A Comprehensive Look at Toxic Chemicals in the Body

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A COMPREHENSIVE LOOK AT TOXIC

CHEMICALS IN THE BODY…

SCIENTIFICALLY VALIDATED.

In a study led by Mount Sinai School of Medicine in

New York, in collaboration with the EWG and

Commonweal, researchers at two major laboratories

found an average of 91 industrial compounds,

pollutants, and other chemicals in the blood and

urine of nine volunteers, with a total of 167

chemicals found in the group. Like most of us, the

people tested do not work with chemicals on the job

and do not live near an industrial facility.

Scientists refer to this contamination as a person’s

body burden. Of the 167 chemicals found, 76 cause

cancer in humans or animals, 94 are toxic to the

brain and nervous system, and 79 cause birth

defects or abnormal development. The danger of

exposure to these chemicals in combination has

never been studied before.

These results represent the most comprehensive

assessment of chemical contamination in individuals

ever performed.

Even so, many chemicals were not included in the analysis that are

known to contaminate virtually the entire U.S. population. Two

examples are Scotchgard and the related family of perfluorinated

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chemicals, and a group of compounds known collectively as

brominated flame retardants.

A more precise picture of human contamination with industrial

chemicals, pollutants and pesticides is not possible because chemical

companies are not required to tell EPA how their compounds are

used or monitor where their products end up in the environment.

Neither does U.S. law require chemical companies to conduct basic

health and safety testing of their products either before or after they

are commercialized. Eighty percent of all applications to produce a

new chemical are approved by the U.S. EPA with no health and

safety data. Eighty percent of these are approved in three weeks.

Only the chemical companies know whether their products are

dangerous and whether they are likely to contaminate people. As a

first step toward a public understanding of the extent of the

problem, the chemical industry must submit to the EPA and make

public on the web, all information on human exposure to commercial

chemicals, any and all studies relating to potential health risks, and

comprehensive information on products that contain their chemicals.

GLOSSARY OF CONTAMINANTS

PCBs —

Industrial insulators and lubricants. Banned in the U.S. in 1976.

Persist for decades in the environment. Accumulate up the food

chain, to man. Cause cancer and nervous system problems.

Dioxins —

Pollutants, by-products of PVC production, industrial bleaching, and

incineration. Cause cancer in man. Persist for decades in the

environment. Very toxic to developing endocrine (hormone) system.

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Furans —

Pollutants, by-products of plastics production, industrial bleaching

and incineration. Expected to cause cancer in man. Persist for

decades in the environment. Very toxic to developing endocrine

(hormone) system.

Metals —

Lead, mercury, arsenic and cadmium — Cause lowered IQ,

developmental delays, behavioral disorders and cancer at doses

found in the environment. For lead, most exposures are from lead

paint. For mercury, most exposures are from canned tuna. For

arsenic, most exposures are from arsenic (CCA) treated lumber and

contaminated drinking water. For cadmium, sources of exposure

include pigments and bakeware.

Organochlorine insecticides.

DDT, chlordane and other pesticides. Largely banned in the U.S.

Persist for decades in the environment. Accumulate up the food

chain, to man. Cause cancer and numerous reproductive effects.

Organophosphate insecticide metabolites —

Breakdown products of chlorpyrifos, malathion and others. Potent

nervous system toxicants. Most common source of exposure is

residues in food. Recently banned for indoor uses.

Phthalates —

Plasticizers. Cause birth defects of male reproductive organs. Found

in a wide range of cosmetic and personal care products. Some

phthalates recently banned in Europe.

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Volatile and Semi-volatile organic chemicals. —

Industrial solvents and gasoline ingredients like xylene and ethyl

benzene. Toxic to nervous system, some heavily used SVOCs

(benzene) cause cancer.

CHEMICALS FOUND IN THE HUMAN BODY

LINKED TO SERIOUS HEALTH PROBLEMS ..

9 PEOPLE TESTED.

Number of chemicals found in

9 people and the health

impact thereto.

HEALTH EFFECT OR

BODY SYSTEMS

AFFECTED Average

number

found in

9 people

Total

found

in all

9

Range

(lowest

and

highest

number

found

in all 9)

Cancer Causing [1] 53 76 [2]

36 to

65

Birth defects /

developmental delays 55

79 [3]

37 to

68

Vision 5 11 [4]

4 to 7

Hormone system 58 86 [5]

40 to

71

Stomach or intestines 59 84 [6]

41 to

72

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Kidney 54 80 [7]

37 to

67

Brain, nervous system 62 94 [8]

46 to

73

Reproductive system 55 77 [9]

37 to

68

Lungs/breathing 55 82 [10]

38 to

67

Skin 56 84 [11]

37 to

70

Liver 42 69 [12]

26 to

54

Cardiovascular system

or blood 55

82 [13]

37 to

68

Hearing 34 50 [14]

16 to

47

Immune system 53 77 [15]

35 to

65

Male reproductive

system 47

70 [16]

28 to

60

Female Reproductive

System 42

61 [17]

24 to

56

[1] Chemicals listed as linked to cancer are those classified by

the National Toxicology Program as "known" human carcinogens, or

"reasonably anticipated" to be human carcinogens; or those

classified by the Environmental Protection Agency as "known" or

"probable" human carcinogens.

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[2] Cancer: 3 heavy metals, 1 phthalate, 9 organochlorine

pesticides, 8 furans, 7 dioxins and 48 PCBs

[3] Birth defects / developmental delays: 4 heavy metals, 2

phthalates, 7 organochlorine pesticides, 8 furans, 7 dioxins, 48

PCBs and 3 other semivolatile or volatile organic compounds

[4] Vision: 1 heavy metal, 1 phthalate, 2 organochlorine pesticides

and 7 other semivolatile or volatile organic compounds

[5] Hormone system: 4 heavy metals, 5 phthalates, 3

organophosphate pesticides and metabolites, 9 organochlorine

pesticides, 8 furans, 7 dioxins, 48 PCBs and 2 other semivolatile or

volatile organic compounds

[6] Stomach or intestines: 3 heavy metals, 3 phthalates, 2




[7] Kidney: 4 heavy metals, 5 phthalates, 3 organochlorine



[8] Brain, nervous system: 4 heavy metals, 4 phthalates, 7




[9] Reproductive system: 4 heavy metals, 2 phthalates, 8

organochlorine pesticides, 8 furans, 7 dioxins and 48 PCBs

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[10] Lungs/breathing: 4 heavy metals, 3 phthalates, 2




[11] Skin: 3 heavy metals, 5 phthalates, 2 organophosphate

pesticides and metabolites, 4 organochlorine pesticides, 8 furans, 7

dioxins, 48 PCBs and 7 other semivolatile or volatile organic

compounds

[12] Liver: 4 heavy metals, 6 phthalates, 3 organochlorine

pesticides, 48 PCBs and 8 other semivolatile or volatile organic

compounds

[13] Cardiovascular system or blood: 4 heavy metals, 2

phthalates, 2 organophosphate pesticides and metabolites, 7

organochlorine pesticides, 8 furans, 7 dioxins, 48 PCBs and 4 other

semivolatile or volatile organic compounds

[14] Hearing: 1 heavy metal, 48 PCBs and 1 other semivolatile or

volatile organic compound

[15] Immune system: 4 heavy metals, 1 phthalate, 6

organochlorine pesticides, 8 furans, 7 dioxins, 48 PCBs and 3 other


[16] Male reproductive system: 4 heavy metals, 5 phthalates, 2

organochlorine pesticides, 7 dioxins, 48 PCBs and 4 other


[17] Female reproductive system: 2 heavy metals, 2 phthalates,

1 organochlorine pesticide, 7 dioxins, 48 PCBs and 1 other

semivolatile or volatile organic compound

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SOME CHEMICALS ARE ASSOCIATED WITH MULTIPLE HEALTH

IMPACTS, AND APPEAR IN MULTIPLE CATEGORIES IN THE

TABLE ABOVE.

HOW DO TOXIC CHEMICALS END UP IN PEOPLE?

Scientists refer to the chemical exposure documented here as an

individual’s “body burden” — the consequence of lifelong exposure

to industrial chemicals that are used in thousands of consumer

products and linger as contaminants in air, water, food, and soil.

There are hundreds of chemicals in drinking water, household air,

dust, treated tap water and food. They come from household

products like detergent, insulation, fabric treatments, cosmetics,

paints, upholstery, computers and TVs, and they accumulate in fat,

blood and organs, or are passed through the body in breast milk,

urine, feces, sweat, semen, hair and nails.

(Easton, et al. 2002, EPA 2002d, OECD 2002, Rudel, et al. 2001,

Thornton, et al. 2000, USGS 2002).

We know that:

• U.S. chemical companies hold licenses to make 75,000

chemicals for commercial use. The federal government

registers an average of 2,000 newly synthesized

chemicals each year.

• The government has tallied 5,000 chemical ingredients

in cosmetics; more than 3,200 chemicals added to food;

1,010 chemicals used in 11,700 consumer products; and

500 chemicals used as active ingredients in pesticides

(EPA 1997c, EPA 2002b, EPA 2002c, FDA 2002a, FDA

2002b, FDA 2002c).

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• In 1998 U.S. industries reported manufacturing 6.5

trillion pounds of 9,000 different chemicals

(EPA 2001), and in 2000 major U.S. industries reported

dumping 7.1 billion pounds of 650 industrial chemicals into

our air and water (EPA 2002a).

HOW MANY TOXIC CHEMICALS ARE IN US? Not known (even this study defines only a fraction of the chemicals

in the nine people tested).

The reason: beyond chemicals that are added to food or used as

drugs, there is no requirement for chemical manufacturers to:

disclose how their chemicals are used or the routes through which

people are exposed; understand the fate of their chemicals in the

environment; measure concentrations of their products in the

environment or in people; or develop and make public analytical

methods that would allow other scientists to gather information.

Companies sometimes develop methods to test for chemicals in the

blood or urine of their workers, but they do not routinely disclose

the methods or results to the government or the public. The

government has spearheaded most of the limited testing that has

been performed for the general population in studies funded by

taxpayers. The government’s studies have not kept pace with the

ever-expanding array of new toxic chemicals. The country’s most

comprehensive program for detecting industrial chemicals in the

human body is run by a government program that reported on 27

chemicals in 2001 (CDC 2001). The chemical industry provided

direct funding for none of this multi-million dollar effort, but instead

paid their trade association’s press office to educate the national

media on the safety of industrial chemicals in the days following the

government’s report release. In their upcoming report on chemical

exposures, CDC is expected to release information on 116

chemicals, or about 70 percent of the number identified in this

study.

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A few types of consumer products, such as cosmetics and home

pesticides, must carry partial ingredient labels so consumers can

make informed choices. Federal law, however, does not require the

chemical industry to disclose ingredients in most household

consumer products, including cleaners, paints and varnishes, and

chemical coatings on clothing and furniture, or the so-called “inert”

ingredients in pesticides, which are typically more than 95 percent of

the retail product. The EPA has compiled a database of more than

1,000 chemicals they believe might be present in 11,700 consumer

products, using data the Agency gathered from chemical

encyclopedias, air sampling studies in the open scientific literature,

and manufacturers. But the companies have classified the chemical

recipes for 9,300 of these products as “confidential business

information.”

The EPA attempts to track local exposures to chemical pollutants

through two testing programs, one for tap water and another for

ambient air. But testing captures only a small fraction of the

chemicals a person is exposed to over the course of a day. At least

165 companies have manufactured the 167 chemicals found in the

test subjects, marketing them under at least 265 trade and

consumer products names (Table 3). By contrast, some local and

state air monitoring programs track only five chemical contaminants,

most of them linked to automobile exhaust. Water suppliers test tap

water for 70 contaminants, but the list excludes hundreds of

chemicals known to contaminate public water supplies [e.g., (USGS

2002)].

RESEARCHERS WARN CONSUMERS ABOUT

HAZARDOUS INGREDIENT IN NAIL POLISH

Growing Scientific Concern About Dibutyl Phthalate (DBP),

Reproductive Age Women and Links to Birth Defects

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WASHINGTON — The EWG today released Beauty Secrets, the

first-ever consumer alert on beauty products that contain dibutyl

phthalate (DBP), a chemical coming under growing scientific

scrutiny because of high levels found in reproductive age women

and possible risks of birth defects.

Scientific concerns about DBP's risks increased recently after a

Centers for Disease Control (CDC) study this fall unexpectedly

found DBP in the bodies of every single person they tested, with

the highest levels in reproductive-age women, the group most at

risk. Scientists are concerned about DBP and reproductive age

women because the chemical causes severe birth defects in lab

animals. According to lab animal studies, DBP can harm nearly

every physical structure in the developing male reproductive

system. The effects include testicular atrophy, absent testes and

reduced sperm count.

Major loopholes in federal law allow cosmetics manufacturers to put

unlimited amounts of industrial chemicals like DBP into personal

care products with no required testing of monitoring for adverse

effects. EWG's initial investigation suggests that DBP is found in

about a third of the nail polishes currently on the market, as well as

a variety of other cosmetic products.

"It's buyer beware when it comes to cosmetics," said Jane

Houlihan, Senior Analyst for EWG and principal author of Beauty

Secrets. "Women who are considering becoming pregnant, or who

are pregnant or nursing, should avoid using any products

containing DBP."

To better identify consumer sources of DBP, the EWG shopped at a

local Rite-Aid, surfed the on-line store Drugstore.com, and

searched the U.S. patent office records for products that contain

DBP in the patent application. EWG found:

• DBP in 37 popular nail polishes, topcoats, and

hardeners, including products by L’Oréal, Maybelline, Oil

of Olay, and Cover Girl (Table 1).

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• Patents proposing to use DBP in a broad range of beauty

and personal care products, including shampoos and

conditioners, lotions, hair growth formulations,

antiperspirants, and sunscreen. Even patents relating to

gum, candy, and pharmaceuticals taken orally propose

DBP as an ingredient.

• Many major manufacturers who propose to use DBP in

cosmetics and related products. Of more than 100

patents analyzed by EWG, Procter & Gamble holds the

most (37) that propose to use DBP in personal care

products. Other major companies with multiple patents

are L’Oréal (10), Lever Brothers (4), and Maybelline (3).

The CDC has postulated that one of the routes of DPB exposure in

young women would be cosmetics and personal care items. DBP is

used to help nail polish form an even film as it dries, as a

consistency enhancer to keep products blended, and as an

ingredient to help cosmetics penetrate the skin. It can be absorbed

through the skin or inhaled as a product is applied.

EWG is a nonprofit environmental research organization with offices

in Washington DC , Seattle WA, and Oakland CA.

ARE YOUR BEAUTY PRODUCTS KILLING YOU?

A new report linking birth defects and health risks with a chemical

used in trendy cosmetics, gives a long overdue wake-up call to the

FDA, consumers and the beauty industry.

If you got out of the shower this morning, blow-dried your hair and

gave your 'do a spritz of VO5 hairspray, you've just poisoned

yourself. If you do this every morning as your regular routine, you

are accumulating these poisons by the bucketful.

But it's not just VO5 that could make you sick. Try Secret Sheer Dry

deodorant, or the suitably named Poison, a perfume by Christian

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Dior. In fact, 52 popular cosmetics are now proven to have toxic

components in varying concentrations -- and they're all over the

place.

