Document JrLe2oN9ey1ZX8N5eQOjgmwz2
AR226-2701
AR226-2701
TORONTO WORKSHOP MATERIALS
September 13-14,2004
Measuring Physical Chemical Properties
& Analytical
M ary A. Kaiser uPont Central Research September 13,14, 2004
# P H ) CCAS
Cmmmmie Centerffft naytm i Sciences
Why not model, rather than measure?
Because these compounds are not well-behaved or predictable.
In ilThe miracles o f science"1
What is "not well-behaved or predictable"?
EPA O P P T P B T P r o file r (used fo r chemicals fo r which there is no experimental data)
Should not be used for the following:
High Molecular W eight Compounds Mixtures Surfactants Highly Fluorinated Compounds Chemicals with Unknown or Variable Composition Inorganic Chemicals Reactive Chemicals Salts (Organic Salts) http://w w w .pbtprofiler.net/chem icals.asp
IS
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Uniqueness of Fluorinated Compounds
C-F bond
Bond energy *C-F *C-H c -ci
116 kcal/mole 99 kcal/mole 79 kcal/mole
Pyrolysis 8Fluorocarbons tend to split the C-C bond rather than the C-F bond
4
Uniqueness of Fluorinated Compounds C-F bond
"Many of these compounds have chemical and physical properties strikingly different from the hydrogen analogs or from analogous compounds of the other halogens where they exist."
Advanced Inorganic Chemistry, F. A. Cottton and G. Wilkinson, Interscience Publishers, New York, 1966,
Method Development Considerations
Use governmental resources as guidelines Maximize use of blanks and spikes Use isotopically enriched or radiolabel
standards
. fi
ai
US Governmental Resources
W W W .EPA.gov/quality/ "...goal is to ensure that environmental programs and decisions are supported by data of the type and quality needed and expected fo r their intended use, and that decisions involving the design, construction, and operation of environmental technology are supported by appropriate quality assured engineering standards and practices."
EPA Quality Manual fo r Environmental Programs, 530 A l, May 5, 2000, page 1-1.
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# I I HI
US Governmental Resources
W W W .O SH A .gov/dts/sltc/m ethod s/om eprotocol Vindex.html Method Evaluation Guidelines
"...a uniform and practical means for evaluating air sampling and analytical methods."
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US Governmental Resources
WWW.FDA.gov/cder/guidance/index.htm Guidance for Industry, Bioanalytical Method Validation "...procedures such as gas chromatography (GC), high-pressure liquid chromatography (LC), combined GC and LC mass spectrometric (M S ) procedures such as LC-MS, LC-MS-MS, GC-MS, and GC-MS-MS..."
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Method Validation
Critical to demonstrate:
Accuracy Precision S p e c ific ity > L in e a rity - LLOQ Recovery Storage stability
Data Acceptability Criteria
Resolution of the chromatographic peak Defined acceptability criteria for recoveries Non-detects in instrument blanks Analyte response at LLOQ >5x matrix blank <20% deviation of standards from nominal
concentration at LLOQ (<15% above LLO Q ) Quality control samples (QC's) within 15% of
nominal value
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Criteria for Repeat Analyses
Poor chromatography Retention times d rift more than +4% within an
analytical run Unacceptable calibration curve (correlation
coefficient <0.9925 .e., R2 should be >0.985) QC's fail Samples outside assay range Inconsistent replicate analyses Sample processing errors; equipment failure
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What do we know today?
What information is currently available?
What additional information is needed?
What level of scientif ic certainty is required?
Physical Properti
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Fluorotelomer Alcohols: Physical Properties
CAS# Molar mass (g/mol) Melting point (C)
Boiling point (C)
4-2 Fluorotelomer
Alcohol 2043-47-2
264
140-143* 1200 (at 50C)2; 992 (at
6-2 Fluorotelomer
Alcohol 647-42-7
364.1
75-80/14mm*
108 (a t 35C)2:
8-2 Fluorotelomer
Alcohol1 678-39-7
8-2 Fluorotelomer
O lef in 21652-58-4
464.12
446.11
46-47*
112-114 at 10mm*
i 1146-147*
3 (a t 21C);
254 (at 25C)4,
10-2
Fluorotelomer
Alcohol
865-86-1 564
! ! ! |
92-93*
!
111-112/10 mm*
1.4 (a t 35C)2,
i 1 !!
