Latest Science on the Toxic Flame Retardant –
“Chlorinated Tris” (aka TDCPP)
Br
O
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O
Heather M. Stapleton
Assistant Professor
Duke University
Nicholas School of the Environment
Durham, NC 27708
Email: heather.stapleton@duke.edu
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www.environmentcalifornia.org
Outline
1. Introduction – The history of flame retardants: PBDEs and new use
chemicals
2. Background Information
a. What regulations govern the use of these chemicals in products?
b. What types of products contain flame retardants?
c. What are the concerns for exposure to FRs in these products?
3. Research Studies:
Identification of New Use FRs: What are the new chemicals being
used in polyurethane foam to meet flammability standards?
Toxicity of TDCPP: Is TDCPP a neurotoxciant and developmental
toxicant? How does its toxicity compare to the pesticide
chlorpyrifos?
4. Conclusions/ Discussion
PBDE Introduction
PBDEs in Swedish Human Milk
PBDE (ng/g lipid)
4
2003: pentaBDE and octaBDE
commercial mixtures banned by
European Union
3
2004: US manufacturers discontinued
production of pentaBDE and octaBDE
2
2007: 11 US states banned use of
pentaBDE and octaBDE
1
2010: PentaBDE and OctaBDE
commercial mixtures added to Stockholm
Convention
0
1970
1975
1980
1985
1990
1995
2000
2005
Year
Source: Norén and Meironyté, 2000; Meironyté, 2002
PBDEs in Human Samples From Around the World
(ng/g
PBDEs
lipid)
Total
Total
PBDE
conc.
(ppb
lipid)
1000
1000
North America
Europe
Japan
100
100
10
10
1
0.1
0.1
0.01
1970
1970
1980
1980
1990
1990
2000
2000
2010
2010
Total PBDE concentrations in human blood, milk and
From Hites et al., 2005
tissue (in ng/g lipid) shown as a function of sampling year.
Major Concerns about PBDEs:
• Rapidly accumulating in humans and environment
• Hormonal disruption
– Animal exposure studies suggest significant impacts on thyroid regulation and
estrogen/androgen pathways
– Associations between PBDEs and thyroid hormones (Turyk et al., 2008; Chevrier
et al., 2010) and reduced fecundability (Harley et al., 2010) in human population
• Developmental effects
– Irreversible learning/behavioral effects in young animals
– Decreased ovarian follicles, sperm counts
– Associations between cryptorchidism and PBDEs in male infants (Main et al.,
2007)
– Associations between PBDE exposure at birth and neurodevelopment in children
(Roze et al., 2009; Herbstman et al., 2010), and reduced birth weight (Chao et al.,
2007)
• Cancer?
– Structures similar to known carcinogens (PCBs, PBBs)
Regulations That Govern the Use of FRs
U.S. Furniture:
• California Technical Bulletin 117
• California Technical Bulletin 603
• Federal Mattress Flammability Standard (CFR 1633)
Electronics:
• Underwriters Laboratory Certifications for Insurance purposes (e.g.
UL 746 and -94 V-2 – E&E)
Textiles:
• Children’s Sleepwear (CPSC)
• Seats in Public Transportation (regulated by specific gov’t agency)
• Seats and Drapes in Public Buildings (NFPA 701, CA TB 133)
• Military tarps (Military)
Building and Construction: (variable)
What is TB 117?
• Promulgated by California Bureau of Home Furnishing and
Thermal Insulation, within the Department of Consumer Affairs
• Requires 12-second open flame testing for polyurethane inside
furniture
• Has required the use of large quantities of halogenated flame
retardants (FR)
• Additive FRs used for PUF
• CA standard affected furniture composition
throughout the U.S.
What Type of Products are Treated with Flame
Retardants in Your Home?
