From Migration to Exposure:

FDA experience

Tim Begley
Office of Food Additive Safety
Center for Food Safety and Applied Nutrition
Food and Drug Administration
 CONCENTRATION IN THE DAILY
DIET

<M> = f aqueous and acidic (Mt 10% Ethanol)

+ falcohol(Mt 50% Ethanol)
+ f fatty(Mt fatty)

Dietary Concentration = <M> x CF

 History
1977- 1983 AD Little Study of Indirect Food
Additive Migration

Polymers Studied: HDPE, LDPE, PS, IPS,

PVC, EVA.

Migrants (14C radiolabelled): BHT, Irganox

1010, Styrene, organo tin stabilizer, di(2-ethyl
hexyl) adipate.

Food simulants: Water, Water/Ethanols,

Heptane, Corn oil, 3% acetic acid.
 Foods Tested in 1977-1983 Study
whole milk, skim milk, orange juice,
margarine, whipped topping, pickle juice,
mayonnaise, vegetable shortening, dry milk,
dry chicken soup, bread, wine, cheese,
bologna, white rice, brown sugar, squash,
sour cream, yogurt, cottage cheese, vanilla
pudding, beef liver, gelatin, apple jelly,
chocolate, lean beef, chicken breast, cola,
fish, whiskey
 History
1988 AD Little Study High Temperature
Migration Testing of Indirect Additives

Polymers Studied: LDPE, HDPE, PP.

Migrants (14C radiolabelled): Irganox 1010,

Irganox 1076.

Temperatures up to 130°C.
 History 1990 A.D. Little Study on
Migration at High Temperature to
Food

• Aqueous Foods with No or Low Fat

• Aqueous Foods with Emulsified Fat
• Aqueous Foods with Free Fat
• Water and Corn oil
 2
µg/dm

1000
1500
2000
2500
3000
3500
4000
4500

500
G

0
ra a
v y t er
(n
B o
ab
y B fa
a t)
Fo ke
od be
C (b an
or
ne an
d an
B a)
ee
G f H
ra as
y h
(1
C 0 %
hi fa
ck t)
en
C
B h So
ab ick up
y en
Fo B
od rot
(tu h
rk
ey
B )
ee
fS
te
w
C
or
n
O
il
Migration of Irganox 1076 from PP at 135°C
Results from the 1990 study to food
Conclusions of these Migration studies

• Oil and water tend to represent the

extremes of migration for non-polar
polymer / non-migrant combinations.

• Polar polymer/migrants not studied (i.e.

PET or polyamide).
Current migration/exposure issue:

Migration of perfluorochemicals
and fluorochemicals.
Why are we interested in perfluoro chemical
migration?

• Perfluoro chemicals found in human serum

(Olsen et al. 1999) .

• May 2000, 3M Company announce phase

out of perfluorooctyl chemistry.

• Elderly in Seatle WA are found to have

perfluoro chemicals in their serum (Olsen
et al. 2003) .
 Why are we interested in perfluoro
chemical migration?
• PFOA is biopersistent / bioaccumulative
• Half-life in human serum is 4.4 years
(Butenhoff et al. 2004).
• Potential concerns for carcinogenesis;
developmental/reproductive and immunotoxic.
• Many fluorochemicals regulated for food-
contact contain PFOA as an impurity and/or
have chemical moieties similar to PFOA.
 Structures of perfluorochemicals
found in human serum
•Perfluoroocatanesulfonate = PFOS
F F F F
O F F F F
-O
S
C F
O
F F F F F
F F F

•Perfluorooctanoic acid = PFOA

F F
F F
F
F
F F
F
F
F F
HO F
F
F
O
 Food package types that contain
fluorochemicals

Polymers
cookware
tubing
gaskets Paper
microwave popcorn
muffin bags
french fry bags
pizza liners
sandwich wrappers
Where are perfluorochemicals for
paper regulated?

• In US approximately 15 materials are

regulated

• BfR also has a number of perfluoro

chemicals regulated
 Types of perfluorochemicals
added to paper

• Perfluoro telomer type

C6 C8 C10 C12 C14 based

• Polymeric type
 Typical structures of perfluoro telomer based
paper coatings
F F F
F F F
F F
F F
F F
F F
F F
F F F F
F F F
F F F F F
F F F F
OH F F
F F
F H F
F F
F F F
F F NH4+
O O
H2N F O S F
O O P
F O NH4+ -O O N
F P S O
F O O P
O O
O
F OH S
F F F N
F O
F
F O S
F F
F F F F F
F F F F
F F F F
F F F
F F
F
F F F F F
F F F
F F
F m/z = 889 F F F F
F
F
F
F
F F m/z 1202
F
m/z =1021 F
Fluorochemical Paper coatings
• Fluorochemical paper concentrations can
be up to 0.5% or 5000 mg/kg.
• Temperature range for paper applications
-5°C – 200+°C.
• Most perfluoro telomer based paper
treatments have molecular weights >1000
but the molecular size is similar to much
smaller molecules.
Migration of chemicals with MW > 1000 ?

