PBDE’s: the 21PBDE’s: the 21stst Century Century PCBPCB

Toxicity of Polybrominated Flame Toxicity of Polybrominated Flame RetardantsRetardants

Catherine Thomasson, MDCatherine Thomasson, MDOregon PSROregon PSR

IntroductionIntroduction

Polybrominated diphenyl ethers (PBDEs) are Polybrominated diphenyl ethers (PBDEs) are commonly used (209 congeners)commonly used (209 congeners)PBDEs are chemically similar to PCBsPBDEs are chemically similar to PCBsHuman health studies have not been conductedHuman health studies have not been conductedAnimal studies show:Animal studies show: Nervous system toxicityNervous system toxicity Reproductive and developmental disruptionReproductive and developmental disruption Endocrine disruptionEndocrine disruption Cancer (at high doses)Cancer (at high doses)

Birbbaum, LS. Sarskal DF. Environmental Health Perspectives (2004) 112:3-17

NTP. Toxiciology and Carcinogenesis Studies CAS No. 11630-13-5 Research Triangle Park, NC: National Toxicology Program, 1986

Chemical StructuresChemical Structures

Polychlorinated Biphenyls

(PCBs)

Polychlorinated dibenzo-p- dioxins (PBDDs)

Why PBDE’s…. & Why NOTWhy PBDE’s…. & Why NOTFlame retardants save livesFlame retardants save livesBrominated flame retardants Brominated flame retardants are most cost effectiveare most cost effective3 major classes of 3 major classes of brominated Flame brominated Flame RetardantsRetardants

Global, transboundary Global, transboundary problemproblemPersistence in environmentPersistence in environmentBioaccumulationBioaccumulationToxicity in animalsToxicity in animalsData gaps in humansData gaps in humans

Global Market Demand for PBDEs Global Market Demand for PBDEs in 2001 (Metric tons)in 2001 (Metric tons)

America Europe Asia All Others Total

Deca BDE 24,500

7,600

23,000 1,050

56,100

Octa BDE

1,500

610

1,500

180

3,790

Penta BDE

7,100

150

150

150

7,500

TBBPA 18,000 11,600 89,400

600 119,000

Major Industrial ProductsMajor Industrial Products

Deca-BDE – Deca-BDE – Polymers for textile backing, Polymers for textile backing,

electrical & electronic electrical & electronic equipmentequipment

More pure 95% Deca-More pure 95% Deca-

Octa-BDE Octa-BDE Plastic housings esp. office Plastic housings esp. office

equipmentequipment More complex mixture of More complex mixture of

penta, octa, hexaPBDE’spenta, octa, hexaPBDE’s

PentaBDEPentaBDE Flexible polyurethane foam Flexible polyurethane foam

(up to 30%)(up to 30%) Cushions; mattresses; carpet Cushions; mattresses; carpet

paddingpadding

Characteristics of PBDEs like PCB’sCharacteristics of PBDEs like PCB’s

Solids with low solubility in waterSolids with low solubility in water

Lower numbers of bromines are Lower numbers of bromines are more bioaccumulative and more bioaccumulative and persistentpersistent

Strong adsorption to Strong adsorption to sediment/sludge with low sediment/sludge with low breakdownbreakdown

Bioaccumulation - (Penta, Octa)Bioaccumulation - (Penta, Octa)

Long Range Transport - Long Range Transport - Evidence of remote Evidence of remote contamination (e.g., Arctic)contamination (e.g., Arctic)

Persistence- t Persistence- t 1/21/2 Atmospheric >2 Atmospheric >2 days; Water >2 mos.; Soil, days; Water >2 mos.; Soil, sediment >6 mos.sediment >6 mos.

Pathways of Exposure?Pathways of Exposure?PBDEs often do not have direct PBDEs often do not have direct chemical bonds to productschemical bonds to products

Indoor Air >> outdoor air levelsIndoor Air >> outdoor air levels May account for ~4%, on average, of May account for ~4%, on average, of

daily intake by inhalation (could be much daily intake by inhalation (could be much higher for some)higher for some)

House DustHouse Dust Wide rangeWide range

Recent study: N = 10. Range: 705-69,000 ppb; Mean: Recent study: N = 10. Range: 705-69,000 ppb; Mean: 12,100 ppb; Median: 2,500 ppb12,100 ppb; Median: 2,500 ppb

Levels in US, UK>>Europe, JapanLevels in US, UK>>Europe, Japan

Computer dismantlers-very high Computer dismantlers-very high levels of DecaBDE.levels of DecaBDE.

