# Presentation: 327797

## Brominated Flame Retardants:Cause for Concern?

- Linda S. Birnbaum, Ph.D., D.A.B.T.
- Michael DeVito, Ph.D.
- NHEERL/ORD/US EPA

## Why BFRs?

- Fire Regulations require a high degree of protection
- Flame Retardants save lives
- Fires generate PHDDs/PHDFs
- 75 different BFRs
- 50% are new substances ( testing required)

## BFRs

- Large variety of chemicals
- ~75 BFRs – and not all alike!
- BFRs may be as common as PCBs
- Banned production of PCBs with less information than we currently have on BFRs
- Identify data gaps and research agenda
- Large variety of issues

## Production of BFRs

- Worldwide - ~500,000 tons/yr of bromine
- $2 billion/year industry
- BFRs- ~ 40% of total bromine usage
- Bromine
- Br-chemicalsBr-polymersBFRs
- Worldwide demand in 2000 for BFRs
- 300x106 BFRs kg/year
- Greatest increased use – Asia
- US usage - ~100X106 kg/yr

## Why should there be action at international level?

- Global, transboundary problem
- Persistence
- Potential for bioaccumulation
- Potential risk for future generations
- Very limited knowledge base
- Precautionary Principle
- Miminize production, emissions, use, exposure
- (Risk/Risk Trade-offs?)

## Major BFR Classes

- Br-Bisphenols
- Br-Diphenyl Ethers
- Br-Cyclododecane
- Br-phenols
- Br-phthallic acid derivatives
- +++++others

## Global Market Demand for BFRs in 1999 (metric tons)

|  | America | Europe | Asia | Total |
| --- | --- | --- | --- | --- |
| TBBPA | 21,600 | 3,800 | 85,000 | 121,300 |
| HBCD | 3,100 | 8,900 | 3,900 | 15,900 |
| DBDE | 24,300 | 7,500 | 23,000 | 54,800 |
| OBDE | 1,370 | 450 | 2,000 | 3,820 |
| PeBDE | 8,290 | 210 | ----- | 8,500 |

## Tetrabromobisphenol A(TBBPA)

## TBBPA(Tetrabromobisphenol A)

- Reactive and Additive BFR
- Phenolic –OH-polymerization
- Major Use –printed circuit boards
- Detected in air, sediment, sewage, sludge
- 	Highly lipophilic, low water solubility
- Limited data in biota
- 	Dimethyl-TBBPA metabolite
- 		eliminated in bile
- 	Little retained in tissues

## TBBPA (con.)

- Acute tox data – oral LD50: 5-10 g/kg
- Low chronic toxicity
- Not teratogenic or mutagenic
- Affects thyroid hormones; estrogenic
- Soil Degradation –aerobic and anaerobic
- t1/2~2mos
- Photodegradation
- t 1/2~<<1day

## Health Effects of TBBPA

- Immunotoxic
- Inhibits T cell activation : blocks CD25 (<3μM)
- Hepatotoxic
- Toxic to primary hepatocytes: destroys mitochondria; membrane dysfunction (inhbits CYP2C9)
- Endocrine Disrupting

## Health Effects of TBBPA (con)Endocrine Disruption

- AhR Effects
- Not relevant for commercial product
- Thyroid
- TBBPA>T4 in relation to binding to transthyretin
- Observed *in vivo*
- Estrogenic
- Inhibits sulfotransferase (decreases estrogen clearance)
- Mostly *in vitro* data

## Hexabromocylododecane(HBCDD)

## HBCDD(hexabromocyclododecane)

- Major use – polystyrene resins>textiles
- ~10,000tons/yr
- Highly lipophilic, low water solubility, low vapor pressure, high BCF, persistent
- Ecotox –
- Algae, daphnia, NOEC = 3 ug/L
- Fish, LC 50>water solubility; PNEC=.03ug/L

## HBCDD (con)

- Toxicity
- High absorption; mild irritant and skin sensitizer; liver effects after repeated exposures (LOEL (rats) ~13 mg/kg/day)
- Need more info: repeated dose studies, repro tox
- Concern for Occupational Settings
- Fulfills POPs Critera
- Persistence, bioaccumulative, toxic, long range transport

## PBDEs

## Major Industrial Products(~67 metric tons/year)

- DBDE – largest volume (75% in EU)
- 97% DBDE; 3% NBDE
- Polymers, electronic equipment>textiles
- OBDE
- 6%HxBDE; 42%HpBDE; 36% OBDE; 13%NBDE; 2%DBDE – multiple congeners (unclear if any PeBDE)
- Polymers, esp. office equipment
- PeBDE
- Textiles – esp. polyurethane foams
- Recommended ban in EU(no production/only import)
- Mainly PeBDE+TeBDE, some HxBDE

