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WASHINGTON WORKS TEFLON DIVISION
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; -AZ2ri(,i$ CC: T. A. Foster
J. J. Hegenbarth - Wilm. T. M. Kemp
W. Raines - M 5625 T. L. Schrenk P. Thistleton
September 28, 1982
TO: R. J. ZIPFEL FROM: 'J. G. LOSCHIAVO
AMMONIUM PERFLUOROOCTANOATE (C-8) IN BLOOD OF TEFLON EMPLOYEES
References:
(1) Letter, T. P. Pastoor to J. G. Loschiavo, 8/25/82, this subject, attached.
(2) Letter, J.. G. Loschiavo to R. J. Zipfel, 7/29/82, this subject, attached.
The purpose of this letter is to summarize and comment on the two reference letters. I initially estimated that 40% of inhaled C-8 vapor is retained in the blood. The remaining 60% of inhaled vapor has four fates:
It is immediately exhaled. t It is inhaled but not absorbed into the body. It is eliminated by the kidneys, intestines, and sweat
glands. It is retained in other body tissues besides blood.
I asked T. P. Pastoor, a Haskell Laboratory Toxicologist, to review my calculations. He used a somewhat different approach but came up with similar results. He estimated the fraction of inhaled C-8 vapor that is retained in the entire body. I, on the other hand, estimated the fraction of inha1ed C-8 retained only in. the blood.
1044W-1
0002:3 9
EID080637
AJP001237
-2It has been estimated from data collected on female employees transferred out of TEFLON, that it takes about 420 days for the body to eliminate half of accumulated C-8 (t 1/2 = 420 days). Using the formula listed on page two of Pastoor's letter, it is estimated that 47% of inhaled C-8 is retained in the entire body. Since I estimated C-8 retention in blood, which contains a fraction of total body water, it is not surprising that Pastoor's estimation is somewhat higher.. Most importantly, both approaches indicate that much less than 100% of inhaled C-8 vapor is retained in the blood. Pastoor estimated that only about one-half of inhaled C-8 vapor is retained in the entire body. This is indeed encouraging. These estimations are rough since they are based on data from only four employees. Pastoor recommends that more human blood C-8 data be collected in order for more accurate estimations to be made. A greater effort-is now being made to gather such data. Attachments
JGL/nsw 1044W-2
AJP001238
000220
EID080638
ES-3&75 REV . 8-81
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IN C O R P O R A T E D
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H a sk e l l Laboratory fo r Toxicology
and In d u stria l Me d ic n e t e / '
Elkton Road, Newark, Delaware 19711:;. ,
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CENTRAL r e s e a r c h a n d d e v e l o p m e n t d e p a r t m e n t
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D. A. E r d m a n T. A. F o s t e r . T. L. Schirenk P. T h i s t l e t o n J. W. Raines G. L. K e n n e d y
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August 25, 1982
PERSONAL AND CONFIDENTIAL
J. G. L O S C H I A V O
P O L Y M E R P R O D U C T S D E P A R T M E N T /;;:
PARKERSBURG
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A M M O N I U M P E M 'L U O R O O C T A N O AT E (c-8)_.:
I T HUMAN" B L O O D
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: - In reference' t o ^ o r ' J u i 29, 1982,'//letter t o R^ J . Zip fe 1
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( R e t e n t i o n 'o f 'A m m o n i u m P e r f l u o r o o c t a n o a t e [C-8] in B l o o d vof;;;<-;i.^?^'X.;|^^
T e f l o n Workers) ; I w o d l d ^ l i ^ ^ t o m a k e ' s e v e r a l i m p o r t a n t s u ^ e s - J ; ^ '..;! < ^ V
tions. A c q u i s i t i o n a n d i n t e r p r e t a t i o n of C-8 b l o o d conce n t r a - ` ,.'f"1;
tions in w o r k e r s is ''very'".Important in^^ u n d e r s t a n d i n g h o w the ' '
' ' ^ '1
h u m a n b o d y h a n d l e s C-8 ^'and h o w a c c u r a t e l y our animai' m o d e l s a t 1-;^
H a s k e l l c o r r e l a t e to .the hv^ah^ situation.. T o better/ interpret;; K,*
these d a t a , 'c o n s i d e r / t h r f o l i o w i n g m o d i f i c a t i o n s
- W. - ;
The 0.006 ppm blood level is termed a "rate" of accumulation when it would be more appro
priate to call it an "average concentration" over the average of 91 days of employment/ Th a v e r a g e b l o o d ; l e v e l of 0.006 p p m /d a y x 91 d a y s gives t h e 'plateau, o r steady-state,, con-;'// centration (0.546 ppm) that more closely represents the dynamic aspects of exposure and elimination.
The calculations assume a volume of distribution/
(Vd) e q u a l to the b l o o d c o m p a r t m e n t o n l y (5.5 //
liters). Since C-8 is water soluble and binds /
protein, the Vd would actually be closer to the ,
volume of total body water (approximately 42...
liters/70 kg man).
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B E T T E R T H IN G S F O R B E T T E R LIV IN G . . .T H R O U G H C H E M IS T R Y
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T o m o r e a c c u r a t e l y a s s e s s t h e ' r e t e n t i o n o f c-8r, . .'. i *.- * . - J... . - .' ;:*
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in the body as well as predict blood levels
anticipated with continued low-level exposure,
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formulas c o m m o n l y ,used. to .e s t i m a t e d r u g - t h e r a p y
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regimen can be employed.
