Structural isomers of perfluorinated alkyl acids, useful tool for source
elucidation?
Anna Kärrman
MTM Research Centre Örebro University, Sweden
Outline
– Structural isomers of perfluorinated alkyl acids– Sources – Analysis and implication on quantification
– Ocurrence in human blood– Distribution in the environment
– Case study after AFFF contamination
– Useful tool for source elucidation?
Introduction – Perfluorinated alkyl acids
Polyfluorinated compounds
Telomer alcohols, Polyfluorinated phosphoric acids, acrylates, olefins...
Perfluorinated compounds
PFOA, PFOS, ...
F
FF
F F
F F
F F
F F
F F
F F
F F
H H
H HO
F
FF
F F
F F
F F
F F
F F
F F
F F
H H
H H
O
OH
O
P
FF
F
F
FF
FF
FF
FF
FF
FF
F
SO
OO
Electro-Chemical Fluorination CellsOctanesulfonyl fluoride
HF + electricity
Perfluorooctanesulfonyl fluoride)(POSF)
Sulfonates (PFOS)Quarternary AmmoniumSaltsAminesAmphoterics
alkylamine
N-Alkylperfluorooctane sulfonamide(FOSA)
AmidesOxazolidinonesAlkoxylatesSilanesCarboxylates (PFOA)
ethylene carbonate
N-Alkylperfluorooctanesulfonamidoethanol
(FOSE)
AdipatesPhosphate EstersFatty Acid EsthersAlcoholsUrethanesCopolymersAcrylates
References : 3M och DuPont
PFOS
PFOA
Synthesis - Electrochemical fluorination
• Impregnation of leather, fabric
• Treatment of paper, e.g. food contact paper
• Fire-fighting foam• Metal plating• Photoindustry
ECF results in mixtures branched/linear isomers (30/70)
CF2=CF2Tetrafluoroethylene
F(CF2CF2)nITelomer A Iodide F(CF2CF2)n-1COO-
n=2-8, even carbon, straight chain
F(CF2CF2)nCH2CH2ITelomer B Iodide F(CF2CF2)nCOO-
F(CF2CF2)nCH2CH2OHTelomer B Alcohol
F(CF2CF2)nCH2CH2OC-(O)CH=CH2Telomer AcrylateMonomer
References : 3M och DuPont * with exception of isopropyl geometry
PFOA
Synthesis - Telomerization
Polymers och elastomers - the major fluoropolymer being PTFE
•Cooking utensils•High temperature app.
– Engines, oils, heat exchangers
Fire-fighting foam• 6:2 FluoroTelomerSulfonate
Telomerization gives the linear structure exclusivly*
PFOS on the Stockholm Convention
Acceptable purpose:• Photo-imaging• Photo-resist and anti-reflective coatings for semi-
conductors• Etching agent for compound semiconductors and
ceramic filters• Aviation hydraulic fluids• Metal plating (hard metal plating)
– only in closed-loop systems• Certain medical devices (such as ethylene
tetrafluoroethylene copolymer (ETFE) layers and radio-opaque ETFE production, in-vitro diagnostic medical devices, and CCD colour filters)
• Fire-fighting foam• Insect baits for control of leaf-cutting ants from Atta
spp. and Acromyrmex spp.
