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PBDE’s: the 21 st Century PCB

PBDE’s: the 21 st Century PCB . Toxicity of Polybrominated Flame Retardants Catherine Thomasson, MD Oregon PSR. Introduction. Polybrominated diphenyl ethers (PBDEs) are commonly used (209 congeners) PBDEs are chemically similar to PCBs Human health studies have not been conducted

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PBDE’s: the 21 st Century PCB

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  1. PBDE’s: the 21st 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 • Reproductive and developmental disruption • Endocrine disruption • 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. 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 Why PBDE’s…. & Why NOT

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

  6. Major Industrial Products • Deca-BDE – • Polymers for textile backing, electrical & electronic equipment • More pure 95% Deca- • Octa-BDE • Plastic housings esp. office equipment • More complex mixture of penta, octa, hexaPBDE’s • PentaBDE • Flexible polyurethane foam (up to 30%) • 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) • House Dust • 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 • 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 (and food) • Large inter-individual differences • Increasing time trends – levels 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 • Cytochrome P450s 2B1/2, 3A • UDP-glucuronyl transferase • DBDE – Liver carcinogen • Rats and mice; high dose • Toxic to the developing brain • Toxic to the developing reproductive system • Endocrine disruptors

  16. Basic Toxicology 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

  17. 80 40 60 100 120 140 160 70 130 The Significance of Small Effects: EFFECTS OF A SMALL SHIFT IN IQ DISTRIBUTION IN A POPULATION OF 260 MILLION mean 100 6.0 million 6.0 million "mentally retarded" "gifted" I.Q.

  18. 40 80 100 120 140 160 60 70 130 5 Point Decrease in Mean IQ mean 95 57% INCREASE IN "Mentally Retarded” Population 2.4 million 9.4 million "gifted" "mentally retarded" I.Q.

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attention, verbal ability, information processing • Psychomotor development • Sustained activity, high level play • Withdrawn, depressed behavior • Hyperactivity Preteen • Word and reading comprehension • Full scale and verbal IQ • 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

  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 • Intestinal absorption of nutrients and contaminants is greater; e.g. calcium, lead • Skin is more permeable • Hand to mouth activity • Close to the ground- high exposure to dust, carpets • 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’sInternational 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

  30. Examples of Alternatives to DecaBDE

  31. Examples of Alternatives to DecaBDE

  32. Less Toxic Flame Retardants

  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

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