EU Scientific Committee on Toxicity, Ecotoxicity and the Environment; EPA: Environmental Protection Agency. 

Exposure data from the CDC.90 CSTEE Tolerable Intake values46 from EPA Reference Doses available at http://www.epa.gov/iris/index.html.

See the Health Care Without Harm website for updates to this table: http://www.noharm.org
For the phthalates BBP, DEHP, DBP, and perhaps for

DINP, this approach is supported by the general consensus that these phthalates act, at least in part,

through a common mechanism when they independently cause harmful effects on the developing male

reproductive system, which appears to be their most

sensitive endpoint. DEHP, BBP, and DBP each

reduce testosterone synthesis in the developing male

organism.6 63 107 109 It should also be noted that antiandrogens that act by blocking the androgen receptor will also likely have a cumulative impact with

chemicals that interfere with testosterone synthesis.

Each mechanism will reduce the effective level of

activated androgen receptors at the level of the

gene—the final common pathway of toxicity. 

For phthalates, the potency of each component in a

mixture can be expressed relative to DEHP, the most

well characterized member of the phthalate family.

Each individual phthalate can then be converted to

a “DEHP-equivalent” for the purpose of estimating

the total potency of a mixture of different phthalates.

This approach is similar to using “toxic equivalency

factors” for estimating the toxicity of complex mixtures of other chemicals, like, for example, dioxins,

that also act through a common mechanism of

action. The DEHP-equivalent potency of the mixture can then be calculated by adding the DEHPequivalency of each individual phthalate. This

approach requires data that directly compares endpoint-specific toxicity of various individual phthalates with DEHP. These calculations assume that the

combined effect of a mixture is additive, though it is

certainly possible for a combination to be more toxic

than the sum of its individual parts. 

Relative potency calculations 

We applied the relative potency approach to phthalates shown to cause reproductive and developmental toxicity in males. Few data are available that

compare these toxic effects from exposures to various

phthalates in the same experiment. However, two

well-controlled studies did compare other phthalates

with DEHP for this endpoint in vivo.64 65 To determine the relative potency, the ability of each phthalate to cause a certain effect was compared with

DEHP. For example, two litters of rats exposed prenatally and through lactation to equal amounts of

DEHP or BBP showed different results. For DEHP,

87% of the infant males displayed female-like areolas/nipples after exposure, but for BBP 70% of the

males displayed this defect.64 This suggests that BBP

is roughly 80% as effective as DEHP at causing this

effect, and therefore, could be assigned a relative

potency value of 0.8. 

Another recent rodent study compared the impacts

of gestational exposures to DEHP, DBP, or DEHP +

DBP on the developing male reproductive tract.

Pregnant rats were given DEHP (100 mg/kg/day),

DBP (100 mg/kg/day), DEHP + DBP (each at 100

mg/kg/day) on gestational days 12-21 by gavage. DBP

and DEHP + DBP caused similar reductions in

anogenital distance in male offspring when compared

to controls, but DEHP at that dose caused no reduction in anogenital distance. The doses chosen, therefore, were too low to detect potential additivity,

since DEHP alone at that dose had no effect. With

respect to male areolae/nipple retention, an additive

response from DEHP + DBP was observed at postnatal day 13, though it did not achieve statistical significance, perhaps as a result of the dose and the

small number of animals in each dose group.163

Relative potencies of several phthalates

Table 5 shows the potencies of four phthalates relative to DEHP. The relative potency of BBP varied

from 1.0 to 0.8 for effects including development of

female-like areolas/nipples, reduced pup weight,

shortened anogenital distance, malformed males, and

reduced testis weights. DBP showed greater variability in its effects compared to DEHP. Hypospadias was

the only effect in which DEHP was much more

potent. Estimating the relative potencies for DBP is

complicated by the fact that DBP was used at lower

doses than DEHP. We ignore this dosing difference,

however, for the purposes of estimating their relative

potency, and still note that DBP is similar to DEHP

in potency for shortened anogenital distance. For

other effects, potency ranged from 0.5 – 0.6 that of

DEHP. DINP showed much less potency than DEHP

in producing malformed males, but about 0.3 the

potency for generating female-like areolas/nipples.

DEP did not produce either malformed males or

male infants with female-like areolas/nipples in these

experiments. In other studies, DEP increased testes

weights, altered Leydig cell structure, and decreased

sperm concentration.19 82 92 However, these studies did

not directly compare DEP to DEHP. 

To calculate exposure in a mixture of phthalates, a

relative potency value must be selected for a phthaAggregate Exposures to Phthalates in Humans 23
late. However, Table 5 shows a variety of relative

potencies for each phthalate. Since a higher relative

potency value means a higher total estimated effective exposure, the highest relative potencies were

selected for each phthalate for the purposes of the

calculations in this paper. This conservative rationale

yields relative potencies for BBP, DBP, DINP, and

DEP of 1.0, 0.9, 0.3, and 0 respectively. 

Relative potency factors determined for BBP, DBP,

DINP and DEP were applied to the phthalate exposures calculated by the CDC for women of reproductive age and other adults. A sample calculation is

shown in Table 6. The exposure level of each phthalate is multiplied by the relative potency to yield the

DEHP-equivalent dose. Unfortunately, relative

potency factors could not be calculated for DCP and

DOP, two phthalates that were measured in the CDC

study, because of lack of experimental data. 

Total phthalate exposures are likely to be higher than

estimates derived from this list since several common

phthalates are not included. These high-production

chemicals include DHP, DIDP, and DOP as well as a

host of new linear chain phthalates.

24 Health Care Without Harm

Table 5. Estimated potencies of phthalates relative to DEHP: 

Reproductive and developmental toxicity in males.

Effect Phthalate Dose Percent of animals Relative

(mg/kg) or size of impact Potency Study

Male infants with DEHP 750 87 1.0 64

female-like areolas/nipples BBP 750 70 0.8

DINP 750 22 0.3

DEP 750 0 0

Reduced pup weight at birth DEHP 750 15 1.0

BBP 750 18 1.0

Malformed males DEHP 750 82 1.0

BBP 750 84 1.0

DINP 750 7.7 0.1

DEP 750 0 0

Reduced testis weights DEHP 750 35 1.0

BBP 750 35 1.0

Shortened anogenital distance DEHP 750 30 1.0

BBP 750 30 1.0

DEHP 750 2.45 1.0 65

DBP 500 2.79 1.1

Percent areolas DEHP 750 88 1.0

At birth in male infants DBP 500 55 0.6

Hypospadias DEHP 750 67 1.0

DBP 500 6.2 0.1

Testicular and epididymal DEHP 750 90 1.0

atrophy or agenesis DBP 500 46 0.5

All phthalates dosed orally. Note that no corrections were made to the effects in experiments where different doses of DEHP and DBP were used.

