Transcript PBDE's the 21st Century PCB

st
21
PBDE’s: the
PCB
Century
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
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
Chemical Structures
Polychlorinated Biphenyls
(PCBs)
Polychlorinated dibenzo-pdioxins (PBDDs)
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
Global Market Demand for PBDEs
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
11,600
89,400
600
119,000
TBBPA 18,000
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

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Flexible polyurethane foam
(up to 30%)
Cushions; mattresses; carpet
padding
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.
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.
Daily U.S. Adult ΣPBDE Intake
20-39 year old Males
PBDEs intake (pg/kg body wt.day)
1400
20-39 year old Females
1,274
1200
1000
811
800
600
511
379
400
212
198
200
0
Meat
Fish
Dairy Products
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
Trends of Toxin Levels
1,000,000
210,675
62,000
100,000
1973 serum
26,370
pg/g or ppt lipid
2003 serum
10,000
1,000
3,980
450
807
122
100
700
58
34
10
1
D io xins
D ibe nzo f ura ns
C o - pla ne r
P CBs
M o no - o rt ho
P CBs
P B D Es
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
Highest PBDE Levels (max 63 ppm)
Yet Found in Wildlife or Humans:
Seabird Eggs (Forster tern) from San
Francisco Bay
Occupational Exposure to
Deca-PBDE in Rubber Workers
270 ng/g highest recorded BDE209 level
Workers wore gloves and cotton
overalls
Median BDE-209 was 35ng/g in
workers compared to 2.5 in nonworkers
BDE-209 was only 32% of BDE
level in workers. Rest of elevated
BDE’s were octa and nona-BDE,
indicating metabolic breakdown.
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
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 &
myelinization
decreased thyroid, ethanol, lead, (PDBE)
apoptosis
signaling
ethanol, lead, mercury
ethanol, cholinesterase inhibitors,
mercury, lead, PCBs
The Significance of Small Effects:
EFFECTS OF A SMALL SHIFT IN IQ DISTRIBUTION IN A
POPULATION OF 260 MILLION
mean 100
6.0 million
"gifted"
6.0 million
"mentally retarded"
40
80
60
70
100
I.Q.
120
140
130
160
5 Point Decrease in Mean IQ
mean 95
57% INCREASE
IN
"Mentally
Retarded”
Population
2.4 million
"gifted"
9.4 million
"mentally retarded"
40
80
60
70
100
I.Q.
120
140
130
160
PCBs: PERVASIVE
DEVELOPMENTAL EFFECTS
Early Childhood

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
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
Neuro toxicity of PDBE’s
No human studies
Concern with levels rising
We are at 10% of levels known to affect
neurodevelopment in rats
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.
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
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)
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
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
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
Approaches to Alternatives
Physically separating
heat producing
elements
Use of naturally flame
resistant materials
Other chemicalshalogen free
Alternatives are Available
National Electronic
Manufacturers
Association set flame
retardant standards.
Numerous alternatives
meet UL94 standard.
Examples of Alternatives to
DecaBDE
Printed circuit
boards
(Computers, cell
phones, stereos,
VCR, DVD players)
Material: Epoxy
Reinforced Plastics
in transportation
&
Technical
Laminates
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
*Organic phosphorus
compounds
*Polyethylene with
magnesium hydroxide
Volvo-eliminated all
PBDE’s
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- Five types of
thermal ciruit breakers
comply with RoHS
Injection
Molding Parts
Used with polypropylene
Dell-Triarylphosphate
and polyethyleneesters used in mechanical
**Ammonium polyphosphate plastic parts
**Magnesium hydroxide
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
Less Toxic Flame Retardants
Red Phosphorus Low human and ecological harm if not mixed with white
or yellow phosphorus
Resorcinol bis
(diphenylphospate (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.
Magnesium
Hydroxide
Insufficient human data, but chemically biodegradable.
Melamine
Low health effects, no evidence of cancer induction,
low bioaccumulation
Antimony
Trioxide
Teratogenic, bioaccumulative, reproductive toxin,
carcinogenic
Northwest Companies
Intel—Does not use
PBDE’s in its products
Hewlett-Packard-Monitor
housings now contain
phosphorus based flame
retardants.
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.
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
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
Endorsers of SB 962
Medical Soc. Metropolitan
Portland
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