Specific exemption:• Photo masks in the semiconductor and liquid crystal
display (LCD) industries• Metal plating (hard metal plating)• Metal plating (decorative plating)• Electric and electronic parts for some colour printers
and colour copy machines• Insecticides for control of red imported fire ants and
termites• Chemically driven oil production• Carpets• Leather and apparel• Textiles and upholstery• Paper and packaging• Coatings and coating additives• Rubber and plastics
Structural isomers of PFOS identified in technical mixtures
enantiomers
Chromatographic separation
Time22.50 25.00 27.50 30.00
%
0
100
22.50 25.00 27.50 30.00
%
0
100 498.95 > 98.74.56e3
Area
26.331247
09061001 Sm (Mn, 2x3) 2: MRM of 11 Channels ES- 498.95 > 79.7
3.44e326.33
24.61
22.36
25.41
26.92
Time3.90 4.00 4.10 4.20
3.90 4.00 4.10 4.20
4: MRM of 6 Channels ES- 498.95 > 98.7 (PFOS99)
1.83e54.10
4.00
4: MRM of 6 Channels ES- 498.95 > 79.7 (PFOS80)
1.84e54.10
3.98
Acquity C18 50*2.1 mm, 1.7µmH2 0:MeOH:2mM NH4 Ac
Acquity C18 100*2.1 mm, 1.7µmH2 0:MeOH:AcN:2mM NH4 Ac
499>99
499>80
Waters Acquity UPLC-Quattro Premier XE
MS - negative electrospray
pfos
80 100 120 140 160 180 200 220 240 260 280 300 320 340 360 380 400 420 440 460 480 500 520 540 560 580 600m/z0
100
%
080916PFOS 1 (0.302) Scan ES- 5.51e6499
77
27710980
999891
127 250183136153154 219217192 233 255
311309283 369345319 333
449399397407
413 443481452 497
500
531502527 557541 578 598
PFOS Full scan MS1 cone voltage 65 V
FF
F
F
FF
FF
FF
FF
FF
FF
F
SO
OO
Molecular ion weight m/z 499
Waters Quattro Premier XE
Product ion scan PFOS
pfos
80 100 120 140 160 180 200 220 240 260 280 300 320 340 360 380 400m/z0
100
%
0
100
%
080916PFOS_7 1 (0.302) Daughters of 499ES- 7.34e680
8080
9998 99
080916PFOS_6 1 (0.302) Daughters of 499ES- 4.07e680
79
80
80
99 99
169168130
280
64 eV
32 eV
FF
F
F
FF
FF
FF
FF
FF
FF
F
SO
OO
[SO3-]
[FSO3-]
“0”-serie [M-CF3 (CF2 )x-] “9”-serie [M- SO3 (CF2 )x
-]
Waters Quattro Premier XE
Branching affects CID
• Most published methods use m/z 99 for quantification– some isomers do not
produce the m/z 99 ion
• Missing fragments can be used for mass spectrometric separation
Langlois et al. Fluoros 2005
Response factors - PFOS
4,4 5,5 4,5 3,5 5 4 3 6 2 1 Linear
499>80 0.75 2.03 1.43 1.58 1.95 1.72 1.08 1.11 0.52 - 1
499>99 - 0.15 - 0.12 0.37 0.28 0.35 0.80 0.71 0.35 1499>130 3.1 27 1.3 27 14 5.7 16 4 0.64 - 1
PFOA
L‐PFOS
1‐CH3PFOS
6‐CH3PFOS4,4‐diCH3PFOS
3/4/5‐CH3PFOS
2‐CH3PFOS
3,5‐diCH3PFOS
4,5/5,5‐diCH3PFOS
Berger U., Kaiser MA., Kärrman A., Barber, JL., van Leeuwen, SPJ. 2011. Recent developments in trace analysis of poly- and perfluoroalkyl substances. Analytical and Bioanalytical Chemistry 400(6) 1625-1635
Quantification using linear response
4,4 5,5 4,5 3,5 5 4 3 6 2 1 Linear
499>80 0.75 2.03 1.43 1.58 1.95 1.72 1.08 1.11 0.52 - 1
499>99 - 0.15 - 0.12 0.37 0.28 0.35 0.80 0.71 0.35 1499>130 3.1 27 1.3 27 14 5.7 16 4 0.64 - 1