F versus H

MW = 1121 MW = 510
 MW = 1121
MW = 510
Molecular Area = 558Ǻ2 Molecular Area = 541Ǻ2

Molecular Volume = 609Ǻ3 Molecular Volume = 530Ǻ3

C71H141 MW = 997 Molecular Volume = 1225Ǻ3

Is PFOA in Perfluorochemical Paper
Coatings and treated Paper Products?
Concentration of PFOA in Perfluoro Paper
Coatings and Paper Products

Material Cp0 PFOA (mg/kg)

Perfluoro paper coating 88 - 160

(not applied)

Popcorn bags 0.3

Muffin bag 0.5
Sub Sandwich wrapper 0.5 – 1.2
Hash brown potato bag 0.9
Migration of PFOA from microwave
popcorn bags?

None detected into oil

T. H. Begley, et al., 2005, Perfluorochemicals:

Potential sources of and migration from food
packaging. Food Additives and Contaminats, 22
(10) 1023-1031.
 Temperature of oil from microwave susceptor
heating

250
T e m p e ra tu re °C

200
150
100
50
0
0 0.5 1 1.5 2 2.5 3 3.5
Time (min)
 Test for perfluorochemical
migration from commercially
produced paper
Test conditions for perfluorochemical
migration

• Food simulating liquids/foods at 100°C

• Single-sided contact with paper
• Contact time 15 minutes
• LCMS analysis for perfluorochemical
 Typical structures of Perfluoro telomer based
paper coatings
F F F
F F F
F F
F F
F F
F F
F F
F F F F
F F F
F F F F F
F F F F
OH F F
F F
F H F
F F
F F F
F F NH4+
O O
H2N F O S F
O O P
F O NH4+ -O O N
F P S O
F O O P
O O
O
F OH S
F F F N
F O
F
F O S
F F
F F F F F
F F F F
F F F F
F F F
F F
F
F F F
F F
F
F
F
C
A
F F
F F
F F F F
F
B F
F
F
F
F F
Migration results for incidental contact, Coating A

0.45
0.4
Relative Migration 0.35
(mg/kg) 0.3
0.25
0.2
0.15
0.1
0.05
0

il
er

r
r

H
H
H
H

te
ga

O
O
O
O
O
at

ut
ne

Et
Et
Et
Et
W

B
Vi

%
%
%
%

30
25
20
10
 R e la tiv e m ig ra tio n (m g /k g )

0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5

W
at
er
Vi
ne
ga
10 r
%
Et
OH
20
%
Et
OH
25
%
Et
OH
30
%
Et
OH
Bu
tt e
r

O
il
Migration results for incidental contact, Coating B
Migration results for incidental contact, Coating C,
paper produce in 1987

0.800
0.700
Relative Migration

0.600
0.500
(mg/kg)

0.400
0.300
0.200
0.100
0.000

il
r
er

te

O
ga
at

ut
ne

Et

Et
W

B
Vi

%
10

25
 Problem for exposure estimates

Water and oil are not the extremes!

 Migration into Emulsions
• Butter = water-in-oil Emulsion (20% / 80%)

• Non-ionic surfactant (polyoxyethylene

sorbitan / oil / water)

• Ionic surfactant (lecithin / oil / water)

Migration from paper, 40°C 1 day

ic
on
ni )
no oy
il
+ (s
c
O ni
io
+
il
O
c
ni
il -io c
ni
O on io
si on
ul -n
Em on ad
si re
ul sp
Em ate
l
co
ho
C
r
te
ut
B
1.2

0.8
0.6
0.4
0.2
1

0
Migration µg/cm2
 Migration of Fluorochemical is
Kinetic to food at 40°C

0.4
0.35
Migration µg/cm 2

0.3
0.25
0.2
0.15
0.1
0.05
0
Chocolate spread Chocolate spread
1 day 10 day
 Do Perfluoro telomer Paper Coatings
Migrate Under Actual Conditions of Use?
Migration from microwave
susceptor into oil
 Results for migration of
fluorotelomer from popcorn bags
Concentration in
Popcorn Oil before 1.4 mg/kg
Heating 4 µg/ dm2

Concentration in
Miglyol after 2 min. 2.1 mg/kg
microwave heating 7µg/ dm2
LCMS analysis of Popcorn for the Migration of
Fluorotelomer from Popcorn bag
9000

8000
Fat Free Popcorn Control Popcorn

7000
LCMS Response

6000
m/z = 1021 --
5000
-- m/z = 1121
4000

3000

2000
m/z = 921 --
1000

0
0 1 2 3 4 5 6 7 8 9 10

T ime (min)
Migration of perfluorotelomer into
microwave popcorn
Brand mg/kg
A 1.2
B 0.8
C 3.8
D 1.2
E 2.1
Conclusions of Migration Tests
• The food simulants water and oil are not
the extremes for these fluorochemicals.
• The soy emulsifier (lecithin, 0.05%) can
change oil into a potent solvent for
migration.
• Fluorotelomers do migrate to food in the
mg/kg (ppm) range.
 F F
F F
F
F F F
F F
F
F Migration to oil = none
F F
F
F
F OH
O
P O
S
O

S
F
F Migration to oil + emulsifier = huge
F
F
F
F F F F F F

F F
F FF F