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