PFOA
L‐PFOS
1‐CH3PFOS
6‐CH3PFOS4,4‐diCH3PFOS
3/4/5‐CH3PFOS
2‐CH3PFOS
3,5‐diCH3PFOS
4,5/5,5‐diCH3PFOS
overestimate
underestimate
Response factors – PFOA isomers
4,4 5,5 4,5 3,5 5 3 4 6 2 Linear
413>369 <0.01 - 0.11 - 0.17 0.03 0.26 0.59 0.01 1
413>219 - 43 - - 11 - 0.22 1 - 1
413>169 0.01 - 0.66 0.12 0.16 0.02 - 3.12 0.03 1
L‐PFOA/2‐CH3PFOA
4,4‐diC
4
3,5‐diCH3PFOA
3/4/6‐CH3PFOA5‐CH3PFOA
4,5‐diCH3PFOA
4,4/5,5‐diCH3PFOA
Quantification using linear response
4,4 5,5 4,5 3,5 5 3 4 6 2 Linear
413>369 <0.01 - 0.11 - 0.17 0.03 0.26 0.59 0.01 1
413>219 - 43 - - 11 - 0.22 1 - 1
413>169 0.01 - 0.66 0.12 0.16 0.02 - 3.12 0.03 1
L‐PFOA/2‐CH3PFOA
4,4‐diC
4
3,5‐diCH3PFOA
3/4/6‐CH3PFOA5‐CH3PFOA
4,5‐diCH3PFOA
4,4/5,5‐diCH3PFOA
overestimate
underestimate
399>119
Challenges in the identification of isomers PFHxS
• Pregnandiol sulfonate isomers
• 399>119 is ”clean”
• 399>80 better than 399>99
• Chromatographic separation possible but can be difficult with ”ordinary” C18
Chan et. al 2009. Rapid communications in mass spectrometry, 23 :405-1410.
399>80
399>99
PFHxS in human serum
Challenges in the identification of isomers PFOS
499>99
499>80a b
PFOS (2.8 ng/g) in Salmon liver
Full scan
MRM
Silcock, P.J., Kärrman, A., Worrall, K., van Bavel, B. 2009. Organohalogen Compounds 71, 1210-1215
498
499
Salmon liver RADAR Spectra
PFOS499>80
XIC 499 m/z
Isotopic interference onPre-cursor mass
b
498
= Simultaneously MRM and Full scan
Product ion experiments
deoxytaurocholate
taurocholatea
b 79.994.9
106.9123.9290.1
In accordance with Benskin et. al 2007. Analytical chemistry, 79 :6455-6464
Occurrence of isomers in human blood
ECF: ~70% linear isomerTelomerization: 100% linear isomer
Preferential accumulation of the linear structure is expected, based on lab studies on rodents
Time24.00 26.00 28.00
26.29
24.40
25.27
Example of PFOA and PFOS in human blood
499>80
PFOS
30 ng/mL
16.00 18.00 20.00 22.00
%
0
100 413>369
PFOA
150 ng/mL
19.23
0
10
20
30
40
50
60
70
80
90
100
L-PFOS 1-PFOS 2-PFOS 3/4/5-PFOS 6-PFOS 4,4-PFOS 4,5/5,5-PFOS
3,5-PFOS
Perc
enta
ge (%
)
Isomers
Low 1-4 ng/mL
Medium 10-20 ng/mL
High 20-60 ng/mL
PFOS isomers in Swedish blood
Males, n=30
95%CI
Berger U., Kaiser MA., Kärrman A., Barber, JL., van Leeuwen, SPJ. 2011. Recent developments in trace analysis of poly- and perfluoroalkyl substances. Analytical and Bioanalytical Chemistry 400(6) 1625-1635
Individual results in the low (1-4 ng/mL) level group
0
10
20
30
40
50
60
70
80
90
L-PFOS 1-PFOS 2-PFOS 3/4/5-PFOS
6-PFOS 4,4-PFOS
4,5/5,5-PFOS
3,5-PFOS
perc
enta
ge o
f the
con
cent
ratio
n (%
)
3.3 ng/mL
3.5 ng/mL
PFOS isomer pattern in human blood from different countries
0
10
20
30
40
50
60
70
80
90
Unidentified (0.86)
Unidentified (0.9)
Dimethyl substituted
Dimethyl substituted
3/4/5-PFOS 1/6-PFOS L-PFOS Unidentified (1.03)
Are
a%
Sweden Australia UK Standard product
Kärrman et al. 2007 Environment International, 33 782-788.
