Document pZ1yVqyny4Zp5LENGNrvM0qd
AR226-2782
FOR DP roar USE ONLY
Copies to:!
Haakell
E. I. du Font de fkaourf and
Laboratory for Toxicology and Industrial Elkton Road, P. 0. Box 50,
Newark, Delaware 19711
Medicine
HASKELL LABOBATORY REPORT 10. 405-82
Material Tested 1) Octanoic acid, pFntadeca-
fiuoro-, aoBoniua sale
"'Ii'4-.^llnN--o7
Other CodeF
I'-Cj-^'-B
14,249
(See page 4-5)
Study Initiated/Completed 1/15/82-3/15/82
^Material Subaltted by
intralResearcH & Osvelopeenc Deparfent Haskell Laboratory
.EFFECT
_
1 CJ-AMMONIUM PERFLDOB
|ON THE ELIMINATION OF
ANOATE FROM RATS AND MICE
Su--ary
Adult male ratfi and lice were given^
______(H-}A,249) 24
hours after dosing with [ Cj-aBBoniiia " ^fluorooetaaoate eel? ([ CJC8).
Although a previous study indicated tha
--------------HHHcould reduce
the scute lethal.effects of C-8l
.there was no sign of enhanced
ellolnatlon of [ "Cl-C-8 via Ch4 feces, uri or exhaled air.
Introduction
A--onlua perfluorooctanoate acid (C-8) is a coapound used -n the application of Teflon* because of its surfactant properties. The aost
notable toxicological effect of C-8 Is liver enlargeaent. C-8 has been detected in huran blood and is elialcaced at an apparently slow rate. Because of known huoan exposure and the potential for hepatic toxiclty, a
means of enhancing C-8 elimination from the body was sought. It was thought
that C-8 would undergo biliary excretion and reabsorptlon like Kepone (Boylan et al., 1978), and thus be susceptible to therapeutic removal by
Company Sanitized. Does no! contain TSCA CB!
^--^--------------------------Jl MA Bpr1e'v1io^u1s11scudyU----BUyshowed chat
'lethal
effect^of C-8.
2 hours This
of
c"8
dosing
protected
doses of rats from the
!4--------------^wlch protective
cotel
nonabsorbed C-8 ID
effect
the
could
be
due
to
acute
Interaction
of
absorption
of
the
administered
C-8
gascrointestloal dose and thereby
tract,
preventing
reducing lethality.
frc -w--as--gRivjueonu2ld4 henohuarsncae ftteher aenlimination of abyrbed C-8
the body,A----fM--
In
urine,
feces,
and
oral expired air
dose of [ Cj-C-8. of rats and
Radioactivity ellalnatea
days.
'iver
On the fourth
was measured.
day, anicals
Blood
were
alee sacrificed
was and
-{xasC'Jir-eCd-8 dIanllyblofoodr
four
to reflect the amount of comanpdo-'nlidver concentrar "ons of (
and
Cl-C-8 were as'ed
retained by the body.
MMBa*-t--e--rl--a*l-1s-
III 1 - Tracor Hark
1 - Packard Tri
Oiclprep-2
Scintillation Counter, Model 16882, Serial 1882020 Carb Sample Qxidlzer, Model 140306*, Serial 1262280
Oxiaorb CO, absorber
Aquasol-2
6 8 -
Methods
Jenco
glass
Mstabos-ls* - glass mouse
rat metabolism cages ^
metabollsa
cages
I
14 CJ-C-8
(0.5
uCl/ng)
Intragastric
Intubation
to
as an aqueous
eight Crl:CD*
solution
was
administered
by
adult
OPM
oale alee
at
a
dose
of
10 qg/kg
young adult (approximately
male
rats,and
to
six
- Otslntlgratlons groups as follows:
Per
Minute).
The ' rats and mice 1".e1r3e z di1v0ideDdPMin/ktgo; wthhreeree
Groi Control Control Treated
Number
Rats
Mice
2
2
3
2
3
2
Treatment
Sacrificed at 24 hours.
Sacrificed at 96 hours.
Dosed wlth|tf----Bp--------^|
(1000 Bg/kg5 2A hours aftedosing with ( CJ-C-8. Ssirlflced at 96 hours.