## Properties

- Solids with low solubility (< 1ug/kg), high log Kow (~6.2)
- Lower congeners are more bioaccumulative, persistentStrong adsorption to soil/sediment/sludge;No significant bodegradation in air/water
- Bioaccumulation - BCF > 5000, Log Kow >5
- Long Range Transport - Evidence of remote contamination (e.g., Arctic)
- Persistence- t 1/2 Atmospheric >2 days;Water >2 mos; Soil, sediment >6 mos

## Sources of Environmental Release

- Polymer Processing
- Formulating/applying to textiles
- Volatilization and leaching during use
- Particulate losses over use/disposal

## PBDEs in Biotic and Abiotic Samples

- Air: 47>99>100>153=154
- Sediment: 99>47 (pattern reflects commercial PeBDE); also some nona and deca
- Sewage Sludge: 1-3mg/kg in US; pattern ~PUFs
- Point sources (~DBDE) --->0.1-5 mg/kg
- Biota: 47>99=100 except if near manufacturing site (pattern does NOT reflect commercial PBDEs)
- Invertebrates_<_Fish<<marine mammals

## PBDEs (con)Ecotoxicity

- PeBDE>>OBDE>DBDE
- Highly toxic to invertebrates
- DBDE/OBDE
- May be low risk to surface water organism and top predators
- Concern for waste water, sediment, and soil organisms
- CONCERNS:
- Presence of lower brominated congeners in OBDE
- Photolytic and/or anaerobic debromination
- Formation of PBDDs/PBDFs

## Slide 22

## PBDEs (con)Photolytic Debromination

- DBDE-NBDE+OBDE (t 1⁄2 = 15 hr)
- OBDE-HpBDE+HxBDE (t 1⁄2 = 40 hr)
- PeBDE-lower PBDEs+ PBDFs
- Composition of photoproducts is not the same as the commercial PBDE mixtures

## Slide 24

## PBDEs (con)Congener Patterns

- Commercial Products
- Environmental Samples
- Human Tissue Samples

## Exposure Routes

- Fish
- Dairy
- Meat
- OTHER?

## Pharmacokinetics of PBDEs

- Absorption – DBDE is poorly absorbed
- Distribution – lipid binding is important
- Fat: 47>99>>>209
- Liver: covalent binding from 99,209
- Metabolism – hydroxylation, debromination, O-methylation
- Excretion – feces is major route

## Neurotoxic Effects

- Developmental Neurotoxicants
- Perinatal; neonatal
- 47,99,153,209
- Spontaneous behavior (mice)/hyperactivity
- Permanent changes in brain function
- Developmental exposure -Increased susceptibility of adults exposed to low doses of PBDEs

## Endocrine Disrupting Effects

- AhR Effects
- not relevant for commercial BFRs
- But combustion can produce PBDDs/PBDFs
- Thyroid
- OH-PBDE metabolites bind to transthyretin
- Effects on T4 seen *in vivo*
- Estrogenic
- OH-PBDEs
- Inhibit sulfotransferase (decreases estrogen clearance)
- Mostly *in vitro* data

## Key Issues:  PBDEs 

- Potential adversity to human health and environment
*In vivo* and *in vitro* studies
- Liver effects; Developmental neurotoxicity; Endocrine disruption
- Contaminants and Combustion Products –PBDFs/PBDDs (Are they present in the environment and in biota?)
- Research Needs
- t 1⁄2 in environment; Remote monitoring data; Chronic health effects
- End of life cycle – release? Breakdown?

## PBDEs in Human Samples

- Pattern of congeners is different from commercial mixtures (and food)
- 47>99 in US and Europe(others: 100,153,183, 209?)
- In Japanese, 99 and 153>47
- Large interindividual differences
- Increasing time trends – levels doubling every 2-5 years
- PBDEs and PCBs levels are not correlated
- In most samples today, PCBs>PBDEs
-  different sources and/or time sequence

## Slide 32

## Slide 33

## Slide 34

## Time Trends of Biotic Levels

- Rapid increases from 70s thru 90s
- Maybe slight decrease in Sweden
- Ban on use of PeBDE?
- Levels still increasing in America
- Continued use of PeBDE?
- ARE LEVELS HIGH ENOUGH TO SEE EFFECTS??? NEED MORE TOX DATA!

## What next?

- More systematic human and environmental monitoring
- More tox data
- Focus on congeners present in people and wildlife, NOT commercial products since they are altered in the environment