Sleep Positioners
Nursing Pillow
Human Exposure to Flame Retardant Chemicals
Flammability Regulations
(Residential = TB 117)
High FR Use in
Commercial Products
(polyurethane foam)
Off-Gassing to Air
Accumulation in Dust
Human Exposure
Diet
Objectives of Study
Because TB 117 appears to drive the use of FRs in foam
containing baby products, we conducted the following study:
1. To determine if the following baby products contain a halogenated flame
retardant:
-car seats, changing tables, portable mattresses, nursing pillows,
sleep positioners
2. To determine which flame retardants were found most frequently in these
products, and when identified, measure the concentration in the foam;
3. To determine if an X-Ray Fluorescence Analyzer can accurately detect
and quantify brominated and chlorinated flame retardants in foam
from these baby products
Environ. Sci. Tech. 45(12): 5323-5331
Methods
-Recruitment letters describing our study were distributed via email to
colleagues and parent listservs;
-Individuals interested in participating mailed a piece of foam (2 cm x 2 cm) to
the study team and filled out a short questionnaire;
-Foam samples were logged into a database and then split in two
(XRF and GC/MS Analysis conducted separately and blind)
-All foam pieces were first screened for the presence of a detectable flame
retardant (FR) using full scan GC/EI-MS and GC/ECNI-MS
-When a FR was positively identified (Mass Spec Database, NIST 2005)
a second quantitative analysis was performed on the foam to measure the
concentration of the FR in the foam using authentic standards.
Foam Samples Collected (n=101)
Baby Product
# of
Samples
Car Seats
21
Changing Table Pads
16
Sleeping Wedge/Positioner
15
Portable Mattresses
13
Nursing Pillows
11
Baby Carriers
5
Rocking Chairs
4
High Chairs
3
Infant Bath Sling
2
Baby Walkers
2
Misc. Samples: Stroller, bath toy, baby tub mat, Bumbo chair, toilet seat
Analysis of the Foam Samples
Foam
Step 1. Place a small piece of foam
into a test tube with dichloromethane
Step 2. Sonicate the test tube for 15 min.
Analysis of the Foam Samples
Step 3. Remove the dichloromethane,
filter out the particles, and then inject
the extract into a GC/MS*.
•Samples are run in full scan mode
•Signals detected are compared against
a NIST mass spectral database
•For commonly known FRs we also now
compare to authentic standards.
Gas Chromatograph Mass Spectrometer
(GC/MS)
*Some sample extracts also run by LC/MS-MS
Agilent Technologies Model 5975
1e+8
PentaBDE
Response
Detected in 4 samples:
- Car Seat (2)
- Portable Mattress
- Rocker
BDE 47
8e+7
BDE 99
6e+7
BDE 100
4e+7
2e+7
BDE 154
BDE 153
0
8
10
12
14
16
18
Time (min)
20
22
24
1e+8
TPP
Tri-aryl
phosphates
Firemaster® 550
Response
8e+7
6e+7
4e+7
2e+7
0
8
10
12
14
16
18
Time (min)
20
22
24
Detected in 17 Samples:
- Car Seat (8)
- Portable Mattress (4)
- Changing Table Pad (4)
- Rocking Chair (1)
Detected in 36 Samples:
- Car Seat (11)
- Changing Table Pad( 8)
- Sleeping Wedge (6)
- Portable Mattress (3)
TDCPP
- Baby Walker (2)
Tris (1,3-dichloroisopropyl) phosphate
- High Chair (2)
- Rocking Chair (1)
- Baby Carrier (1)
- Nursing Pillow (1)
- Infant Bath Sling (1)
8e+7
Response
6e+7
4e+7
2e+7
0
8
10
12
14
16
18
Time (min)
20
22
24
Response
3e+7
Detected in 14 Samples:
- Nursing Pillow (9)
- Infant Bath Sling (2)
- Baby Carrier (1)
- Sleeping Wedge (1)
- Portable Crib (1)
TCEP
Tris (2-chloroethyl) phosphate
2e+7
*Relatively low response of TCEP……and
“bump” suggests degradation…….
