Plastics and Human Health

Oregon

Physicians for Social

Responsibility

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•Chemical background:•Current knowledge and regulatory policies •Complex Interactions and vulnerability

•Review of familiar plastics•Concerns:

•Endocrine disruptors•Dose response patterns

•Bisphenol A•Phthalates•What you and your patients can do

OverviewIntroduction

Introduction

“When an activity raises threats of harm to human health or the environment, precautionary measures should be takeneven if some cause and effect relationships are not fully established scientifically.”

Wingspread Conference, 1998

Precautionary Principle

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Introduction

Proven Harm

Partially Proven Harm

Not Yet Recognized Harm

Forever Unrecognized

Harm

Toxic Iceberg

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Introduction

Our Chemical Environment: Regulatory Control in the U.S.

• More than 82,000 in U.S. commerce

• 2,800 produced/imported >1mill. lbs/yr

• Almost 4.25 billion pounds of toxic chemicals are reported to the EPA as released into the environment each year (TRI)

Introduction

Hazard Data for Chemicals Produced

in Excess of 1 Million lbs/yr

0 10 20 30 40 50 60 70 80 90 100

Percentage Tested

Acute Toxicity

Environmental Fate

Ecotoxicity

Mutagenicity

Chronic Toxicity

ReproductiveToxicity

Full Set of BasicToxicity Tests

7% Full* Set of Basic Information

US E.P.A. (1998) Chemical Hazard Data Availability Study: What Do We Really Know About the Safety of High Production Volume Chemicals?

Introduction

Historical Perspective─ 1920s: many new chemicals in

industry

─ 1940s and 50s: new chemical innovations for the home─ Exposure of developing fetuses

─ 1960’s: first data associating synthetic chemicals and health impacts

─ 1976: first over-arching chemical legislation enacted

─ Now: no changes have been made to the legislation…

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Introduction

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Health Outcomes

Complex Interactions

Social Environmen

t

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Genetics

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Nutrition

Toxic Exposure

s

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Introduction

Children are More Vulnerable

• Organs are immature and developing– Brain & blood/brain barrier in infants– Developing immune system– Liver and kidney less efficient– Skin is more permeable, 2x surface area of adults

• Greater exposure– Ingest more per pound– More surface area/weight

in lungs and intestines– More contaminants dwell

close to ground– Hand/mouth behaviors http://www.flickr.com/photos/johnmueller/342618825/

Introduction

Important Considerations

• Evaluation of risk is inadequate:– Concurrent exposures to multiple chemicals:

• Additive and synergistic effects

• Only single chemical testing

– Timing and dose of exposures

– Interpretation of animal data

• With increasing scientific understanding, we often find greater toxicity at lower levels of exposure

Types of Plastics

Plastics As We Know Them:Safer vs. Not-So-Safe

1 - polyethylene terephthalate (new

evidence)

2 - high density polyethylene

3 - polyvinyl chloride

4 - low density polyethylene

5 - polypropylene

6 - polystyrene

7 - other (often polycarbonate)

Plastics

#1 - Polyethylene Terephthalate

• Food & beverage containers– Single-use water bottles– Microwave food trays– Food packaging films

• Clothing– Polyester, polar fleece

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Plastics

Use one time, avoid heating or long-term storage

#2 - High Density Polyethylene

• Opaque bottles– Milk jugs– Detergent bottles

• Gas tanks• Pipes and tubing• Plastic Lumber• Plastic bags

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Plastics

#3 - Polyvinyl Chloride (PVC)• Teething rings• Pacifiers• Toys (inflatable)• Pipes, Tubing• Medical equipment• Shower curtains• Clothing• Synthetic leather• Window frames• Siding

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Plastics

Major health concerns – avoid and replace

#4 – Low Density Polyethylene

• Plastic wraps• Flexible bottles• Plastic baggies• Flexible tubing• Furniture• Dental appliances• Lab pipettes and

tips

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Plastics

#5 - Polypropylene

• Trays• Food storage containers• Some baby bottles

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Plastics

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#6 - Polystyrene

• Clear food containers

• Styrofoam – food trays– Disposable cups,

bowls

• Packaging material• Insulation• Coolers• Lab equipment

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Plastics

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#7 “Other” - often Polycarbonate

• Some baby bottles• Reusable drink bottles• Lining of food cans • Cutlery• Food dishes, containers• Dental fillings, sealants• Eyeglass lenses• Compact Discs

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Plastics

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Pros and Cons of Plastics

Benefits:• Current technology and lifestyle

– Medical, sanitary– Construction, transportation– Information transfer

Adverse effects:• Environment and other organisms• Human Health Impacts

– Bisphenol-A and Phthalates

Health Concerns

Endocrine Disruptors

•May adversely affect:

–Development–Reproduction–Nervous function–Immune function

•Greater risk for fetuses and young children

Bisphenol A and Phthalates are examples found in plastics

Action of Endocrine Disruptors

• Mimic estrogen, androgens, progesterone– Block hormones by binding to receptors

• Interfere with endocrine signaling paths– Interfere with thyroid

• Researchers expect that more effects will be found.

