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Exposure Assessment and Risk Characterization of Certain Fluoroorganic Chemicals Used in

Food Packaging

Stephen Korzeniowski, Robert C. Buck, Hsu-nan Huang, and Mary Kaiser

3rd International Symposium onFood Packaging

Ensuring the Safety, Quality and Traceability of Foods

17-19 November 2004Barcelona, Spain

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Poster Abstract

• The results of an exposure assessment and risk characterization study are reported for consumer paper food packaging articles manufactured with DuPont products. The goal was to develop a more in depth understanding of the magnitude of potential exposure to certain fluoroorganics that may occur through consumer use of commercial paper packaging.

• An additional goal was to develop a risk characterization based on Margins of Exposure (MOE's) approach. Results from a variety of tested articles will be presented showing MOE's of all > 30,000. Paper packaging was one of the articles tested in this study.

• Extraction studies were performed on paper packaging using a variety of solvents including water and ethanol and various cooking oils. Results from these studies as well as a review of the analytical challenges and significant method development efforts will be provided.

• The implications of this body of work and path forward will also be discussed.

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CF2=CF2 (TFE)

F(CF2CF2)nI (Telomer A)

F(CF2CF2)nCH2CH2I (Telomer B)

F(CF2CF2)nCH2CH2OH (Telomer BA)Straight Chain Alkyl

Sales Products

F(CF2CF2)nCH2CH2OC(O)C(R)=CH2

Zonyl® TM (R=CH3) ; Zonyl® TAN (R=H)

n = 2-8

Surfactants• Anionic - Phosphate, Carboxylate, Sulfonate

• Nonionic - Ethoxylate• Betaine

Polymers• Acrylic• Ester• Amide• Urethane• Urea

Raw Materials

5 Test Compounds

Represent Majority Product Line

DuPont Fluorotelomer Product Groups: Intermediates, Surfactants, Polymers

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How do they Work ?

• The fluorotelomer

functionality is

attached to a

functional

backbone which

adheres to the

substrate surface.

• The fluorocarbon

chain orients

perpendicular to

the surface, at the

air interface.

• CFCF33 Groups give Groups give veryvery low surface tension low surface tension

• Oil, grease and water repellent surfaceOil, grease and water repellent surface

CFCF33

|(CF2)n

|(CH2)2

|

Paper Substrate

CFCF33

|(CF2)n

|(CH2)2

|

CFCF33

|(CF2)n

|(CH2)2

|

CFCF33

|(CF2)n

|(CH2)2

|Backbone

bulk paper properties are unaffected

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Risk CharacterizationRisk is a function of Hazard and Exposure

• Hazard Assessment– Determine potential hazard(s) from toxicity testing linked to routes of

exposure

• Exposure Assessment– Routes of Exposure : Oral, Dermal, Inhalation– Determine how people come in contact with our products, how much & how

often

Risk = f (Exposure, Hazard)

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Environmental Fate & Effects

• Physical / chemical properties• Environmental compartments• Fate (abiotic & biotic)• Effects : aquatic, terrestrial

Exposure

• Product Trails, Mass Balance• Human & Environmental

Exposure Assessment• Risk Characterization

Toxicology

• Acute & Chronic Studies

• Oral, Dermal, Inhalation

• Pharmacokinetics

Human HealthRisk Assessment

Environmental

Risk Assessment

Analytical • Product & Substrate Analysis• Method Development and

Validation• Chemical “Standards”• External Labs

Academic Collaboration

Communication• Publications• Presentations

DuPontChemicalSolutionsEnterprise

dProduct Stewardship

Business Process

Science-Based Product Stewardship Approach

Manufacturing Technology

• Process Improvements• Facilities Re-engineering• Emissions Reduction

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Product StewardshipThrough the Entire “Life-Cycle”

DuPontManufacturing

IndustrialProcessing

Professional Use/Installation

ConsumerUse

Disposal

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Scope of the Exposure Assessment and Risk Characterization: Consumer Article Study

DuPontManufacturing

IndustrialProcessing

Professional Use/Installation

ConsumerUse

Disposal

Focus of the Assessment:• Direct use of the article;• Home fabrication using the article;• Incidental exposure to the article;• Care and maintenance of the article; and,• Foreseeable misuse of the article.