A report released jointly July 10 by Coming Clean, the EWG and

Health Care Without Harm details the extent to which a toxic family

of chemicals known as phthalates (THAY-lates) are used in everyday

household products, especially beauty products like nail polish,

lipstick and perfumes.

The report, titled "Not Too Pretty: Pthalates, Beauty Products and the

FDA," has its basis in a 1999 FDA study of toxins in the general

population of the U.S. From a sample of 1,029 people, every one of

them tested positive for phthalates in their blood or urine. Scientists

at the Centers for Disease Control singled out a subgroup of 289

people with a particularly high incidence of phthalates: women of

childbearing age. These women were found to have daily exposures

of phthalates ranging from 2.5 to 22 times the normal for the rest of

the general population, with 5 percent showing levels of 75 percent or

higher of the acceptable daily amounts.

Judging from the 5 percent of women with dangerously high test

results, it can be assumed that every day, as many as 2,000,000

women of childbearing age are exposed to toxic levels of phthalates.

Phthalates have been shown to cause a wide array of health

problems, from liver and kidney failure to heart, lung and blood

pressure problems. The most worrisome aspect by far is the

phthalates' effect on the reproductive development of fetuses and

infants, particularly the reproductive tracts of males.

Phthalates are metabolized in humans once ingested or absorbed

through the skin. In pregnant women, phthalates pass through the

placenta to be absorbed by the fetus. In nursing women, phthalates

are found in breast milk, which means infants are ingesting these

chemicals as they develop. In male fetuses -- and infants especially -

- the phthalates have been shown to cause testicular atrophy and a

reduced sperm count, among other serious health problems.

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Dr. Stephen Safe of Texas A&M University notes that some in the

medical community have expressed concerns about phthalate

exposure and human health. "It's hard to be specific until more

medical data is available," Dr. Safe says, "but if people have

concerns, they should limit their use of these products."

The HCWH report is the first to document and link the deleterious

effects of phthalates to male reproductive development. Women of

childbearing age were shown to be the most at-risk demographic, and

it is reasonable to attribute this in large part to one fact: the beauty

industry. According to Charlotte Brody, executive director of HCWH,

"With all the variables involved, the only one that doesn't apply on a

large scale to both men and women is the use of cosmetics."

Global Pollutants

Phthalates are plasticizers. In cosmetics, they are used to add texture

and luster to the product. Ninety percent of the world's plasticizers

are used to soften PVC (vinyl) and make it pliable. The other 10

percent have been used in many kinds of manufacturing for 30 years,

beginning with medical products like IV bags, gloves and blood bags,

but also paints, lubricants, adhesives, toys, food containers, and, of

course, cosmetics.

The use of phthalates in manufacturing is widespread, and has such a

long history that phthalates have wormed their way into every corner

of the globe. Traces are present in virtually every person on the

planet. The phthalate DEHP has been found in Antarctica and in deep-

sea jellyfish 3,000 feet below the ocean's surface.

Different phthalates can be found in consumer products like shower

curtains, umbrellas, adhesives, children's toys, and countless other

manufactured goods. PVC, being incredibly cheap to produce, is the

preferred product for the world's manufacturers. With phthalates, you

can easily turn PVC into any number of products.

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Since the FDA does not regulate the use of pthalates in cosmetics and

beauty aids, manufacturers are not required to disclose them as

ingredients.

Says the report: "Taken as a whole, the lab results indicate that a

substantial fraction of cosmetics companies may be hiding phthalates

on store shelves within the containers of their products, with no

warning for pregnant women who might want to avoid purchasing

products that contain chemicals linked to birth defects."

DEHP, the primary phthalate found in medical supplies, has been

found toxic in studies of patients who spend considerable amounts of

time in hospitals, mainly newborns and the elderly. But other

phthalates, including DEP, DBP, BBP, DCP, DOP and DINP, were last

studied nearly 20 years ago.

According to FDA spokesperson Kimberly Rawlings, "Phthalates were

shown to be safe for topical use in 1984, and there have been no

further studies by the FDA on this subject since then."

In a recent Dallas Morning News story on phthalates and the

cosmetics industry, Rod Irvin, a spokesman for the American

Chemistry Council's Phthalate Esters Panel, said that "[p]hthalates

are among the most-studied products out there. They have a long

record of safe use, with no reports or evidence of harm to human

health." Additionally, the industry group has spent "millions" studying

the compounds and has found no reason for concern.

In November 2000, the Environmental Working Group released a

report that stated, "Phthalates are recognized as toxic substances

under environmental law, but companies are free to use unlimited

amounts in cosmetics."

The FDA in the past has considered each of these phthalates

separately when studying their toxicity. If you're a dialysis patient,

then you're at risk for poisoning because you're getting twice the

amount of DEHP recommended with each visit. That's bad. But if

you're a dialysis patient and you wear a lot of makeup and spend a

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lot of time playing with your grandchildren and their toys, your

exposure could be deadly.

Not in the many-faceted eyes of the FDA, though. Its consideration of

disparate exposure to phthalates is the main loophole manufacturers

use to claim that phthalates are safe. Without recognizing that all

members of the phthalate family accumulate to cause the same

health problems, phthalate manufacturers are able to claim that each

individual chemical is not harmful at the documented levels.

HCWH tested 72 of the following kinds of cosmetics: Nail polish,

fragrances (perfumes, body oils, etc.), hairsprays, deodorants and

lotions. Fifty-two of these contained phthalates as ingredients, though

none were listed on the labels. Most of the pthalate-containing

products are household names: Aqua Net Professional Hair Spray;

Degree Original Solid Deodorant; Nivea Créme lotion; Elizabeth

Arden's Red Door fragrance; Calvin Klein's Eternity perfume.

As Brody of HCWH points out, this is just the beginning: "It's

impossible to know without testing which products contain

phthalates. Just because some of the lotions we tried tested negative

doesn't mean [all lotions are] clean." Until the manufacturers are

required to label phthalates, there's no way to know for sure.

Early Warnings

This is only the latest in a long series of warnings about the dangers

of phthalates, which have been used extensively since the early

1970s. The biggest commotion over phthalates came in 1998, when

the Danish government issued a well-publicized ban on toys

containing phthalates because of concern that children were being

exposed to toxic chemicals when they put toys in their mouths. Lego,

the Danish toymaker, quickly responded by reformulating its toy

factories to phase out the use of phthalates in production of its toys.

Since then, there has been steadily growing awareness of the

dangers of phthalates. Network news programs have discussed the

dangers in toys, cosmetics and beauty products, and even in fish that

live in polluted waters. Despite all this, the battle against phthalates

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has been a stalemate: The EU continues to extend its temporary ban

on toys for children aged 3 and under, but European manufacturers

are lobbying to institute a voluntary reporting system for all other

products similar to what is in place in the U.S.

Stacy Malkan of HCWH is urging people to distribute the lists of

phthalate-containing products far and wide, to discuss the topic of

phthalates in cosmetics and medical supplies with their health care

provider, and to contact the FDA to demand an industry-wide ban on

phthalates in cosmetic products. In addition, the groups releasing the

report are preparing to launch a national ad campaign.

As the report makes clear, non-toxic alternatives are readily

available: "The limited testing done for Not Too Pretty reveals that

the same big companies that produce phthalate-laced beauty

products, also make similar products without phthalates ... L'Oreal

markets Jet Set nail polish without DBP but puts the phthalate in its

Maybelline brand."

Without public pressure, however, there will be no incentive for the

$20 billion-a-year cosmetics industry to phase out all phthalates. And

women who continue to douse themselves in Christian Dior's Poison

may be helping the perfume live up to its name.

REFERENCES:

Blount BC, MJ Silva, SP Caudill, LL Needham, JL Pirkle, EJ

Sampson, GW Lucier, RJ Jackson, JW Brock. October 2000. Levels

of seven urinary phthalate metabolites in a human reference

population. Environmental Health Perspectives. 108(10):979-982.

Castleman, BI, and GE Ziem. 1994. American Conference of

Governmental Industrial Hygienists: Low Threshold of Credibility.

American Journal of Industrial Medicine. 26:133-143.

Center for the Evaluation of Risks to Human Reproduction (CERHR),

National Toxicology Program, U.S. Department of Health and

18

Human Services. October 2000. NTP-CERHR Expert Panel Report on

Di n Butyl Phthalate. NTP-CERHR-DBP-00.

Dearman RJ, Cumberbatch M, J Hilton, HM Clowes, I Fielding, JR

Heylings, I Kimber. 1996. Influence of dibutyl phthalate on dermal

sensitization to fluorescien isothiocyanate. Fundam Appl Toxicol

1996 Sep;33(1):24-30.

Ema M, Amano H, Ogawa Y. 1994. Characterization of the

developmental toxicity of di-n-butyl phthalate in rats. Toxicology

86:163-174.

Ema M, Kurosaka R, Amano H, Ogawa Y. 1995. Comparative

developmental toxicity of n-butyl benzyl phthalate and di-n-butyl

phthalate in rats. Arch Environ Contam Toxicol 28:223-228(1995).

Ema M, Miyawaki E, Kawashima K. 1998. Further evaluation of

developmental toxicity of di-n-butyl phthalate following

administration during late pregnancy in rats. Toxicol Lett:87-

93(1998).

Environmental Protection Agency (EPA). 1990. Integrated Risk

Information System. Dibutyl phthalate, CASRN 84-74-2. October

1990. Available online at http://www.epa.gov/ngispgm3/iris/

Foster PM, BG Lake, LV Thomas, MW Cook, SD Gangolli. 1981.

Studies on the testicular effects and zinc excretion produced by

various isomers of monobutyl-o-phthalate in the rat. Chem Biol

Interact 1981 Mar 1;34(2):233-8.

Gall H, Kohler A, and Peter RU. 1999. Anaphylactic shock reaction

to dibutyl-phthalate-containing capsules. Dermatology.

199(2):169-70.

Gray LE, Jr, Wolf C, Lambright C, Mann P, Price M, Cooper RL,

Ostby J. 1999. Administration of potentially antiandrogenic

pesticides (procymidone, linuron, iprodione, chlozolinate, p,p'-DDE,

and ketoconazole and toxic substance (dibutyl- and diethylhexyl

phthalate, PCB 169, and ethane dimethane sulphonate) during

sexual differentiation produces diverse profiles of reproductive

19

malformations in the male rat. Toxicol Ind Health 15:94-

118(1999).

Kohn MC, Parham F, Masten SA, Portier CJ, Shelby MD, Brock JW,

Needham LL. October 2000. Human Exposure Estimates for

Phthalates. Environmental Health Perspectives 108(10).

Marsman DS. 1995. NTP technical report on toxicity studies of

dibutyl phthalate (CAS No. 84-74-2) administered in feed to F344

rats and B6C3F1 mice. NIH Publication 95-3353. Research Triangle

Park: National Toxicology Program.

Moline JM, Golden A, Bar-Chama N, Smith E, Rauch M, Chapin R,

Perreault S, Schrader S, Suk W, Landrigan P. September 2000.

Exposure to hazardous substances ad male reproductive health: a

research framework. Environmental Health Perspectives. 108(9).

Mylchreest E, Cattley RC, Foster PM. 1998. Male reproductive tract

malformations in rats following gestational and lactational exposure

to di(n-butyl) phthalate: An antiandrogenic mechanism? Toxicol Sci

43:47-60(1998).

Mylchreest E, Sar M, Cattley RC, Foster PMD. 1999. Disruption of

androgen-regulated male reproductive development by di(n-butyl)

phthalate during late gestation in rats is different from flutamide.

Toxicol Appl Pharmacol 156:81-95(1999).

Mylchreest E, Wallace DG, Cattley RC, Foster P. 2000. Dose-

dependent alternations in androgen-regulated male reproductive

development in rats exposed to di_n-butyl) phthalate during late

gestation. Toxicol Sci(2000).

Paulozzi LJ. 1999. International trends in rates of hypospadias and

cryptorchidism. Environmental Health Perspectives. 107(4). April

1999.

Roach, SA and SM Rappaport. 1990. But they are not thresholds: A

critical analysis of the documentation of threshold limit values.

American Journal of Industrial Medicine. 17:727-753.

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Roe D, Pease W, Florini K, and. Silbergeld E. 1997. Toxic

Ignorance. Environmental Defense. Washington DC. Summer 1997.

Sainio EL, Engstrom K, Henriks-Eckerman ML, Kanerva L. 1997.

Allergenic ingredients in nail polishes. Contact Dermatitis

Oct;37(4):155-62.

Swan SH, Elkin EP, Fenster L. 2000. The question of declining

sperm density revisited: An analysis of 101 studies published 1934-

1996. Environmental Health Perspectives. 108(10). October 2000.

Toppari, J, Larsen JC, Christiansen P, Giwercman A, Grandjean P,

Guillette Lj Jr, Jegou B, Jensen, TK, Jouannet P, Keiding N, Leffers

H, McLachlan JA, Meyer O, Muller J, Meyts, E R-D, Scheike T,

Sharpe R, Sumpter J, Skakkebaek NE. August 1996. Male

reproductive health and environmental xenoestrogens.

Environmental Health Perspectives. 104. Supplement 4.

Wine R, Li L_H, Barnes LH, Gulati DK, Chapin RE. 1997.

Reproductive toxicity of di-n-butyl phthalate in a continuous

breeding protocol in Sprague-Dawley rats. Environ Health Perspect

105:102-107 91997).

CCAANN LLOOWW DDOOSSEESS OOFF SSYYSSTTEEMMIICC,, TTOOXXIICC CCHHEEMMIICCAALLSS HHUURRTT MMEE?? Hundreds of studies in the peer-reviewed literature show that

adverse health effects from low dose exposures are occurring in the

population, caused by unavoidable contamination with PCBs, DDT,

dioxin, mercury, lead, toxic air pollutants, and other chemicals. The

health effects scientists have linked to chemical exposures in the

general population include premature death, asthma, cancer, chronic

bronchitis, permanent decrements in IQ and declines in other

measures of brain function, premature birth, respiratory tract

infection, heart disease, and permanent decrements in lung capacity

(EPA 1996, EPA 2000, Gauderman, et al. 2002, Jacobson and

Jacobson 2002, Jacobson, et al. 2002, Kopp, et al. 2000,

21

Longnecker, et al. 2001, NAS 2000, NTP 2002, Pope, et al. 2002,

Salonen, et al. 1995, Sydbom, et al. 2001).

A growing body of literature links low dose chemical exposures in animal studies to a broad range of health effects previously unexplored in high dose studies. In low dose testing, scientists are using sophisticated techniques to measure subtle but important changes in the functioning of apparently undamaged organ systems, including alterations in immune function (such as antibody response), enzyme activity, hormone levels, cellular changes in tissues, neurobehavioral parameters, organ growth, and hormone and neurotransmitter receptor levels. Importantly, many low dose effects are detected following developmental exposure. These tests focus on the effects of chemical exposures comparable to those that occur in the general population, and far below the levels that have traditionally been considered safe based on the results of studies that feed lab animals high doses of a given compound. Using these protocols, scientists are finding that low doses of chemicals can be far more harmful than previously believed.

