1. PBDE’s: the 21 st Century PCB Toxicity of Polybrominated Flame Retardants Catherine Thomasson, MD Oregon PSR

2. Introduction Polybrominated diphenyl ethers (PBDEs) are commonly used (209 congeners) PBDEs are chemically similar to PCBs Human health studies have not been conducted Animal studies show: Nervous system toxicity Nervous system toxicity Reproductive and developmental disruption Reproductive and developmental disruption Endocrine disruption Endocrine 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

3. Chemical Structures Polychlorinated Biphenyls (PCBs) Polychlorinated dibenzo-p- dioxins (PBDDs)

4. Why PBDE’s…. & Why NOT Flame retardants save lives Brominated flame retardants are most cost effective 3 major classes of brominated Flame Retardants Global, transboundary problem Persistence in environment Bioaccumulation Toxicity in animals Data gaps in humans

5. Global Market Demand for PBDEs in 2001 (Metric tons) AmericaEuropeAsia All Others Total Deca BDE24,500 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 TBBPA18,00011,600 89,400 600 119,000

6. Major Industrial Products Deca-BDE – Polymers for textile backing, electrical & electronic equipment Polymers for textile backing, electrical & electronic equipment More pure 95% Deca- More pure 95% Deca- Octa-BDE Octa-BDE Plastic housings esp. office equipment Plastic housings esp. office equipment More complex mixture of penta, octa, hexaPBDE’s More complex mixture of penta, octa, hexaPBDE’sPentaBDE Flexible polyurethane foam (up to 30%) Flexible polyurethane foam (up to 30%) Cushions; mattresses; carpet padding Cushions; mattresses; carpet padding

7. Characteristics of PBDEs like PCB’s Solids with low solubility in water Lower numbers of bromines are more bioaccumulative and persistent Strong adsorption to sediment/sludge with low breakdown Bioaccumulation - (Penta, Octa) Long Range Transport - Evidence of remote contamination (e.g., Arctic) Persistence- t 1/2 Atmospheric >2 days; Water >2 mos.; Soil, sediment >6 mos.

8. Pathways of Exposure? PBDEs often do not have direct chemical bonds to products Indoor Air >> outdoor air levels May account for ~4%, on average, of daily intake by inhalation (could be much higher for some) May account for ~4%, on average, of daily intake by inhalation (could be much higher for some) House Dust Wide range Wide range Recent study: N = 10. Range: 705-69,000 ppb; Mean: 12,100 ppb; Median: 2,500 ppb Levels in US, UK>>Europe, Japan Levels in US, UK>>Europe, Japan Computer dismantlers-very high levels of DecaBDE.

9. Daily U.S. Adult ΣPBDE Intake

10. PBDEs in Humans Pattern of congeners is different from commercial mixtures from commercial mixtures (and food) (and food) Large inter-individual differences Increasing time trends – levels doubling every 2-5 years doubling every 2-5 years North American Levels ~ 10-100 times levels in Europe/Japan

11. Trends of Toxin Levels

12. PBDE levels in US and NW Where PBDEs are banned, levels in humans decrease Flame Retardants in the Bodies of Pacific Northwest Residents: A Study on Toxic Body Burden, Northwest Environment Watch: September 29, 2004

13. Highest PBDE Levels (max 63 ppm) Yet Found in Wildlife or Humans: Seabird Eggs (Forster tern) from San Francisco Bay

14. Occupational Exposure to Deca-PBDE in Rubber Workers 270 ng/g highest recorded BDE- 209 level Workers wore gloves and cotton overalls Median BDE-209 was 35ng/g in workers compared to 2.5 in non- workers BDE-209 was only 32% of BDE level in workers. Rest of elevated BDE’s were octa and nona-BDE, indicating metabolic breakdown.

15. Mammalian Toxicity Liver toxicity Enzyme Induction Enzyme Induction Cytochrome P450s 2B1/2, 3A UDP-glucuronyl transferase DBDE – Liver carcinogen Rats and mice; high dose Rats and mice; high dose Toxic to the developing brain Toxic to the developing reproductive system Endocrine disruptors

16. Toxicity-related Concepts : specific processes disrupted by neurodevelopmental toxicants proliferationradiation, ethanol, mercury, cholinesterase inhibitors migrationradiation, mercury, ethanol differentiationethanol, nicotine, mercury, lead synaptogenesisradiation, ethanol, lead, triethyl tin, parathion, PCBs gliogenesis & decreased thyroid, ethanol, lead, (PDBE) myelinization apoptosisethanol, lead, mercury signalingethanol, cholinesterase inhibitors, mercury, lead, PCBs Basic Toxicology

17. The Significance of Small Effects: EFFECTS OF A SMALL SHIFT IN IQ DISTRIBUTION IN A POPULATION OF 260 MILLION 160140120100 80 6040 70130 I.Q. mean 100 6.0 million "gifted" 6.0 million "mentally retarded"

18. 5 Point Decrease in Mean IQ 16014012010080 60 40 mean 95 70130 2.4 million " gifted " 9.4 million " mentally retarded " 57% INCREASE IN "Mentally Retarded” Population I.Q.