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Exposure Assessment and Risk Characterization Work Process

ConceptualizeExposure

QuantifyExposure

Develop RiskCharacterization

Conduct Peer Review

IssueFinal Report

DevelopHazard

Assessment

AnalyticalData

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Articles Included in the Assessment

Quantitative Evaluation of:

• Medical garments

• Carpeting

• Carpet care products

• Textiles (Apparel)

• Thread sealant tape

• Cookware

• Membranes (Apparel)

• Food Contact Paper

Quantitative Evaluation (Ingredients-basis) of:

• Stone, tile and wood sealants

• Industrial floor waxes and wax removers

• Latex paint

• Home and office cleaning products

• Textiles (Upholstery)

• Textiles (Home)

• Textiles (Technical)

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Food-Contact Paper Types

• Linerboards

• Folding Cartons

• Bags

• Flexible Packaging

• Support Cards

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Food-Contact Paper : Conceptual Exposures

• Exposure Pathways Quantified

– Dermal Contact

– Ingestion via Hand-to-Mouth

– Ingestion of Food

• Exposure Pathway dealt with as Uncertainty

– Paper Mouthing

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Food Exposure Factors: Examples

Dermal• Mass Available for transfer ng/cm2

• Fraction Transferred • Skin Surface Area• Dermal Absorption Coefficient• Exposure Time to Perspiration• Exposure Frequency (events/day)

Hand-to-Mouth• Mass Available for transfer ng/cm2

• Fraction Transferred• # Contact Events• Saliva Transfer Factor• Oral Absorption factor

Ingestion of Food• Mass Available for Transfer• Fraction Transferred• Contact Area: Paper-Food• Food Consumption Rate• Fraction of Consumed Food in

Contact with paper• Exposure Frequency/Duration• Oral Absorption Factor

Vapor Inhalation• Various Rates and Exposure

Factors - Time, Frequency, Duration

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Risk CharacterizationMargins of Exposure

Applicable Health Benchmark

Estimated Human ExposureMOE =

•Ratios of estimated human exposure levels to relevant health benchmarks

•Calculated separately for each article, each endpoint, and each receptor

•Aggregate MOE calculated to consider multiple-article exposure

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Overall Results and Conclusions

• Based on the exposure assessment and risk

characterization:

– Margins of exposure (MOEs, or “safety ratio) for all articles tested

ranged from 30,000 to 9 billion for Reasonable Maximum Exposure

scenarios (highly conservative)

– DuPont paper and packaging products had MOEs all >100,000

• The study reaffirms that our products are safe for their

intended uses

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Analytical Development and Characterization of Fluoroorganic Species in Food Packaging

• Develop a representative recovery analytical procedure for perfluorooctanoic acid (PFOA) in various oil matrixes– goal to develop method suitable primarily for microwave

packaging testing

• Construct a sensitive, specific and rugged analytical method for quantifying PFOA or its methyl ester (PFOME)

• Perform recovery analyses of PFOA/PFOME in fractionated coconut oil (MIGLYOL), silicone oils, corn oil, and olive oil– at room temperature and at 232oC for 5 minutes

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Recovery Analytical Procedure

• Spike a 1g oil sample with known concentrations of PFOA in acetone

• For room temperature recovery skip to next step, for 232oC recovery heat sample vials in an oven to temperature for 5 minutes

• Add 1mL of methanolic HCl to esterify PFOA to PFOME. Heat to 60oC for 30 minutes

• Extract organic layer and analyze via GC/MS.

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Analytical Detection Procedure

• Quantify the extracted PFOME by gas chromatography / mass spectrometry (GC/MS) technique

• Acquire heightened sensitivity through the use of chemical ionization, negative mode (NCI)

• Selectivity is produced by the selected ion monitoring (SIM) option

• Quantify analyte with external standard calibration

• Draft analytical method has a demonstrated limit of detection (LOD) of 1 ppb and a limit of quantitation of 5 ppb

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Equipment and Supplies: Oil Studies

Agilent GC 6890N US10206015Agilent MSD 5973Network US10482241Agilent Autosampler/Injector 7683 US20414158

CN14523138Edwards vacuum pump G1099-80023Agilent Enhanced ChemStation Version D.00.00.38DB-1ms 30m X 0.25mm X 0.25µm capillary columnUltra High Purity helium carrier gas MG IndustriesUltra High Purity methane reagent gas MG IndustriesMettler AE 163 analytical balance 86796

Acetone EM Science HR-GC AX0110-1Hydrogen Chloride, Methanol Reagent 10

TCI America X0041Methyl perfluorooctanoate, Oakwood Products, Inc. (98%) 002278 lot # T19LAcetonitrile, EMD Chromo. grade AX0142-1Hexanes, EM Science Chromo. grade HX0298-6MILLI-Q water

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Representative External Standard Calibration Curve

y = 44.472x + 36.653

R2 = 0.9994

0

1000

2000

3000

4000

5000

6000

0 20 40 60 80 100 120 140

conc. (ppb)

are

a

PFOME Standards range from 1.2 ppb to 120 ppb.