Low dose studies often identify toxic effects at levels far below those

identified as the “no effect” level in high dose studies. For instance,

through low dose studies of bisphenol A (BPA), a plasticizer chemical

commonly used in dental sealants and plastic water bottles,

scientists have revealed health effects at levels 2,500 times lower

than EPA’s “lowest observed effect” dose, with adverse outcomes

ranging from altered male reproductive organs and aggressive

behavior, to abnormal mammary gland growth, early puberty, and

reduced breast feeding.

In the face of a powerful and growing body of literature linking low

dose chemical exposures and health harms in the general

population, the chemical industry continues to claim that low dose

exposures to hundreds of chemicals simultaneously is safe. These

claims, however, are nearly always based on a lack of scientific

information on the toxicity of low-dose exposures, not on a

definitive, scientific proof of safety.

High dose animal studies provide the foundation for federal exposure

limits for contaminants in consumer products, drinking water, food,

22

and air. Indeed, the nation’s regulatory system for chemical

exposures is dependent on the notion that high dose studies will

reveal completely, the toxic properties of a chemical being tested.

We now know that this is not true. A number of factors, each of

which can be as important as the exposure dose, determine a

compound's toxicity:

• Timing. The timing of a dose can often determine the

toxicity of the chemical. Low dose chemical exposures

during fetal development or infancy are known to

produce more serious toxic effects than similar

exposures during adulthood for many chemicals. Lead

and mercury are the classic examples, where low dose

exposures in utero and during infancy cause permanent

brain and nerve damage, while the same doses cause no

observable effects in adults. Few high dose studies, with

the exception of those required for food use pesticides,

target vulnerable periods of development. Most high

dose studies include only adult animals. Low dose

studies almost always involve exposures in utero,

through multiple generations, and into old age.

• Genetic vulnerability. Some people are more

susceptible to environmental contaminants because of

genetic factors. For example, EPA-funded research has

documented a 10,000-fold variability in human

respiratory response to airborne particles (including

allergens and pharmaceuticals) (Hattis, et al. 2001).

This variability explains, in part, why we all breathe the

same air, but not all of us have asthma attacks.

Laboratory animal studies, often conducted with

genetically uniform animals, cannot reveal genetically

induced adverse effects that may occur in a small but

significant percentage of a highly diverse human

population.

23

• Mechanisms and unexpected results. Chemicals

produce a spectrum of health effects that can both vary

with dose, and affect the target organ in different ways

depending on dose. For instance, some chemicals

produce opposite effects at high and low doses – a

phenomenon called biphasic dose response. Some

produce different effects at high and low doses. Some

produce adverse effects at low doses, but not at higher

doses. DES, a potent synthetic estrogen, has been

shown to stimulate prostate growth at 0.02, 0.2, and 2

mg/kg-day, but inhibit prostate growth at doses of 100

and 200 mg/kg-day (vom Saal, et al. 1997).

Perchlorate, a component of rocket fuel that

contaminates drinking water, causes changes in the size

of certain parts of the brain at 0.01 – 1 mg/kg-day, but

not at 30 mg/kg-day (Argus 1998). Current government

testing regimes do not require tests to define different

effects of chemicals across a wide range of doses.

WWHHAATT AARREE TTHHEE PPOOSSSSIIBBLLEE HHEEAALLTTHH EEFFFFEECCTTSS OOFF LLOOWW DDOOSSEE EEXXPPOOSSUURREESS TTOO TTOOXXIICC CCHHEEMMIICCAALLSS?? Health professionals are not trained to link health problems to an

individual’s chemical exposure, but it is increasingly evident that

background exposures to industrial chemicals and pesticides are

contributing to a portion of the steady increase in some health

problems in the population.

Cancer.

Between 1992 and 1999, cancer incidence increased for many forms

of the disease, including breast, thyroid, kidney, liver, abdominal

cavity connective tissue, skin and some forms of leukemia. The

incidence of childhood cancer increased by 26 percent between 1975

and 1999, with the sharpest rise estimated for brain and other

nervous system cancers (50 percent increase) and acute

24

lymphocytic leukemia (62 percent increase). The incidence of

testicular cancer also rose between 1973 and 1999 (NCI 2002). The

probability that a US resident will develop cancer at some point in

his or her lifetime is 1 in 2 for men and 1 in 3 for women (ACS

2001). Just 5 to 10 percent of all cancers are linked to inherited,

genetic factors (ACS 2001). For the remainder, a broad array of

environmental factors play a pivotal role.

• This study found 79 carcinogens in nine people. On

average, each study participant contained 53 chemical

carcinogens.

Major nervous system disorders.

Several recent studies have determined that the reported incidence

of autism is increasing, and is now almost 10 times higher than in

the mid-1980’s (Byrd 2002, Chakrabarti and Fombonne 2001, Yang,

et al. 2000). The number of children being diagnosed and treated for

attention deficit disorder (ADD) and attention deficit hyperactivity

disorder (ADHD) has also increased dramatically in the past decade

(Robison, et al. 1999, Robison, et al. 2002, Zito, et al. 2000). The

causes are largely unexplained, but environmental factors, including

chemical exposures, are considered a potential cause or contributor.

Environmental factors have also been increasingly linked with

Parkinson’s disease (Checkoway and Nelson 1999, Engel, et al.

2001).

• This study found 94 nervous system toxins in nine

people. On average, each study participant contained 62

nervous system toxins.

Defects of the reproductive system.

Studies show that sperm counts in certain parts of the world are

decreasing (Swan, et al. 2000, Toppari, et al. 1996). Scientists have

measured significant regional differences in sperm count that cannot

be explained by differences in genetic factors (Swan, et al. in press).

Girls may be reaching puberty earlier, based on comparing current

25

appearance of breast development and pubic hair growth with

historical data (Herman-Giddens, et al. 1997). Incidence of

hypospadias, a birth defect of the penis, doubled in the United

States between 1970 and 1993, and is estimated to affect one of

every 125 male babies born (Paulozzi, et al. 1997). The incidence of

undescended testicles (cryptorchidism) and testicular cancer also

appear to be rising in certain parts of the world (Bergstrom, et al.

1996, McKiernan, et al. 1999, Toppari, et al. 1996). Testicular

cancer is now the most common cancer in men age 15 to 35 [NCI

(National Cancer Institute), 2000 #244]. Several studies have

suggested links between developmental exposure to environmental

contaminants and cryptorchidism or testicular cancer (Hardell, et al.

in press, Hosie, et al. 2000, Toppari, et al. 1996, Weidner, et al.

1998).

• This study found 77 chemicals linked to reproductive

damage in nine people. On average the nine subjects

contained 55 reproductive toxins.

AARREENN''TT TTHHEESSEE CCHHEEMMIICCAALLSS TTEESSTTEEDD?? Although most people assume that chemicals in consumer products

are thoroughly tested before they are sold, there is no legal

requirement to test most chemicals for health effects at any stage of

production, marketing, and use.

Under the Toxic Substances Control Act, chemical companies can

continue making chemicals and putting new compounds on the

market without conducting any studies of their effects on people or

the environment. Some companies conduct rudimentary screening

studies prior to production, but fewer than half of all applications to

the EPA for new chemical production include any toxicity data at all.

The government approves 80 percent of these applications with no

restrictions, usually in less than three weeks. When data are

provided, they are typically cursory in nature, because the

government lacks authority to request anything more than that.

Eight of 10 new chemicals win approval in less than three weeks, at

26

an average rate of seven a day. If there are no data, the

government justifies approval with results of computer models that

estimate if a chemical will harm human health or the environment

(EPA 1997a, GAO 1994).

For chemicals that are already on the market, the EPA can request

data only when it can substantiate that the chemical is causing

harm, which it generally cannot do without the toxicity data it is

seeking to request. In practice, this means that studies are required

only after independent scientists have accumulated a body of

evidence demonstrating potential harm, a process that typically

takes decades.

In general, the more recently a chemical has been introduced into

commerce, the less scientists understand its toxicity, and the less

likely it is that scientists will know how to test for it in people and

the environment. The few chemicals or chemical families that have

been well-studied are those for which scientists uncovered, often

accidentally, environmental catastrophes that can include

widespread pollution of the environment or human population.

WWHHAATT MMUUSSTT TTHHEE CCHHEEMMIICCAALL IINNDDUUSSTTRRYY DDOO?? The chemical industry tightly controls the testing and the

information flow on any issue related to their products. Chemical

companies are not required to prove the safety of their products or

disclose methods that could be used to test for their chemicals in the

environment or the human body.

Typically only after a compound has been on the market for

decades, and has contaminated a significant portion of the

environment, do independent scientists learn how to detect and

quantify it. At that point, the Centers for Disease Control and

Prevention (CDC) may choose to include the chemical in its national

biomonitoring program. Even then there is no guarantee that the

manufacturer will provide CDC with the methodology to detect it, or

that the methods will be reliable. For example, three years after 3M

27

announced that it was removing perfluorinated chemicals in

Scotchgard from the market, chiefly because 3M found that the

human population is widely contaminated with the chemicals, the

CDC has yet to develop a method it considers reliable that would

allow it to add the chemicals to its national biomonitoring program.

At a minimum, people have a right to know what chemicals are in

their bodies and what harm they might cause. The sole source of

this information is the chemical manufacturers themselves, who

historically have not provided it to government officials even as they

have resisted efforts to make the information public.

Without disclosure of information on the environmental fate, human

contamination, and health effects of these chemicals, regulators

cannot effectively prioritize efforts to reduce the health risks from

the current contaminant load in the human population.

Regardless of whether or not Congress revises the nation’s laws or

policies:

• The chemical industry must submit to EPA and make

public on individual company web sites, all internal

studies on the properties, environmental fate, potential

human exposure pathways and exposure levels,

concentrations in workers and the general population,

levels in the environment, worker and community

health, measured effects in wildlife, toxicity,

mechanisms of action and any other information

relevant to human exposures and potential health effects

for all chemicals reasonably likely to be found in people,

drinking water, or indoor air.

WWHHAATT SSHHOOUULLDD TTHHEE GGOOVVEERRNNMMEENNTT DDOO?? This study, combined with work from the Centers for Disease Control

and Prevention, and a thorough review of the scientific literature

reveal a ubiquitous and insidious pollution of the human population

with hundreds of chemicals, pollutants, and pesticides. In large

28

measure this is the result of a regulatory system that leaves the EPA

with few tools to study the health effects or the extent of human

exposure to the thousands of chemicals found in consumer products.

Revisions to the nation’s laws and policies governing chemical

manufacture and use include the following provisions:

• Industry must be required to prove the safety of a

chemical before it is put on the market.

• The EPA must have the unencumbered authority to

request any and all new data on a chemical that is

already on the market.

• The EPA must have the clear authority to suspend a

chemical’s production and sale if the data requested are

not generated, or if they show that the chemical, as

used, is not safe for the most sensitive portion of the

exposed population.

• Chemicals that persist in the environment or bio-

accumulate in the food chain must be banned.

• Chemicals found in humans, in products to which

children might be exposed, in drinking water, food, or

indoor air, must be thoroughly tested for their health

effects in low dose, womb-to-tomb, multi-generational

studies focused on known target organs, that include

sensitive endpoints like organ function and cognitive

development. Studies to define mechanisms of action

(how a chemical harms the body) must be conducted.

• The chemical industry must develop and make public

analytical methods to detect their chemicals in the

human body, and conduct bio-monitoring studies to find

the levels of their chemicals in the general population.

29

• Chemical manufacturers must fully disclose the

ingredients of their products to the public.

TTHHEE RREEGGUULLAATTOORRYY PPRREECCEEDDEENNTT OOFF PPEESSTTIICCIIDDEESS At first blush these statutory changes appear a radical departure

from current policies, but in fact, the chemical industry already

complies with these standards for pesticide products, proof that the

industry can meet the same safety standards with commercial

chemicals.

Pesticides in food are regulated under section 408 of the Food Drug

and Cosmetic Act, which requires chemical companies to show that

there is a “reasonable certainty of no harm” from exposure to a

pesticide, for all exposed individuals, including explicit consideration

of the fetus, infant and small child. This standard, which is well

defined in case law and regulations, applies to all uses and all routes

of exposure to a pesticide (food, air, and water considered

together). “Reasonable certainty of no harm” is protective of the

public health, particularly where the finding is contingent on fetal

and infant exposure, but is not so protective that it cannot be met,

or that companies can argue that it is onerous.

Section 408 also requires that pesticides with common mechanisms

of toxicity be added together when assessing compliance with the

reasonable certainty of no harm standard. This means that groups of

pesticides, for example, all organophosphates, are added together

when measuring compliance. In contrast, TSCA does not require that

regulators assess the additive risks. Many major chemical classes

commonly used in consumer products are characterized by common

mechanisms of toxicity - phthalates, perfluorinated chemicals, and

polybrominated diphenyl ethers, for example - and none are

assessed in aggregate by EPA.

When data are not available, legal exposures for infants and children

are required to be 10 times lower than for adults, and economic

30

benefits are not allowed as an escape valve, or a means to permit

higher risk.

To ensure that these tough standards can be met, the other

governing statute, FIFRA (the Federal Insecticide Fungicide and

Rodenticide Act), grants the EPA administrator broad (virtually

unlimited) authority to request data, and to suspend the sale of the

product when data are not generated (section 3, particular 3(c)2(B),

and section 6).

The legislative history of FIFRA is instructive. Beginning in the early

1980’s a series of congressional committee investigations and GAO

reports documented that basic health studies had not been

conducted for most pesticides on the market at that time. In

response, Congress amended FIFRA in 1988 to require that all

pesticides be “re-registered,” which meant that they had to be

tested by contemporary standards and re-evaluated for their health

risks.

This forced the EPA to deal with the same problem that they face

today when considering a comprehensive testing program for toxic

chemicals: what to do with all the chemicals already on the market?

EPA’s response, which largely was successful, albeit slow, was to

impose strict timelines for testing and re-evaluation while granting

EPA clear authority to require any test for any pesticide, and the

authority to suspend the sale of a pesticide if the manufacturer

refuses to do the test or fails to submit it on time. Compare this with

TSCA where EPA must go through a rulemaking just to get one test

on one chemical.

As a result of these amendments, EPA now requires about 120 tests

for pesticide registration. These tests range from acute and chronic

toxicity, to metabolism, environmental fate and residue chemistry.

These tests include toxicity tests that will support regulatory decision

making, not the superficial screening tests being conducted under

the HPV testing program. EPA has reevaluated nearly all pesticides

of any significance, starting in the early 1990’s with more than 100

31

pesticide active ingredients in about 20,000 different products

applied to food crops. There is no reason that these same test

requirements could not be applied in a tiered fashion to commercial

chemicals regulated under TSCA.

Testing requirements alone have driven many compounds from the

market. One good example is methoxychlor, a DDT relative, which

was banned with little fanfare in 1999 when the manufacturer simply

refused to conduct required health studies. Another good example is

pesticides used in aircraft cabins. In 1995 EPA asked all

manufacturers of pesticides applied inside commercial airplanes to

do the exposure studies needed to show the use was safe. Not a

single manufacturer of more than 200 products was willing to do the

tests (because they knew that the use was not safe), and all uses of

pesticides inside aircraft were unceremoniously banned in the United

States in 1998.