1e+7
0
10
15
Time (min)
20
25
2,2-bis(chloroethyl)triethylene bis[bis(2-chloroethyl)phosphate]
“V6”
TCEP
LC/MS-MS for TCEP and “V6”
V6
TCEP
TCEP
MS-MS (Agilent 6410B triple quadrupole)
Positive electrospray ionization
Gas: 350°C ; 10 L/min
Nebulizer: 40 psi
Capillary: 4000 V(+)
MS2 Scans: 250-620 m/z; fragmentor: 80V
V6
LC/HRMS Spectra of New Cl-OPFR
Relative Abundance
ObservedNL:
MS
5.89E5
638.9741
100
80
60
636.9769
40
642.9682
20
0
100
644.9649
632.9392
638.9747
60
7.03
100
NL:
2.96E5
Predicted
MS
C H O Cl
640.9717
80
RT: 0.00 - 10.00
17 33 8
6 P 2:
C 17 H 33 O 8 Cl 6 P 2
pa Chrg 1
636.9776
642.9688
40
20
644.9658
0
80
CABF17#1771
RT: 7.03 AV: 1 T:
FTMS + p ESI
Full ms
[250.00-2000.00]
640.9712
635
5.61
640
m/z
645
60
NL:
3.36E7
TIC F: FTMS
+ p ESI Full
ms
[250.002000.00] MS
CABF17
40
TCPP
8.96
Tris (1-chloro-2-propyl)phosphate
20
0.52 0.74 1.06
0
0
1
1.87 2.20 2.64 3.21 3.64
2
3
4.28
4
6.39
4.84 5.36
5
Time (min)
6
6.82
7.67
7
9.14
9.27
8.29 8.89
8
9
10
Detection of Flame Retardants
in Baby Products
Product
#
Samples
% with Flame
Retardant
Car Seat
21
100
Changing Table Pad
16
94*
Infant Sleep Positioners
15
53
Portable Mattresses (e.g “Pack-n-play”)
13
85*
Nursing Pillows
11
100
Baby Carriers (e.g. “Baby Bjorn”)
5
40
*one samples had chemicals in foam, but they were unidentifiable
Flame Retardants in Baby Foam
# of
Detects
Concentration
(mg/g foam)
PentaBDE
4
38 - 53
ƩTBB and TBPH (Firemaster 550)
17
6 - 43
Triphenyl phosphate and Triaryl phosphates
1
1 - 10
V6/Tris (2-chloro-ethyl) phosphate (TCEP)
15
Unknown
Unknown Cl-OPFR/TCPP
6
Unknown
Tris(1-chloro-2-propyl)phosphate (TCPP)
16
0.02 - 14
Tris(1,3-dichloro-2-propyl)phosphate (TDCPP)
36
0.05- 124
Peaks Unidentified
10
No Significant peaks observed
11*
Flame Retardant
* Phthalates present at low levels
Flame Retardants in Couch Foam (n=100)
# of
Detects
Flame Retardant
PentaBDE
18
ƩTBB and TBPH (Firemaster 550)
13
Triphenyl phosphate and Triaryl phosphates
9**
V6/Tris (2-chloro-ethyl) phosphate (TCEP)
1
Unknown Cl-OPFR/TCPP
0
Tris(1-chloro-2-propyl)phosphate (TCPP)
0
Tris(1,3-dichloro-2-propyl)phosphate (TDCPP)
44
Peaks Unidentified
15
* Similar to tricresyl phosphates
(Preliminary data; Research in Progress)
Cl
Chlorinated Organophosphates
O
O
O
P
Tris(2-chloroethyl)phosphate (TCEP)
O
• Carcinogen
Cl
• Phased out in Europe
Cl
• California Prop 65 list
Cl
O
O P
Tris(1-chloro-2-propyl)phosphate (TCPP)
O
• Replaced TCEP
O
• Little toxicity information
Cl
Cl
Tris(1,3-dichloro-2-propyl)phosphate (TDCPP)
Cl
O
O P
Cl
Cl
O
• Phased out of use in children’s sleepwear in late 1970s due to
mutagenicity (Gold et al. 1978)
O
• Probable carcinogen (WHO, US CPSC)
Cl
Cl
Cl
• Replaced tris(2,3-dibromopropyl)phosphate in children’s sleepwear in
1977 in US
• In Vitro Neurotoxicity Similar to Chlorpyrifos (Dishaw et al., 2011)
How Toxic is TDCPP?