Daily U.S. Adult Daily U.S. Adult ΣΣPBDE IntakePBDE Intake

1,274

212

511

811

198

379

0

200

400

600

800

1000

1200

1400

Meat Fish Dairy Products

PB

DE

s in

tak

e (

pg

/kg

bo

dy

wt.

da

y)

20-39 year old Males 20-39 year old Fem ales

PBDEs in HumansPBDEs in Humans

Pattern of congeners is different Pattern of congeners is different

from commercial mixtures from commercial mixtures

(and food)(and food)

Large inter-individual differencesLarge inter-individual differences

Increasing time trends – levels Increasing time trends – levels

doubling every 2-5 yearsdoubling every 2-5 years

North American Levels ~ 10-100 times levels North American Levels ~ 10-100 times levels in Europe/Japanin Europe/Japan

Trends of Toxin LevelsTrends of Toxin Levels

3,980

122

807

210,675

700

34

62,000

58

450

26,370

1

10

100

1,000

10,000

100,000

1,000,000

Dioxins Dibenzofurans C o-planerP CBs

Mono-orthoP CBs

PBDEs

pg

/g o

r p

pt

lipid

1973 serum

2003 serum

PBDE levels in US and NWPBDE levels in US and NW

Where Where PBDEs are PBDEs are banned, banned, levels in levels in humans humans decreasedecrease

Flame Retardants in the Bodies of Pacific Northwest Residents: A Study on Toxic Body Burden, Northwest Environment Watch: September 29, 2004

Highest PBDE Levels (max 63 ppm) Highest PBDE Levels (max 63 ppm) Yet Found in Wildlife or Humans:Yet Found in Wildlife or Humans:

Seabird Eggs (Forster tern) from San Seabird Eggs (Forster tern) from San Francisco BayFrancisco Bay

Occupational Exposure to Occupational Exposure to Deca-PBDE in Rubber WorkersDeca-PBDE in Rubber Workers

270 ng/g highest recorded BDE-209 270 ng/g highest recorded BDE-209 levellevel

Workers wore gloves and cotton Workers wore gloves and cotton overallsoveralls

Median BDE-209 was 35ng/g in Median BDE-209 was 35ng/g in workers compared to 2.5 in non-workers compared to 2.5 in non-workersworkers

BDE-209 was only 32% of BDE level BDE-209 was only 32% of BDE level in workers. Rest of elevated BDE’s in workers. Rest of elevated BDE’s were octa and nona-BDE, indicating were octa and nona-BDE, indicating metabolic breakdown.metabolic breakdown.

Mammalian ToxicityMammalian ToxicityLiver toxicityLiver toxicity Enzyme InductionEnzyme Induction

Cytochrome P450s 2B1/2, 3ACytochrome P450s 2B1/2, 3A

UDP-glucuronyl transferaseUDP-glucuronyl transferase

DBDE – Liver carcinogen DBDE – Liver carcinogen Rats and mice; high doseRats and mice; high dose

Toxic to the developing brainToxic to the developing brain

Toxic to the developing Toxic to the developing reproductive systemreproductive system

Endocrine disruptorsEndocrine disruptors

Toxicity-related Concepts: specific processes disrupted by neurodevelopmental toxicants

proliferation radiation, ethanol, mercury, cholinesterase inhibitors

migration radiation, mercury, ethanol

differentiation ethanol, nicotine, mercury, lead

synaptogenesis radiation, ethanol, lead, triethyl tin, parathion, PCBs

gliogenesis & decreased thyroid, ethanol, lead, (PDBE)

myelinization

apoptosis ethanol, lead, mercury

signaling ethanol, cholinesterase inhibitors, mercury, lead, PCBs

Basic Toxicology

The Significance of Small Effects: The Significance of Small Effects: EFFECTS OF A SMALL SHIFT IN IQ DISTRIBUTION IN A EFFECTS OF A SMALL SHIFT IN IQ DISTRIBUTION IN A

POPULATION OF 260 MILLIONPOPULATION OF 260 MILLION

160140120100806040

70 130I.Q.

