Sarah Janssen, M.D., Ph.D., M.P.H.Science Fellow, Natural Resources Defense Councilsjanssen@nrdc.org

Hormonal Effects ofChemical Pollutants –

Endocrine Disruptors andReproductive Health

Increasing Incidence of HealthConditions

• Infertility• Premature births• Birth defects of genitalia• Early onset of puberty• Cancer - testicular• Neurological conditions – ADHD, autism• Insulin resistance/Diabetes• Obesity

Endocrine Disruptor• “An exogenous agent that interferes with

the synthesis, secretion, transport,binding, action, or elimination of naturalhormones in the body that are responsiblefor the maintenance of homeostasis,reproduction, development, and /orbehavior.”

U.S. EPA, February 1997

• Or in simpler terms:

“A substance which interferes with naturalhormones.”

Endocrine disruptors and health

• Abnormal development of reproductiveorgans or neurological system

• Reduced fertility – male and female• Poor birth outcomes – LBW/IUGR, SA• Development of pre-cancerous/cancerous

lesions• Lower IQ• Behavioral abnormalities

Synthetic Estrogens

• Seven women ages 15-22 presented at theMassachusetts GeneralHospital with clear celladenocarcinoma of thevagina, 1966-69

Herbst, AL. et al N Engl J Med 1971,284:878. The Wood siblings

From: www.desexposure.com

Diethylstilbestrol - DES

Estradiol

DES Health Effects - Female• Vaginal cancer (clear-cell adenocarcinoma)• Gross and cellular structural abnormalities of

reproductive organs: fallopian tubes, uterus,cervix, and vagina

• Suppression of cell-mediated immunity• Infertility (5x)• Preterm labor• Uterine fibroids• Breast cancer• Trans-generational effects – DES granddaughters

DES Health Effects - Male

• Cryptorchidism• Testicular

hypoplasia• Epididymal cysts• Semen

abnormalities• Reduced fertility• Testicular cancer

Lessons from DES

• The placenta is not a barrier• Exposure to the mother can have

unexpected, delayed effects in the offspring• Exposure to a hormonally-active chemical

may result in a variety of adverse healtheffects

• Unusual diseases are easier to trace to anenvironmental cause than are commondiseases

Embryonic Development & Vulnerability

Children are More Vulnerableto All Toxins

• Immature brain, blood/brain barrier;• Eat, breathe & drink more per kg;• GI & skin 2x surface area v. adult;• Outside more & closer to ground;• Hand/mouth behaviors;• Mouth breathers;• Lower enzyme levels.

Wts of after in utero exposure to 1 part per billion DES

Estrogenic agents and obesity

Newbold, et al. 2005. Developmental Exposure to Estrogenic Compounds and Obesity. Birth Defects Research (Part A) 73:478–480.

Common Endocrine DisruptorsBanned in US

PCBsPesticides

DDTDBCPChlordecone (Kepone)Hexachlorobenzene

Not intentionally madeDioxinsFuransPAHs

Still in usePesticides

AtrazineEndosulfanLindane

Flame retardantsPBDEsBFRs/CFRs

Plasticizersphthalatesbisphenol A

Heavy MetalsLeadMercury

Biomonitoring

• Increasingly being used to determine whatcontaminants are in biological tissues

• Gauge of how effective policy initiatives tolimit exposure are

• Where is it happening?– CDC – NHANES– State initiatives – California– Non-governmental Organizations

Individual v. Population Effects

• Almost always impossible to pinpoint thecause of a human health condition to onechemical or exposure

– Timing– Dose– Mixtures

• “I wonder” ?

The Significance of Small Effects:

160140120100806040

70 130I.Q.

mean 100

6.0 million "gifted"

6.0 million "mentally retarded"

5 Point Decrease in Mean IQ

160140120100806040

mean 95

70 130

2.4 million "gifted"

9.4 million "mentally retarded"

57% INCREASE IN

"MentallyRetarded”Population

I.Q.