Vapor Pressure 25C)4: 252 (at 713 (a t 25C)4: 45.90 (at
(Pa) 25 C f
145.2 (at 25C)5 25C)5
14.9 (at 25C)**
144 (a t 25 C)4: 13.27 (a t 25C)5
W ater solubility (m g/Lat25C)
0.71+0.04663 0.137+0.053 0.001**
[Log Kow i
3.5-5.5** 2272 +/-
5.93** 50,100-
jKoc
umm
1868**
316,200**
....... :
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Fluorotelomer Alcohols: Physical Properties
CAS #
4-2 6-2 8-2 8-2 10-2
Fluorotelom er Fluorotelom er Fluorotelom er Fluorotelom er Fluorotelom er
Alcohol
Alcohol
Alcohol1
O lefin
Alcohol
2043-47-2
647-42-7
678-39-7
21652-58-4
865-86-1
M olar mass (q/mol) Melting pom! ^C)
264
Boiling point (Cl 140-143*
364.1
464.12
46-47*
112-114 at
75-80/14mm* 10mm*
446.11 146-147*
564 92-93* 111-112/10
1200 (at 50C)2: 108 (a t 35C)2' 3 (at 21C);
Vapor Pressure 992 (at 25C)4: 713 (at 25C)4: 254 (at 25C)4: 14.9 (at (Pa) 252 (at 25 C f 145.2 (at 25C)5 45.90 (at 25C)5 25C)**
Water solubility
(mg/L at 25C) Log Kovv
*" -1' ..
0.71+0.04663 0.137+0.053 3.5-5.5**
0.001**
2272 +/-
50,100-
1868**
316.200**
|(5 ) 1 Themiracles of science*
1.4 (a t 35C)2: 144 (at 25 C f 13.27 (at 25C)5
16
\^
References for Fluorotelomer Alcohol: Physical Properties (previous slide)
1 Data are taken from Kaiser, Cobranchi,Kao, Krusiv, Marchione, and Buck, J . Chem. Eng. Data, 49(4), 912-916, 2004, unless otherwise noted.
2 Krusic, Marchione, Davidson, Kaiser, Kao, Richardson, Botelho, W aterland, and Buck, submitted.
3 Cobranchi and Kaiser, E A S , 2001 4 Stock, Ellis, Deleebeeck, Muir, and Mabury, ES& T , 38,1693-1699,
2004. 5 Lei, W ania, M athers, and Mabury, J . Chem. Eng. Data, 49,1013-1022,
2004. * Oakwood Products, In c., http://www.oakwoodchemical.com
**TRP
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Physical Properties of Perf luorocarboxylic Acids
CAS# Molar mass (g/mol)
C8 acid 335-67-1 414.07
C9 acid 375-95-1 464.08
iC10 acid 335-76-2 514.09
C11 acid 2058-94-8 564.09
C12 acid
SiStiassvssiBaroiW ^snwiSssssKa^^asuiarem w ssoe itim iSim fS*' :
|307-55-1
614.1
451; 55-562'*' 71-772;67-70*'
107-1092'*'*'
Melting point (C)
56,4-57.93,4 68-73#'59-62* 83-852,#:77-81* 96-1012
105-108*
218 at 740 mm 160at 60 mm 245at 740 mm
Bolling point (C)
189-1921
133 (solid-state VP offree
Vapor Pressure (Pa) acid)1
Water solubility (mg/L 3700; 3400-
(100 Pa)2 (8 Pa)2
~10 mm (at o c f_ _ _ _ _ _ _
(100 Pa)2'*'*
| !
< i I !
;
at 25C) Koc
95002
,w 3iisg^ r.B m 3B ggsBgsgiem iS3ari^B ^^
l 1.41............
Shinoda e t a/.,(CF2)2CF(CF2)4COOH Melting Point, 13-14 C.
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Physical Properties of Perfluorocarboxylic Acids
.
CAS# Molar mass (g/mol)
C8 acid 335-67-1 414.07
C9 acid 375-95-1 464.08
C10 acid 335-76-2 514.09
C11acid 2058-94-8 564.09
C12 acid 307-55-1 614.1
451; 55-562'*' 71-772;67-70'
107-1092'*'*' 105-
Melting point (C)
S6.4-57.93'4 68-73*'59-62* 83-852'*'77-81* 96-1012 218at740 mm 160at60 mm 245at 740 mm
n '" *
...... ^
489492L** 133 (solid-state
VP offree
(100 Pal? .JflE a l?_____ non Pat2*'* -10 mm(at
Vapor Pressure (Pa) acid)1
0C)*
Water solubility (mg/L at 3700; 3400-
25C) 95002
' ' _ --
Shinoda e t al.,(C?z)zC?{C?z\CO O H Melting Point, 13-14 C.
