Endocrine disruptors: Endocrine disruptors: Clinical and Public health Clinical and Public health

implicationsimplications

Nimi Singh, MD, MPHNimi Singh, MD, MPHDivision of Adolescent Health and MedicineDivision of Adolescent Health and Medicine

Department of PediatricsDepartment of PediatricsUniversity of MinnesotaUniversity of Minnesota

DisclosureDisclosure

I have no relevant financial relationships to I have no relevant financial relationships to disclosedisclose

I am not on any Speakers BureauI am not on any Speakers Bureau I do not intend to discuss unapproved uses of I do not intend to discuss unapproved uses of

a commercial producta commercial product

IntroductionIntroduction

Age of onset of puberty in girls Age of onset of puberty in girls has decreased significantly in has decreased significantly in the last few decades…why? the last few decades…why?

……and what can we do about it?and what can we do about it?

Overview:Overview:

Precocious puberty in girlsPrecocious puberty in girls Etiology: Endocrine disruptorsEtiology: Endocrine disruptors Effects on vertebratesEffects on vertebrates Effects on humans in particularEffects on humans in particular Clinical implicationsClinical implications Public Health implications Public Health implications

Normal Puberty Normal Puberty Onset of puberty: Onset of puberty:

– 85%:85%: Breast bud development in girls by age 8Breast bud development in girls by age 8 Testicular enlargement by age 9 in boys Testicular enlargement by age 9 in boys

– 15%: 15%: Adrenarche (axillary / public hair)Adrenarche (axillary / public hair)

Based on Sexual maturity rating by Tanner Based on Sexual maturity rating by Tanner and Marshall, British orphanages, 1969and Marshall, British orphanages, 1969

Herman-Giddens, et al. Herman-Giddens, et al. ((PediatricsPediatrics 1997;99(4):505-512) 1997;99(4):505-512)

17,000 girls between ages of 3-12 years17,000 girls between ages of 3-12 years Controlled for BMI (fat cells convert estrogens into Controlled for BMI (fat cells convert estrogens into

DHEA, causing axillary hair development and linear DHEA, causing axillary hair development and linear growth, or “adrenarche”) growth, or “adrenarche”)

Onset of puberty occurring earlier than previously seen:Onset of puberty occurring earlier than previously seen:– By 8 years of age:By 8 years of age:

14.7% of Caucasian girls (thelarche: 10%)14.7% of Caucasian girls (thelarche: 10%)50% of African-American girls (thelarche: 38%)50% of African-American girls (thelarche: 38%)

Onset of menstruation: NO significant changeOnset of menstruation: NO significant change– Caucasian girls: 12.8 years of ageCaucasian girls: 12.8 years of age– African-American girls: 12.1 years of ageAfrican-American girls: 12.1 years of age

“ “Normal” Puberty in GirlsNormal” Puberty in Girls

Mean age of Mean age of menarchemenarche (U.S.: 12.4 years) (U.S.: 12.4 years)

has NOT changed significantly in 50 yearshas NOT changed significantly in 50 years– Slightly higher in Caucasians, slightly lower in Slightly higher in Caucasians, slightly lower in

African-Americans and Mexican-AmericansAfrican-Americans and Mexican-Americans(Chumlea WC et al, Pediatrics, 2003 Jan; 111 (1): 110-3)(Chumlea WC et al, Pediatrics, 2003 Jan; 111 (1): 110-3)

What HAS changed is mean age of isolated What HAS changed is mean age of isolated breast bud developmentbreast bud development (“thelarche”) (“thelarche”)

Response of the Biomedical Response of the Biomedical CommunityCommunity

Kaplowitz et al (1999):Kaplowitz et al (1999):– New definition of “Precocious puberty”: New definition of “Precocious puberty”:

Breast bud or axillary hair development inBreast bud or axillary hair development in Caucasian girls less than Caucasian girls less than 77 years of ageyears of age

African-American girls less than African-American girls less than 66 years of age years of age

Pediatric Endocrine community: Pediatric Endocrine community: ““Redefining ‘normal’ doesn’t address why it’s Redefining ‘normal’ doesn’t address why it’s happening”happening”

Colon and Caro et al.Colon and Caro et al.(Environmental Health Perspectives 2000; 108(9) )(Environmental Health Perspectives 2000; 108(9) )