mean 100

6.0 million "gifted"

6.0 million "mentally retarded"

5 Point Decrease in Mean IQ5 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.

PCBs: PCBs: PERVASIVE PERVASIVE

DEVELOPMENTAL EFFECTSDEVELOPMENTAL EFFECTS Early ChildhoodEarly Childhood

Memory, attention, verbal ability, information Memory, attention, verbal ability, information processingprocessing

Psychomotor developmentPsychomotor development Sustained activity, high level playSustained activity, high level play Withdrawn, depressed behaviorWithdrawn, depressed behavior HyperactivityHyperactivity

PreteenPreteen Word and reading comprehensionWord and reading comprehension Full scale and verbal IQFull scale and verbal IQ Memory and attentionMemory and attention

Neuro toxicity of PDBE’sNeuro toxicity of PDBE’s

No human studiesNo human studies

Concern with levels risingConcern with levels rising

We are at 10% of levels known to affect We are at 10% of levels known to affect neurodevelopment in ratsneurodevelopment in rats

DecaBDE-Animal ResearchDecaBDE-Animal Research

In adult mice, DecaBDE produced irreversible changes in brain

function that worsened with age

Deca was absorbed in neonatal mice.

Levels in the brain continued to increase in mice exposed only once suggesting a targeting of the brain or increased uptake.

10-65% of Deca was absorbed from the diet of lab rats.

•Viberg H, et. Al. Toxicol Sci. 2003;76:112-20.

•National Toxicology Program. NC: National Toxicology Program, 1986.

PDBE Effect on ThyroidPDBE Effect on Thyroid

Thyroid hormone needed for brain development.Thyroid hormone needed for brain development.

PBDE & PCB similar in chemical structure to PBDE & PCB similar in chemical structure to thyroid hormone.thyroid hormone.

PBDE metabolites bind to transthyretin an PBDE metabolites bind to transthyretin an important binding protein especially for the fetus important binding protein especially for the fetus to carry T4 in the blood.to carry T4 in the blood.

Induction of UDP-glucuronyl transferase at high Induction of UDP-glucuronyl transferase at high doses to increase breakdown of T4doses to increase breakdown of T4

Endocrine DisruptionEndocrine Disruption

AhR Effects-Same receptor induced by dioxinAhR Effects-Same receptor induced by dioxin

Anti-Androgenic- delay in puberty in male rats Anti-Androgenic- delay in puberty in male rats

Estrogenic Activity-Using study methods developed Estrogenic Activity-Using study methods developed to identify other chemicals with PCB like action to identify other chemicals with PCB like action called the Endocrine Disrupter Screening Programcalled the Endocrine Disrupter Screening Program

Hydroxy-PBDEs Hydroxy-PBDEs Sulfotransferase inhibited which is needed for Sulfotransferase inhibited which is needed for

metabolism of estrogen (mostly metabolism of estrogen (mostly in vitro)in vitro)

DecaBDE degrades into more DecaBDE degrades into more toxic productstoxic products

DecaBDE is photolytically unstable, forming breakdown products in both natural and artificial media.

Seven breakdown products of DecaBDE accumulated in carp exposed to DecaBDE.

Trout fed DecaBDE were found to have increasing levels of hexaBDE when not further exposed to any PBDEs indicating DecaBDE breaks down once ingested and metabolized. •Söderström Environ Sci Technol. 2004 Jan 1;38(1):127-32.

•Stapleton. Environ Sci Technol. 2004 Jan 1;38:112-9.

•Kierkegaard. SETAC-Europe Congress, Copenhagen, 1995

Risks to fetus, infants and Risks to fetus, infants and childrenchildren

PBDEs cross the placenta PBDEs cross the placenta

Infants and children more Infants and children more susceptible to most toxinssusceptible to most toxins

Blood/brain barrier not fully developedBlood/brain barrier not fully developed Intestinal absorption of nutrients and Intestinal absorption of nutrients and

contaminants is greater; e.g. calcium, contaminants is greater; e.g. calcium, leadlead

Skin is more permeableSkin is more permeable Hand to mouth activityHand to mouth activity Close to the ground- high exposure to Close to the ground- high exposure to

dust, carpetsdust, carpets Receive mother’s toxins through breast Receive mother’s toxins through breast

milkmilk

Impetus for AlternativesImpetus for Alternatives

EU’s Directive on Restriction of EU’s Directive on Restriction of Hazardous Substances (RoHS)Hazardous Substances (RoHS) mandates the phase out of all mandates the phase out of all polybrominated biphenyls (PBBs) and polybrominated biphenyls (PBBs) and PBDEs in new electrical and electronic PBDEs in new electrical and electronic equipment sold in the European Union equipment sold in the European Union starting in 2006starting in 2006

EcolabelingEcolabeling requires plastics >25gm to requires plastics >25gm to be bromine and chlorine free.be bromine and chlorine free.