Ill
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References for Physical Properties of Perfluorocarboxylic Acids (previous slide)
P
1. U S EPA Hazard Assessment of Perfluorooctanoic Acid and its Sa lts, OPPT, Risk Assessment Division, U S EPA, 2002 and J . Franklin, "Screening Assessment of the Potential fo r Long-Range Transport of Perfluoro-octanoic Acid", Solvay Research <& Technology, 2003.
2. Detecting and Quantifying Low Levels of Fuoropolymer Polimerization Aids", S P I, Washington, DC 2003.
3. Shinoda, Hato, and Hayashi, J . Phys. Chem., 7, 909,1972. 4 Note: Shinoda e t al.,(CF2)2CF(CF2)4COOH Melting Point = 13-14 C.
* Oakwood Products, In c., http://www.oakwoodchemical.com
# Sigma -Aldrich Co., https://www.sigmaaldrich.com
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'titiir
ANALYSIS
1
Analytical Options fo r 8-2 Telomer B Alcohol
Properties: - Structure: CF3-(CFz)7-CH2-CH2-OH
- W ater solubility: 150 jg/l
- Melting point: 44C - Boiling point: 213C at 760 mm Hg - Vapor pressure: 3 Pa at 21C or 254 at 25 C - UV: none fo r 225-400 nm
1. SC -FID
- limited sensitivity and selectivity
pfc"
20-
P15- 5 * l p g / m L
10- m 40 pg/rnL
ro 5-
3a446
uo- ,, > . ,
___________ --
6"----,----1----.----1----1----1 i i i - i 1 ' i D 2 4 6 8 rrin
2. SC-M S
-must have volatile materials - Martin et al., Anal. Chem., 74 (2002) 584;
- PC I and N C I with methane; air sampling
- Ellis et al., J . Am. Soc. Mass Spectrom., 14 (2003) 1177;
- N C I, PC I spectra interpretation of Telomer alcohols;
3. LC-MS - desirable fo r compatibility with
acid-type compounds;
Background and Matrix Effects
Blanks, spikes, matrix, and calibration standard medium are very important
Solvent may contain low-levels of PFOA that can be enriched in the sample work up process
Spike recovery data are essential for each system Matrix can interfere, especially if chromatographic
resolution is insufficient Calibration standards should be made in same
matrix as sample Isotopically enriched standards are preferred, if
available Guard column is helpful for gradient runs
Mb
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'J'SiIrumorosiut11
CElr & SU %
05102004-05
100-1
Guard Column
Useful in gradient measurements
0*11 b-- J--'?
S' X
8h. u&&ul m a or ct or
QAA592
2: MRM of 1 Channel ES414.92 > 369.8 2.41e4
Internal standard
%-
0-t
05102004-05
100-
I I i I" I | I I I I | I I I I I I I I I |--r-r-i--r-|--i i i i |
I | I I I I | il
I I ( I " I I I | I I "I.. 1: MRM of 1 Channel E S TIC 2.41e4
%
From guard
\column
..I....I...i....r I I I I I I I I I I--I
5.00
10.00
l i I i l 1 I "I .................I--I
15.00
I I I I I--I
20.00
I i I I I
25.00
TimeI--I
I I I" I I 1 1 I 1 1 1
30.00
1L
I
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Analytical Issues
Standards >Telomers(no certified standards) 8telomers come as even numbered mixtures) Perf luoro Acids * Telomer acids are even numbered 8Carboxylic acids are made either by the telomer process (even numbered) or electrof luorination (up to 15 % branched)
See: Martin et al., ES&T, 38(13), 248A-255A, (2004)
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"Standards?": Perf luorooctanoic acid produced by __ _________ electrochemical processes____________
F CSS Assav-1-2 Q u a ltro 1C Q24-371S 100-1
%-
SoiierisorbO O S 200X2.1mm 20%2m M AM M A S0% MeOK S.Q4
IS 415>370
"^linear
12- Ju n -20 0410:4 5:40
!arson
6: MRM of 1 Channel ESTIC
3.25e4
Q -^ rrr-rx Q2-4-3719
100-1
%-
1 I 1 1 1 ' I 1 1 ' I 1 1 r I I I I I I I T T H - p
I I r r r r r r t i | ' ' I ' ` I ' 1 1 ` ' ' T
C8 413>369
linear
branching 5.77
0-* 1.00
3.00
9.00
...............