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PFOME Recovery Results: Oil Matrices

Test Oil T 0CPFOA Spike Range (ppb)

PFOME % Recovery

MIGLYOL 20-22 10-100 73-117

232 10-200 0-49

Silicone Oil (PS) 20-22 100 12-13

232 100 8

Silicone Oil (AA) 20-22 10-100 0

232 ND ND

Corn Oil 20-22 500-1500 3-5

232 50-200 0.5-1

Olive Oil 20-22 50-150 8-12

232 50-150 4-40All controls were non-detect ND is not determinedLOD = 1 ppb; LOQ = 5 ppb

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PFOA Oil Recovery Result Summary

• MIGLYOL room temperature experiment produced acceptable recoveries between 70% to 120%

• MIGLYOL at 232oC for 5 minutes experiment produced significantly lower recoveries between 0% to 49%

• Both Silicone Oils tested at room temperature and elevated temperature produced negligible recoveries

• Corn oil at room temperature yield 3-5% recoveries and at 232oC yield even lower (0.5-1%) recoveries

• Olive oil at room temperature yield 8-12% recoveries and 0-40% recoveries at elevated temperature

Conclusion• Use of the oils tested to conduct paper and packaging extraction analyses for

PFOA is unlikely to provide a meaningful result due to unacceptably low recoveries– It appears that the PFOA is reacting with the subject oils and therefore preventing appropriate

recovery

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Food Simulant Extraction Studies

• Ethanol solutions explored as food simulants for paper extraction studies to determine potential PFOA levels in paper and packaging

• Tested both 10% and 50% Ethanol solutions• Although not as desirable, determine if these

simulants can be used as a surrogate for oil extractants/simulants

• Other analytes were also considered in this study

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PFOA Analyses in Paper:Ethanol Simulants

• LC/MS/MS for sensitivity and selectivity• Require 5x signal to background at LOQ

– Minimize sample contact with fluoropolymers• HPLC parts and tubing• Autosampler vial caps

• 13C-PFOA dual isotopic internal standard corrects for matrix effects

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Paper Sample

Subsample #11 gram

Subsample #21 gram

Extract 2 Hrs

Centrifuge

Vial #1 Vial #2 Spike

Extract 2 Hrs

Centrifuge

Vial #1 Vial #2 Spike

Shaker Sample Preparation

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Experimental Conditions• Sciex API 4000 (Multiple Reaction Monitoring Mode)

– PFOA (413 to 369 m/z)– Dual 13C PFOA IS (415 to 370 m/z)

• HPLC Agilent 1100– Genesis C8 Column (2.1 mm x 50 mm, 4 um particle 120 Angstom)– Mobile Phase A: 2 mMolar ammonium acetate in nanopure H2O– Mobile Phase B: Methanol– 10 uL Injection Volume– Isocratic at 65% solvent B– PFOA Peak Elution 1.0 minute

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PFOA Calibration Curve 50% EtOH

PFOA Standard

Concentration (ng/mL)

13-C-PFOA Internal Standard

Concentration (ng/mL)

Average PFOA Area Response

(413 > 369 transition)

Average 13C-PFOA Internal Standard Area

Response (415 > 370 transition)

0.1 5.00 75093. 2781000. 0.5 5.00 322430. 2745900. 1.0 5.00 629740. 2794800. 5.0 5.00 2854000. 2707400.

20.0 5.00 5366700. 2545000.

Area Ratio vs Analyte Concentration (PFOA)- "Linear" Regression ("1 / x" weighting): y = 0.21 x + 0.00761 (r = 1.0000)

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20Analyte Concentration, ng/mL

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.3

Are

a R

atio

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Example Chromatogram (LLOQ Standard)

Sample Name: "Calibration 0.1 PPB" Sample ID: "" File: "Data072804 Covance 50%004.wiff"Peak Name: "PFOA" Mass(es): "412.9/368.9 amu"Comment: "" Annotation: ""