Another great example of the power of FIFRA’s data generation

authority involves the toxic byproducts of chlorinating tap water. The

Safe Drinking Water Act does not give the EPA authority to require

toxicity tests for drinking water contaminants. As a result, the

agency is forced to negotiate test programs with polluters or the

affected industry, or to pay for the testing from their own research

funds. But because chlorine is a pesticide (it kills microbes in water),

EPA was able to use the data call-in authority of FIFRA to require the

chlorine industry to do a broad range of toxicity tests on chlorination

byproducts that they otherwise had not planned to do.

WWHHAATT CCAANN YYOOUU DDOO?? Some exposures to pesticides and industrial chemicals are

unavoidable. Persistent pollutants, some banned for decades, still

contaminate the environment and end up in the food we eat, the

water we drink, and the air we breathe.

Yet even exposures to persistent pollutants can be reduced through

a varied diet that contains fewer meat and high fat dairy products.

32

Other chemical exposures, like toxic substances in household

cleaners, can be avoided altogether.

SOME SIMPLE TIPS FOR REDUCING EXPOSURES

TO INDUSTRIAL CHEMICALS ARE:

• Eat fewer processed foods, which often contain chemical

additives.

• Eat organic produce. It's free of pesticides and

preservative chemicals.

• Don't microwave food in plastic containers, use glass or

ceramics.

• Run your tap water through a home filter before

drinking. Filters can reduce levels of common tap water

pollutants.

• Eat fewer meat and high fat dairy products, which

contain higher levels of some pollutants.

• Reduce the number of cosmetics and other personal care

products you use, which can contain harmful chemicals

and can be sold with no safety testing.

• Avoid artificial fragrances.

• Don’t use stain repellants on clothing, bedding or

upholstery.

• Reduce the number of household cleaners you use. Try

soap and water first.

• Avoid using gasoline-powered yard tools - use manual or

electric tools instead.

33

• Avoid breathing gasoline fumes when you're filling your

car - sit inside the car, for instance.

• Eat seafood known to be low in PCB and mercury

contamination, including wild Alaska salmon and canned

salmon. Avoid canned tuna - it contains mercury.

• Adopt a diet of cleansing, alkaline foods

• Eat mineral-rich foods

Particularly if you're pregnant, try to follow the tips listed above. Is

there someone in your household who can take over using

household cleaners and pumping gas while you're pregnant? Eat

canned salmon instead of canned tuna. Paint the baby room well

before you conceive. Don't use nail polish, which contains chemicals

linked to birth defects in laboratory studies.

FFIIRRSSTT--TTIIMMEE MMOOMMSS WWIITTHH AA NNEEWW BBAABBYY …… GGEETT TTEESSTTEEDD!!

If you are a first-time mom, at least six-months pregnant or with a

newborn baby, you can volunteer to participate in an important

scientific study to identify levels of industrial chemicals in breast

milk. Widely considered the very best food for babies, breast milk

also carries traces of industrial pollutants that bind to breast milk

fat. With funding from philanthropic foundations, we have initiated a

study with a major national laboratory to test a limited number of

breast milk samples from first-time moms, for a number of industrial

chemicals that concern scientists, including brominated flame

retardants. Would you be interested in participating in this scientific

study? The cost to you is nothing. Your results would be anonymous,

used in scientific publications, and your participation could advance

science and regulatory policy in ways that could make breast milk an

even better source of nutrition for babies.

34

DOCUMENTED REFERRENCES AND PERTINENT

STUDIES LINKING SYSTEMIC TOXINS AND

CHEMICALS TO DEGENERATIVE ILLNESSES:

1. Akhtar, N, SA Kayani, MM Ahmad and M Shahab. 1996.

Insecticide-induced changes in secretory activity of the

thyroid gland in rats. J Appl Toxicol 16(5): 397-400.

2. ATSDR (Agency for Toxic Substances and Disease

Registry). 1992. Toxicological profile for 2-hexanone:

Health effects chapter. Available online at

http://www.atsdr.cdc.gov/toxpro2.html#Final.


Registry). 1994a. Toxicological profile for chlordane:




Registry). 1994b. Toxicological profile for

chlorodibenzofurans (CDFs): Health effects chapter.

Available online at



Registry). 1994c. Toxicological profile for

hexachlorocyclohexanes: Health effects chapter.

Available online at



Registry). 1995a. Toxicological profile for diethyl

35

phthalate (DEP): Health effects chapter. Available online

at http://www.atsdr.cdc.gov/toxpro2.html#Final.


Registry). 1995b. Toxicological profile for mirex and

chlordecone: Health effects chapter. Available online at



Registry). 1995c. Toxicological profile for xylenes:




Registry). 1997. Toxicological profile for di-n-

octylphthalate (DNOP): Health effects chapter. Available

online at http://www.atsdr.cdc.gov/toxpro2.html#Final.


Registry). 1998a. Toxicological profile for chlorinated

dibenzo-o-dioxins (CDDs): Health effects chapter.

Available online at



Registry). 1998b. Toxicological profile for chlorpyrifos:




Registry). 1999a. Toxicological profile for cadmium:




Registry). 1999b. Toxicological profile for ethylbenzene:

36




Registry). 1999c. Toxicological profile for lead: Health

effects chapter. Available online at



Registry). 2000a. Toxicological profile for arsenic: Health

effects chapter. Available online at



Registry). 2000b. Toxicological profile for polychlorinated

biphenyls (PCBs): Health effects chapter. Available



Registry). 2001. Toxicological profile for

pentachlrophenol: Health effects chapter. Available



Registry). 2002a. Toxicological profile for DDT, DDE,

DDD: Health effects chapter. Available online at




hexachlorobenzene: Health effects chapter.



Registry). 2002c. Toxicological profile for methoxychlor:

Health effects chapter. Availble online at


37

21. Bernard AM, de Russis R, Normand JC, Lauwerys RR.

1989. Evaluation of the subacute nephrotoxicity of

cyclohexane and other industrial solvents in the female

Sprague-Dawley rat. Toxicol Lett 45:271-80.

22. BIBRA (The British Industrial Biological Research

Association). 1988. Toxicity profile for cetylpyridinium

chloride (CPC).

23. Blount BC, Silva MJ, Caudill SP, Needham LL, Pirkle

JL, Sampson EJ, Lucier GW, Jackson RJ, Brock JW. 2000.

Levels of seven urinary phthalate metabolites in a

human reference population. Environ Health Perspect

108:979-82.

24. Bogh IB, Christensen P, Dantzer V, Groot M, Thofner

IC, Rasmussen RK, Schmidt M, Greve T. 2001. Endocrine

disrupting compounds: effect of octylphenol on

reproduction over three generations. Theriogenology

55:131-50.

25. Boockfor FR, Blake CA. 1997. Chronic administration

of 4-tert-octylphenol to adult male rats causes shrinkage

of the testes and male accessory sex organs, disrupts

spermatogenesis, and increases the incidence of sperm

deformities. Biol Reprod 57:267-77.

26. Cal EPA (California Environmental Protection Agency).

1998. Lindane (gamma hexachlorocyclohexane)

toxicological summary. Department of Pesticide

Regulation Medical Toxicology Branch. Available online

at

http://www.cdpr.ca.gov/docs/toxsums/toxsumlist.htm.

27. California Department of Pesticide Regulation. 1997.

Malathion: Summary of toxicology data. Available online

38

at

http://www.cdpr.ca.gov/docs/toxsums/toxsumlist.htm.

28. Cammarota M, Bevilaqua LR, Viola H, Kerr DS,

Reichmann B, Teixeira V, Bulla M, Izquierdo I, Medina

JH. 2002. Participation of CaMKII in neuronal plasticity

and memory formation. Cell Mol Neurobiol 22:259-67.

29. CERHR (Center for the Evaluation of Risks to Human

Reproduction). 2000a. NTP-CERHR expert panel report

on butyl benzyl phthlate (BBP), NTP-CERHR-BBP-00,

National Toxicology Program Center for the Evaluation of

Risks to Human Reproduction. Available online at

http://cerhr.niehs.nih.gov/news/phthalates/report.html.


Reproduction). 2000b. NTP-CERHR expert panel report

on di (2-ethylhexyl) phthalate (DEHP), NTP-CERHR-

DEHP-00, National Toxicology Program Center for the

Evaluation of Risks to Human Reproduction. Available

online at



Reproduction). 2000c. NTP-CERHR expert panel report

on di-n-butyl phthalate (DBP), NTP-CERHR-DBP-00,





Reproduction). 2000d. NTP-CERHR expert panel report

on di-n-octyl phthalate (DnOP), NTP-CERHR-DnOP-00,




39

33. CIR . 2002. 84th Meeting of the CIR expert panel

results. Available online at http://www.cir-

safety.org/staff_files/results.pdf.

34. Cornu MC, Lhuguenot JC, Brady AM, Moore R,

Elcombe CR. 1992. Identification of the proximate

peroxisome proliferator(s) derived from di (2-ethylhexyl)

adipate and species differences in response. Biochem

Pharmacol 43:2129-34.

35. CPChem (Chevron Phillips Chemical Company LP).

2000. Material Safety Data Sheet for ethylcyclohexane.

Available online at

http://www.cpchem.com/specialtychem/products/MSDS/

ETHYLCYCLOHEXANE.pdf.

36. Dewailly E, Ayotte P, Bruneau S, Gingras S, Belles-

Isles M, Roy R. 2000. Susceptibility to infections and

immune status in Inuit infants exposed to

organochlorines. Environ Health Perspect 108:205-11.

37. Duty SM, Singh NP, Silva MJ, Barr D, Brock JW, Ryan

L, Herrick RF, Christiani DC, Hauser R. in press 2003.

The relationship between environmental exposures to

phthalates and DNA damage in human sperm using the

neutral comet assay. Environ Health Perspect

38. EPA (Environmental Protection Agency). 1994.

Chemical Summary for Cyclohexane (EPA 749-F-94-

011a). Office of Pollution Prevention and Toxic

Substances (EPA OPPTS). Available online at

http://www.epa.gov/chemfact/s_cycloh.txt.


Malathion Reregistration Eligibility Decision: Toxicology

Chapther. Available online at

http://www.epa.gov/oppsrrd1/op/malathion.htm.

40


Malathion risk assessment: Review of malathion incident

reports. Available online at

http://www.epa.gov/pesticides/op/malathion.htm

(accessed January 2003).

41. EPA (Environmental Protection Agency). 2002a.

Methoxychlor; Tolerance Revocations: Final Rule.

Federal Register July 17, 2002, Volume 67, Number

137:46906-46909.

42. EPA (Environmental Protection Agency). 2002b.

Health Effects of PCBs. Available online at

http://www.epa.gov/opptintr/pcb/effects.html#Cancer

(accessed January 21, 2003).

43. Eskenazi B, Warner M, Mocarelli P, Samuels S,

Needham LL, Patterson DG, Jr., Lippman S, Vercellini P,

Gerthoux PM, Brambilla P, Olive D. 2002. Serum dioxin

concentrations and menstrual cycle characteristics. Am J

Epidemiol 156:383-92.

44. Field EA, Price CJ, Sleet RB, George JD, Marr MC,

Myers CB, Schwetz BA, Morrissey RE. 1993.

Developmental toxicity evaluation of diethyl and

dimethyl phthalate in rats. Teratology 48:33-44.

45. Gray LE, Jr., Ostby J, Furr J, Price M, Veeramachaneni

DN, Parks L. 2000. Perinatal exposure to the phthalates

DEHP, BBP, and DINP, but not DEP, DMP, or DOTP,

alters sexual differentiation of the male rat. Toxicol Sci

58:350-65.

46. Guo YL, Hsu PC, Hsu CC, Lambert GH. 2000. Semen

quality after prenatal exposure to polychlorinated

biphenyls and dibenzofurans. Lancet 356:1240-1.

41

47. Hosie S, Loff S, Witt K, Niessen K, Waag KL. 2000. Is

there a correlation between organochlorine compounds

and undescended testes? Eur J Pediatr Surg 10:304-9.

48. HSDB (Hazardous Substances Data Bank). 2002.

Cetylpyridinium chloride. National Library of Medicine

(NLM) Toxicology Data Network (TOXNET¨) Available

online at http://toxnet.nlm.nih.gov/cgi-

bin/sis/htmlgen?HSDB.htm.

49. IPCS. 1991. Environmental Health Criteria 124:

Lindane. World Health Organization - International

Programme on Chemical Safety Available online at

http://www.inchem.org/pages/ehc.html.

50. IPCS. 1997. Environmental Health Criteria 195:

Hexachlorbenzene. World Health Organization -

International Programme on Chemical Safety Available

online at http://www.inchem.org/pages/ehc.html.

51. IUCLID (International Uniform Chemical Information

Database). 2001. Data set: Didodecyl 3,3-

thiodipropionate. US EPA AR201-13379B. December 14,

2001 Available online at

http://www.epa.gov/chemrtk/thiobpad/c13379rs.pdf.

52. Katsuda S, Yoshida M, Isagawa S, Asagawa Y, Kuroda

H, Watanabe T, Ando J, Takahashi M, Maekawa A. 2000.

Dose- and treatment duration-related effects of p-tert-

octylphenol on female rats. Reproductive Toxicology

14:119-126.

53. Kogevinas M. 2001. Human health effects of dioxins:

cancer, reproductive and endocrine system effects. Hum

Reprod Update 7:331-9.

42

54. Kohn MC, Parham F, Masten SA, Portier CJ, Shelby

MD, Brock JW, Needham LL. 2000. Human exposure

estimates for phthalates. Environ Health Perspect

108:A440-2

55. Kreckmann KH, Baldwin JK, Roberts LG, Staab RJ,

Kelly DP, Saik JE. 2000. Inhalation developmental

toxicity and reproduction studies with cyclohexane. Drug

Chem Toxicol 23:555-73.

56. Laws SC, Carey SA, Ferrell JM, Bodman GJ, Cooper

RL. 2000. Estrogenic activity of octylphenol,

nonylphenol, bisphenol A and methoxychlor in rats.

Toxicol Sci 54:154-67.

57. Lin GH, Hemming M. 1996. Ocular and dermal

irritation studies of some quaternary ammonium

compounds. Food Chem Toxicol 34:177-82.

58. Lin GH, Voss KA, Davidson TJ. 1991. Acute inhalation

toxicity of cetylpyridinium chloride. Food Chem Toxicol

29:851-4.

59. Ljung B. 2002. EU reaches agreement to impose ban

on use of toxics in cosmetic products. The Bureau of

National Affairs, Inc. Volume 229:November 27, 2002.

60. Longnecker MP, Klebanoff MA, Zhou H, Brock JW.

2001. Association between maternal serum

concentration of the DDT metabolite DDE and preterm

and small-for-gestational-age babies at birth. Lancet

358:110-4.

61. Malley LA, Bamberger JR, Stadler JC, Elliott GS,

Hansen JF, Chiu T, Grabowski JS, Pavkov KL. 2000.

Subchronic toxicity of cyclohexane in rats and mice by

inhalation exposure. Drug Chem Toxicol 23:513-37.

43

62. Mocarelli P, Gerthoux PM, Ferrari E, Patterson DG, Jr.,

Kieszak SM, Brambilla P, Vincoli N, Signorini S,

Tramacere P, Carreri V, Sampson EJ, Turner WE,

Needham LL. 2000. Paternal concentrations of dioxin

and sex ratio of offspring. Lancet 355:1858-63

63. Monti D, Chetoni P, Burgalassi S, Najarro M, Saettone

MF. 2002. Increased corneal hydration induced by

potential ocular penetration enhancers: assessment by

differential scanning calorimetry (DSC) and by

desiccation. Int J Pharm 232:139-47.