Puerto Rico: dramatic increase in precocious puberty Puerto Rico: dramatic increase in precocious puberty since 1979: 7 per 1000 (highest known rates in the world)since 1979: 7 per 1000 (highest known rates in the world)

70% of these were actually premature thelarche, with 70% of these were actually premature thelarche, with menstruation occurring at the normal timemenstruation occurring at the normal time

Environmental contaminants?Environmental contaminants?– Hormones in dairy or beef?Hormones in dairy or beef?– Pharmaceutical waste products (Premarin, OCPs)?Pharmaceutical waste products (Premarin, OCPs)?– Man-made chemicals in the environment?Man-made chemicals in the environment?

Synthetic pesticides: bioaccumulation, storage in fatSynthetic pesticides: bioaccumulation, storage in fat Plastics used for packaging, storing, preserving foodsPlastics used for packaging, storing, preserving foods

Colon and Caro et al., 2000 (cont.):Colon and Caro et al., 2000 (cont.):

Looked at girls from ages 6 months to 8 Looked at girls from ages 6 months to 8 years:years:– 41 girls with premature thelarche41 girls with premature thelarche– 35 age-matched “controls” (no signs of 35 age-matched “controls” (no signs of

puberty)puberty) Measured blood Phthalate esters Measured blood Phthalate esters

– Results were positive for:Results were positive for: 68% of girls with thelarche68% of girls with thelarche 17% of girls without thelarche (at much lower levels)17% of girls without thelarche (at much lower levels)

Premature thelarchePremature thelarche(Cromer and Gordon, Pediatrics 2009; 124; 779-801)(Cromer and Gordon, Pediatrics 2009; 124; 779-801)

U.S. 2008: EPA and National Institute of Environmental Health expert U.S. 2008: EPA and National Institute of Environmental Health expert panel:panel:– Secular trend of increased isolated early breast development in girls Secular trend of increased isolated early breast development in girls

(U.S., Puerto Rico, China)(U.S., Puerto Rico, China)– Adverse health effects:Adverse health effects:

Early sexual debutEarly sexual debut Higher risk of sexual abuse/ non-consensual sexHigher risk of sexual abuse/ non-consensual sex Possible increased risk of breast cancer later in lifePossible increased risk of breast cancer later in life

– Etiology:Etiology: Endocrine disruptorsEndocrine disruptors Effect persists when studies control for BMI Effect persists when studies control for BMI

Diamanti-Kandarakis E Diamanti-Kandarakis E et al.et al. 2009 Endocrine-Disrupting Chemicals: An 2009 Endocrine-Disrupting Chemicals: An Endocrine Society Scientific Statement. Endocrine Society Scientific Statement. Endocrine ReviewsEndocrine Reviews 30(4):293- 30(4):293-342.342.

Endocrine Disrupting ChemicalsEndocrine Disrupting Chemicals

Endocrine Disruptors (“EDs”):Endocrine Disruptors (“EDs”):– Synthetic chemicals that disrupt the body’s normal endocrine Synthetic chemicals that disrupt the body’s normal endocrine

functions by mimicking or blocking endogenous hormonesfunctions by mimicking or blocking endogenous hormones

Effects:Effects:– Reproductive system (breast cancer, prostate cancer, endometriosis, Reproductive system (breast cancer, prostate cancer, endometriosis,

infertility, malformations in developing fetus)infertility, malformations in developing fetus)– Thyroid effectsThyroid effects– Altered insulin and glucose metabolism (Bisphenol A: Alonso-Altered insulin and glucose metabolism (Bisphenol A: Alonso-

Magdalena, Environ. Health Perspect., Sept. 2005)Magdalena, Environ. Health Perspect., Sept. 2005)– Neurodevelopmental effects (PBDE’s in cord blood and IQ, Neurodevelopmental effects (PBDE’s in cord blood and IQ,

Environmental Health Perspectives, 2010)Environmental Health Perspectives, 2010)

Endocrine Disrupting ChemicalsEndocrine Disrupting Chemicals

Examples :Examples :– Medications:Medications: DES (1938-1974: used to prevent miscarriage) DES (1938-1974: used to prevent miscarriage)– Insecticides:Insecticides: (DDT, DDE) (DDT, DDE)– Herbicides:Herbicides: (organophosphates, organochlorates) (organophosphates, organochlorates)– Fungicides:Fungicides: Atrazine Atrazine – Industrial organic chemicals:Industrial organic chemicals: Bisphenol-A (BPA), Phthalates, Bisphenol-A (BPA), Phthalates,