Health

Other Endocrine Disruptors

• DES (diethylstilbestrol)• Dioxin and dioxin-like compounds• Polychlorinated biphenyls (PCBs)• DDT and other pesticides • Hormone-containing

pharmaceuticals

Health

Low Dose• Historical Reference Doses for toxicity:

– Bisphenol A (BPA): 50 μg/kg/day* – Phthalates: DEHP: 20 μg/kg/day

DBP: 100 μg/kg/day

DEP: 800 μg/kg/day

• Studies show adverse effects at much lower doses – parts per trillion for some effects of BPA

*μg/kg/day = parts per billion (ppb)

Health

Non-monotonic Dose Response Curve

• Different from traditional dose-response curve

• U-shaped and inverted U-shaped

• Low doses can stimulate response, high can inhibit

Many endocrine disruptors have non-monotonic curves

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Health

Potential Effects of Endocrine Disruption

• Falling age of puberty in girls • Increasing rates of obesity and diabetes• Male genital abnormalities• Regional decreases in sperm count • Increasing rates of endocrine-related

cancers – breast, prostate

• Increasing rates of neurobehavioral problems: autism, hyperactivity

Health

Bisphenol A

Bisphenol A (BPA)

• What we know• Health Concerns and exposure• Consensus Statements• Action to regulate• What can be done

Bisphenol A: What We Know

• Backbone of Polycarbonate plastic– Resin code: #7 (other)

• Known since 1930s to be estrogenic• Mechanism of action

– Binds to both nuclear and cell membrane receptors

• Rapidly metabolized and cleared– Human exposure is continuous

• High volume chemical: >6 billion pounds per year

BPA

Center for the Evaluation of Risks to Human Reproduction

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Bisphenol A: Health Concerns

• Reproductive effects-male and female • Insulin resistance, diabetes & obesity• Altered brain development• Cancer

– Prostate – Breast – Decreased antioxidant enzymes

• Recurrent miscarriages• Altered immune function• Behavioral effects

– Alters attention, activity

BPA

Human BPA Exposure

• BPA in 95% of US population (CDC)• Widespread use = widespread

exposure • Concentrations in humans similar to

levels causing harm in animals

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BPA

Sources of BPA Exposure

• Food and drink containers are primary source – Leaching:

• Into water at room temperature • With heating• With repeated washing of material• With acidic or basic foods/liquids

• Maternal exposure– Breast milk – Prenatal exposure

• Indoor & outdoor air • Dialysis tubing

BPA

Literature regarding BPA

• 115 published in vivo studies of low-dose BPA effects– “Significant” effects in 94

• 90% of government-funded studies found adverse effects

• 0% of industry-funded studies found adverse effects

BPA

• National Toxicology Program, April 2008

•First government acknowledgement of possible harm

•Controversy over evaluation of existing data•Panel chosen for lack of expertise

• Chapel Hill Consensus Statement, November 2007

•Response to NTP assessment•38 BPA experts•Reviewed published BPA literature to date

Two Recent Statements on BPA

National Toxicology Program, April 2008

• First government acknowledgement of possible harm

• Controversy over evaluation of existing data

• Panel chosen for lack of expertise

• Findings:–“some concern…”–“the possibility that bisphenol A may alter human development cannot be dismissed.”

Two Recent Statements on BPA

Chapel Hill Consensus Statement, November 2007

• Response to NTP assessment

• 38 BPA experts• Reviewed published BPA

literature to date• Findings:

•Non-monotonic dose-response curves

•Concentrations in humans similar to levels causing harm in animals

•Sensitivity to BPA varies with life stage

Recent BPA Decisions

• December 2006– San Francisco ban

• April 2008– Canada labels BPA as “dangerous

substance”– Nalgene will stop using BPA in bottles– Wal-Mart and Toys-R-Us will stop carrying

products w/ BPA

BPA

What You Can Do About BPA

• Avoid canned foods and drinks • Use alternatives to #7 baby bottles:

– Breast feed, glass bottles

• Use alternative sippy cups: – #2,4,5, stainless steel

• Use alternatives to polycarbonate for storing food and water:– glass, ceramic, safer plastics: #2,4, 5

• Never heat/cook/microwave food in any plastic

Phthalates

Phthalates

• What we know• Health Concerns and exposure

– Reproductive Health Concerns

• Regulations • What you and your patients can do

Phthalates: What We Know

• Large class of chemicals– Large molecules like DEHP

make vinyl (PVC) flexible and durable

– Smaller molecules (DEP, DBP, DMP) are found in perfumes, lotions, cosmetics, and time-release medications