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Assumptions:
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-f The b l o o d l ^ e l y C p , is a t a p l a t e a u 7 ' v ' :,v- :.'.''j^(steady7:st^te)i7concentration:. ( i . e . *
a b s o r p t i o n .and' e l i m i n a t i o n a p p r o x i m a t e l y
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" T h e yol\ame of; d i s t r i b u t i o n , Vd, is in. total body water, or 42 liters.
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- The d a i l y dose-;(D/T) is 0.081 mg/day.
' . - T h e 'elimination, h a l f - l i f e ,. t - 1/2, .i s ..r .... .
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^ e s t i m a t e d f rbm^a ^ l i t e r a t u r e r e p o f t ori v "
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- where f = fraction absorbed - s o l v i n g for f ,
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0.546 mg/1' 42 1 :day
1.44 *. t 1/2 D .. 1.44 .t 1/2 0.081 mg/il
- then:
t 1/2 (days)
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% Absorbed
30 .
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depending on the actual t 1/2, we can estimate
o n l y t h a t g r e a t e r t h a n 30% of. a t m o s p h e r i c C-8 is
absorbed. This is in general, agreement with your
estimate, but until we know the actual t 1/2 we will
not be able to accurately calculate fractional
absorption. .
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AJP001240
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R e g a r d i n g these c a l c u l a t i o n s a n d in r e s p o n s e to"//::/..
your suggestions in the July 29 memorandum,
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- More human/data is necessary from two y
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1/ c u r r e n t ^employees for d e t e r m i n a t i o n 'V `A '-,r'{ of p l a t e a u ,,(steady-state)V.cbncen;tia/^
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EID080641
PERSONAL AND CONFIDENTIAL
CC: .0. M. Cordrey - .D . A. Erdman
T. A. Foster T. L. Schrenk P. Thistleton G. L. Kennedy - Haskell Lab. T. P. Pastoor - Haskell Lab. July 29, 1982
TO: FROM:
R. J. ZIPFEL J: G. LOSCHIAV O ' />/.f.
. RETENTION OF AMMONIUM PERFLUOROOCTANOATE (C-8) IN BLOOD OF TEFLON EMPLOYEES
Using data from the FLAIR* program and from air sampling records, it is estimated that 40% of inhaled C-8 vapor is retained in the blood (see attachment). This estimate is rough since it is based on only four data points. Also, the rate of C-8 absorption varies by individual. Air C-8 levels are also variable.
Data on males only were used due to potential sex differences in C-8 absorption and.elimination as observed in rat studies. Data on Fine Powder/Dispersion employees only were used to eliminate the variable of particle size. .In areas where a significant portion of airborne C-8 is contained in polymer particles, blood retention should be less than 40% of inhaled C-8. This reduced blood C-8 retention is due to the airborne particle size distribution. Large particles (i.e., particles > 5 microns in diameter) will not likely reach the lung alveolar region. It is in the alveolar region where inhaled gases and vapors are absorbed into the blood. Probably for this reason, TEFLON FEP Operators have significantly lower blood C-8 levels than Fine Powder/Dispersion Operators.
According to G. L. Kennedy, Haskell Laboratory Toxicologist, not more than 20% of inhaled C-8 accumulates in body tissues besides blood. Rat studies indicate that 10 to 20% of inhaled C-8 is pooled or accumulated by other body tissues.
*FLAIR - 1uoropolymers Laboratory Analysis information Retrieval.
0885W-1
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EID080642
AJP001242
2
The remaining 40% of inhaled C-8 has 3 potential fates: o It is exhaled back out. o It is inhaled but not absorbed into the body, o It is eliminated by the kidneys or intestines. The following additional information is needed to determine more accurately the fate of inhaled C-8: o More blood C-8 data on males who left TEFLON, o More blood C-8 data on new male TEFLON employees, o More blood C-8 data on new female TEFLON employees, o Data on amount of C-8 excreted over a 24-hour period
following exposure. o Particle-size distribution of airborne polymer particles
containingC-8. o Perform a Haskell Laboratory stu.dy using radiolabel 1ed C-8
to determine where and how much C-8 is stored in the body immediately after exposure. o Data on C-8 content in exhaled air during exposure.
Attachment
JGL/n sw 0885W-2
AJP001243
000225
EID080643
CALCULATIONS AND DATA
Blood C-8 accumulation rates in four male Fine Powder/Dispersion Operators with less than 550 days of service are as follows:
0.0093 ppm C-8 in blood/workday 0.0080 ppm C-8 in blood/workday 0.0043 ppm C-8 in blood/workday 0.0022 ppm C-8 in blood/workday
1 = 0.0060
Personal air sample results in moles per billion (mpb) C-8 on these Operators during the same period are:
<0.03, 0.09, 0.12, 0.12, 0.15, 0.24, 0.24, 0.66, 0.69, 0.73, 0.75, and 1.39
T = 0.46 mpb or 8.2 ug./m3
Average male has 5,500 gm. of blood in his body and inhales 10 m3 of air over an 8-hour shift doing light work.(^)
At a C-8 concentration of 0.46 mpb (8.1 ug./m^), an average male would inhale 81 ug. of C-8 during an 8-hour shift.
If all C-8 inhaled was retained in the blood, an average male would accumulate C-8 in blood at a rate of:
81 ug. C-8/workday 5.5 X 109 ug. blood X 10
= 0.0147 ppm C-8 in blood workday
However, the average daily C-8 accumulation rate we observe in new employees is only 0.0060 PPm .wC-ofrikdTaPy 00c*. Therefore, of the total
C-8 inhaled, about
X 100 = 40%j 40% is retained in blood.
AJP001244
( ^ Radiological Health Handbook, U.S. Department of Health, Education, and Welfare; Revised Edition, January, 1970, (pp. 215 and 216).
J GL/nsw 0885W-3
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E1D080644