Parabens, PBDE’s (flame retardants)Parabens, PBDE’s (flame retardants)– Metals:Metals: Mercury, Arsenic, Tin, Chromium Mercury, Arsenic, Tin, Chromium– Dioxin:Dioxin: by-product of waste-burning incinerators by-product of waste-burning incinerators– PCB’s:PCB’s: coolants and insulating fluids (banned in 1976), also coolants and insulating fluids (banned in 1976), also

termed “persistent organic pollutants” or “POP’s”termed “persistent organic pollutants” or “POP’s”

Endocrine Disrupting Chemicals Endocrine Disrupting Chemicals

Routes of exposure:Routes of exposure:– Direct contact (water, air, food)Direct contact (water, air, food)

Agricultural and home use: insecticides, herbicides, Agricultural and home use: insecticides, herbicides, fumigants, fungicidesfumigants, fungicides

Industrial work: Detergents, resins, plasticizers, disinfectant Industrial work: Detergents, resins, plasticizers, disinfectant bleachesbleaches

Chemical/ manufacturing processes: by-productsChemical/ manufacturing processes: by-products Plasticizers: leach out of plastics (food containers, IVF bags Plasticizers: leach out of plastics (food containers, IVF bags

and tubing), released into the air when burnedand tubing), released into the air when burned Additives in cosmetics, shampoos, lotions, etc..Additives in cosmetics, shampoos, lotions, etc.. Other: Teflon, flame-retardant cloth, cloth dyes (denim), Other: Teflon, flame-retardant cloth, cloth dyes (denim),

computer casings, carscomputer casings, cars

Endocrine Disrupting ChemicalsEndocrine Disrupting Chemicals Biochemical features:Biochemical features:

– Poorly degraded: persist in the environment for decades or Poorly degraded: persist in the environment for decades or longer (DDT longer (DDT →→DDE)DDE)

– Fat-soluble: accumulate in fat (higher levels in children and Fat-soluble: accumulate in fat (higher levels in children and women, in obese individuals), harder for body to detoxifywomen, in obese individuals), harder for body to detoxify

– Crosses the placenta: exposure to fetus in uteroCrosses the placenta: exposure to fetus in utero– Bio-accumulate up the food chain ( greatest exposure: fatty Bio-accumulate up the food chain ( greatest exposure: fatty

foods, fish from contaminated water)foods, fish from contaminated water)– Ubiquitous, widespread in the environmentUbiquitous, widespread in the environment

CDC (2005): Average American tests positive for 148 of 200 CDC (2005): Average American tests positive for 148 of 200 chemicals testedchemicals tested

In cord blood and meconium of newborns (vertical transmission) In cord blood and meconium of newborns (vertical transmission) and in concentrations of ng/dLand in concentrations of ng/dL

Endocrine Disrupting ChemicalsEndocrine Disrupting Chemicals

Toxic effects:Toxic effects:– Often have ‘estrogen-like’ effects (termed “xeno-Often have ‘estrogen-like’ effects (termed “xeno-

estrogens”) disrupting normal endocrine functioningestrogens”) disrupting normal endocrine functioning

– Plants and animal species have been showing toxic Plants and animal species have been showing toxic effects for over 60 yearseffects for over 60 years

– Humans now showing significant effectsHumans now showing significant effects

Toxic effects of EDsToxic effects of EDs Animals:Animals:

– 1960’s: Rachel Carson “Silent Spring” (birds and 1960’s: Rachel Carson “Silent Spring” (birds and pesticides), eventually led to ban of DDT in U.S.pesticides), eventually led to ban of DDT in U.S.