See the Health Care Without Harm website for updates to this table: http://www.noharm.org
Exceeding tolerable intakes

DEHP-equivalent exposures from the CDC data

were calculated and compared to some current tolerable intakes. Clearly, in this sample population, DBP

is the individual phthalate with the highest estimated

exposure and the one that tends to drive aggregate

exposures, expressed as DEHP-equivalents, most

sharply toward the tolerable intake. As seen in Table

7, 5% of women of reproductive age from the general

population in the CDC study show evidence of exposure to just DBP, expressed as DEHP-equivalency,

that is 75% of the FDA’s oral tolerable intake. This is

without any consideration of exposure to additional

phthalates with toxic impacts that are additive to

those of DBP. If, for example, one of these women

were to be exposed to DEHP from a medical procedure, 25% or less of FDA’s calculated tolerable

intake would be necessary before her aggregate exposure would exceed safe levels. Women from the general population who happen to be in the top 5% of

exposure for DEHP, BBP, and DBP will exceed the

tolerable intake without any additional exposure

from medical care. Total maximum exposure to just

DBP, BBP, and DEHP, based on these estimates,

would be on the order of 130 μg/kg/day. Assuming

that DBP, BBP, and DEHP are roughly equivalent in

potency for impacts on male reproductive development, that daily exposure to these three phthalates

would exceed the DEHP tolerable intake by 3 fold.

One study describes the co-variability of exposure to

several of these phthalates, or the extent to which

exposures to one correlates with exposures to another.91 In the NHANES sample population, DBP exposure was highly correlated with BBP exposure and

BBP exposure was moderately correlated with DEHP.

This suggests that there may be common exposure

sources for some phthalates, and that women with

high DBP levels are also likely to have higher levels

of BBP. 

Aggregate Exposures to Phthalates in Humans 25

Table 6. Using relative potency values to calculate the DEHP-equivalent dose

individual phthalates in women of reproductive age in the CDC study

Phthalate Women of reproductive age Relative potency DEHP-equivalent

95th percentile/max potency (μg/kg/day)

(μg/kg/day)

DEP 90 (95%) 0 0

170 (max)

DBP 32 0.9 29

113

BBP 4.5 1.0 4.5

7.8

DCP 0.24

0.45

DEHP 3.8 1.0 3.8

10

DOP 0.65

1.5

DINP 3.7 0.3 0.9

7.8

Exposure data from the CDC.90 Relative potency values calculated above. The DEHP-equivalent dose is the product of the exposure and the relative potency. The total DEHP-equivalent dose is the sum of the individual doses. 
Limits of the relative

potency approach

The aggregate exposure calculations shown above

highlight some of the limitations of the relative

potency approach. For example, the lack of comparison data for DEP in Table 6 resulted in a relative

potency factor of 0 even though the compound

shows reproductive effects in other studies.19 82 92 The

lack of comparison data limits the utility of this

approach when a large number of phthalates are at

issue because it may underestimate total potency of a

mixture. In addition, a low relative potency for one

endpoint may be unrelated to a relative potency calculated for a different endpoint. Although it would

be useful to use No-Observable-Adverse-EffectLevels (NOAEL) for comparison purposes, those

dose estimations have not been determined for many

of these impacts on the developing male reproductive system, and the calculations were based on single-dose studies. Finally, value judgments are used to

assign an actual relative potency number to a chemical that will be used to determine equivalent doses.

The wide variation in relative potencies observed in

Table 5 can demonstrate close to a one-to-one

equivalence or a one-to-ten equivalence for the same

phthalate. 

A significant exposure problem

The relative potency calculations suggest that aggregate exposures to phthalates in the general population are, in many cases, near to, or above regulatory

levels for the developing male reproductive toxicity

endpoint. Assuming that the population sample studied by the CDC is representative of the total US

population, census data reveal the public health

implications of the data. 

If the CDC sample is representative of the general

US population, approximately 2 million women of

reproductive age would be exposed to just DBP on a

daily basis at levels, expressed as DEHP-equivalents,

that are 75% or more of the tolerable intake for

DEHP. DEHP, BBP, DINP, and other phthalates add

to this number. An unknown number of these 2 million women who happen to be pregnant run the risk

of being exposed to unsafe levels of DEHP, if they

require medical care provided from DEHP-containing medical devices, even if the DEHP exposures are

well below the FDA’s tolerable intake. These women

will not have been free of phthalates before medical

care is provided. On the contrary, as we have seen,

baseline exposures in the general population are significant and set the stage for potentially unsafe levels

of exposure to phthalates from any number of

sources. 

These exposure estimates are disturbing even if only

in utero male developmental toxicity is considered.

The wider spectrum of health effects caused by

phthalates adds additional concern to the widespread

exposures in the general population. 

26 Health Care Without Harm

Table 7. Calculated daily intake of individual phthalates 

from the CDC study referenced to DEHP and compared to regulatory levels 

for DEHP. (μg/kg/day) for the most highly exposed women 

of reproductive age in the general population

Group Total DEHP- EPA FDA TDI Health Canada CSTEE 

Women of reproductive equivalent dose Reference Dose Oral TDI TDI 

age-top 5% (DEHP) (DEHP) (DEHP) (DEHP)

DBP 29 or higher 22 40 44 50

BBP 4.5 or higher 22 40 44 50

DEHP 3.8 or higher 22 40 44 50

DINP 0.9 or higher 22 40 44 50

Abbreviations: TDI: tolerable daily intake; EPA: US Environmental Protection Agency; FDA: US Food and Drug Administration; CSTEE: Science

Committee of Toxicity, Ecotoxicity and the Environment for the European Union. The mixture contained DEHP, DBP, BBP, DINP, and DEP. Note that

the table only reflects a DEHP-equivalent dose for the male reproductive toxicity endpoint. DCP and DOP could not be included due to the lack

of comparative experimental data. See the Health Care Without Harm website for updates to this table:http://www.noharm.org
Aggregate Exposures to Phthalates in Humans 27

Table 8. US Census 2000 data and National Center for Health Statistics 

calculations of samples in the CDC study

To Calculate Category Number

Women in upper 

95th percentile Adults 20-44 104,004,252

Women 20-44 52,938,164

Women 20-44 95th percentile 2,646,908

Children born to women 

in upper 95th percentile Births to women 20 to 40 in 2001 3,579,886

Births to women in 95th percentile or above 178,994

Male births to women in 95th percentile or above 89,497

US Census 2000 data from http://www.census.gov. Birth data from the National Vital Statistics Report at http://www.cdc.gov/nchs/. Note that

the CDC sample of reproductive age women was between 20 and 40, not 44 as provided in Census data. An approximate estimate of this category would be 2 million for reproductive age women. 
28 Health Care Without Harm

A Legacy of Inadequate Responses 

Phthalates have become ubiquitous environmental

and human contaminants. The concern over their

potential impacts on human health expressed by the

FDA, NTP, Health Canada, and the EU Scientific

Committees and the CDC’s documentation of aggregate exposures in humans reinforces the need to seriously examine and learn from the legacy of industry

and government policies surrounding their use. 

Inadequate industry solutions

The chemical industry has dealt with regulatory pressures on phthalates by proposing voluntary agreements and switching to alternative plasticizers. In

1986, DEHP in chew toys came under scrutiny in the

US. Toy makers responded by entering into a voluntary agreement with the US Consumer Product

Safety Commission to substitute DINP for DEHP. 7

In 1998, toy makers assured the public and US regulators that the voluntary agreement had successfully

removed DEHP from children’s toys in 1986.