64. Murature DA, Tang SY, Steinhardt G, Dougherty RC.

1987. Phthalate esters and semen quality parameters.

Biomed Environ Mass Spectrom 14:473-7.

65. NAS (National Academy of Sciences). 2000.

Toxicological Effects of Methylmercury. Washington DC,

National Academy Press Avalable online at

http://www.nap.edu/books/0309071402/html/.

66. NTP (National Toxicology Program). 1982. TR-212

carcinogenesis bioassay of di(2-ethylhexyl)adipate (CAS

No. 103-23-1) in F344 Rats and B6C3F1 mice (feed

study). NTIS# PB82-185927.

67. NTP (National Toxicology Program). 2001. Chemical

Repository: 2-Ethylhexyl glycidyl ether.

68. NTP (National Toxicology Program). 2002. 10th

Report on Carcinogens.

http://ehp.niehs.nih.gov/roc/toc10.html.

69. OEHHA . 1997a. Public health goal for ethylbenzene in

drinking water. California Environmental Protection

Agency, Office of Environmental Health Hazard

Assessment - Pesticide and Environmental Toxicology

44

Section Oakland, CA Available online at

http://www.oehha.org/water/phg/allphgs.html.

70. OEHHA . 1997b. Public health goal for

pentachlorophenol in drinking water. California

Environmental Protection Agency, Office of

Environmental Health Hazard Assessment - Pesticide and

Environmental Toxicology Section Oakland, CA Available

online at http://www.oehha.org/water/phg/allphgs.html.

71. OEHHA . 2002. Draft: Public health goal for di-(2-

ethylhexyl)adipate in drinking water. California

Environmental Protection Agency, Office of

Environmental Health Hazard Assessment - Pesticide and

Environmental Toxicology Section Oakland, CA Available

online at

http://www.oehha.org/water/phg/pdf/DEHAposting5300

2.pdf.

72. Oehlmann J, Schulte-Oehlmann U, Tillmann M,

Markert B. 2000. Effects of endocrine disruptors on

prosobranch snails (Mollusca: Gastropoda) in the

laboratory. Part I: Bisphenol A and octylphenol as xeno-

estrogens. Ecotoxicology 9:383-397.

73. Ozmen, G and MT Akay. 1993. The effects of

malathion on some hormone levels and tissues secreting

these hormones in rats. Vet Hum Toxicol 35(1): 22-4.

74. Pellizzari ED, Hartwell TD, Harris BS, 3rd, Waddell RD,

Whitaker DA, Erickson MD. 1982. Purgeable organic

compounds in mother's milk. Bull Environ Contam

Toxicol 28:322-8.

75. Persky V, Turyk M, Anderson HA, Hanrahan LP, Falk

C, Steenport DN, Chatterton RJ, Freels S, Consortium

GL. 2001. The effects of PCB exposure and fish

45

consumption on endogenous hormones. Environmental

Health Perspectives 109:1275-1283.

76. Raychoudhury SS, Blake CA, Millette CF. 1999. Toxic

effects of octylphenol on cultured rat spermatogenic cells

and Sertoli cells. Toxicol Appl Pharmacol 157:192-202.

77. Roman BL, Peterson RE. 1998. In utero and

lactational exposure of the male rat to 2,3,7,8-

tetrachlorodibenzo-p-dioxin impairs prostate

development. 1. Effects on gene expression. Toxicol Appl


78. Roman BL, Timms BG, Prins GS, Peterson RE. 1998.

In utero and lactational exposure of the male rat to

2,3,7,8- tetrachlorodibenzo-p-dioxin impairs prostate

development. 2. Effects on growth and

cytodifferentiation. Toxicol Appl Pharmacol 150:254-70.

79. Sinha, N, B Lal and TP Singh. 1991. Pesticides

induced changes in circulating thyroid hormones in the

freshwater catfish Clarias batrachus. Comp Biochem

Physiol C 100(1-2): 107-10.

80. Timms BG, Peterson RE, vom Saal FS. 2002. 2,3,7,8-

tetrachlorodibenzo-p-dioxin interacts with endogenous

estradiol to disrupt prostate gland morphogenesis in

male rat fetuses. Toxicol Sci 67:264-74.

81. Warner M, Eskenazi B, Mocarelli P, Gerthoux PM,

Samuels S, Needham L, Patterson D, Brambilla P. 2002.

Serum dioxin concentrations and breast cancer risk in

the Seveso Women's Health Study. Environ Health

Perspect 110:625-8.

82. WHO (World Health Organization). 1996. Guidelines

for drinking-water quality, 2nd ed. Vol. 2. Health criteria

46

and other supportive information. Geneva, World Health

Organization. pp. 523-530.

83. Yoshida M, Katsuda S, Takenaka A, Watanabe G, Taya

K, Maekawa A. 2001. Effects of neonatal exposure to a

high-dose p-tert-octylphenol on the male reproductive

tract in rats. Toxicol Lett 121:21-33.

REFERENCES CONTINUED

1. 3M. 2000. 3M to pare Scotchguard Products: one

long-lasting compound is cited (Comment by Charles

Reich, Executive Vice President of Specialty Material

Markets for 3M). The Washington Post. May 17, 2000.

2. 3M. Executive Summary: Environmental monitoring -

multi-city study water, sludge, sediment, POTW effluent

and landfill leachate samples U.S. EPA Administrative

Record AR226-1030a111, 2001.

3. ACS (American Cancer Society). 2001. Cancer Facts &

Figures 2001. Available online at

http://www.cancer.org/docroot/STT/stt_0_2001.asp?sit

earea=STT&level=1.

4. Adriani W, Della Seta D, Dessi-Fulgheri F, Farabollini F,

Laviola G. in press 2003. Altered profiles of

spontaneous novely seeking, impulse behavior, and

response to d-amphetamine in rats perinatally exposed

to bisphenol-A. Environ Health Perspect.

5. Alworth LC, Howdeshell KL, Ruhlen RL, Day JK, Lubahn

DB, Huang TH, Besch-Williford CL, vom Saal FS. 2002.

Uterine responsiveness to estradiol and DNA

methylation are altered by fetal exposure to

diethylstilbestrol and methoxychlor in CD-1 mice:

effects of low versus high doses. Toxicol Appl


47

6. Ankley GA, Touart L. 2002. Short-term fish

reproduction assay and discussion of the fish screening

assays detailed review paper. Presentation by

Environmental Protection Agency, Office of Research

and Development, National Health and Environmental

Effects Research Laboratory scientists to National

Advisory Council for Environmental Policy and

Technology’s Endocrine Disruptor Methods Validation

Subcommittee (EDMVS) Third Plenary Meeting, March

25-27, 2002.

7. Argus. 1998. Oral (drinking water) two-generation (one

litter per generation) reproduction study of ammonium

perchlorate in rats. Argus Research Laboratories Inc.

(Horsham, PA) Protocal no, 1416-001.

8. Ash M, Ash I, eds. 2000.Handbook of Industrial

Chemical Additives-Second Edition. Synapse

Information Resources.

9. Ashley DL, Bonin MA, Cardinali FL, McCraw JM, Wooten

JV. 1994. Blood concentrations of volatile organic

compounds in a nonoccupationally exposed US

population and in groups with suspected exposure. Clin

Chem 40:1401-4.


Registry). 2000. Toxicological profile for polychlorinated

biphenyls (PCBs): Health effects chapter. Available



Registry). 2002a. Toxicological profile for DDT, DDE,

DDD: Health effects chapter. Available online at




48

hexachlorobenzene: Health effects chapter.


13. Auer C. 2000. May 16, 2000 Email message from

Charles Auer (EPA) to OECD. EPA administrative record

number AR226-0629.

14. Bergstrom R, Adami HO, Mohner M, Zatonski W,

Storm H, Ekbom A, Tretli S, Teppo L, Akre O, Hakulinen

T. 1996. Increase in testicular cancer incidence in six

European countries: a birth cohort phenomenon. J Natl

Cancer Inst 88:727-33.

15. Bevan CL, Porter DM, Prasad A, Howard MJ,

Henderson LP. 2002. Environmental estrogens alter

early development in Xenopus laevis. Environ Health

Perspect online October 28, 2002.

16. Blount BC, Silva MJ, Caudill SP, Needham LL, Pirkle

JL, Sampson EJ, Lucier GW, Jackson RJ, Brock JW.

2000. Levels of seven urinary phthalate metabolites in

a human reference population. Environ Health Perspect

108:979-82.

17. Bove FJ, Fulcomer MC, Klotz JB, Esmart J, Dufficy EM,

Savrin JE. 1995. Public drinking water contamination

and birth outcomes. Am J Epidemiol 141:850-62.

18. Burdock G, ed. 1994.Fenaroli's Handbook of Flavor

Ingredients, Volume II, 3rd Edition. Ann Arbor, MI:CRC

Press.

19. Byrd RS. 2002. The Epidemiology of Autism in

California: A Comprehensive Pilot Study. Available

online at

http://mindinstitute.ucdmc.ucdavis.edu/news/study_fin

al.pdf.

20. CDC (Centers for Disease Control and Prevention ).

2002. National Report on Human Exposure to

49

Environmental Chemicals. Frequently Asked Questions.

Available online at

http://www.cdc.gov/nceh/dls/report/FAQs/#whyimport

ant. Accessed January 13, 2003.

21. CDC (Centers for Disease Control and Prevention).

2001. National Report on Human Exposure to

Environmental Chemicals. March 2001. Available online

at

http://www.cdc.gov/nceh/dls/report/PDF/CompleteRep

ort.pdf.

22. CDC (Centers for Disease Control). 1997. Facts on

Lead. Available online at

http://www.cdc.gov/nceh/lead/guide/1997/docs/factlea

d.htm.


Reproduction). 2000. NTP-CERHR Expert Panel Report

on Di-Isononyl Phthalate. National Toxicology Program

Center for the Evaluation of Risks to Human

Reproduction. Available online at

http://cerhr.niehs.nih.gov/news/newtabdehp.PDF.

24. Chakrabarti S, Fombonne E. 2001. Pervasive

developmental disorders in preschool children. Jama

285:3093-9.

25. Checkoway H, Nelson LM. 1999. Epidemiologic

approaches to the study of Parkinson's disease etiology.

Epidemiology 10:327-36.

26. Colerangle JB, Roy D. 1997. Profound effects of the

weak environmental estrogen-like chemical bisphenol a

on the growth of the mammary gland of Noble rats.

Journal of Steroid Biochemistry & Molecular Biology

60:153-160.

50

27. CTFA (Cosmetic Toiletry and Fragrance Association).

2002. International Cosmetic Ingredient Dictionary and

Handbook, 9th Edition.

28. Darnerud PO, Eriksen GS, Johannesson T, Larsen PB,

Viluksela M. 2001. Polybrominated diphenyl ethers:

occurrence, dietary exposure, and toxicology. Environ

Health Perspect 109 Suppl 1:49-68.

29. Dean TN, Kakkanaiah VN, Nagarkatti M, Nagarkatti

PS. 1990a. Immunosuppression by aldicarb of T cell

responses to antigen-specific and polyclonal stimuli

results from defective IL-1 production by the

macrophages. Toxicol Appl Pharmacol 106:408-17.

30. Dean TN, Selvan RS, Misra HP, Nagarkatti M,

Nagarkatti PS. 1990b. Aldicarb treatment inhibits the

stimulatory activity of macrophages without affecting

the T-cell responses in the syngeneic mixed lymphocyte

reaction. Int J Immunopharmacol 12:337-48.

31. Dessi-Fulgheri F, Porrini S, Farabollini F. 2002. Effects

of perinatal exposure to bisphenol A on play behavior of

female and male juvenile rats. Environ Health Perspect

110 Suppl 3:403-7

32. Dewailly E, Ayotte P, Bruneau S, Gingras S, Belles-

Isles M, Roy R. 2000. Susceptibility to infections and

immune status in Inuit infants exposed to

organochlorines. Environ Health Perspect 108:205-11.

33. Dickey C, Santella RM, Hattis D, Tang D, Hsu Y,

Cooper T, Young TL, Perera FP. 1997. Variability in

PAH-DNA adduct measurements in peripheral

mononuclear cells: implications for quantitative cancer

risk assessment. Risk Anal 17:649-56.

34. Easton MD, Luszniak D, Von der GE. 2002.

Preliminary examination of contaminant loadings in

51

farmed salmon, wild salmon and commercial salmon

feed. Chemosphere 46:1053-74.

35. Ecobichon DJ, Stephens DS. 1973. Perinatal

development of human blood esterases. Clin Pharmacol

Ther 14:41-7.

36. Engel LS, Checkoway H, Keifer MC, Seixas NS,

Longstreth WT, Jr., Scott KC, Hudnell K, Anger WK,

Camicioli R. 2001. Parkinsonism and occupational

exposure to pesticides. Occup Environ Med 58:582-9.

37. EPA (Environmental Protection Agency). 1972. DDT

ban takes effects. EPA press release. December 31,

1972. Available online at

http://www.epa.gov/history/topics/ddt/01.htm.

38. EPA (Environmental Protection Agency). 1996. PCBs:

Cancer Dose-Response Assessment and Application to

Environmental Mixtures EPA/600/P-96/001F.

September 1996. Available online at

http://www.epa.gov/ORD/WebPubs/pcb/.

39. EPA (Environmental Protection Agency). 1997a.

Chemistry Assistance Manual for Premanufacture

Notification Submitters. Office of Pollution Prevention

and Toxics. EPA 744-R-97-003. March 1997.


Source Ranking Database, Version 3.0. Developed by

Versar and Geomet for the Economics, Exposure and

Technology Division. Office of Pollution Prevention and

Toxics. U.S. Environmental Protection Agency.

41. EPA (Environmental Protection Agency). 1997c.

Source Ranking Database. EPA Office of Pollution

Prevention and Toxics, Economics, Exposure, and

Technology Division, Exposure Assessment Branch

(EAB).

52

42. EPA (Environmental Protection Agency). Analysis to

Support Standards for Lead in Paint, Dust, and Soil:

Volume 1 EPA 747-R-97-006, 1998a.


Chemical Hazard Data Availability Study: What Do We

Really Know About the Safety of High Production

Volume Chemicals? Office of Pollution Prevention and

Toxics. April 1998. Available online at

http://www.epa.gov/oppt/chemtest/hazchem.htm.

44. EPA (Environmental Protection Agency). Endocrine

Disruptor Screening and Testing Advisory Committee

(EDSTAC) Final Report. Washington DC, 1998c.

45. EPA (Environmental Protection Agency). 2000. Draft

dioxin reassessment. Available online at

http://cfpub.epa.gov/ncea/cfm/dioxreass.cfm?ActType

=default.

46. EPA (Environmental Protection Agency). 2001. Office

of Pollution Prevention and Toxics. TSCA Inventory

Reporting. Personal communication. March 5, 2001.

47. EPA (Environmental Protection Agency). 2002a. 2000

TRI Data Release. Available online at

http://www.epa.gov/tri/tridata/tri00/.