– 1976: Congress passes “Toxic Substances Control Act”1976: Congress passes “Toxic Substances Control Act”(but no other substances have been regulated)(but no other substances have been regulated)

– Lake Apopka, FloridaLake Apopka, Florida 1980: Accidental release of difocol (DDT-like pesticide) 1980: Accidental release of difocol (DDT-like pesticide) Massive efforts made to clean up lakeMassive efforts made to clean up lake 1990’s: Alligators in Lake Apopka, Florida1990’s: Alligators in Lake Apopka, Florida

– Low hatch rate (20%)Low hatch rate (20%)– High death rate of babiesHigh death rate of babies– Feminization of males (malformed penises, ambiguous genitalia) Feminization of males (malformed penises, ambiguous genitalia)

2000: Toft et al.: persistent effects in male fish (low sperm counts)2000: Toft et al.: persistent effects in male fish (low sperm counts)

Toxic effects of EDsToxic effects of EDs Humans:Humans:

– Last 50 years: EDs widely dispersedLast 50 years: EDs widely dispersed– Epidemiologic evidence of “synthetic estrogen” effect:Epidemiologic evidence of “synthetic estrogen” effect:

Premature thelarche (Puerto rico, U.S., China)Premature thelarche (Puerto rico, U.S., China)

Sperm count down by 40% in US and Europe, more Sperm count down by 40% in US and Europe, more pronounced in agricultural areas (Carlsen et al., 1992; pronounced in agricultural areas (Carlsen et al., 1992; Andersen et al., 2000; Swan et al, 2003)Andersen et al., 2000; Swan et al, 2003)

Denmark: mothers working as gardeners had male Denmark: mothers working as gardeners had male infants with higher rates of cryptorchidism as infants with higher rates of cryptorchidism as compared to infants of non-exposed mothers (Weidner compared to infants of non-exposed mothers (Weidner et al., 1998)et al., 1998)

Toxic effects in Humans Toxic effects in Humans (cont.)(cont.) Evidence of “synthetic estrogen” effect:Evidence of “synthetic estrogen” effect:

– 1970-1990’s: rate of hypospadias in U.S. has doubled from 1970-1990’s: rate of hypospadias in U.S. has doubled from 20 to 40 males per 10,000 (Paulozzi et al., 1996) 20 to 40 males per 10,000 (Paulozzi et al., 1996)

– Increasing rates of gynecomastia in otherwise normal Increasing rates of gynecomastia in otherwise normal adolescent males adolescent males

1990: 49% (Biro, et al.,)1990: 49% (Biro, et al.,) Phthalates and “pubertal gynecomastia”: Durmaz et al., Jan 2010: Phthalates and “pubertal gynecomastia”: Durmaz et al., Jan 2010:

significant correlation (p<0.01, n=40, controls=21)significant correlation (p<0.01, n=40, controls=21)

– Other: Endometriosis, Uterine fibroids, Breast cancer, Other: Endometriosis, Uterine fibroids, Breast cancer, Benign Prostatic HypertrophyBenign Prostatic Hypertrophy

ED’s in the food systemED’s in the food system(Institute for Agriculture and Trade Policy, Aug 2009)(Institute for Agriculture and Trade Policy, Aug 2009)

Intentional:Intentional:– Steroid growth promoters (beef cattle, 8X more anabolic than Steroid growth promoters (beef cattle, 8X more anabolic than

testosterone)testosterone)– Arsenic growth promoters (chicken feed, promotes angiogenesis)Arsenic growth promoters (chicken feed, promotes angiogenesis)– rbGH (increases milk production, increases mastitis/ use of rbGH (increases milk production, increases mastitis/ use of

antibiotics in cows, which has increases antibiotic resistance in antibiotics in cows, which has increases antibiotic resistance in bacteria)bacteria)

– Synthetic pesticides (27 are defined as ED’s by European Union, Synthetic pesticides (27 are defined as ED’s by European Union, another 73 are being studied by EPA)another 73 are being studied by EPA)

Unintentional:Unintentional:– Food packaging (polyvinyl chloride (PVCs), Bisphenol A, Food packaging (polyvinyl chloride (PVCs), Bisphenol A,

Polyethylene tetrachloride (PET) )Polyethylene tetrachloride (PET) )– Refeeding of contaminated animal fat to other animals and fishRefeeding of contaminated animal fat to other animals and fish

Mechanism of action of ED’sMechanism of action of ED’s(challenges to demonstrating causality)(challenges to demonstrating causality)