However, toys containing DEHP were found the

same year at national chain stores in the US.37 145

Currently, the $70 billion European PVC industry is

actively lobbying the European Commission for a

voluntary approach to regulating PVC in the EU.125

Voluntary agreements fail to ensure safety because

compliance is optional and usually unsupervised by

the industry, regulators, or outside groups. When

industry voluntarily proposes to solve one phthalate

problem by switching to another phthalate or plasticizer, the substitution decision can be weighted

toward solutions that are easier for the industry

rather than safer for consumers. Changing to different plasticizers is relatively easy for manufacturers

since alternative phthalates or other plasticizers of

PVC can often be produced in the same facilities.

Since voluntary agreements allow companies to market consumer products with substitute plasticizers,

leaching and exposure problems remain with new

concerns about the safety of the substitutes.

Plasticizer leaching problems can be avoided by

switching to materials that are inherently flexible,

requiring no plasticizers to impart flexibility.

Recent controversies surrounding PVC and phthalates in toys and medical products have led to the

substitution of alternative plasticizers. The chemical

industry estimates that there are approximately 50-

100 plasticizers in commercial use.47 Common nonphthalate plasticizers in flexible PVC include

adipates (e.g., DEHA), citrates (e.g., ATBC), phosphates (e.g., DEHPA), and trimellitates (e.g.,

TETM). Most are poorly characterized toxicologically, but a summary of some known properties from a

Danish EPA report is shown in Table 9.28 Non-phthalate plasticizers can also leach from PVC causing

exposures, though the degree of leaching may vary

from that of phthalates.26 In addition, alternative

plasticizers may share some of the liver, reproductive,

and developmental toxicity features of phthalates.

The No-Observable-Adverse-Effect-Levels

(NOAEL) for reproductive toxicity of these common

alternative plasticizers varies from 28 – 100

mg/kg/day compared with a 3.7 – 2,800 mg/kg/day

for DEHP.28 153

Inadequate government solutions

Government approaches to phthalate regulation

have not protected consumers and hospital patients

from aggregate phthalate exposures. A patchwork of

governmental policies and regulations usually considers only individual chemicals and individual products. No regulatory agency is adding up the multiple

phthalate exposures from multiple sources in order to

draw safety conclusions. 

Regulatory authority is dispersed both among governmental agencies and within agencies and is separated

by product category, such as consumer products, pesticides, medical devices, pharmaceuticals, food, and

cosmetics. This separation creates formidable barriers
to regulatory control of aggregate exposures to toxic

chemicals of all sorts from multiple sources. A phthalate prohibited or limited for one use can be present

in high concentrations in another product. For example, the allowable concentration of DEHP is limited

in food containers but not in medical devices. In light

of the multiple applications of phthalates in a wide

variety of products, focusing on only one product or

class of products is unlikely to have a substantive

impact on total population-wide exposures. 

Regulatory authority is also limited. For example, the

Federal Food, Drug, and Cosmetics Act (FDCA)

authorizes the FDA to regulate food, drugs, medical

devices, and cosmetics. The Agency can deny the

marketing of cosmetics that contain “a poisonous or

deleterious substance which may render it injurious

to health.”51 However, with the exception of color

additives, which must be shown to be safe, the burden of proof is on the FDA to demonstrate violations

of this provision. 

The FDA does not review the safety of cosmetic

products or cosmetic ingredients before they are marketed. It cannot require manufacturers to do safety

testing of products before they are marketed and has

no reporting requirements. The FDA maintains a

voluntary data collection program. Cosmetic companies that wish to participate forward data to the

agency. If the FDA wishes to remove a cosmetic

product from the market, it must first prove that the

product may be injurious to users, improperly

labeled, or otherwise violates the law. 

In addition to the FDCA, the Fair Packaging and

Labeling Act requires labeling of ingredients on cosmetic products offered for sale, but not those used in

professional salons or given away. Unfortunately, fragrances that are claimed to be protected by trade

secret provisions in the law do not have to identify

ingredients on the label. 

Aggregate Exposures to Phthalates in Humans 29

Table 9. Properties of some alternative plasticizers

Source: 28 Abbreviations: NOAEL: No-Observable-Adverse-Effect-Level; LOAEL: Lowest-Observable-Adverse-Effect-Level. 

See the Health Care Without Harm website for updates to this table: http://www.noharm.org

Plasticizer

DEHA

ATBC

DEHPA

TETM

Properties

Easily migrates

Water soluble

Expected to be

bioaccumulative

Water soluble

Heat resistant

Easily migrates

Expected to be

bioaccumulative

Current/Potential PVC Use

Cling wrap, medical products,

packaging

Toys, medical products,

packaging

Medical products, cabling,

flooring, wall coverings,

packaging

Medical products, packaging,

cables, floor and wall coverings

Effects

Negative effects on liver, kidney,

spleen, and fetus

Liver adenomas and carcinomas 

Skeletal and ureter defects 

Toxic to crustaceans

NOAEL: fetal toxicity 28 mg/kg/day

Decreased blood pressure and respiration

Central nervous system toxicity

Decreased body weights in male

offspring

NOAEL: reproductive toxicity

100 mg/kg/day

Increased liver weights 

Causes weakness, irritability,

headache, second-degree skin

burns, and eye irritation in

humans

Harmful to algae, crustaceans,

fish

NOAEL: insufficient data

Skin and eye irritation 

Increased liver and spleen weights

LOAEL: liver and spleen

42 mg/kg/day
In 1976, the FDCA was amended to allow the agency

to regulate the testing, marketing, and use of medical

devices. New medical products proposed for the market must undergo pre-market testing, but the use of

medical devices already on the market in 1976 and

considered safe at that time was allowed to continue.

New devices made of substantially the same formulations were also readily allowed entry to the market.

As a consequence, phthalate-containing medical

products have been on the market for over 30 years,

and manufacturers claim a record of safety. What

they fail to acknowledge, however, is that no one has

ever studied the impacts of phthalate exposure from

their products on the reproductive development of

young boys. Reports of clotting disorders and

cholestasis that may be attributable to DEHP exposure from medical devices are infrequently publicized

or addressed. Indeed, if a medical practitioner wished

to identify products containing phthalates, in most

cases it would be impossible since the FDA does not

require identifying labeling and manufacturers are

often reluctant to disclose product formulations. 

Sometimes, phthalate-containing PVC products are

regulated according to the age of potential consumers. Recently, the EU banned the use of certain

phthalates in PVC toys designed for the mouths of

children under three. This approach is unlikely to

protect children since children of all ages routinely

handle products designated for older children or

adults. 

Despite the reality of aggregate exposures, phthalates

have been regulated individually. What may appear

to be a “tolerable” level of exposure to a single compound can actually contribute to an unsafe aggregate

exposure. In addition, the tolerable daily intake levels are ordinarily determined by assessing the toxicity

of a single compound. Presumed “safe” levels virtually never take into account other similar compounds

that have additive toxic effects and to which people

are regularly exposed. 