Fish

• Important source of nutrition• Common contaminants

– PCBs– Mercury

• FDA/EPA Advisory– tilefish, king mackerel, shark, and swordfish

• Tuna

Fish recommendations• Eat a variety of fish types• Know about fish advisories for your region

– www.epa.gov/ost/fish/

• Use fish guides for ocean fish– NRDC fish guides and Mercury calculator

http://www.nrdc.org/mercury)– Monterey Bay Aquarium (http://www.mbayaq.org/)

• When cooking – remove fatty portions of fish

Other Dietary advice

• Dioxins and other fat-soluble contaminantsin fatty tissue – PCBs, PBDEs- Limit consumption of high fat meat &

dairy

• Eat organic produce when possible

Pesticides

• Can contaminate food or drinking water• Are also frequently used in and around

homes– Pets– Indoor pests– Lawns and Gardens– Head lice and scabies– Rural areas

Neurotoxicity of Pesticidesin Children

Recommendations• Eat a variety of produce

• Buy organic produce when possible

• Review guides of products most likely to becontaminated www.foodnews.org/walletguide.php

• Wash and peel outer leaves

• Utilize IPM in the home, at work, school, other

• Use non-pesticide approaches for head lice andscabies

Bisphenol A

Phthalates

Bisphenol A

• Over 6 billion poundsproduced each year

• Developed as estrogenicdrug 1930s

• Building block ofpolycarbonate plastic

• Food can lining• Dental sealant

7PC

Animal studies

• Reproductive toxin– Lower sperm counts– Prostate hyperplasia/cancer– Mammary cancer

• Developmental toxin- altered onset of puberty - decreased anogenital distance- oocyte anueploidy

• Neurological toxin• Obesogen/Insulin Resistance

7PC

Policy

• BPA has not been banned in any state orcountry – although legislation has beenintroduced

• FDA has approved BPA as a food additive

• National Toxicology Program draft report• Health Canada - “dangerous substance”

7PC

Public perception

• Market for baby bottles changed – Walmart, Sears

• "Baby Bargains," a best-selling guide to baby products,have advised parents to stop using bottles made ofpolycarbonate plastic.

"If you are shopping for bottles, choose analternative made from BPA-free plastic or glass,"

"If you have polycarbonate bottles, throw them out."

7 PC

What are the alternatives?

• Non-polycarbonate plastic or glass babybottle

• Born-Free (polyamide)• Polypropylene

• Unlined stainless steel bottle• Eat fresh food when possible,

- frozen over canned• Buy processed food in cardboard or brick

containers

Bisphenol A

Phthalates

Phthalates and PVC

• Make PVC flexible and soft• Not tightly bound, migrates with use• Ubiquitous exposure• General Uses

- Building materials - Toys- Clothing - Childcare Products- Packaging - Cosmetics and- Medical Devices personal care products- Air fresheners

PVC3

Phthalates: Anti-Androgens“Phthalate Syndrome”

– Absent testes, prostategland, seminal vesicles

– Testicular atrophy– Decreased sperm count– Decreased fertility– Cryptorchidism– Hypospadias –

decreased AGD

Fisher J. Reproduction.127:305-15, 2004

What can you do?

• Avoid buy PVC “vinyl” products• Avoid using synthetic scents to mask

odors• Avoid exposure to phthalates

– Fragrance free cosmetics and personal careproducts

– Soft pliable plastic toys for children

• Support legislation in California thatwould limit exposure to these chemicals.

Chemicals in Breast milk• PCBs• Pesticides – banned and currently in use• Dioxins• Flame retardants• Plasticizers• Heavy metals• Solvents

• http://www.nrdc.org/breastmilk

Recommendations• Benefits of breast feeding outweigh the risks

from pollution.

• Breastmilk is superior to formula because– provides vital trace nutrients and antibodies not found

in formula– benefits the mother by promoting weight loss and

bone strength– promotes brain and nervous system development– can lessen the effects of some toxic exposures

Baby formula is not an equivalentsubstitute for breast milk.

• Formula is lacking in many of the vital tracenutrients and antibodies found in breast milk.– babies get sick more often than breast fed babies.

• Infant formula may contain other toxins or bediluted with contaminated water

• Soy formulas can have very high levels of plant-derived estrogens (phytoestrogens)– the long term health effects are not very well studied.

Take home messages

• Hormonally-active agents exist in drugs,cosmetics, dietary supplements, pesticides,consumer products, and industrialchemicals.

• Laboratory animal experiments suggest thatexposures to these agents could beimpacting reproductive health.

• The developing fetus, infants and childrenare most vulnerable because their organsare still developing

Take home messages, cont’d

• Consequences of early life exposures aresometimes manifest until adulthood and canbe permanent and irreversible

• Chemicals can have multiple sites of actionwith multiple effects.

• The impacts of exposures to mixtures ofchemicals is not understood

Resources

Natural Resources Defense Councilwww.nrdc.org

Simple Stepswww.simplesteps.org