Sanitized. Does not contain TSCA CBl Company
After dosing, rats and alee were placed in individual glass etaboli-- chaBberg. Exhaled C was crapped in two tandea iapiagers containing 1.0 H
NaOB, followed by a water trap. Saoplee (2 oL) were taken froa the iapingerB at 24 hours, 48 hours, 72 hours, and 96 hours and added to 15 aL Aqaesol2 scintillation fluid. The saaples were cleared and acidified with several drops of glacial acetic acid. Feces Mere blended with approximately 1-2 L water, weighed, and 0.5 g was oxidized and counted. At 24 hours and 96 hours, aniaals were sacrificed by chlorofom anesthesia. Using a beparinized .
syringe, approximately 1-2 L of blood was reaoved froa the Ice via heart puncture an.1 approximately 8 oL of blood was reaoved froa the inferior vena
cava of the rats. Livers were reaoved from rats and nice, hoBOgenlzed, weighed, and 0.5 g saaples was oxidized and counted. Saople oxidation was
pe.f.
a Packard Tri-Carb*. CO- froa the oxidizer BBS collected
and OL .- - . 8 aL of Qxisorb CO,, absorber and 12 aL of Oxiprep-2.
Results and Discussion
A. Effect oflJBUB--ii--l01I1140]-^"8 Elirination.
,_ EliainatLan and distribution results for rats dosed with or without
^^HMBaBaagare presented in Figures I and 2. The results for aice
'are presented in Figures 3, 4 and 5.
For both rats and mice, the prinary route of excretios as urinary,
f.-ilowed by fecal and expired air^ For both species,jfhe quantitative
difference In elimination bettfeenyiiHBH^iiBBMHBH sad control aniaals ess not profound. Only rat fecal excretion of" C showed a statistically significant difference; instead of enhancing C-8 fecal eliaination, as expected ,UiiMMM|llMiliMtreataent slightly reduced the 96-hour curulatlve C-excretion (p < O.uOl). Mouse fecal eliaination of C showed the saae trend, however no statistical coaparisons could
be aade since fecal saules froa only one animal could be taken. Since
no overt increases in C-8 eliaination were noted, it was concluded
thacTfliiiiBBMBaaalM^aIsneffective in enhancing the eliaination of C-8
froa the body.
The corn-nt ration of (' CJ-C-8 in blood and liver confiras the lack
of enhanced C-8 eliainacion. Figures 2 and 5 show the 96 hour liver and blood concentrations for rats and mice, respectively. There was no
M_,_-^.
*
^ ..,,
^ ^ tissue concentrations between and control aniaals. Since there was no d decrement of [ Cj-C-8 in these indicator
tissues, it can be assumed that the body load of C-8 was unchanged by
These results contradict a previous studygfiriUB^ which showed
protection, aost likely because of differences in the absorption of C-8.
In the previous study much of ths dose as_probably still in the
gastrointesclnal tract whenuBaBBBBBBBBB^asadministered. The
nonabsorbed C-8 then associated ^CtftHllBIBBBBCI wss reaoved before absorption could occur, and thus prevented the acute lethal effects of
C-8.
'-^s.----------------------6'
B. CoBparison of (^Cj-C-S ElleinstiOD in Bafcs and Mice.
Since there were no notable ^reaCeAand control saiisals, the
differences
between ghblestyraaine-^
rcaotaspavnssoonoicoef BcBhSe mspadeec.ie-epecific Sdaties.pfoosritieoanchansdpeecxieerateiroen poofoleCd-8 aisaS a
eliKtnTaatbiolen 1anpdresents a comparison of ale rat vs. a&le loose ( C}-C-8
nearly
the
saae
distribution. After 96 for both species (6.5Z
hours,
fecal
elioination
BBS
ouse
expired
significantly
aore
(p
<
vs. 6.0, dose); however, the 0.001) C in the air (5.4Z dose)
than the rat (1.6Z dose). flosc.BOtably, significantly less (p < 0.01) f Cj-C-8
the
ouse
excreted
vs. 21.6Z~diwey.This dlfference--tn-tt^i^innfIc7a-e-euxrciareettoehna--a^it^t-eTerlayt^e(t8d-.-^
a greater I CJ-C-8 concentration
C-8/gB liver; p < 0.001).
in
ouse
liver
(53.2
vs.