European regulatory action

Phthalates have been identified as a priority for

action in Europe. In 1998, the Oslo and Paris

Commission (OSPAR) listed DBP and DEHP among

substances for priority action. The 13 countries

named as Contracting Parties agreed to make

“...every endeavor to move towards the target of

cessation of discharges, emissions and losses of hazardous substances by the year 2020. We emphasize

the importance of the precautionary principle in this

work.”101 143 That same year, Sweden passed an

Environmental Bill that states “all uses of phthalates

and other plasticizers with harmful or potentially

harmful effects should be phased out on a voluntary

basis.”142 The phase-out of DEHP is prioritized and

further measures including prohibition are to be

introduced if the voluntary phase-out fails. In 1999,

a PVC Strategy in Denmark included an Action Plan

for reducing and phasing out phthalates in soft plastics.102 The Plan prioritizes large uses and emissions of

phthalates and includes bans, taxes, levies, subsidies,

public-sector green purchasing, and eco-labeling. In

2001, the Swedish National Chemicals Inspectorate

(KEMI) recommended to the Swedish Government

that, “The Swedish PVC industry should continue its

work to phase out DEHP and should broaden that

work so as also to include DBP and BBP, insofar as

these phthalates are used.”85 KEMI also recommended the “rapid phase-out of DEHP and other fertilityimpairing phthalates in feed tubes for premature

babies.”85

30 Health Care Without Harm
Aggregate Exposures to Phthalates in Humans 31

Alternatives to Phthalates

The reality of aggregate phthalate exposures calls for

fundamental changes in chemical manufacture, use,

and regulatory policies. These high production volume chemicals permeate the market in large numbers of products and contaminate people, wildlife,

and ecosystems throughout the world. Speaking of

DEHP-containing PVC medical devices, the Health

Canada Expert Advisory Panel concluded that “The

level of concern, even though the concerns are based

entirely on data derived from animal research, is

nevertheless too high to recognize status quo as an

option.”69

Material substitution

Since PVC accounts for 90% of global phthalate use,

converting to PVC-free materials would substantially

reduce global contamination with phthalates.

Alternative, inherently pliable plastics can substitute

for nearly every flexible PVC product on the market

today.160 However, even if all phthalate use in PVC

were eliminated, the residual use of non-PVC phthalate-containing products with which people come

into contact would likely contribute to continued

human exposure. For these end uses, including cosmetics, inks, adhesives, paints, and food packaging,

phthalate-free alternatives can also readily be substituted. 

Plastics that compete with PVC include polyolefins

(polyethylene and polypropylene), ethylene vinyl

acetate (EVA), polyurethane, and silicone. These

plastics compete with PVC “on the cost/performance

requirements” of particular applications.81 A subclass of polyolefins, called metallocene polyolefins, is

especially competitive with PVC. Metallocene polyolefins are inherently flexible and can be tailored to

specific applications. They compete with PVC in

flexible medical products, packaging film, wire and

cable insulation, transportation, flooring, and

geomembranes.”81

Implementing alternatives

A wide variety of companies and institutions have

initiated PVC phase-out policies for all or part of

their product lines. Concerns over PVC include

phthalates, metal stabilizers (lead, cadmium, organotins), toxicants used during manufacturing (vinyl

chloride, ethylene dichloride), toxicants generated

during manufacture and disposal (dioxins, furans),

performance, and its poor recyclability (less than 1

percent annually in the US).162 Table 10 shows

numerous examples from the auto industry, building

and construction uses, cabling, packaging, toys, and

medical products. Industry giants moving away from

PVC include prominent global corporations based in

Japan, the EU, and the US. 

Identifying alternatives

Alternatives to PVC products in health care and

construction can be found in four online databases:

Database on Non-PVC Products

for Health Care Institutions 

Aarhus County, Denmark

http://cold.aaa.dk/pvc/english/index.htm

The database provides health care professionals with

a comprehensive, easily searched, and readily available tool for identifying PVC-free products. Released

online in January 2002 in English, the database

includes hundreds of PVC-free products in seven

categories: cleaning articles, empty packaging, hospital supplies, hospital supplies packaging, kitchen articles, kitchen articles packaging, and office supplies. 
Sustainable Hospitals Project, 

Lowell Center for Sustainable Production 

Massachusetts, USA 

www.sustainablehospitals.org

The website includes lists of alternative products for:

bedding covers, catheters, enteral feeding products,

gloves, intravenous (IV) solutions, office products,

and other products. 

Greenpeace PVC Alternatives Database: 

Building the Future

http://www.greenpeaceusa.org/toxics/vinylhouse.htm

or

http://www.greenpeace.org/%7Etoxics/pvcdatabase/ 

The database includes alternatives to PVC in construction, for both flexible and rigid PVC applications. Flexible products covered include flooring, wall

coverings, and electrical equipment. 

Healthy Building Network

http://www.healthybuilding.net

See PVC section on webpage

32 Health Care Without Harm

Table 10. Examples of companies and institutions with PVC phase-out policies 

Type Companies

Auto Nissan (Japan), General Motors (USA), Mercedes Benz (Germany), Toyota (Japan), Opel (Germany), Honda

(Japan), Ford (UK), Daimler Benz (Germany)

Building / Construction Construction Res. Centre (UK), Reserve Centre (UK), Tate Gallery (UK), Krohnengen School (Norway), Society of

Danish Engineers (Denmark), Nike (Netherlands), JM (Sweden), Svenska (Sweden), Anglian Water Services (UK),

Eco AB (Sweden), Borastapeter (Sweden)

Cabling Matsushita Electric (Japan), North German Television (Germany), Bilbao Metro System (Spain), US Navy (USA),

P&O Cruises (UK), Deutsche Bahn (Germany), London Underground (UK), Eurotunnel (UK), Sumitomo (Japan),

German Telekom (Germany), Nippon Telegraph (Japan), Ricoh (Japan)

Home / Consumer Sony (Japan), Kinnarps (Sweden), Toppan Printing Co. (Japan), AEG Electronics (Germany), Vorwerk (Germany),

Electrolux (Sweden), OBI (Germany), Ikea (Sweden), Bene (Austria), EWE Kuechen (Austria), Hennes & Mauritz

(Denmark), Nike (USA)

Medical Braun-Melsungen (Germany), Fresenius (Germany), Terumo (Japan), Kaiser Permanente (USA), Baxter Healthcare

(USA), Catholic Healthcare West (USA), SMZ Ost Hospital (Austria), Universal Health Services (USA), Tenet

Healthcare Corp (USA)

Packaging The Body Shop (UK), Migros (Switzerland), Tengelmann (Germany), Nestle (Spain, France), Evian (France), Sony

(EU), Wella (Germany), Neals Yard (UK), SPAR (Austria), BILLA (Austria), ADEG (Austria), LoeWA (Austria), MEINL

(Austria), Matas (Denmark), Ica (Sweden), Konsum (Sweden), Waitrose (UK), Perrier (Spain), Fonvella (Spain),

Bayer (Germany), Helene Curtis (USA), Den-Mat (USA), Evian (EU), Spa (Belgium), Greenseal (USA), Carlsberg

Italia (Italy), VegiWash (USA), Federated Group (USA), Eagle Family Foods (USA), Proctor & Gamble (Japan),