Sample Index: 1 Sample Type: Standard Concentration: 0.1000 ng/mL Calculated Conc: 0.1268 ng/mL Acq. Date: 07/28/2004 Acq. Time: 08:52:47 AM Modified: Yes RT Window: 30.0 secExpected RT: 1.09 minUse Relative RT: No Int. Type: Manual Retention Time: 1.08 minArea: 70143. countsHeight: 9029.7 cpsStart Time: 0.824 minEnd Time: 1.28 min

0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0 2.2 2.4 2.6 2.8 3.0Time, min

0.00

200.00

400.00

600.00

800.00

1000.00

1200.00

1400.00

1600.00

1800.00

2000.00

2200.00

2400.00

2600.00

2800.00

3000.00

3200.00

3400.00

3600.00

3800.00

4000.00

4200.00

4400.00

4600.00

4800.00

5000.00

5200.00

5400.00

5600.00

5800.00

6000.00

6200.00

6400.00

6600.00

6800.00

7000.00

7200.00

7400.00

7600.00

7800.00

8000.00

8200.00

8400.00

8600.00

8800.00

9000.00

9200.00

9400.00

9600.00

9800.00

1.00e4

1.02e4

1.04e4

1.06e4

Intensity, cps

Sample Name: "Calibration 0.1 PPB" Sample ID: "" File: "Data072804 Covance 50%004.wiff"Peak Name: "DUAL 13C PFOA(IS)" Mass(es): "414.9/369.9 amu"Comment: "" Annotation: ""

0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0 2.2 2.4 2.6 2.8 3.0Time, min

0.0

5000.0

1.0e4

1.5e4

2.0e4

2.5e4

3.0e4

3.5e4

4.0e4

4.5e4

5.0e4

5.5e4

6.0e4

6.5e4

7.0e4

7.5e4

8.0e4

8.5e4

9.0e4

9.5e4

1.0e5

1.1e5

1.1e5

1.2e5

1.2e5

1.3e5

1.3e5

1.4e5

1.4e5

1.5e5

1.5e5

1.6e5

1.6e5

1.7e5

1.7e5

1.8e5

1.8e5

1.9e5

1.9e5

2.0e5

2.0e5

2.1e5

2.1e5

2.2e5

2.2e5

2.3e5

2.3e5

2.4e5

2.4e5

2.5e5

2.5e5

2.6e5

2.6e5

2.7e5

2.7e5

2.8e5

2.8e5

2.9e5

2.9e5

3.0e5

3.0e5

3.1e5

3.1e5

3.2e5

3.2e5

3.3e5

3.3e5

3.4e5

3.4e5

3.5e5

3.5e5

3.6e5

3.6e5

3.7e5

Intensity, cps

1.07

0.1 ng/mL PFOA 5.0 ng/mL 13C-PFOA IS

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PFOA Method Validation in Paper Simulants

Extraction Solvent

Fortification0.5x

Fortification1x

Fortification2x

Fortification % Recovery 106 ± 9 106 ± 7 105 ± 4IS Response % 82 ± 7 86 ± 10 82 ± 8Fortification % Recovery 101 ± 5 103 ± 5 102 ± 3IS Response % 88 ± 6 87 ± 9 94 ± 2

Avg. ± St. Dev. (n=9)

10% Ethanol

50% Ethanol

Three treated paper samples fortified in triplicate at each level

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Food Simulant Extraction Studies

• Ethanol solutions explored as food simulants for paper extraction studies

• Tested both 10% and 50% Ethanol solutions

Conclusion• Methods have been developed to readily use

ethanol/water mixtures as food simulants for the determination of PFOA in food packaging

• An LOQ of 100 ppt and an LOD of 10 ppt were established in these matrices

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Sources

Sewer

Air

wwtpAgric. Soil

SurfaceWater

FreshwaterSediment

Sea

Estuary & Marine Sediment

Natur. SoilGrassland

Landfill

Incineration

FocusAreas

Environmental Compartments Under Study

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E-Fate Studies Approach

Raw Materials Products

Abiotic

• Photolysis - Air• Photolysis - Water• Hydrolysis• Partitioning• Adsorption-Desorption (Kd)• Aging / Sequestration

• Hydrolytic Stability• Incineration• Photolysis

Biotic• Sludge : Aerobic• Soil : Aerobic, Anaerobic

• Respiration Inhibition• Sludge: Aerobic• Soil : Aerobic, Anaerobic• Sediment : Anaerobic

Studies are underway. Biotic results are expected during the 1Q-4Q 2005 time period

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Acknowledgments

• Mike Mawn• Miguel Botelho• Barbara Larsen• Rhea Holtzman