19. PCBs: PERVASIVE DEVELOPMENTAL EFFECTS Early Childhood Memory, attention, verbal ability, information processing Memory, attention, verbal ability, information processing Psychomotor development Psychomotor development Sustained activity, high level play Sustained activity, high level play Withdrawn, depressed behavior Withdrawn, depressed behavior Hyperactivity HyperactivityPreteen Word and reading comprehension Word and reading comprehension Full scale and verbal IQ Full scale and verbal IQ Memory and attention Memory and attention

20. Neuro toxicity of PDBE’s No human studies Concern with levels rising We are at 10% of levels known to affect neurodevelopment in rats

21. DecaBDE-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.

22. PDBE Effect on Thyroid Thyroid hormone needed for brain development. PBDE & PCB similar in chemical structure to thyroid hormone. PBDE metabolites bind to transthyretin an important binding protein especially for the fetus to carry T4 in the blood. Induction of UDP-glucuronyl transferase at high doses to increase breakdown of T4

23. Endocrine Disruption AhR Effects-Same receptor induced by dioxin Anti-Androgenic- delay in puberty in male rats Estrogenic Activity-Using study methods developed to identify other chemicals with PCB like action called the Endocrine Disrupter Screening Program Hydroxy-PBDEs Sulfotransferase inhibited which is needed for metabolism of estrogen (mostly in vitro) Sulfotransferase inhibited which is needed for metabolism of estrogen (mostly in vitro)

24. DecaBDE degrades into more toxic 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

25. Risks to fetus, infants and children PBDEs cross the placenta Infants and children more susceptible to most toxins Blood/brain barrier not fully developed Blood/brain barrier not fully developed Intestinal absorption of nutrients and contaminants is greater; e.g. calcium, lead Intestinal absorption of nutrients and contaminants is greater; e.g. calcium, lead Skin is more permeable Skin is more permeable Hand to mouth activity Hand to mouth activity Close to the ground- high exposure to dust, carpets Close to the ground- high exposure to dust, carpets Receive mother’s toxins through breast milk Receive mother’s toxins through breast milk

26. Impetus for Alternatives EU’s Directive on Restriction of Hazardous Substances (RoHS) mandates the phase out of all polybrominated biphenyls (PBBs) and PBDEs in new electrical and electronic equipment sold in the European Union starting in 2006 Ecolabeling requires plastics >25gm to be bromine and chlorine free. “Brominated flame retardants should not be used where suitable replacements are available, and future efforts should encourage the development of further substitutes.” - World Health Organization’s International Program on Chemical Safety 1999

27. Approaches to Alternatives Physically separating heat producing elements Use of naturally flame resistant materials Other chemicals- halogen free

28. Alternatives are Available National Electronic Manufacturers Association set flame retardant standards. Numerous alternatives meet UL94 standard.

29. Examples of Alternatives to DecaBDE Printed circuit boards (Computers, cell phones, stereos, VCR, DVD players) Material: 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 in transportation & Technical Laminates *Organic phosphorus compounds *Polyethylene with magnesium hydroxide Volvo-eliminated all PBDE’s

30. Examples of Alternatives to DecaBDE **Electronic Housings **Wiring Parts NFR-Polyphenylene Sulfide NH-Ammonium polyphosphate & Aluminum tryhydroxide Toshiba: Flame resistant plastic Panasonic/MatushitaDe veloped halogen free low voltage internal wires Switches Sockets NFR- Ceramics and self extinguishing plastics Schurter Schurter- 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

31. Examples of Alternatives to DecaBDE Furniture, textiles 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 Insulation NFR- Triaryl Phosphates The Axon Group-Since 2003, all Axon cables for automotive industry has complied with RoHS Stadium Bleachers NFR- Metal NH-Triaryl phosphates isopropylated

32. Less Toxic Flame Retardants Red Phosphorus Low human and ecological harm if not mixed with white or yellow phosphorus Resorcinol bis (diphenyl- phospate (RDP) Minimal Effects on human health, little data available on bioaccumulation but chemically unlikely. (ATH) Aluminum Trihydroxide Mineral flame retardant. Low impact on fish and wildlife, non-toxic to humans. (most common FR) Ammonium Polyphosphate Used in plastics. Low impact on ecosystem and humans-Recommended. MagnesiumHydroxide Insufficient human data, but chemically biodegradable. Melamine Low health effects, no evidence of cancer induction, low bioaccumulation Antimony Trioxide Teratogenic, bioaccumulative, reproductive toxin, carcinogenic

33. Northwest Companies Intel—Does not use PBDE’s in its products Hewlett-Packard-Monitor housings now contain phosphorus based flame retardants.

34. Companies who Have or are planning phase out of DecaBDE Apple, Intel, IBM, Brother, Daikin, Dell, Ericsson, Hewlett Packard, Panasonic/Matsushita, Mitsubishi, NEC, Samsung, Compaq, Sharp, Sony, Toshiba, Hitachi, Fujitsu Siemens, ViewSonic, Konica/Minolta, Schurter, Bivar (Irvine, CA), Motorola and Xerox.

35. Advice 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

36. What is being done about PBDEs? Penta and Octa BDE no longer being produced Products with Penta and Octa banned in EU, CA, NY & MI DecaBDE slated for phase out in ME & HI Businesses like Intel, HP & IKEA voluntarily phasing out PBDEs Current legislation in OR & WA to phase out Penta, Octa, & DecaBDE

37. Endorsers of SB 962 Oregon Pediatric Society Oregon Academy of Family Physicians Oregon Pediatric Nurse Practitioner Assn Oregon Nurses Association Nurse Practitioners of Oregon Medical Society of Metropolitan Portland March of Dimes, Oregon Chapter Oregon Parent Teacher Association Oregon Developmental Disabilities Coalition Oregon Council Trout Unlimited Oregon Environmental Council Oregonian Oregon Family Action Coalition Team (FACT) Oregon Learning Disabilities Association Oregon Center for Environmental Health Oregon State Public Interest Research Group Sierra Club, Oregon Chapter Medical Soc. Metropolitan Portland