Victoria's Secret (USA), Shiseido (Japan), Henry Thayer (USA), Ito-Yokado (Japan), Simple Green (USA), Educa

Sallent (Spain), IRMA (Denmark), am/pm (Japan), Lawson (Japan), Seven-Eleven (Japan), Mycal (Japan), Seiyu

(Japan), Jusco (Japan), Consumers Co-operative (Japan), Daiei (Japan), Kao (Japan), Lion (Japan), Dean Foods

(USA), Cargill (Brazil)

Toys APRICA Kassai (Japan), McDonalds (EU, Australia), Young Epoch (Japan), Pilot Ink (Japan), Tomy (Japan), First

Years (USA), Early Start (USA), LEGO (Denmark), Playmobil (Germany), Chicco (Italy), Ravensburger (Netherlands),

BRIO (Sweden), Bandai (Japan), Ambitoys (Netherlands), Artbaby (Argentina), Babelito (Argentia), Grazioli (Italy),

Kiko International (Spain), Little Tikes (USA), Novatex (Germany), Continua (Germany), Fashy (Germany), Mapa

(Germany), Sassy Products (USA), Mattel (USA), A-One (Japan), Ampa Hispania (Spain), Tiny Love (USA), People

Co. (Japan), Juguetes y Herrajes Joal (Spain), Toho (Japan), Tolico (Denmark), Giochi Preziosi (Italy), Lamaze (USA),

Play by Play (Spain)

Sources: 66 70
Aggregate Exposures to Phthalates in Humans 33

Conclusions

Phthalate use:

Phthalates are produced in the millions of tons annually worldwide and used in a wide variety of consumer

and industrial products. These chemicals readily

escape into the environment and contaminate the

world’s ecosystems. Environmental contamination

and direct contact with phthalate-containing products results in virtually ubiquitous human exposures. 

Phthalate toxicity:

Health effects that may result from exposure to the

phthalates differ among the various individual compounds and depend on the timing and the size of

the dose. Young, developing organisms are inherently more vulnerable to exposure to some phthalates.

In particular, the developing male reproductive tract

appears to be the most sensitive endpoint, although

effects on the liver, kidneys, lungs, and blood clotting are also of concern. In animal tests considered

relevant to humans, several of the phthalates,

including DEHP, DBP, BBP, and perhaps DINP, interfere with male reproductive tract development and

are toxic to cells in the testes responsible for assuring normal sperm and hormone production. DEP

appears to have little impact on reproductive tract

development but in test tube experiments alters the

microscopic appearance of cells responsible for

testosterone production. 

Human exposure:

Human exposure to DEHP from PVC medical

devices used in patient care has been known for

some time. Expert panels of the US National

Toxicology Program and Health Canada, as well as

the Food and Drug Administration, have recently

reviewed the toxicity of DEHP and considered exposures to patients that may result from the use of

DEHP-containing equipment. Each review has independently concluded that some patients are likely to

be exposed to potentially unsafe amounts of DEHP

while receiving medical care. 

The CDC has discovered that phthalate exposures are

virtually ubiquitous in the general population and that

women of reproductive age experience some of the

highest exposure levels to phthalates that interfere

with normal male reproductive tract development. 

Public health implications:

In this report, we have attempted to summarize what

is known about human exposures to phthalates and

to consider the potential health impacts of exposure

to real-world mixtures of these chemicals. Using a

relative potency approach, based on what is known

about mechanisms of action and available experimental data, it becomes clear that a large number of

women of reproductive age are sufficiently contaminated with phthalates to the point of significantly

increasing the risk of abnormal development in male

fetuses and baby boys. Women of reproductive age

who require medical care may be exposed to additional phthalates, largely DEHP, in the medical setting, that will add significantly to their existing

exposure acquired from the non-medical world in

which we all live. Using CDC sample data, an estimated 5% of women of reproductive age from the

general population are contaminated with 75% or

more of the amount of just DBP that may begin to

impair normal reproductive tract development. Many

of these women will also be regularly exposed to significant amounts of BBP and DEHP, so that their

aggregate exposures will pose even greater risks.

When any of these women requires medical care that

exposes them to additional DEHP from PVC medical

devices, even more is added. 

Where are these phthalates coming from in the general population? No one knows for certain, but perhaps the high exposures to DBP in women of

reproductive age provide a clue, at least for that
phthalate. DBP is used in a variety of cosmetic and

personal care products. Recent testing identifies DBP

in some hair spray, perfume, and deodorants.159 Many

nail polishes also have large quantities of DBP.

Unfortunately, labeling requirements are sufficiently

lax that cosmetic ingredients considered part of the

fragrance need not be identified on the label. For

many consumer products, however, virtually no

labeling requirements exist. Moreover, a large number of synonyms used for various phthalates complicate a label search. As a result, it is extraordinarily

difficult to identify phthalate-containing products

and to begin to narrow down the sources of widespread general population exposures. 

“Balkanization”

of chemical policy:

Chemical policy in the US is severely “Balkanized”161

and requires major revisions. For example, the Food

and Drug Administration is responsible for food contaminants (including phthalates), drug ingredients

(including phthalates), medical devices (including

phthalate-containing PVC products), and cosmetics

(including phthalates). Unfortunately, each of these

activities is a responsibility of a different division

within FDA, each of which carries out its work in

isolation from the others. Moreover, the enabling legislation that authorizes the Agency to monitor these

various products differs considerably among food,

drugs, medical devices, and cosmetics. As a consequence, when the medical device division considers

the safety of exposure to DEHP, they consider only

medical devices and not the real world of population-wide exposures to multiple phthalates from multiple sources. And, when the cosmetics division

considers phthalates in personal care products, not

only do they limit their concerns to products in their

domain, but they must prove the likelihood of harm

with no requirement that manufacturers will supply

safety data. 

When the Consumer Products Safety Commission

considers the safety of phthalates in, for example,

children’s toys, they consider only the phthalate that

may leach out of the toy when a child chews on it,

and not the other phthalates that that same child

may be exposed to from contaminated food, contaminated air, or medical care. 

And when the Environmental Protection Agency

considers whether or not to allow phthalates in a

pesticide formulation, they examine those proposals

one at a time, failing to consider aggregate exposures

to multiple phthalates from multiple sources. 

As a result, phthalates permeate the environment

and contaminate large populations of people

throughout the world. Phthalates are in the blood of

pregnant women at levels of concern, particularly

when the contaminants are considered in the aggregate. Phthalates cross the placenta and contaminate

breast milk. Relevant animal tests show that phthalates interfere with normal fetal development. The

length of the period of susceptibility to relatively low

levels of phthalate exposure in humans is not known.

But, animal tests suggest that, with respect to male

reproductive tract development, boys may remain

vulnerable to phthalate exposure beyond fetal life

until early puberty, since testes undergo rapid change

at several stages, including later childhood.69

What is needed:

Manufacturers of phthalates continue to produce

large amounts and sell them to product manufacturers who use them in thousands of products.

Manufacturers have consistently argued that there is

no evidence that anyone has been harmed by phthalates. However, as we have noted, and as confirmed

by the NTP Expert Panel and FDA, no study has

ever examined the impacts of phthalate exposure on

the developing male reproductive tract in people.