48. EPA (Environmental Protection Agency). 2002b. Fact

Sheets on New Active Ingredients. Available online at

http://www.epa.gov/opprd001/factsheets/factsht2.htm

and http://www.epa.gov/opprd001/factsheets/.

49. EPA (Environmental Protection Agency). 2002c.

Pesticides Industry Sales And Usage 1994 and 1995

Market Estimates. Available online at

http://www.epa.gov/oppbead1/pestsales/95pestsales/.

50. EPA (Environmental Protection Agency). 2002d.

Revised draft hazard assessment of PFOA and its salts

53

November 4, 2002 U.S. EPA Administrative Record

AR226.


Childhood Cancer - America's children and the

environment: A first view of available measures. Office

of Children's Health Protection. Available online at

http://yosemite.epa.gov/ochp/ochpweb.nsf/content/chil

dhood_cancer.htm. Accessed January 16, 2003.

52. Eriksson J, Forsen T, Tuomilehto J, Osmond C, Barker

D. 2000a. Fetal and childhood growth and hypertension

in adult life. Hypertension 36:790-4.

53. Eriksson JG, Forsen T, Tuomilehto J, Jaddoe VW,

Osmond C, Barker DJ. 2002. Effects of size at birth and

childhood growth on the insulin resistance syndrome in

elderly individuals. Diabetologia 45:342-8.

54. Eriksson JG, Forsen T, Tuomilehto J, Osmond C,

Barker DJ. 2000b. Early growth, adult income, and risk

of stroke. Stroke 31:869-74.

55. Eriksson JG, Forsen T, Tuomilehto J, Winter PD,

Osmond C, Barker DJ. 1999. Catch-up growth in

childhood and death from coronary heart disease:

longitudinal study. Bmj 318:427-31.

56. Eriksson JG, Forsen TJ. 2002. Childhood growth and

coronary heart disease in later life. Ann Med 34:157-

61.

57. EWG (Environmental Working Group). 2000. Rocket

Science. Available online at

http://www.ewg.org/reports/perchlorate/pr.html.

58. Facciolo RM, Alo R, Madeo M, Canonaco M, Dessi-

Fulgheri F. 2002. Early cerebral activities of the

environmental estrogen bisphenol A appear to act via

54

the somatostatin receptor subtype sst(2). Environ

Health Perspect 110 Suppl 3:397-402

59. Farabollini F, Porrini S, Dessi-Fulgherit F. 1999.

Perinatal exposure to the estrogenic pollutant bisphenol

A affects behavior in male and female rats. Pharmacol

Biochem Behav 64:687-94.

60. Farm Chemicals Handbook. 2001. Meister Pro

Information Resources.

61. FDA (Food and Drug Administration). 2002a. Chemical

Ingredients found in Cosmetics. Available online at

http://www.cfsan.fda.gov/~dms/cos-chem.html.

62. FDA (Food and Drug Administration). 2002b. EAFUS:

A Food Additive Database. Available online at

http://www.cfsan.fda.gov/~dms/eafus.html.

63. FDA (Food and Drug Administration). 2002c. The List

of "Indirect" Additives Used in Food Contact

Substances. Available online at

http://www.cfsan.fda.gov/~dms/opa-indt.html.

64. Folmar LC, Hemmer MJ, Denslow ND, Kroll K, Chen J,

Cheek A, Richman H, Meredith H, Grau EG. 2002. A

comparison of the estrogenic potencies of estradiol,

ethynylestradiol, diethylstilbestrol, nonylphenol and

methoxychlor in vivo and in vitro. Aquat Toxicol

60:101-10.

65. Forsen T, Eriksson J, Tuomilehto J, Reunanen A,

Osmond C, Barker D. 2000. The fetal and childhood

growth of persons who develop type 2 diabetes. Ann

Intern Med 133:176-82.

66. GAO (General Accounting Office). 1994. Toxic

Substances Control Act: Preliminary Observations on

Legislative Changes to Make TSCA More Effective

(Testimony, 07/13/94, GAO/T-RCED-94-263).

55

67. Gauderman WJ, Gilliland GF, Vora H, Avol E, Stram D,

McConnell R, Thomas D, Lurmann F, Margolis HG,

Rappaport EB, Berhane K, Peters JM. 2002. Association

between air pollution and lung function growth in

southern California children: results from a second

cohort. Am J Respir Crit Care Med 166:76-84.

68. Giesy JP, Kannan K. 2001. Global distribution of

perfluorooctane sulfonate in wildlife. Environ Sci

Technol 35:1339-42.

69. Giesy JP, Pierens SL, Snyder EM, Miles-Richardson S,

Kramer VJ, Snyder SA, Nichols KM, Villeneuve DA.

2000. Effects of 4-nonylphenol on fecundity and

biomarkers of estrogenicity in fathead minows

(Pimephales promelas). Environmental Toxicology &

Chemistry 19:1368-1377.

70. Ginsberg G, Hattis D, Sonawane B, Russ A, Banati P,

Kozlak M, Smolenski S, Goble R. 2002a. Evaluation of

child/adult pharmacokinetic differences from a

database derived from the therapeutic drug literature.


71. Ginsberg G, Smolenski S, Hattis D, Sonawane B.

2002b. Population distribution of aldehyde

dehydrogenase-2 genetic polymorphism: implications

for risk assessment. Regul Toxicol Pharmacol 36:297-

309.

72. Gladen BC, Rogan WJ. 1995. DDE and shortened

duration of lactation in a northern Mexican town. Am J

Public Health 85:504-8.

73. Godfrey KM, Barker DJ. 2001. Fetal programming and

adult health. Public Health Nutr 4:611-24.

74. Gruters A, Jenner A, Krude H. 2002. Long-term

consequences of congenital hypothyroidism in the era

56

of screening programmes. Best Pract Res Clin

Endocrinol Metab 16:369-82.

75. Gupta C. 2000. Reproductive malformation of the

male offspring following maternal exposure to

estrogenic chemicals. Proceedings of the Society of

Experimental Biology & Medicine 224:61-68.

76. Guy WS, Taves DR, Brey WS. Organic

fluorocompounds in human plasma: prevalance and

characterization. In: Biochemistry involving carbon-

fluorine bonds. A symposium sponsored by the Division

of Fluorine and Biological Chemistry at the 170th

meeting of the American Chemical Society. Chicago, IL.

August 26, 1975. Washington DC:American Chemical

Society, 1976;117 - 134.

77. Hajoui O, Flipo D, Mansour S, Fournier M, Krzystyniak

K. 1992. Immunotoxicity of subchronic versus chronic

exposure to aldicarb in mice. Int J Immunopharmacol

14:1203-11.

78. Hales CN, Barker DJ. 2001. The thrifty phenotype

hypothesis. Br Med Bull 60:5-20.

79. Hardell L, van Bavel B, Lindstršm G, Carlberg M,

Dreifaldt AC, Wijkstršm H, Starkhammar H, Eriksson M,

Hallquist A, Kolmert T. in press. Increased

Concentrations of Polychlorinated Biphenyls,

Hexachlorobenzene and Chlordanes in Mothers to Men

with Testicular Cancer. Environ Health Perspect [Online

19 December 2002].

80. Harris CA, Santos EM, Janbakhsh A, Pottinger TG,

Tyler CR, Sumpter JP. 2001. Nonylphenol affects

gonadotropin levels in the pituitary gland and plasma of

female rainbow trout. Environmental Science &

Technology 35:2909-2916.

57

81. Hattis D, Ginsberg G, Sonawane B, Smolenski S, Russ

A, Kozlak M, Goble R. in press. Differences in

pharmacokinetics between children and adults--II.

Childrens' variability in drug elimination half-lives and

in some parameters needed for physiologically based

pharmacokinetic modeling. Risk Anal.

82. Hattis D, Russ A, Goble R, Banati P, Chu M. 2001.

Human interindividual variability in susceptibility to

airborne particles. Risk Anal 21:585-99.

83. Hayes T, Haston K, Tsui M, Hoang A, Haeffele C, Vonk

A. 2002a. Herbicides: Feminization of male frogs in the

wild. Nature 419:895-6.

84. Hayes TB, Collins A, Lee M, Mendoza M, Noriega N,

Stuart AA, Vonk A. 2002b. Hermaphroditic,

demasculinized frogs after exposure to the herbicide

atrazine at low ecologically relevant doses. Proc Natl

Acad Sci U S A 99:5476-80.

85. Hayes TB, Haston K, Tsui M, Hoang A, Haeffele C,

Vonk A. in press. Atrazine-induced hermaphroditism at

0.1 ppb in American Leopard frogs (Rana pipiens):

Laboratory and field evidence. Environ Health Perspect.

86. Heinrich A. 2000. The Pherolist. Available online at

http://www.nysaes.cornell.edu/fst/faculty/acree/pheron

et/cpds/14al.html.

87. Herman-Giddens ME, Slora EJ, Wasserman RC,

Bourdony CJ, Bhapkar MV, Koch GG, Hasemeier CM.

1997. Secondary sexual characteristics and menses in

young girls seen in office practice: a study from the

Pediatric Research in Office Settings network. Pediatrics

99:505-12.

88. Honma S, Suzuki A, Buchanan DL, Katsu Y, Watanabe

H, Iguchi T. 2002. Low dose effect of in utero exposure

58

to bisphenol A and diethylstilbestrol on female mouse

reproduction. Reprod Toxicol 16:117-22

89. Hooper K, McDonald TA. 2000. The PBDEs: an

emerging environmental challenge and another reason

for breast-milk monitoring programs. Environ Health

Perspect 108:387-92.

90. Hosie S, Loff S, Witt K, Niessen K, Waag KL. 2000. Is

there a correlation between organochlorine compounds

and undescended testes? Eur J Pediatr Surg 10:304-9.

91. Howdeshell KL, Hotchkiss AK, Thayer KA,

Vandenbergh JG, vom Saal FS. 1999. Exposure to

bisphenol A advances puberty. Nature 401:763-4.

92. Hulla JE, Miller MS, Taylor JA, Hein DW, Furlong CE,

Omiecinski CJ, Kunkel TA. 1999. Symposium overview:

the role of genetic polymorphism and repair deficiencies

in environmental disease. Toxicol Sci 47:135-43.

93. Ikezuki Y, Tsutsumi O, Takai Y, Kamei Y, Taketani Y.

2002. Determination of bisphenol A concentrations in

human biological fluids reveals significant early prenatal

exposure. Hum Reprod 17:2839-41.

94. IPCS (International Programme on Chemical Safety).

1989. Environmental Health Criteria 84: DDT and its

derivatives - environmental aspects. World Health

Organization - International Programme on Chemical

Safety. Available online at

http://www.inchem.org/pages/ehc.html.

95. IRIS (Integrated Risk Information System). 2003a.

Dibutyl phthalate (CASRN 84-74-2): Reference dose for

chronic oral exposure (RfD) - last revised in 1990.

Available online at http://toxnet.nlm.nih.gov/.

59

96. IRIS (Integrated Risk Information System). 2003b.

Methoxychlor: CASRN: 72-43-5. Available online at

http://toxnet.nlm.nih.gov/.

97. Jacobson JL, Jacobson SW. 1996. Intellectual

impairment in children exposed to polychlorinated

biphenyls in utero. N Engl J Med 335:783-9.

98. Jacobson JL, Jacobson SW. 2002. Association of

prenatal exposure to an environmental contaminant

with intellectual function in childhood. J Toxicol Clin

Toxicol 40:467-75.

99. Jacobson JL, Janisse J, Banerjee M, Jester J, Jacobson

SW, Ager JW. 2002. A benchmark dose analysis of

prenatal exposure to polychlorinated biphenyls. Environ

Health Perspect 110:393-8.

100. Kagawa J. 2002. Health effects of diesel exhaust

emissions-a mixture of air pollutants of worldwide

concern. Toxicology 181-182:349-53.

101. Kawai K, Nozaki T, Nishikata H, Aou S, Takii M, Kubo

C. in press. Aggressive behavior and serum

testosterone concentration during the maturation

process of male mice: the effects of fetal exposure to

bisphenol A. Environ Health Perspect.

102. Kirschner. 1996. Growth Of Top 50 Chemicals Slowed

In 1995 From Very High 1994 Rate. Chemical &

Engineering News, April 8, 1996. Available online at

http://pubs.acs.org/hotartcl/cenear/960408/growth.ht

ml.

103. Klassen CD, ed. 1996.Casarrett & Doull's Toxicology:

The Basic Science of Poisons:The McGraw-Hill

Companies, Inc.

104. Kloas W, Lutz I, Einspanier R. 1999. Amphibians as a

model to study endocrine disruptors: II. Estrogenic

60

activity of environmental chemicals in vitro and in vivo.

Science of the Total Environment 225:59-68.

105. Kolpin DW, Furlong ET, Meyer MT, Thurman EM,

Zaugg SD, Barber LB, Buxton HT. 2002.

Pharmaceuticals, hormones, and other organic

wastewater contaminants in U.S. streams, 1999-2000:

a national reconnaissance. Environ Sci Technol

36:1202-11.

106. Kopp MV, Bohnet W, Frischer T, Ulmer C, Studnicka

M, Ihorst G, Gardner C, Forster J, Urbanek R, Kuehr J.

2000. Effects of ambient ozone on lung function in

children over a two-summer period. Eur Respir J

16:893-900.

107. Kwak H, Bae M, Lee M, Lee Y, Lee B, Kang K, Chae C,

Sung H, Shin J, Kim J, Mar W, Sheen Y, Cho M. 2001.

Effects of nonylphenol, bisphenol A, and their mixture

on the viviparous swordfish (Xiphophorus helleri).

Environmental Science & Technology 20:787-795.

108. Lippman M, Bolan G, Huff K. 1976. The effects of

estrogens and antiestrogens on hormone-responsive

human breast cancer in long-term tissue culture.

Cancer Res 36:4595-601.

109. Longnecker MP, Klebanoff MA, Zhou H, Brock JW.

2001. Association between maternal serum

concentration of the DDT metabolite DDE and preterm

and small-for-gestational-age babies at birth. Lancet

358:110-4.

110. Makris S, Raffaele K, Sette W, Seed J. 1998. A

Retrospective Analysis of Twelve Developmental

Neurotoxicity Studies Submitted to USEPA Office of

Prevention, Pesticides and Toxic Substances (OPPTS).

111. Markey CM, Luque EH, Munoz de Toro M,

Sonnenschein C, Soto AM. 2001. In utero exposure to

61

bisphenol A alters the development and tissue

organization of the mouse mammary gland. Biology of

Reproduction 65:1215-1223.

112. McKiernan JM, Goluboff ET, Liberson GL, Golden R,

Fisch H. 1999. Rising risk of testicular cancer by birth

cohort in the United States from 1973 to 1995. J Urol

162:361-3.

113. Meironyte D, Noren K, Bergman A. 1999. Analysis of

polybrominated diphenyl ethers in Swedish human

milk. A time-related trend study, 1972-1997. J Toxicol

Environ Health A 58:329-41.

114. Merck & Co. Inc. The Merck Manual of Diagnosis and

Therapy. Section 1. Nutritional Disorders: Chapter 3.

Vitamin Deficiency, Dependency, and Toxicity, 2002.

115. Mocarelli P, Brambilla P, Gerthoux PM, Patterson DG,

Jr., Needham LL. 1996. Change in sex ratio with

exposure to dioxin. Lancet 348:409.