J ................................ .jV m r m o f 1 C h a n n e l E S -
T IC S9Se5
Branched
distribution may vary
considerably from lot
to lot.
H'l |""i.ViT
Time
14.00
15.00
|<S5
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f|
I
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"Standards?": Su rf Ion S i l l (perf luorononanoic acid)
S111 A Assav-1 -1 Quattro LC
Q24-36-92
SpherisorbODS 200X2.1 mm 20%2m NIAMM A C80% MeOH
12Jun-20O403:27:31 larsen
6: MRM of 1 Channel ESTIC
6.31e4 Area
1 j l ! J 1 | i i l j 1 i . I 1 I I I | 1 i 5 . ............................. 1 1 1 r | I < 1 I |
1 00
2.00
3.00
4.00
5.00
1Time s io '........7 00 '".OQ......... 9.6b" ' "ib o o ''' ii!od '12.00...... 13.00 "loo ' 1500
8-2 TBA Soil and Sediment Adsorption Study
Within three hours (less than one hour in freezedried activated sludge), 100% of 14C-labeled 8-2 TBA initially added to the test system partitioned to soil and sediment
Koc ranged from 572 to 4941 (mean for 5 soils = 2272)
Note: This is a short-term (24 hour) adsorption
study.
OECD 106: Guidelines fo r the testing of chemicals, "Adsorption/desorption using a batch equilibrium method", January 21,2000.
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.f
Implications of 8-2 TBA Soil Sediment Adsorption Study
I f the 8-2 Telomer B alcohol is formed as a degradation product in soil or in sediment, it will stick to the soil or sediment and not be generally available for transport.
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PFOA Soil and Sediment Adsorption Study
W ithin 24 hours, equilibrium was reached with some PFOA remaining in water phase.
Koc ranged from 48.8 to 229 for one sludge and 4 soils.
N ote: This is a s h o rt-te rm (24 hour) adsorption study.
OECD 106: Guidelines fo r the testing of chemicals, "Adsorption/desorption using a batch equilibrium method", January 21,2000.
More Analytical Issues
................................... I............... ........................................... ..... ... m u
1M R,
i ... !,,'
... M................ .. "
... --
Fluorinated Polymer Samples
made from mixtures of mixtures
- not soluble in common solvents
usually available as dispersion with surfactants, etc.
s
Fluorotelomer-Based Polymer Sample Issues
Difficult to remove f luorinated polymer from dispersed system
Difficult to determine sorbed residuals unless compete dissolution is performed
Difficult to get molecular weight distribution due to solubility, "mixed composition", lack of standards (M A L D I/M S may be required)
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8-2 TBA - plasma and tissues procedures
Fat Liver
Kidney
Plasma
Extraction:
0.3 g fa t, (spike), dissolve in 6 mL
heptane
Clean-up:
5PE: Si, 500 mg /10 mL (1 S T )
1. 1 mL acetone and 2 mL heptane
2. Load heptane extract 3. Wash with 6 mL heptane 4. Elute with 1 mL IP A
m.
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Extraction:
0.5 g tissue; (spike), add 2 mL water, 15 jl/L HCI04;
extract with 6 mL hexane; 15 min vortex; centrifuge
Clean-up:
SPE: Si, 500 mg /10 mL (1 S T )
1. 1 mL IP A and 2 mL hexane
2. Load hexane extract 3. Wash with 6 mL
hexane 4. Elute with 1 mL IP A
Extraction:
0.25 mL plasma +0.25 mL water +1 mL M TBE;
15 min vortex; centrifuge
No Clean-up fo r plasma
Challenges (biological and environmental matrices )
Complex mixtures of chemical species Need multiple methods (no one size fits all) Need clean matrix fo r calibration curves Need well characterized standards
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Validation Considerations
Matrix-based six (6) points (nonzero) standard curve*
Simplest curve fitting* 3 x 3x 3 demonstration (high QC, LLOQ, mid QC) on
three days in triplicate to access accuracy and precision* Stab ility studies fo r sample, extracts, and standards* Isotopically enriched materials (13C-13C, D, etc.) should also be strongly considered in complex matrices
Data review (internal and 3rd party)
G uidance fo r Industry: Bioanalytical Method Validation, U S FDA, May, 2001
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'air
Physical property and analytical data... to stand the test of time.......
Mss
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Thank you fo r your attention.
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