0
10
20
30
40
50
60
70
80
90
100
L-PFOA 3/4/6-PFOA
perc
enta
ge(%
)
Isomers
Low 0.5-2.8 ng/mL
Medium 1.3-4.6 ng/mL
High 2.1-8.4 ng/mL
Ski wax technician 99 ng/mL
PFOA isomers in Swedish blood
Males, n=31
Isomer distribution in the environment
Isomer profiles in the environment around a AFFF point source
www.google.com
Bergen Airport
27
Soil chromatograms
PFOS
499>99
499>80
1-PFOS3,5- and 4,4-PFOS
28
PFOA
413>219
413>169
413>369
5-PFOA
PFOS isomers in soil
29Kärrman, A., Elgh-Dalgren, K., Lafossas, C., Møskeland, T. 2011. ”Environmental distribution of structural isomers of perfluoroalkyl acids after aqueous fire-fighting foam (AFFF) contamination”. Environmental Chemistry 8(4) 372-380
PFOS isomers in soil
0
10
20
30
40
50
60
70
80
90
100
L‐PFOS 1‐PFOS 2‐PFOS 6‐PFOS 3/4/5‐PFOS 3,5‐PFOS 4,5/5,5‐PFOS 4,4‐PFOS
% ot total con
centrtation (ng/g d.w.)
0 m 10 m 40 m 75 m 100 m 150 m 200 m
63% 84%
30
….water, sediment, biota
Seepage water n=3
Sedimentn=3
Crab n=1
Fish liver n=4
59.6%78.5%
79.7% 88.4%
31
PFOA isomers
Soil Water
……not detected in sediment and biota
32
PFOS isomers in marine mammals
33
Ho S
Ri S
MiW
Ha P, Fi W Pi W, Ws D
Greenland
NorwayIceland
0
1
2
3
4
5
6
7
8
9
10
ringed seal 1984ringed seal 1998
2060
8284868890929496
ringed seal 2006
pilot whale 1986pilot whale 2001pilot whale 2006
% o
f tot
al c
once
ntra
tion
L‐PFOS 1‐PFOS 2‐PFOS 6‐PFOS 3/4/5‐PFOS 3,5‐PFOS 4,5/5,5‐PFOS 4,4‐PFOS
Rotander A, Kärrman A, van Bavel B, Polder A, Rigét F, Auðunsson GA, Víkingsson G, Gabrielsen GW, Bloch D, Dam M.“Increasing levels of long-chain perfluorocarboxylic acids (PFCAs) in Arctic and North Atlantic marine mammals 1984-2009” Chemosphere In Press
PFOS isomers in mink from Sweden
0%
20%
40%
60%
80%
100%
West coast West coast Central urban Central urban North Inland North Inland North Inland
4,4‐PFOS
4,5/5,5‐PFOS
3,5‐PFOS
3/4/5‐PFOS
6‐PFOS
2‐PFOS
1‐PFOS
L‐PFOS
Rotander A, Kärrman A, et al., Not published
Useful tool for source elucidaton?
Useful tool for source elucidation?
Pitfalls:• Biotic and abiotic fractionation of structural
isomers– Branched isomers more water soluable compared
to the linear isomer– Different bioaccumulation, linear lower excretion
rate
soil water biota
36
Useful tool for source elucidation?
Oppertunities:• Tracking exposure sources
– Differentiate between ”historic” (ECF) and ”current” (telomerization) production
• Human pattern influenced by unknown factor, which can help determine the exposure source
– Precursor metabolization?
??
Thanks for your attention