116. Mocarelli P, Gerthoux PM, Ferrari E, Patterson DG, Jr.,

Kieszak SM, Brambilla P, Vincoli N, Signorini S,

Tramacere P, Carreri V, Sampson EJ, Turner WE,

Needham LL. 2000. Paternal concentrations of dioxin

and sex ratio of offspring. Lancet 355:1858-63.

117. Mylchreest E, Sar M, Cattley RC, Foster PM. 1999.

Disruption of androgen-regulated male reproductive

development by di(n-butyl) phthalate during late

gestation in rats is different from flutamide. Toxicol

Appl Pharmacol 156:81-95.

118. Mylchreest E, Wallace DG, Cattley RC, Foster PM.

2000. Dose-dependent alterations in androgen-

regulated male reproductive development in rats

exposed to Di(n-butyl) phthalate during late gestation.


62

119. Nagel SC, vom Saal FS, Thayer KA, Dhar MG,

Boechler M, Welshons WV. 1997. Relative binding

affinity-serum modified access (RBA-SMA) assay

predicts the relative in vivo bioactivity of the

xenoestrogens bisphenol A and octylphenol.

Environmental Health Perspectives 105:70-76.

120. NAS (National Academy of Sciences). 2000.

Toxicological Effects of Methylmercury. Washington DC,

National Academy Press Available online at

http://www.nap.edu/books/0309071402/html/.

121. NCI (National Cancer Institute (NCI). 2000. Testicular

Cancer: Questions and Answers. Available online at

http://cis.nci.nih.gov/fact/6_34.htm. Accessed January

16, 2003.

122. NCI (National Cancer Institute). 1996. SEER Cancer

Statistics Review. 1973-1996. Available online at

http://www.seer.ims.nci.nih.gov/Publications/CSR1973

_1996/.

123. NCI (National Cancer Institute). 1997. SEER Cancer

Statistics Review. 1973-1997. Available online at

http://www.seer.ims.nci.nih.gov/Publications/CSR1973

_1997/.

124. NCI (National Cancer Institute). 2002. Overview of

the SEER Cancer Statistics Review, 1973-1999

(overview in a single PDF file). Available online at

http://seer.cancer.gov/csr/1973_1999/sections.html#o

verview.

125. NIH (National Institutes of Health). 2002a. National

Library of Medicine's Special Information Service's

ChemIDplus. Available online at

http://chem.sis.nlm.nih.gov/chemidplus/.

63

126. NIH (National Institutes of Health). 2002b. National

Library of Medicine's Special Information Service’s

TOXNET. Available online at http://toxnet.nlm.nih.gov.

127. NTP (National Toxicology Program). 2002. 10th

Report on Carcinogens.

http://ehp.niehs.nih.gov/roc/toc10.html.

128. OECD (Organization for Economic Co-Operation and

Development). 2002. Draft Assessment of

perfluorooctane sulfonate (PFOS) and its salts:

Complete assessment. September 16, 2002

ENV/JM/RD(2002)17.

129. OEHHA (Office of Environmental Health Hazard

Assessment). 2002. Chemicals known to the State to

cause cancer or reproductive toxicity. State of

California Environmental Protection Agency. Available

online at

http://www.oehha.ca.gov/prop65/prop65_list/62802list

A.html.

130. Olsen GW, Burris JM, Lundberg JK, Hansen KJ, Mandel

JH, Zobel LR. Final Report: Identification of

fluorochemicals in human sera. III. Pediatric

participants in a group A streptococci clinical trial

investigation U.S. EPA Administrative Record AR226-

1085: Study conducted by Corporate Occupational

Medicine, Medical Department, 3M Company, 220-3W-

05, St. Paul, MN, 2002.

131. Olson LJ, Erickson BJ, Hinsdill RD, Wyman JA, Porter

WP, Binning LK, Bidgood RC, Nordheim EV. 1987.

Aldicarb immunomodulation in mice: an inverse dose-

response to parts per billion levels in drinking water.

Arch Environ Contam Toxicol 16:433-9.

132. Ong KK, Dunger DB. 2002. Perinatal growth failure:

the road to obesity, insulin resistance and

64

cardiovascular disease in adults. Best Pract Res Clin

Endocrinol Metab 16:191-207.

133. Palanza PL, Howdeshell KL, Parmigiani S, vom Saal

FS. 2002. Exposure to a low dose of bisphenol A during

fetal life or in adulthood alters maternal behavior in

mice. Environ Health Perspect 110 Suppl 3:415-22.

134. Paulozzi LJ. 1999. International trends in rates of

hypospadias and cryptorchidism. Environ Health

Perspect 107:297-302.

135. Paulozzi LJ, Erickson JD, Jackson RJ. 1997.

Hypospadias trends in two US surveillance systems.

Pediatrics 100:831-4.

136. Perera F, Rauh V, Tsai WY, Kinney P, Camann D, Barr

D, Bernert T, Garfinkel R, Tu Y-H, Diaz D, Dietrich J,

Whyatt RM. 2003. Effects of transplacental exposure to

environmental pollutants on birth outcomes in a mult-

ethnic population. Environ Health Perspect 111:201-

205.

137. Pope CA, 3rd, Burnett RT, Thun MJ, Calle EE, Krewski

D, Ito K, Thurston GD. 2002. Lung cancer,

cardiopulmonary mortality, and long-term exposure to

fine particulate air pollution. Jama 287:1132-41.

138. Pottenger LH, Domoradzki JY, Markham DA, Hansen

SC, Cagen SZ, Waechter JM, Jr. 2000. The relative

bioavailability and metabolism of bisphenol A in rats is

dependent upon the route of administration. Toxicol Sci

54:3-18.

139. Ramos JG, Varayoud J, Sonnenschein C, Soto AM,

Mu–oz de Toro M, Luque EH. 2001. Prenatal exposure

to low doses of bisphenol A alters the periductal stroma

and glandular cell function in the rat ventral prostate.

Biology of Reproduction 65:1271-1277.

65

140. Renner R. 2001. At odds over PBDEs. Environ Sci

Technol. November 28, 2001:Online Policy News.

141. Robison LM, Sclar DA, Skaer TL, Galin RS. 1999.

National trends in the prevalence of attention-

deficit/hyperactivity disorder and the prescribing of

methylphenidate among school-age children: 1990-

1995. Clin Pediatr (Phila) 38:209-17.

142. Robison LM, Skaer TL, Sclar DA, Galin RS. 2002. Is

attention deficit hyperactivity disorder increasing

among girls in the US? Trends in diagnosis and the

prescribing of stimulants. CNS Drugs 16:129-37.

143. Rudel RA, Brody JG, Spengler JD, Vallarino J, Geno

PW, Sun G, Yau A. 2001. Identification of selected

hormonally active agents and animal mammary

carcinogens in commercial and residential air and dust

samples. J Air Waste Manag Assoc 51:499-513.

144. Sakaue M, Ohsako S, Ishimura R, Kurosawa S,

Kurohmaru M, Hayashi Y, Aoki Y, Yonemoto J, Tohyama

C. 2001. Bisphenol-A affects spermatogenesis in the

adult rat even at a low dose. J Occup Health 43:185-

190.

145. Salonen JT, Nyyssonen K, Salonen R. 1995. Fish

intake and the risk of coronary disease. N Engl J Med

333:937; author reply 938.

146. Sams C, Mason HJ. 1999. Detoxification of

organophosphates by A-esterases in human serum.

Hum Exp Toxicol 18:653-8.

147. SCF (Scientific Committee on Food). 2002. Opinion of

the Scienfic Committee on Food on Bisphenol A.

European Commission Health & Consumer Protection

Directorate – Scientific Committee on Food. May 3,

2002.

66

148. Schettler T, Stein J, Reich F, Valenti M. In Harm's

Way: Toxic Threats to Child Development: Greater

Boston Physicians for Social Responsibility, 2000.

149. Schonfelder G, Flick B, Mayr E, Talsness C, Paul M,

Chahoud I. 2002a. In utero exposure to low doses of

bisphenol A lead to long-term deleterious effects in the

vagina. Neoplasia 4:98-102.

150. Schonfelder G, Wittfoht W, Hopp H, Talsness C, Paul

M, Chahoud I. 2002b. Parent bisphenol A accumulation

in the human maternal-fetal-placental unit. Environ

Health Perspect 110:A703-A707.

151. Schwartz J. Gestational exposure to perchlorate is

associated with measures of decreased thyroid function

in a population of California neonates (thesis).

Berkeley, CA:University of California, 2001.

152. Selvan RS, Dean TN, Misra HP, Nagarkatti PS,

Nagarkatti M. 1989. Aldicarb suppresses macrophage

but not natural killer (NK) cell-mediated cytotoxicity of

tumor cells. Bull Environ Contam Toxicol 43:676-82.

153. She J, Petreas M, Winkler J, Visita P, McKinney M,

Kopec D. 2002. PBDEs in the San Francisco Bay Area:

measurements in harbor seal blubber and human

breast adipose tissue. Chemosphere 46:697-707.

154. Shelby MD, Newbold RR, Tully DB, Chae K, Davis VL.

1996. Assessing environmental chemicals for

estrogenicity using a combination of in vitro and in vivo

assays. Environ Health Perspect 104:1296-300.

155. Shirazi MA, Erickson BJ, Hinsdill RD, Wyman JA. 1990.

An analysis of risk from exposure to aldicarb using

immune response of nonuniform populations of mice.

Arch Environ Contam Toxicol 19:447-56.

67

156. Sorensen N, Murata K, Budtz-Jorgensen E, Weihe P,

Grandjean P. 1999. Prenatal methylmercury exposure

as a cardiovascular risk factor at seven years of age.

Epidemiology 10:370-5.

157. Stettler N, Bovet P, Shamlaye H, Zemel BS, Stallings

VA, Paccaud F. 2002. Prevalence and risk factors for

overweight and obesity in children from Seychelles, a

country in rapid transition: the importance of early

growth. Int J Obes Relat Metab Disord 26:214-9.

158. Swan SH, Brazil C, Brobnis EZ, Liu F, Kruse RL, Hatch

M, Redmon JB, Wang C, Overstreet JW, and the Study

for Future Families Research Group. in press January

2003. Geographic differences in semen quality of fertile

US males. Environ Health Perspect.

159. Swan SH, Elkin EP, Fenster L. 2000. The question of

declining sperm density revisited: an analysis of 101

studies published 1934-1996. Environ Health Perspect

108:961-6.

160. Sydbom A, Blomberg A, Parnia S, Stenfors N,

Sandstrom T, Dahlen SE. 2001. Health effects of diesel

exhaust emissions. Eur Respir J 17:733-46.

161. Tabata A, Kashiwada S, Ohnishi Y, Ishikawa H,

Miyamoto N, Itoh M, Magara Y. 2001. Estrogenic

influences of estradiol-17 beta, p-nonylphenol and bis-

phenol-A on Japanese medaka (Oryzias latipes) at

detected environmental concentrations. Water Sci

Technol 43:109-116.

162. Takai Y, Tsutsumi O, Ikezuki Y, Hiroi H, Osuga Y,

Momoeda M, Yano T, Taketani Y. 2000a. Estrogen

receptor-mediated effects of a xenoestrogen, bisphenol

A, on preimplantation mouse embryos. Biochem

Biophys Res Commun 270:918-921.

68

163. Takai Y, Tsutsumi O, Ikezuki Y, Kamei Y, Osuga Y,

Yano T, Taketan Y. 2000b. Preimplantation exposure to

bisphenol A advances postnatal development.

Reproductive Toxicology 15.

164. Tavera-Mendoza L, Ruby S, Brousseau P, Fournier M,

Cyr D, Marcogliese D. 2002a. Response of the

amphibian tadpole (Xenopus laevis) to atrazine during

sexual differentiation of the testis. Environ Toxicol

Chem 21:527-31.

165. Tavera-Mendoza L, Ruby S, Brousseau P, Fournier M,

Cyr D, Marcogliese D. 2002b. Response of the

amphibian tadpole Xenopus laevis to atrazine during

sexual differentiation of the ovary. Environ Toxicol

Chem 21:1264-7.

166. Thornton JW, McCally M, Houlihan J. 2000.

Biomonitoring of industrial pollutants: health and policy

implications of the chemical body burden. Public Health

Reports 117:1-15.

167. Thornton JW, McCally M, Houlihan J. 2002.

Biomonitoring of industrial pollutants: health and policy

implications of the chemical body burden. Public Health

Rep 117:315-23.

168. TIACT (Texas Institute for Advancement of Chemical

Technology). Chemical hormesis: beneficial effects at

low exposures, adverse effects at high exposures.

College Station, TX, 1998.

169. Toppari J, Larsen JC, Christiansen P, Giwercman A,

Grandjean P, Guillette LJ, Jr., Jegou B, Jensen TK,

Jouannet P, Keiding N, Leffers H, McLachlan JA, Meyer

O, Muller J, Rajpert-De Meyts E, Scheike T, Sharpe R,

Sumpter J, Skakkebaek NE. 1996. Male reproductive

health and environmental xenoestrogens. Environ

Health Perspect 104 Suppl 4:741-803.

69

170. Tripathy D, Benz CC. Hormones and Cancer. In: Basic

and Clinical Endocrinology (Greenspan FS, Strewler GJ,

eds). Stamford, CT:Appleton & Lange, 1997;724-740.

171. Ulrich EM, Caperell-Grant A, Jung SH, Hites RA,

Bigsby RM. 2000. Environmentally relevant

xenoestrogen tissue concentrations correlated to

biological responses in mice. Environ Health Perspect

108:973-7.

172. USGS (United States Geological Survey). 2002.

National Reconnaissance of Pharmaceuticals,

Hormones, and Other Organic Wastewater

Contaminants in Streams of the U.S., 1999-2000.

Available online at

http://toxics.usgs.gov/regional/emc_surfacewater.html.

173. vom Saal FS, Cooke PS, Buchanan DL, Palanza P,

Thayer KA, Nagel SC, Parmigiani S, Welshons WV.

1998. A physiologically based approach to the study of

bisphenol A and other estrogenic chemicals on the size

of reproductive organs, daily sperm production, and

behavior. Toxicology & Industrial Health 14:239-60.

174. vom Saal FS, Timms BG, Montano MM, Palanza P,

Thayer KA, Nagel SC, Dhar MD, Ganjam VK, Parmigiani

S, Welshons WV. 1997. Prostate enlargement in mice

due to fetal exposure to low doses of estradiol or

diethylstilbestrol and opposite effects at high doses.

Proc Natl Acad Sci U S A 94:2056-61.

175. Wade MG, Foster WG, Younglai EV, McMahon A,

Leingartner K, Yagminas A, Blakey D, Fournier M,

Desaulniers D, Hughes CL. 2002a. Effects of subchronic

exposure to a complex mixture of persistent

contaminants in male rats: systemic, immune, and

reproductive effects. Toxicol Sci 67:131-43.

70

176. Wade MG, Parent S, Finnson KW, Foster W, Younglai

E, McMahon A, Cyr DG, Hughes C. 2002b. Thyroid

toxicity due to subchronic exposure to a complex

mixture of 16 organochlorines, lead, and cadmium.