Not one. 

But lack of evidence can hardly be used as evidence

of safety when no one has ever looked. The increasing incidence of hypospadias, undescended testes,

and testicular cancer, and declining sperm counts in

the US and many other parts of the world suggests

that a closer look at many reproductive tract toxicants and endocrine disruptors is urgently needed in

people.16 With respect to phthalates, however, evidence from relevant animal studies and from limited

studies of non-reproductive tract impacts in hospitalized patients is sufficient to require phasing out the

use of many of the phthalates. As the Health Canada

panel concluded, “the status quo is not an acceptable

option.” 

34 Health Care Without Harm
Regulatory agencies charged with protecting medical patients, public health, and the environment

must substantially revise procedures and protocols

to consider the potential impacts of phthalate exposures cumulatively, rather than as single chemical

exposures. 

Finally, phthalates serve as a case study that demonstrates the failure of current chemical policy in the

US. Regulatory authority is spread among agencies

that compete with one another rather than cooperate. Lines of communication are limited and infrequently used. No one agency is authorized to look at

the “big picture”, which can have tragic consequences. In Europe, vigorous debate is underway

regarding the phase-out of the general use of many

phthalates in consumer products. Public health and

the environment can only be truly protected when

safer materials are substituted far upstream in the

manufacturing process. Humans have demonstrated

the capacity to contaminate every nook and cranny

of every ecosystem and every developing fetus with

synthetic chemicals that can impair normal development. Now we need to demonstrate that we can

change. 

First, we need to recognize that a major overhaul of

current regulatory policy is long overdue. Under the

current framework, government approval simply does

not provide adequate real-world protection from

chemical exposures. The FDA, the EPA, the CPSC,

and other government agencies, with necessary

authorization, must begin to transform their makebelieve regulatory framework into a new, sciencebased system that properly considers the reality of

aggregate exposures to toxic chemicals and that

requires meaningful pre-market testing of commercial chemicals. Second, consumers must insist on the

right to know about what chemicals are in commercial products and must have unhindered access to

toxicity and exposure data. Third, manufacturers can

and must shift to cleaner production practices that

produce cleaner, sustainable products more suited to

the contemporary world and the one that we will

leave to future generations. 

Aggregate Exposures to Phthalates in Humans 35
36 Health Care Without Harm

Appendix I. 

MEHP Exposures through 

Medical Procedures

In its safety assessment of DEHP, the FDA noted

that patients are also exposed to MEHP, the highly

toxic monoester metabolite of DEHP. MEHP is

formed in medical products as DEHP degrades over

time resulting in patient exposure to both phthalates.

MEHP is formed by the action of lipases in stored

blood and plasma and by hydrolysis in IV fluids. The

FDA cited studies that measured MEHP in hospital

patients undergoing coronary bypass, hemodialysis,

and peritoneal dialysis. In addition, the Agency

acknowledged that nursing infants could receive significant doses of MEHP in breast milk from mothers

undergoing hemodialysis. To estimate the amount of

MEHP exposure, the FDA needed to calculate the

relative potency of MEHP so that its level could be

expressed in terms of DEHP concentration. 

Relative potency of MEHP 

The FDA used testicular toxicity to develop a relative

potency calculation for DEHP and MEHP exposures

from medical products.153 First, the Agency examined

the relative potency of MEHP and DEHP to cause

testicular toxicity. Second, the FDA compared the

abilities of the two compounds to cause maternal toxicity as a comparison. Finally, a relative potency factor of 10 was assigned to MEHP after considering the

differences in experimental results. This means that

the FDA considers MEHP to be 10-fold more effective in causing testicular toxicity than DEHP.

FDA conclusions

The FDA calculated the equivalent dose of DEHP

for MEHP exposure from a variety of medical procedures and then added it to the DEHP dose to yield

an aggregate dose of DEHP and MEHP. The Agency

found that procedures that did not exceed the tolerable intake when considering only DEHP still did not

exceed it when considering both DEHP and MEHP.

However, the data shows that considering MEHP

had a large impact on the dose. 

Table 11 shows that infusion of crystalloid solutions

is far below the tolerable intake when only DEHP is

considered. However, when both DEHP and MEHP

are considered, the biologically relevant dose increases by 30-fold and draws much closer to the tolerable

intake. In addition, several procedures that were less

than the tolerable intake when only considering

DEHP exposure, became close to the limit when

MEHP was considered. These procedures include

replacement transfusions in neonates and orthotopic

heart transplants. 

The FDA decided not to account for aggregate exposures to DEHP and MEHP using the relative potency

method. The Agency stated that “because of uncertainties associated with the relative potency of

DEHP:MEHP and resulting estimates of DEHP

equivalent dose, the TI/Dose ratios based on the

dose of DEHP-equivalents received by patients will

not be used to support regulatory decision making.”153 

Limitations of the FDA approach

In determining the relative potency of MEHP, the

FDA made certain value judgments. The variation

seen in potencies derived from studies with a testicular endpoint ranged from 2 to more than 1,000.

Potencies derived using maternal effects in mice varied from 2 to 80.153 The Agency chose a value of 10

using the testicular endpoint. The authors of this

report illustrate the quantitative consequence of this

decision in Table 12.

Table 12 shows that choosing a mid-range relative

potency for MEHP of 80 instead of 10 significantly

increases the DEHP-equivalent dose calculated for

various medical procedures. In fact, using the higher

relative potency number increases the DEHP-equivalent dose of DEHP + MEHP by 2 – 8 fold. The

result influences judgments about the safety of various procedures as shown below.
The consequence of choosing a different relative

potency for MEHP can be seen by comparing the

aggregate dose of DEHP and MEHP released to

patients during various medical procedures. Table 12

shows that a relative potency of 80 significantly

changes the total exposure to patients. 

When considering only DEHP exposure, infusion of

IV crystalloid solutions has TI/DEHP ratio of 120

indicating that the DEHP dose is far below the TI. If

MEHP is added to the dose consideration by using

relative potency of 10, the ratio becomes 4.44. In

contrast, when a relative potency of 80 is used, the

ratio becomes 0.57. Under these conditions, infusion

of crystalloid IV solutions would exceed the tolerable

intake. In fact, all the procedures in Table 13 show a

DEHP-equivalent dose that exceeds the tolerable

intake if a relative potency of 80 is used instead of 10

to calculate the added impact of MEHP. 

Aggregate Exposures to Phthalates in Humans 37

Table 11. Tolerable intake compared to DEHP and DEHP+MEHP 

Procedure TI/DEHP TI/DEHP+MEHP

Infusion of IV crystalloid solutions 120 4.44

Adult transfusion /ECMO 0.2 0.03

Neonate exchange transfusion 0.03 0.02

Neonate replacement transfusion 2.0 1.75

CABG cardiopulmonary bypass 0.6 0.30

Orthotopic heart transplant 2.0 1.00

Artificial heart transplant 0.25 0.12

Data source: 153 Abbreviations: TI: tolerable intake. 

See the Health Care Without Harm website for updates to this table: http://www.noharm.org

Table 12. DEHP equivalent doses for various medical procedures depending on

MEHP relative potency value. Doses in mg/kg/day. 