DEHP: http://cerhr.niehs.nih.gov/chemicals/dehp/dehp.html

DEHP = di(2-ethylhexyl) phthalate

DEP = diethyl phthalate

DBP = dibutyl phthalate

DMP = dimethyl phthalate

Phthalates

Sources of Exposure to Phthalates

• 1 billion pounds produced annually worldwide

• 2000: CDC found high levels of phthalates in Americans– Women of child-bearing age had highest

levels– Found in blood, urine, breast milk,

amniotic fluid• A ubiquitous contaminant

– Found in air, soil, water, sediment

Phthalates

Phthalates in Consumer Products

• Vinyl plastic (PVC)– Toys, inflatable mattresses

• Fragrance– Soap, lotion, detergent, air fresheners, etc.

• Other common products:– Paint– Adhesives – Car interiors– Wood finishes – Detergents– Solvents– Shower Curtains http://www.flickr.com/photos/desiitaly/2254327579/

Phthalates

Phthalates in Medicine

• Tubing• IV bags• Gloves• Bags containing

plasma • Time-released

drugs

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Phthalates

Exposure Issues with Phthalates

• People exposed to many simultaneously– 84% exposed to 6+ at the same time

• Multiple exposures not considered when EPA determines safe dose

• Different phthalates have the same mechanism of action– Effect is additive

Phthalates

Phthalates Toxicity

• Degree of toxicity related to:– Metabolites (different from parent

compounds)– Route of exposure:

• Inhalation, ingestion, injection, dermal

– Age at exposure

Phthalates

Phthalates: Health Concerns

• Endocrine system– Thyroid – Insulin resistance

• Obesity• Diabetes

– Male reproductive problems

• Allergies, asthma

Phthalates

Phthalates: Potential Reproductive Effects

• High dose and low dose risk• Early puberty in females• Male reproductive effects:

– Lowered semen quality– Testes (Leydig) cells vulnerable– Reproductive effects in infants

• Swan, et al. (2005) study on male infants:– Urine levels of mothers’ phthalate

metabolites postive correlation with shorter ano-genital distance (AGD) http://www.flickr.com/photos/nirak/206930221/

Phthalates

Phthalates: Reproductive Effects

• Swan, et al., 2005 - Human male infants:– 85 mother-son pairs– Measured 9 phthalate metabolites in prenatal

urine samples– Examined Ano-Genital Distance (AGD) in

newborn males (5-16 mo)– Urine levels of 4 metabolites inversely

correlated w/ AGD– Shorter AGD increased risk of undescended

testes, smaller penis size, and small scrotum

Phthalates

Regulation of Phthalates

• European Union 2005– Banned 3 phthalates in all toys and

childcare products; 3 others banned in mouthing toys

• San Francisco 2006– Banned manufacture, distribution, or sale

of toys intended for ages < 3 years with certain levels of six phthalates

• California 2009– Similar restrictions to take effect 1/1/09

Phthalates

What You Can Do (and Advise Patients to Do) About

Phthalates• Avoid using PVC (#3)

– Use phthalate-free medical equipment

– Toys, bottles, sippy cups• Use fragrance-free products

– Laundry– Personal care products– Cleaning– Air fresheners

What You Can Do About Plastics

• Avoid using plastic containers in microwave, all cooking.– Cling wraps: beware especially in microwave or oven

• Use alternative packaging; especially with food & drink.

• Avoid plastic bottled water unless water supply questionable

• Bring your own take-home containers to restaurants

• Avoid over-use of detergents or overly abrasive cleaners for plastic items

• Use alternatives to non-stick cookware, stain resistant products

Guiding Principles

• Toxic exposures are preventable.• Traditional toxicological paradigms

may not be appropriate for every toxicant.

• Since “proof” of harm materializes slowly, generations are at risk and may be harmed before adequate regulatory response occurs.

• A regulatory system capable of preventing (as well as responding to) exposures is needed to truly protect health.

Resources

• Environmental Health Perspectives http://www.ehponline.org/

• The Collaborative on Health and the Environment http://www.healthandenvironment.org/

• Environmental Working Group www.ewg.org• Agency for Toxic Substances and Disease Control

Registry www.atsdr.cdc.gov/• Oregon Department of Environmental Quality

(DEQ) http://www.oregon.gov/DEQ/• National Toxicology Program-Center for the

Evaluation of Risks to Human Reproduction (CERHR); http://cerhr.niehs.nih.gov/reports/index.html

• Our Stolen Future http://www.ourstolenfuture.org• Health Care Without Harm http://www.noharm.org