““Brominated flame retardants should Brominated flame retardants should not be used where suitable not be used where suitable replacements are available, and future replacements are available, and future efforts should encourage the efforts should encourage the development of further substitutes.”development of further substitutes.” - - World Health Organization’sWorld Health Organization’s International Program on Chemical International Program on Chemical Safety 1999Safety 1999

Approaches to AlternativesApproaches to Alternatives

Physically separating Physically separating heat producing heat producing elementselements

Use of naturally flame Use of naturally flame resistant materialsresistant materials

Other chemicals-Other chemicals-halogen freehalogen free

Alternatives are Available Alternatives are Available

National Electronic National Electronic Manufacturers Manufacturers Association set flame Association set flame retardant standards. retardant standards.

Numerous alternatives Numerous alternatives meet UL94 standard.meet UL94 standard.

Examples of Alternatives to Examples of Alternatives to DecaBDEDecaBDE

Printed circuit Printed circuit boardsboards

(Computers, cell (Computers, cell phones, stereos, phones, stereos, VCR, DVD players)VCR, DVD players)

Material: EpoxyMaterial: Epoxy

NFR- Polyphenylene sulphide

NH- Reactive nitrogen and phosphorus constituents, Ammonium polyphosphate, and Aluminum trihydroxide

Sony - Developed bromine free circuit boards for television sets, VCRs and DVD players

Hitachi- Developed phosphorous based flame retardants for printed circuit boards

Reinforced Plastics Reinforced Plastics in transportation in transportation & & Technical Technical LaminatesLaminates

*Organic phosphorus compounds

*Polyethylene with magnesium hydroxide

Volvo-eliminated all PBDE’s

Examples of Alternatives to Examples of Alternatives to DecaBDEDecaBDE

**Electronic **Electronic HousingsHousings

**Wiring Parts**Wiring Parts

NFR-Polyphenylene Sulfide

NH-Ammonium polyphosphate & Aluminum tryhydroxide

Toshiba: Flame resistant plastic

Panasonic/MatushitaDeveloped halogen free low voltage internal wires

Switches Switches SocketsSockets

NFR- Ceramics and self extinguishing plastics

SchurterSchurter- Five types of thermal ciruit breakers comply with RoHS

Injection Molding Parts

Used with polypropylene and polyethylene-**Ammonium polyphosphate

**Magnesium hydroxide

Dell-Triarylphosphate esters used in mechanical plastic parts

Examples of Alternatives to Examples of Alternatives to DecaBDEDecaBDE

Furniture, Furniture, textilestextiles

NFR-Wool & Leather

NH-Ammonium polyphosphate

Serta- mattresses use fire barrier technology, no PBDEs

IKEA-Phased out BFR’s and is working to be halogen free

Wire & Cable Wire & Cable

InsulationInsulation

NFR- Triaryl Phosphates The Axon Group-The Axon Group-Since Since 2003, all Axon cables for 2003, all Axon cables for automotive industry has automotive industry has complied with RoHScomplied with RoHS

Stadium Bleachers

NFR- Metal

NH-Triaryl phosphates isopropylated

Less Toxic Flame RetardantsLess Toxic Flame RetardantsRed PhosphorusRed Phosphorus Low human and ecological harm if not mixed with white Low human and ecological harm if not mixed with white

or yellow phosphorusor yellow phosphorus

Resorcinol bisResorcinol bis

(diphenyl-(diphenyl-phospate (RDP)phospate (RDP)

Minimal Effects on human health, little data available Minimal Effects on human health, little data available on bioaccumulation but chemically unlikely.on bioaccumulation but chemically unlikely.