NOT a simple dose-response relationshipNOT a simple dose-response relationship

Age at exposureAge at exposure– Effects of exposure in adulthood different than exposure in childhoodEffects of exposure in adulthood different than exposure in childhood– Fetal and post-natal exposure linked to adult diseaseFetal and post-natal exposure linked to adult disease– Prenatal exposure in utero linked to abnormalities at birth/ in childhoodPrenatal exposure in utero linked to abnormalities at birth/ in childhood

Recognition of multiple exposuresRecognition of multiple exposures– Contamination of environment by multiple compoundsContamination of environment by multiple compounds– Multiple exposures: synergistic effectMultiple exposures: synergistic effect– ““One-cause-one effect” not reflective of true environmental exposureOne-cause-one effect” not reflective of true environmental exposure

Mechanism of action of ED’sMechanism of action of ED’s

Non-traditional dose-response dynamics:Non-traditional dose-response dynamics:– Very low levels of exposure during critical developmental Very low levels of exposure during critical developmental

window (when organism is extremely sensitive/ vulnerable window (when organism is extremely sensitive/ vulnerable to chemical exposure, such as in utero)to chemical exposure, such as in utero)

– Low doses exert more powerful physiological effects than Low doses exert more powerful physiological effects than higher doses in some instanceshigher doses in some instances

Trans-generational (epigenetic) effects:Trans-generational (epigenetic) effects:– Effect is not on DNA directly, but to regulation of DNA via Effect is not on DNA directly, but to regulation of DNA via

DNA methylation and histone acetylationDNA methylation and histone acetylation– Changes in DNA regulation get passed on to future Changes in DNA regulation get passed on to future

generations (propensity towards insulin resistance and generations (propensity towards insulin resistance and obesity)obesity)

Public HealthPublic Health

U.S. Regulation of manufactured chemicals:U.S. Regulation of manufactured chemicals:– 80,000 chemicals in use today80,000 chemicals in use today– 7,000 are produced or imported a year (25,000 lbs/ yr)7,000 are produced or imported a year (25,000 lbs/ yr)– NOT considered a food or a drug, therefore do not NOT considered a food or a drug, therefore do not

come under the jurisdiction of the FDAcome under the jurisdiction of the FDA

– NO TESTS DONE TO DETERMINE TOXICITYNO TESTS DONE TO DETERMINE TOXICITY

– Chemicals only pulled from market after years of Chemicals only pulled from market after years of research documenting ill effects PLUS strong research documenting ill effects PLUS strong advocacy efforts (DDT, BPA)advocacy efforts (DDT, BPA)

Public Health InterventionsPublic Health Interventions

EDUCATIONEDUCATION– Of the publicOf the public– Of the Health Care community Of the Health Care community

RESEARCH and ADVOCACYRESEARCH and ADVOCACY– Increased research on ED’s Increased research on ED’s – Burden of proof needs to be on safety, NOT harm Burden of proof needs to be on safety, NOT harm (“precautionary principle”)(“precautionary principle”)– Support efforts to get strong governmental regulationSupport efforts to get strong governmental regulation

LOBBYINGLOBBYING– Need “champions” to take up cause Need “champions” to take up cause

(premature sexual development: not a priority health issue of the Puerto (premature sexual development: not a priority health issue of the Puerto Rican health authorities, therefore not much has been done)Rican health authorities, therefore not much has been done)

Clinical interventions: Clinical interventions: Prevention and EducationPrevention and Education

Pediatric Environmental Health ToolkitPediatric Environmental Health Toolkit(http://www.psr.org/resources/pediatric-toolkit.html)(http://www.psr.org/resources/pediatric-toolkit.html)– Endorsed by the AAPEndorsed by the AAP

Anticipatory guidance (prenatal to teen visits)Anticipatory guidance (prenatal to teen visits) Environmental health desk reference cardEnvironmental health desk reference card

– Toxin/ topic (lead, mercury, indoor air pollutants, PCB’s…)Toxin/ topic (lead, mercury, indoor air pollutants, PCB’s…)– Health effects summaryHealth effects summary– Sources and Routes of exposureSources and Routes of exposure– Prevention strategyPrevention strategy

Free downloadable materials Free downloadable materials Free on-line PEHT trainingFree on-line PEHT training

Individual-level InterventionsIndividual-level Interventions 1. REDUCE EXPOSURE:1. REDUCE EXPOSURE:

– Educate self and family membersEducate self and family members– Dietary recommendations:Dietary recommendations:

Peel fruits and vegetables or wash with diluted vinegar Peel fruits and vegetables or wash with diluted vinegar Buy organic foods when possibleBuy organic foods when possible Cut down on/avoid fatty foods ( cheeses, fatty meats, fatty fish) Cut down on/avoid fatty foods ( cheeses, fatty meats, fatty fish) Avoid heating foods in plastic containers (use glass, ceramic)Avoid heating foods in plastic containers (use glass, ceramic)

– Avoid using herbicides and pesticides (use baits/traps Avoid using herbicides and pesticides (use baits/traps instead)instead)

– Eliminate pesticide use in schoolsEliminate pesticide use in schools– Avoid giving children plastic teething toys (use cloth)Avoid giving children plastic teething toys (use cloth)– Avoid cosmetics, soaps, shampoos containing Avoid cosmetics, soaps, shampoos containing

Parabens and other known endocrine disruptorsParabens and other known endocrine disruptors

Individual-level InterventionsIndividual-level Interventions 2. INCREASE ELIMINATION: 2. INCREASE ELIMINATION:

– Exercise (lymphatics, lungs)Exercise (lymphatics, lungs)– Keep well-hydrated (first phase of liver detoxification, kidneys)Keep well-hydrated (first phase of liver detoxification, kidneys)– Reduce fat stores Reduce fat stores – Regulate bowel function (eat veggies, fiber, take probiotics especially Regulate bowel function (eat veggies, fiber, take probiotics especially

after antibiotic use) after antibiotic use) – Only put on your skin what you’d be willing to eat (safecosmetics.com, Only put on your skin what you’d be willing to eat (safecosmetics.com,

natural food-based alternatives)natural food-based alternatives)

3. REDUCE EFFECTS BY OPTIMIZING HOMEOSTASIS:3. REDUCE EFFECTS BY OPTIMIZING HOMEOSTASIS:– Get enough sleep Get enough sleep – Reduce stress Reduce stress – Eat a well-balanced diet high in anti-oxidants and phyto-nutrientsEat a well-balanced diet high in anti-oxidants and phyto-nutrients

Research and Advocacy: Research and Advocacy:

European Union:European Union: June 2005: Over 100 research scientists convened to review the data on June 2005: Over 100 research scientists convened to review the data on

endocrine disruptorsendocrine disruptors

Prague Declaration, a joint signed statement (15 countries): Prague Declaration, a joint signed statement (15 countries):

“ “In view of the magnitude of the potential risks associated with endocrine disruptors, In view of the magnitude of the potential risks associated with endocrine disruptors, we strongly believe that scientific uncertainty should not delay precautionary action we strongly believe that scientific uncertainty should not delay precautionary action on reducing the exposures to and the risks from endocrine disruptors”on reducing the exposures to and the risks from endocrine disruptors”

2007: Manufacturers are required to provide basic data on the properties of 2007: Manufacturers are required to provide basic data on the properties of thousands of chemical substances. The European Chemicals Agency will thousands of chemical substances. The European Chemicals Agency will then review the chemicals, and require substitutions of the most dangerous then review the chemicals, and require substitutions of the most dangerous ones (“precautionary principle”)ones (“precautionary principle”)

Research and AdvocacyResearch and Advocacy

U.S., 2009:U.S., 2009:– MINNESOTA: MINNESOTA:

First state in the nation to ban Bisphenol A in manufacturing of baby First state in the nation to ban Bisphenol A in manufacturing of baby bottles, sippy cups and food containers intended for children under 3 bottles, sippy cups and food containers intended for children under 3 years of age (January 2010)years of age (January 2010)

700 studies total, 12 in humans700 studies total, 12 in humans Driving force: not science alone, but also consumer advocacy groupsDriving force: not science alone, but also consumer advocacy groups Note: Canada declared BPA a “toxin” earlier in the same yearNote: Canada declared BPA a “toxin” earlier in the same year

– Toys Toys ЯЯ Us, Nalgene, Gerber and Playtex to eliminate use of Us, Nalgene, Gerber and Playtex to eliminate use of BPA in all products (consumer preferences drives industry!!)BPA in all products (consumer preferences drives industry!!)