177. Waller K, Swan SH, DeLorenze G, Hopkins B. 1998.

Trihalomethanes in drinking water and spontaneous

abortion. Epidemiology 9:134-40.

178. Weidner IS, Moller H, Jensen TK, Skakkebaek NE.

1998. Cryptorchidism and hypospadias in sons of

gardeners and farmers. Environ Health Perspect

106:793-6.

179. Welshons WV, Nagel SC, Thayer KA, Judy BM, Vom

Saal FS. 1999. Low-dose bioactivity of xenoestrogens in

animals: fetal exposure to low doses of methoxychlor

and other xenoestrogens increases adult prostate size

in mice. Toxicol Ind Health 15:12-25.

180. Wetherill YB, Petre CE, Monk KR, Puga A, Knudsen

KE. 2002. The xenoestrogen bisphenol A induces

inappropriate androgen receptor activation and

mitogenesis in prostatic adenocarcinoma cells.

Molecular Cancer Therapeutics 1:515-524.

181. Wine RN, Li LH, Barnes LH, Gulati DK, Chapin RE.

1997. Reproductive toxicity of di-n-butylphthalate in a

continuous breeding protocol in Sprague-Dawley rats.

Environ Health Perspect 105:102-7.

182. Yang JZ, Agarwal SK, Foster WG. 2000. Subchronic

exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin

modulates the pathophysiology of endometriosis in the

cynomolgus monkey. Toxicol Sci 56:374-81.

183. Zito JM, Safer DJ, dosReis S, Gardner JF, Boles M,

Lynch F. 2000. Trends in the prescribing of

71

psychotropic medications to preschoolers. Jama

283:1025-30.

184. Zoeller TR, Dowling AL, Herzig CT, Iannacone EA,

Gauger KJ, Bansal R. 2002. Thyroid hormone, brain

development, and the environment. Environ Health

Perspect 110 Suppl 3:355-61.

WHAT ABOUT SKIN CARE PRODUCTS … ARE THEY SAFE?

FDA CANNOT REQUIRE COMPANIES TO DO SAFETY

TESTING OF THEIR COSMETIC PRODUCTS BEFORE

MARKETING. — FDA OFFICE OF COSMETICS AND COLORS

(FDA 1995)

Most consumers would be surprised to learn that the government

does not require health studies or pre-market testing for cosmetics

and other personal care products before they are sold. According to

the government agency that regulates cosmetics, the FDA's Office

of Cosmetics and Colors, "...a cosmetic manufacturer may use

almost any raw material as a cosmetic ingredient and market the

product without an approval from FDA" (FDA 1999).

The toxicity of product ingredients is scrutinized almost exclusively

by a self-policing industry safety committee, the Cosmetic

Ingredient Review (CIR) panel. Because testing is voluntary and

controlled by the manufacturers, many ingredients in cosmetics

products are not safety tested at all. Environmental Working

Group's analysis of industry and government sources shows that:

• Eighty-nine (89) percent of 10,500 ingredients used in

personal care products have not been evaluated for

safety by the CIR, the FDA, nor any other publicly

accountable institution (FDA 2000, CIR 2003).

72

The absence of government oversight for this $35 billion industry

leads to companies routinely marketing products with ingredients

that are poorly studied, not studied at all, or worse, known to pose

potentially serious health risks.

The Environmental Working Group's (EWG's) six-month computer

investigation into the health and safety assessments on more than

10,000 personal care product ingredients found major gaps in the

regulatory safety net for these products. To help people use what

we learned we developed an online rating system that ranks

products on their potential health risks and the absence of basic

safety evaluations. The core of the analysis compares ingredients in

7,500 personal care products against government, industry, and

academic lists of known and suspected chemical health hazards.

Our analysis shows that ingredients in cosmetics range from

essentially harmless components like table salt and oatmeal, to

chemicals known to cause cancer in humans. Notably, natural

ingredients are no more likely to have been assessed for safety

than synthetic chemicals. Individual ingredients vary tremendously

in their ability to soak through the skin. Some absorb in only

miniscule amounts, while others can quite easily penetrate the skin

to the blood vessels below. Few individual ingredients pose

excessive risks, but most people use many products in the course

of a day, so it well may be that these risks are adding up. A survey

of 2,300 people conducted as part of this research effort shows that

the average adult uses 9 personal care products each day, with 126

unique chemical ingredients. More than a quarter of all women and

one of every 100 men use at least 15 products daily.

Little research is available to document the safety or health risks of

low-dose repeated exposures to chemical mixtures like those in

personal care products, but the absence of data should never be

mistaken for proof of safety. The more we study low dose

exposures, the more we understand that they can cause adverse

effects ranging from the subtle and reversible, to effects that are

more serious and permanent.

73

Overall, our investigation of product safety shows cause for

concern, not alarm. Much more study is needed to understand the

contribution of exposures from personal care products to current

human health trends.

EWG safety assessment of 7,500 personal care product labels,

documented in this web-based review, shows that:

• Just 28 of the 7,500 products we analyzed have been

fully assessed for safety by the cosmetic industry's self-

regulating panel, the Cosmetic Ingredient Review (CIR).

All other products — 99.6 percent of those examined —

contain one or more ingredients never assessed for

potential health impacts by the CIR. This panel, run and

funded by the cosmetic industry's trade association, is

billed as the organization that "thoroughly reviews and

assesses the safety of ingredients used in cosmetics" on

behalf of the industry (CIR 2004). The government does

not systematically review the safety of personal care

products and has banned or restricted just nine of the

more than 10,000 ingredients used in personal care

products.

• One of every 120 products on the market contains

ingredients certified by government authorities as known

or probable human carcinogens, including shampoos,

lotions, make-up foundations, and lip balms

manufactured by Almay, Neutrogena, Grecian Formula,

and others. An astonishing one-third of all products

contain one or more ingredients classified as possible

human carcinogens.

• Seventy-one hair dye products contain ingredients

derived from carcinogenic coal tar. These products have

all been granted a specific exemption from federal rules

that deem products to be adulterated when they contain

ingredients that can harm human health. Coal tar

74

containing products include dyes made by Clairol,

Revlon, L'Oreal, and others. Coal tar hair dyes are one of

the few products for which FDA has issued consumer

advice on the benefits of reducing use, in this case as a

way to potentially "reduce the risk of cancer" (FDA

1993).

• Fifty-five percent of all products assessed contain

“penetration enhancers,” ingredients that can increase a

product's penetration through the skin and into the

bloodstream, increasing consumers' exposures to other

ingredients as well. We found 50 products containing

penetration enhancers in combination with known or

probable human carcinogens.

• Nearly 70 percent of all products contain ingredients that

can be contaminated with impurities linked to cancer

and other health problems. Studies by FDA and

European agencies show that these impurities are

common, in some cases occurring in nearly half of all

products tested (FDA 1996, DTI 1998). Some

manufacturers buy ingredients certified by an

independent organization called United States

Pharmacopeia (USP). These ingredients may contain

lower levels of harmful impurities, but the criteria for

certification are not public. There are no federal

standards for ingredient purity. While it seems likely that

some companies purchase or manufacture refined,

purified ingredients, it is equally likely that many do not.

Consumers and government health officials have no way

to know.

• Fifty-four products violate recommendations for safe use

set by the industry's self-regulating Cosmetic Ingredient

Review board. Most of these products contain

ingredients found unsafe for the intended use of the

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product they are found in. Examples include ingredients

found unsafe for use in baby products but used in diaper

cream, ingredients found unsafe for use on injured or

damaged skin contained in products marketed

specifically for use on chapped and injured skin, and

ingredients not safe for sprays but found in spray

products. Brand name products found in violation of

industry recommendations include Neutrogena, Desitin,

Herbal Essences, and Rite Aid.

• In its 67-year history of monitoring cosmetic safety, FDA

has banned or restricted just nine personal care product

ingredients (FDA 2000). In its review of 1,175

ingredients, the industry's safety panel has found just

nine ingredients (a different nine) unsafe for use in

cosmetics (CIR 2003). By contrast, 450 ingredients are

banned for use in cosmetics in the European Union,

although the vast majority of these have never been

used by the industry. The regulatory vacuum in the U.S.

gives cosmetic companies tremendous leeway in

selecting ingredients, while it transfers potentially

significant and largely unnecessary health risks to the

users of the products.

Many leading cosmetics companies may have failed to formulate

their products with customer health as a top concern. According to

an EWG Safety Assessment Rating for personal care products, the

products with the highest health concerns in 25 different product

categories contain ingredients linked to cancer, pregnancy

problems, and other potential health issues

(See table below: Scores range from 0 to 10, with 10 being of

highest health concern. You may click on various products for

information):

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Product Category Score

1 Clairol Natural Instincts Haircolor, Level 2, Sahara 02

Hair Dye 10.0

2 Elizabeth Arden Ceramide Plump Perfect Moisture Cream SPF 30

Facial Moisturizer/Treatment

9.6

3 Skin Success Eventone Fade Cream, For Oily Skin

Anti-Aging Treatment 9.5

4 Klear Action Acne Treatment System

Acne Treatment/Medication

9.4

5 Nivea for Men After Shave Balm, Mild with Bonus Face Wash

Shaving Products 9.3

6 OPI Nail Treatments Nail Envy, Natural Nail Strengthener

Nail Treatments 9.3

7 St. Ives Apricot Scrub, Gentle For Sensitive Skin

Exfoliator 9.3

8 Neutrogena T-Gel Shampoo, Stubborn Itch Control

Shampoo 9.3

9 NARS Balanced Foundation Foundation 9.3

10 Dove Face Care Essential Nutrients, Cream Cleanser

Facial Cleanser 9.2

11 DDF Anti-Wrinkle Eye Renewal Treatment

Eye Treatment 9.2

12 Revlon SkinLights Face Illuminator Powder Bronzer,

Powder 9.2

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Warm Light

13 Dial Dial Antibacterial Hand Soap with Vitamin E Moisture Beads

Liquid Hand Soap 9.2

14 Maybelline Full 'N Soft Mascara

Mascara 9.2

15 Alpha Hydrox Moisturizing Body Wash, Sea Mist

Body Wash/Cleansers 9.2

16 Nioxin Bionutrient Actives Scalp Therapy, for Normal Hair

Hair Regrowth Treatment 9.1

17 Igia Epil-Stop & Foam, 6-in-1 Hair Removal System AT956

Depilatory Cream/Hair Remover

9.1

18 St. Ives Apricot Hand & Foot Scrub

Foot Odor/Cream/Treatment

9.1

19 Murad APS Oil-Free Sunblock Sheer Tint

Sunscreen/Tanning Oil 9.1

20 Healing Garden Green Teatheraphy Exfoliating Body Scrub, Balance

Body Scrubs 9.0

21 NARS Cream Eye Shadow Compact

Eye Makeup 9.0

22 Te Tao Tea for Body, Anti-Stress Bath Soak

Bath Oils/Salts/Bubbles 9.0

23 Biolage by Matrix Daily Leave-In Tonic

Conditioner 9.0

24 L'Oreal Visible Lift Line Minimizing Concealer

Concealer 8.9

25 DDF Fade Cream SPF 30 Skin Coloring 8.9

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Because the FDA has no legal authority to require safety

assessments of cosmetics, products safety is by default the

responsibility of the industry and its own appointed Cosmetic

Ingredient Review panel. This voluntary policing arrangement has

been a failure. EWG's analysis of 7,500 personal care product labels

found that some cosmetic companies use known human

carcinogens in products, manufacture scores of products containing

ingredients in direct contraindication of industry hazard

assessments, widely use chemicals that are likely to be

contaminated with harmful impurities, and add to thousands of

products ingredients that industry assessments show lack basic

information needed to support their safety.

To improve the safety of personal care products EWG recommends

that manufacturers:

• Remove from products all chemicals classified as known

or possible human carcinogens, reproductive toxins, and

developmental toxins. Manufacturers are currently

reformulating products in Europe to comply with this

restriction.

• Certify that ingredients do not have impurities classified

as known or probable human carcinogens, reproductive

toxins, or developmental toxins.

• Conform with the recommendations of the CIR and

reformulate products to eliminate ingredients that are

deemed unsafe for the intended use of the product.

• Congress should amend the Federal Food Drug and

Cosmetic Act to provide FDA with clear and

unencumbered authority to request any and all safety

studies that it deems necessary to assess the safety of

cosmetics and other personal care products.

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REFERENCES:

Cosmetics Ingredient Review (CIR) (2003). 2003 CIR Compendium,

containing abstracts, discussions, and conclusions of CIR cosmetic

ingredient safety assessments. Washington DC.

Cosmetics Ingredient Review (CIR) (2004). CIR information

available at http://www.cir-safety.org, accessed May 6 2004.

Department of Trade and Industry, UK (DTI) (1998). A survey of

cosmetic and certain other skin-contact products for n-

nitrosamines.

Food and Drug Administration (FDA) (1993). Hair Dye Dilemmas.

FDA Consumer. April 1993. Accessed online May 6 2004 at

http://vm.cfsan.fda.gov/~dms/cos-818.html.

Food and Drug Administration (FDA) (1995). FDA Authority over

Cosmetics. Center for Food Safety and Applied Nutrition. Office of

Cosmetics and Colors Fact Sheet. February 3 1995. Accessed online

May 6 2004 at http://www.cfsan.fda.gov/~dms/cos-206.html.

Food and Drug Administration (FDA) (1996). Are nitrosamines in

cosmetics a health hazard? Accessed online May 6 2004 at

http://vm.cfsan.fda.gov/~dms/qa-cos25.html. Updated November

1996.

Food and Drug Administration (FDA) (1999). Diethanolamine and

Cosmetic Products. Office of Cosmetics and Colors Fact Sheet. Dec

9, 1999. Accessed online May 6 2004 at

http://vm.cfsan.fda.gov/~dms/cos-dea.html.

Food and Drug Administration (FDA) (2000). Prohibited Ingredients

and Related Safety Issues. Office of Cosmetics and Colors Fact

Sheet. March 30, 2000. Accessed online May 20 2004 at

http://www.cfsan.fda.gov/~dms/cos-210.html.

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Thank you to the EWG, CDC, CIR, NIH, FDA, USDA and Matt

Wheeland for much of the information contained herein.

SUMMARY

During the last 40 years America has experienced a catastrophic

situation of insidious, degenerative disease. In America today heart

disease amongst women has now surpassed men by 65,000 per

year. Today over 7,000 people every day in America die from

degenerative disease! Every 3 minutes a woman comes down with

breast cancer and 1 of every 10 women will lose a breast to this

horrific disease. Every 4 minutes a man comes down with prostate

cancer. The next 10 years will see cancer overtake heart disease as

the Nations #1 killer. In 2002 there were 2,900,000,000

prescriptions written in the United States that’s 1200 pills for every

man, woman and child. In 2005 there will be 4,000,000

prescriptions written based upon current trends. Chemical

depression is not only an epidemic; it is a pandemic with over

70,000,000 in 2002 people being treated for some form of mental

illness.

The impact on human health as a result of the ingestion of toxic

chemicals and materials from the air, food, water and through the

skin is quite apparent.

Through internal cleansing and resting the system on a regular

basis perhaps we can control the onslaught of alien chemicals and

toxins in the body.

Lets keep our bodies clean from the inside out and the outside in

and perhaps we can ensure long, healthy and vibrant lives for

every American man, woman and child.

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