(ATH) Aluminum(ATH) Aluminum

TrihydroxideTrihydroxide

Mineral flame retardant. Low impact on fish and Mineral flame retardant. Low impact on fish and wildlife, non-toxic to humans. (most common FR)wildlife, non-toxic to humans. (most common FR)

Ammonium Ammonium PolyphosphatePolyphosphate

Used in plastics. Low impact on ecosystem and Used in plastics. Low impact on ecosystem and humans-Recommended.humans-Recommended.

MagnesiumMagnesium

HydroxideHydroxide

Insufficient human data, but chemically biodegradable.Insufficient human data, but chemically biodegradable.

MelamineMelamine Low health effects, no evidence of cancer induction, Low health effects, no evidence of cancer induction, low bioaccumulationlow bioaccumulation

Antimony Antimony TrioxideTrioxide

Teratogenic, bioaccumulative, reproductive toxin, Teratogenic, bioaccumulative, reproductive toxin, carcinogeniccarcinogenic

Northwest CompaniesNorthwest Companies

Intel—Does not use Intel—Does not use PBDE’s in its productsPBDE’s in its products

Hewlett-Packard-Monitor Hewlett-Packard-Monitor housings now contain housings now contain phosphorus based flame phosphorus based flame retardants. retardants.

Companies who Have or are Companies who Have or are planning phase out of DecaBDEplanning phase out of DecaBDE

Apple, Intel, IBM, Brother, Daikin, Dell, Apple, Intel, IBM, Brother, Daikin, Dell, Ericsson, Hewlett Packard, Ericsson, Hewlett Packard, Panasonic/Matsushita, Mitsubishi, NEC, Panasonic/Matsushita, Mitsubishi, NEC, Samsung, Compaq, Sharp, Sony, Samsung, Compaq, Sharp, Sony, Toshiba, Hitachi, Fujitsu Siemens, Toshiba, Hitachi, Fujitsu Siemens, ViewSonic, Konica/Minolta, Schurter, Bivar ViewSonic, Konica/Minolta, Schurter, Bivar (Irvine, CA), Motorola and Xerox. (Irvine, CA), Motorola and Xerox.

Advice to patientsAdvice to patients

Breast milk is the healthiest food for babies

Avoid crumbling furniture foam

Reduce consumption of animal fat, especially fish high in fat such as sardines, farm-raised salmon, and other local fish from waterways with fish advisories

Vacuum areas with infants and toddlers frequently to lower dust levels

What is being done about What is being done about PBDEs?PBDEs?

Penta and Octa BDE no longer Penta and Octa BDE no longer being producedbeing producedProducts with Penta and Octa Products with Penta and Octa banned in EU, CA, NY & MIbanned in EU, CA, NY & MIDecaBDE slated for phase out DecaBDE slated for phase out in ME & HIin ME & HIBusinesses like Intel, HP & Businesses like Intel, HP & IKEA voluntarily phasing out IKEA voluntarily phasing out PBDEsPBDEsCurrent legislation in OR & WA Current legislation in OR & WA to phase out Penta, Octa, & to phase out Penta, Octa, & DecaBDEDecaBDE

Endorsers of SB 962Endorsers of SB 962

Oregon Pediatric SocietyOregon Pediatric SocietyOregon Academy of Family Physicians Oregon Academy of Family Physicians Oregon Pediatric Nurse Practitioner AssnOregon Pediatric Nurse Practitioner AssnOregon Nurses AssociationOregon Nurses AssociationNurse Practitioners of OregonNurse Practitioners of OregonMedical Society of Metropolitan PortlandMedical Society of Metropolitan PortlandMarch of Dimes, Oregon ChapterMarch of Dimes, Oregon ChapterOregon Parent Teacher AssociationOregon Parent Teacher AssociationOregon Developmental Disabilities CoalitionOregon Developmental Disabilities CoalitionOregon Council Trout UnlimitedOregon Council Trout UnlimitedOregon Environmental CouncilOregon Environmental CouncilOregonianOregonianOregon Family Action Coalition Team (FACT)Oregon Family Action Coalition Team (FACT)Oregon Learning Disabilities AssociationOregon Learning Disabilities AssociationOregon Center for Environmental HealthOregon Center for Environmental HealthOregon State Public Interest Research GroupOregon State Public Interest Research GroupSierra Club, Oregon ChapterSierra Club, Oregon Chapter

Medical Soc. Metropolitan Portland