RPF = 10 RPF = 80

Procedure DEHP MEHP DEHP equivalent DEHP equivalent 

Infusion of IV crystalloid solutions 0.005 0.013 0.14 1.0

Adult transfusion /ECMO 3.0 2.0 23 163

Neonate exchange transfusion 22.6 0.68 29 77

Neonate replacement transfusion 0.3 0.0043 0.34 0.64

CABG cardiopulmonary bypass 1.0 0.1 2.0 9.0

Orthotopic heartTransplant 0.3 0.03 0.6 2.7

Artificial heart transplant 2.4 0.26 5.0 23

Data source: 153 Abbreviations: RPF: relative potency factor. 

See the Health Care Without Harm website for updates to this table: http://www.noharm.org
Exposures from medical

procedures exceed

tolerable intake 

The FDA Safety Assessment of DEHP Released from

PVC Medical Devices reveals several procedures that

expose patients to levels of DEHP close to the tolerable intake. When MEHP is also considered, the

exposures provided even by common medical treatments such as IV infusions can draw close to or

exceed the tolerable intake depending on the relative

potency of MEHP used to calculate the aggregate

exposure. This is in addition to the aggregate exposures to other phthalates calculated above. 

38 Health Care Without Harm

Table 13. Tolerable intake compared to DEHP and DEHP+MEHP doses 

using different relative potency factors.

RPF = 10 RPF = 80

Procedure TI/DEHP TI/DEHP+MEHP TI/DEHP+MEHP

Infusion of IV crystalloid solutions 120 4.44 0.57

Adult transfusion /ECMO 0.2 0.03 0.00

Neonate exchange transfusion 0.03 0.02 0.01

Neonate replacement transfusion 2.0 1.75 0.93

CABG cardiopulmonary bypass 0.6 0.30 0.07

Orthotopic heart transplant 2.0 1.00 0.22

Artificial heart transplant 0.25 0.12 0.03

Data source: 153 Abbreviations: RPF: relative potency factor; TI: tolerable intake. 

See the Health Care Without Harm website for updates to this table: http://www.noharm.org
Aggregate Exposures to Phthalates in Humans 39

Appendix II. 

Phthalate Toxicity

The toxicity of phthalates to mammals is shown in

Table 14. Note that these effects are dose-dependent

and that humans are not necessarily exposed to the

levels that elicit these effects in animal studies.

Impacts also depend on the route of exposure,

species differences in metabolism, distribution, excretion, and tissue sensitivity. Critical windows of vulnerability during development significantly influence

both the dose required to elicit an impact and the

nature of the impact. 

Table 14. Toxicity of phthalates to various mammalian organ systems

Part 1 of 4

Organ

Adrenal gland

Bone

Brain

Blood

Fetus/Embryo

Phthalate

DEP

DHP

BBP

BBP

DEP

BBP

DBP

DIBP

DINP

BBP

DBP

Species

Rat

Mouse

Rat

Cerebellar explants

newborn rat

Rat

Rat

Human lymphocytes

in vitro

Mouse

Human lymphocytes

in vitro

Rat

Rat

Rat

Rat

Rat

Rat

Rat

Rat

Rat

Mouse

Effect

Elevated organ weight

Decreased organ weight

Reduced bone marrow cellularity

Inhibit outgrowth of nerve fibers and glial cells in vitro

Increased weight

Myelomonocytic leukemia

DNA damage to lymphocytes

Anemia 

DNA damage to lymphocytes

Mononuclear cell leukemia, reduced white blood cell counts

Decreased hemoglobin, decreased number of red blood cells

Increased post-implantation loss; deformed vertebral

column and ribs, cleft palate, fused sternebrae

Reduced pup weight at birth

Reduced fetal weight, increased resorptions, increased

skeletal defects

Embryo-fetal death, decreased fetal weight

Birth defects in the prosencephalon, the optic system, and

the mandibular and maxillary processes

Transferred to placenta and embryo

Increased post-implantation loss; deformed vertebral

column and ribs, cleft palate, fused sternebrae

Decreased fertility, fewer litters per pair, fewer pups per

litter, fewer pups born alive

Study

19

92

2

84

19

89

88

112

88

20

150

40

64

121

39

130

130

40

92
40 Health Care Without Harm

Table 14. Toxicity of phthalates to various mammalian organ systems

Part 2 of 4

Organ

Fetus/Embryo

Heart

Kidneys

Liver

Phthalate

DEP

DHP

DIDP

DINP

MBP

MEHP

DEHP

DEP

MEHP

DBP

DEHP

DHP

DINP

DBP

DEHP

DEHP

DEP

DIDP

Species

Mouse

Rat

Mouse

Rat

Rat

Rat

Rat

Rat

Rat

Rat

Rat

Rat granulosa cells

Isolated rat heart

Rat

Rat

Rat

Rat

Mouse

Rat

Rat

Rat

Rat

Rhesus monkey

Rat, Mouse

Rat

Rat liver microsomes

Rat

Rat 

Rat 

Effect

Reduced pup size in offspring 

Increased incidence of supernumerary ribs 

Decreased fertility, decreased number of litters per pair,

decreased number of live pups per litter, decreased

number of pups born alive

Skeletal defects in the fetus

Reduced offspring survival in both generations

Reduced pregnancy weight gain

Skeletal and visceral birth defects, reduced offspring

viability and weight gain

Birth defects in the prosencephalon, the optic system, and

the mandibular and maxillary processes in vivo; growth

retardation, dysmorphogenesis in vitro

Deformed vertebral column, deformed ribs, dilation of

renal pelvis, cleft palate, fused sternebrae

Increased pre- and post-implantation loss, impaired

uterine function

Maternal lethality, litter resorption, reduced fetal weight

Inhibition of estradiol production

Decrease in heart rate 

Increase in heart weight 

Decrease in heart rate and blood pressure

Causes renal cysts

Reduction in creatinine clearance; cystic changes

Decreased organ weight

Transitional cell carcinoma

Decreased transferrin levels, increased haemosiderin levels

Activate laurate hydroxylation in vitro

Inhibit mitochondrial respiration; peroxisome proliferation

Abnormalities in histology, reduction in liver function

Hepatocellular carcinoma

Hepatocellular adenoma

Activate laurate hydroxylation in vitro

Abnormal enzyme levels, elevated cholesterol and

triglyceride levels.