Research and AdvocacyResearch and Advocacy

U.S.:U.S.:– Sept ‘09: Environmental Protection Agency: Sept ‘09: Environmental Protection Agency:

To regulate six high-profile chemicals: BPA, phthalates, brominated To regulate six high-profile chemicals: BPA, phthalates, brominated flame retardants, perfluorinated compounds (non-stick coatings and flame retardants, perfluorinated compounds (non-stick coatings and food packaging), some parafins, benzidine dyes.food packaging), some parafins, benzidine dyes.

To revise 1976 Toxic Substances Law (required the EPA to prove a To revise 1976 Toxic Substances Law (required the EPA to prove a toxic substance “presents and unreasonable risk of injury to health or toxic substance “presents and unreasonable risk of injury to health or the environment” and to “consider the cost of restricting its use” to the environment” and to “consider the cost of restricting its use” to industry, and choose the “least burdensome” approach in regulating industry, and choose the “least burdensome” approach in regulating industry)industry)

Some “champions” in the U.S…Some “champions” in the U.S…

Charlotte Brody, RNCharlotte Brody, RN– Founder of “Health care without harm”, Executive Founder of “Health care without harm”, Executive

Director of “Commonweal” in Bolinas, CADirector of “Commonweal” in Bolinas, CA David Wallinga, MD, MPH David Wallinga, MD, MPH

– Director, Food and Health Program, Institute for Director, Food and Health Program, Institute for Agriculture and Trade Policy, Minneapolis, MNAgriculture and Trade Policy, Minneapolis, MN

Environmental Working GroupEnvironmental Working Group Physicians for Social ResponsibilityPhysicians for Social Responsibility

Industry and Govt. Research Industry and Govt. Research (Environmental Working Group)(Environmental Working Group)

The story of Bisphenol A (BPA):The story of Bisphenol A (BPA):– 1930’s: BPA A found to have synthetic estrogen properties1930’s: BPA A found to have synthetic estrogen properties– 1940’s: BPA used to make “polycarbonate” plastics1940’s: BPA used to make “polycarbonate” plastics– 1982: National Toxicology Program: Lowest Adverse Effect Level: 50 1982: National Toxicology Program: Lowest Adverse Effect Level: 50

mg/kg/dmg/kg/d– 1997: First study showing toxic effects in humans at much lower doses1997: First study showing toxic effects in humans at much lower doses– 2003: NIH nominates BPA for evaluation, and hires Scientific 2003: NIH nominates BPA for evaluation, and hires Scientific

International, an independent research contractor to evaluate effects of International, an independent research contractor to evaluate effects of BPABPA

– SI hand-pick 15 scientists for expert panel, but exclude scientists with SI hand-pick 15 scientists for expert panel, but exclude scientists with most research experience with BPA to minimize “bias”most research experience with BPA to minimize “bias”

– 2006: SI, and therefore FDA conclude that “BPA is safe” at current 2006: SI, and therefore FDA conclude that “BPA is safe” at current exposure levelsexposure levels

Industry and Govt. Research Industry and Govt. Research (Environmental Working Group)(Environmental Working Group)

The story of Bisphenol A (BPA):The story of Bisphenol A (BPA):

– February 2007: SI found to have corporate clients such as DOW and BASFFebruary 2007: SI found to have corporate clients such as DOW and BASF

– April 2007: Chapel Hill Panel: “BPA toxic at low levels”April 2007: Chapel Hill Panel: “BPA toxic at low levels”

– 2008: Health Canada deems BPA “toxic” based on scientific review2008: Health Canada deems BPA “toxic” based on scientific review Over 100 studies demonstrate toxic effects at low dose (breast and prostate Over 100 studies demonstrate toxic effects at low dose (breast and prostate

damage, early puberty, behavioral problems)damage, early puberty, behavioral problems)

– 2008: Nestle, Abbott and Mead Johnson announce intent to eliminate BPA2008: Nestle, Abbott and Mead Johnson announce intent to eliminate BPA

– 2009: 2009: Harvard study: students who drink from plastic bottles have 70% higher Harvard study: students who drink from plastic bottles have 70% higher

concentrations of BPA than those who drink from stainless steelconcentrations of BPA than those who drink from stainless steel Several states ban use of BPA in manufacturingSeveral states ban use of BPA in manufacturing