Objectives:
1. To determine the toxicity of TDCPP in rat neuronal cells and
compare its toxicity to the known neurotoxicant pesticide
chloryprifos; (published paper)
2. To determine the toxicity of TDCPP to fish embryos to better
understand its potential effects on development
(work currently in progress)
PC 12 In Vitro Cell Model
• Transformed rat neuronal cell line11
– Higher dosing levels necessary
• Established in vitro model of neural development12,13
– Replicates in vivo effects of OP pesticides
• Mechanisms of toxicity
11. Greene and Tischler 1976
12. Song et al 1998
13. Jameson et al 2006
µM
60
TD
µM CP
P
T
50
D
µM CP
P
TD
C
PP
a
20
a
µM
80
C
o
50 ntr
µM ol
C
PF
4 Day Exposure
10
20
TD
µM CP
P
T
50
D
µM CP
P
TD
C
PP
10
C
o
50 ntr
µM ol
C
PF
DNA (mg/dish)
Effects on Cell Numbers
100
6 Day Exposure
a
b
b
b
c
40
20
0
Dishaw et al., 2011
Effects on Ability of Cells to Grow
Properly
300
300
250
b
a
200
a,b
150
100
Dopaminergic
c
a
a
250
200
150
100
50
50
B
PP
TD
PP
TC
50
µM
EP
µM
50
50
µM
TC
C
PP
TD
on
µM
C
50
C
PP
50 TD
µM CP
TD P
C
PP
µM
TD
µM
10
20
on
t
µM rol
C
PF
C
tr
ol
0
0
50
TH (nmol/mg DNA/h)
Dopaminergic
TH (nmol/mg DNA/h)
350
Dishaw et al., 2011
TDCPP is Present in Indoor Environments
• TDCPP detected in indoor air collected from office buildings in
Boston, MA (Webster et al., 2010, geometric mean value of 1.2
ng/m3) and in indoor air filters from hotels in Japan (Takigami et al
2009)
• TDCPP measured in dust collected from Boston, MA (Webster et al.,
2010)
• TDCPP concentrations ranging from <20 to 630,000 ppb; average
concentrations highest in automobile dust (26,105 ng/g)
• TDCPP measured in dust collected from Durham, NC (Research in
Progress) Range from 416 – 96,810 ppb (average 5980 ppb).
• Significant associations between TDCPP in house dust and a
decrease in free Thyroxine (T4) and an increase in prolocatin
(Meeker and Stapleton, 2010)
Children’s Exposure to Flame Retardants in Dust
•
Children are spending more time indoors
• Indoor environments are often more polluted than
outdoor environments
•
Children have a high number of hand-to-mouth contacts
http://www.theage.com.au/articles/2006/05/02/1146335739915.html
Conclusions (Part 1)
• Flame retardants (FR) were detected in more than 80% of the baby
products tested, and all but one was halogenated;
• TDCPP, and Firemaster 550, appear to be the dominant FRs used
in polyurethane foam in products sold in the U.S. (both in baby
products and couches);
• TDCPP is as potent a neurotoxicant as the pesticide chlorpyrifos in
rat neuronal cells in vitro;
• TDCPP exposure in zebrafish embryos affects survivorship and
induces developmental abnormalities, similar to chlorpyrifos.
• TDCPP is present in indoor air and dust in almost all homes in the
U.S. Exposure to children is higher than adults from dust exposure.
What Industry Will Try to Tell You
• The European Union Risk Assessment Demonstrates that TDCPP is
Safe
• Response: This risk assessment lacked any recent measured
data on TDCPP; nor did it evaluate children’s exposure to
TDCPP from use of baby products
• Removing TDCPP as a flame retardant will decrease fire safety and
put more children in danger
• Response: This is not true. Suitable replacements are available
to replace TDCPP in foam. The EPA conducted an alternatives
assessment for polyurethane foam in 2005
A Daycare Infant Mattress Certified to
Meet CFR 1633 (Federal Flammability
Open Flame Standard)
Foam removed for analysis and
Identification of Flame Retardant
Acknowledgements
•
•
Research funding provided by National Institutes of Health
(Grant number R01 ES016099)
Collaborators and Colleagues:
Dr. Thomas Webster
Boston Univ.
•
•
•
Dr. Marie Lynn Miranda
Duke Univ.
Dr. Arlene Blum, Dr. Susan Klosterhaus, Rebecca Anthopolos (Duke University),
Deborah Watkins (Boston University), Saskia van Bergen
Laboratory Group: Sarah Eagle, Smriti Sharma, Dr. Craig Butt, Dr. Ellen Cooper,
Pamela Noyes (PhD student), Elizabeth Davis (PhD student), Simon Roberts (PhD
student), Laura Dishaw (PhD student), Alex Keller (undergraduate),
Study Participants