Abnormal enzyme levels, reduced cytoplasmic basophilia,

increased eosinophilia

Altered pathology, peroxisome proliferation

Study

92

52

92

155

75

64

114

130

38

43

129

34

119

19

126

158

27

92

20

58

118

4

87

89

105

118

139

17

95
Aggregate Exposures to Phthalates in Humans 41

Table 14. Toxicity of phthalates to various mammalian organ systems

Part 3 of 4

Organ

Liver

Lungs

Mucosa

Ovaries

Pituitary

Prostate

Spleen

Developmental/

reproductive

effects

Phthalate

DINP

DMP

DEHP

DIDP

DBP

DIBP

DINP

BBP

MEHP

DEP

BBP

DEP

DBP

DEHP

DBP

BBP

BBP

DBP

Species

Rat 

Rat

Rat 

Human pre-term

infants

Rat 

Human lymphocytes

Human lymphocytes

Rat

Rat

Rat granulosa cells

Rat

Rat

Mouse

Rat

Rat

Rat

Rat

Rat

Rat

Rat

Rat

Rat

Rat

Rat

Human sperm

Rat

Effect

Carcinoma and adenoma

Spongiosis hepatitis

Increased organ weight in females

Respiratory distress, pathological changes similar to

hyaline membrane disease

Increased width alveolar septa, inflammatory reactions,

increased numbers macrophages and pneumocytes

DNA damage

DNA damage

Reduced organ weight

Reduced organ weight

Reduced estradiol production in vitro

Elevated organ weight 

Atrophy of the prostate

Increased weight

Absent or partially developed ventral prostate

Anterior prostate agenesis

Increased hemoglobin, ferritin, and haemosiderin levels 

Male infants with female-like areolas/nipples; shortened

anogenital distance; reduced testis weights, reproductive

malformations in males

Decreased testosterone, increased FSH

Reduced fetal testis weights, increased retarded testicular

descent

Reduced sperm production, reduced testis weight

Atrophy of the testis, seminal vesicles; decreased

testosterone, increased FSH and LH; immature

sperm cells

Fetuses with undescended testes; decreased anogenital

distance in male infants

Hypospadias; absent or partially developed epididymis,

seminal vesicles, reduced weights of testis components;

seminiferous tubule degeneration, interstitial cell

hyperplasia and cell adenoma

Decreased mating, fertility, pregnancy 

Decreased sperm mobility in vitro

Leydig cell adenomas in male offspring; fetal rats with

decreased testosterone levels and increased Leydig

cell numbers

Study

20

150

52

128

60

88

88

114

109

97

19

2

92

108

104

58

64

109

121

134

2

42

108

157

56

54
42 Health Care Without Harm

Table 14. Toxicity of phthalates to various mammalian organ systems

Part 4 of 4

See the Health Care Without Harm website for updates to this table: http://www.noharm.org

Organ

Developmental/

reproductive

effects

Testes

Thymus

Thyroid

Uterus

Phthalate

DBP

DEHP

DEP

DHP

DINP

DPP

MEHP

MBP

MPP

BBP

DEP

BBP

DBP

DINP

Species

Human sperm

Rat

Rat

Rat

Rat

Rat

Human sperm

Rat

Mouse

Rat

Rat, Leydig cell culture

Mouse

Rat

Rat

Rat

Rat

Rat Sertoli cells

Rat Sertoli cells

Rat Sertoli cells

Rat 

Rat 

Rat 

Rat 

Mouse

Rat

Effect

Decreased sperm density in university students with DBP

in semen

Disorganization of seminiferous tubule structure in male

offspring

Sertoli cell vacuolation; atrophy of seminiferous tubules;

loss of spermatogenesis

Testicular, epididymal atrophy, and testicular agenesis;

hemorrhagic testes; hypospadias in male offspring

Male infants with female-like areolas/nipples, shortened

anogenital distance, reduced testis weights, reproductive

malformations in males

Induction of Leydig cell tumors

Decreased sperm mobility in vitro

Sertoli cell/gonocyte detachment in vitro

Decreased sperm concentration

Increased testes weights 

Alteration in Leydig cell structure

Decreased fertility, decreased percentage of mobile sperm,

decreased sperm concentration; decreased weights of

testis, epididymis, and seminal vesicles; atrophy of

seminiferous tubules

Male infants with female-like areolas/nipples; reproductive

malformations in male infants

Increased testes weights

Testicular hyperplasia, testicular tumors

Altered testicular enzymes, decreased progesterone binding

Inhibits FSH-stimulated cAMP accumulation in Sertoli cells

in vitro; increases lactate secretion; decreases ATP

levels in vitro

Inhibits FSH-stimulated cAMP accumulation in Sertoli cells

in vitro; 

Inhibits FSH-stimulated cAMP accumulation in Sertoli cells

in vitro; increases lactate secretion

Thymus atrophy

Elevated organ weight 

Decreased uterine decidual growth

Decreased uterine weight, decreased progesterone levels

Decreased weight

Endometrial hyperplasia and fibrous thickening;

endometrial adenocarcinoma

Study

106

8

124

65

64

12

56

94

92

19

82

92

64

114

150

55

7

71

71

2

19

44

41

92

150
Aggregate Exposures to Phthalates in Humans 43

References 

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3. Agency for Toxic Substances and Disease Registry. Draft toxicological profile for di-(2-ethylhexyl) phthalate. Syracuse

Research Corporation . Contract No. 205-1999-00024 U.S. Department of Health and Human Services. 2000.

4. Agency for Toxic Substances and Disease Registry. Draft toxicological profile for di-n-butyl phthalate. Syracuse

Research Corporation. Contract No. 205-1999-00024 U.S. Department of Health and Human Services. 1999.

5. Agency for Toxic Substances and Disease Registry. Toxicological profile for diethyl phthalate. Sciences International,

Inc. under subcontract Research Triangle Institute. Contract No. 205-93-0606 U.S. Department of Health and

Human Services. 1995. 

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breeding protocol in Sprague-Dawley rats. Environ Health Perspect 105:102-107. 1997.

158. Woodward KN. Phthalate esters, cystic kidney disease in animals and possible effects on human health: a review. Hum

Exp Toxicol 9:397-401.1990.

159. Found at the website: www.nottoopretty.org Results from testing with Stat Analysis, Chicago, IL. 2002.

160. For example, substitutes are widely available for most PVC products used in health care. A notable exception is for

packaging red blood cells. Here, PVC offers a unique advantage: DEHP acts as an unregulated preservative of red

blood cells.The US Food and Drug Administration does not regulate DEHP as an additive. Baxter International, a

leading producer of DEHP-softened PVC red blood cell bags, also markets a non-DEHP-softened red blood cell bag,

which uses butyryl-trihexyl citrate as a plasticizer. Both bags preserve red blood cells for the same length of time.

Plastics Week, “Citrus-Based Plasticizer to Replace DEHP in Big Medical Applications”, 2/10/92. 

161. If globalization is the increasing interconnectedness of peoples and places through converging processes of economic,

political, and cultural change, then balkanization is a counteraction to the integrating and homogenizing effects of

globalization. Whereas globalization acts as connective mechanism... balkanism refers to fragmentation and separation. Taking its name from the divisive and conflict-ridden Balkan region of Europe, balkanization has come to refer to

any region in the world faced with internal turmoil and schisms, in this case, the regulatory structure and safety net for

phthalate exposure. See http://www.countrywatch.com/@school/balkanization.htm for more information on ‘balkanization’.

162. The recycling rate was determined based on the vinyl industry’s estimate of 18 million pounds of PVC recycled per

year. Jebens (1997), estimated PVC consumption at 18 billion pounds per year, bringing us to am estimate of less

than 1%.

163. Foster P, Turner K, Barlow N. Anti-androgenic effects of a phthalate combination on in utero male reproductive development in the Sprague-Dawley rat: additivity of response? Poster presentation. Society of Toxicology annual meeting.

March 2002.

Aggregate Exposures to Phthalates in Humans 49