30.7 og
equ.
for
rats
and
5.22
for
Additionally, the alee. Apparently the
liver/blood
ratio
--s
1.17
concentrating and/or retaining [
rat liver. The
C]-C-8
to
ouse liver is capable of
a greater extent than the
greater accuwiation of ( parallels tee greater sensitlvicy of the
CJ-C-8 in the ouse liver
underlying cause of involve either the
this
specie-specific
aosasg liver to C-8.
accuiulation in the
TSss
liver
igbt
Chs
kidoey
ay ifi -nich the esereCes the coapound.
liver
iaeerpsrstss
G-8
sr
the
say
References
I,--te_nPila--a--&A>., Baskell Laboratory, Unpublished Data :
2. BUsoeylan, J. J., J. L. Egle, and P. S. Guzeliau (1978). "Cholestyraaioe:
as a new therapeutic Science 199:893-5.
approach
for
chlordecone
(Kepone)
poisoning",
H-!4,6ii
h -
.-nmz.d.Doec^c^inTSCAC3i
Comply ^o-"'-"1'
H-14.249
^M^' m^\ Report by: ------TiMJEiy Reaeak-dh P. Paetoor/ Toxicologist /
Approved by:
Q5^JLJ>^^------L Gerald L. Kennedy ,'Jri
S-e-c---tio--n S__ui>pe&rvvi.soourr i Accuute ITnHvIMesBtUig*'"a*t*i--on--s-
TPP;tac:WP:13.4 Dace Issued: September 17, Haskell Report tto. 405-82
1982
^on^TSCACBl
5 -
San^d-Does"01
^TOpaWJ
Urine
Expired
Air
Feces
TABLE 1
^
Cimulative
Percent
of
Dose
Becovered
*^.
(a) '' '!'
Male Rat 24-Hour
06-Hour
6.5 ^ 1.7(8)
21.6 j; 2.^(5)
Hale Mouse
24--Hour
96-Hour
4.2 j; 2.2(5) 8.8 ^ 6.4(4)
1.3 jt 0.1(8) 4.4 ^ 1.4(8)
1.6 ^ 0.2(5) 6.5 ^ 2.1(5)
2.9 ^ 1.0(5)
3.8^2.7(4)
5.4 ^ 0.9(4) 6.6 ^ 1.2(3)
Liver
Blood
ug Equivalent C-8/g Tissue
Male Rat 24--Hour
96-Hour
34.9 ^ 2.8(2) 30.7^ 2.1(5)
24.5 ^ 0.6(2) 18.0^ 1.6(5)
Hale Mouee
24-Hour
A9&6J->fJl&o*uMr^
69.0 (I)
53.2 ^ 7.0(4)
18.5 (!)
10.2^ 0.7(4)
Table 1. Ellalnatloa and Distribution of [ C)-C-8 In Rats and Mice.
w
^
'
"
"
5
1
"
1
.
'
"."^
c
^
"
.
"
'
^
c
w
f5i
CL h-
I <D
S M
s3 h>- (-.
Q> a
B)
O'S IX ft
- P-
I
lit 0
-^
^
I
B >-,-
+ -<
U ft.
0
?
CD
CUMULATIVE PERCENT DOSE
Figure #2 - Microgram
of liver and blood of
equivalents rats.
of
C-8
per
gram
8 -
it.zed.Do^""^0"^1150^021
Company Sanitized.-oe.. -.
0.0 100
focmol, *eoMrmi.
"WAtIO ----nun;
204)
'a-O 4(M) 50.0 60.0 70.0
TIME (HOURS)
80.0
90.0 100.0
Figure #3 urine and
- Cumulative
COz of mice.
% dose
of
14 C
excreted
in
the
9 -
,lcontain7SCACBl
Sanitized. Does no'
QttafS^
UJ
(/)
0 Q
U
OS.
bJ OL
LJ >
<
_3 t
3 0
(rTMCATC
0.0 10.0 20.0 30.0 40.0 50.0 60.0 70.0 80.0 90.0 100.0
TIME (HOURS)
Figure #4 - Cumulative % dose of C excreted in the feces of mice. Mote: only one animal in treated group.
10 -
,
^^S^3 ^^sc^ -.;-yofl.
ny-"'?'s
W1
-"'
Figure #5 - Microgram equivalents of C-8 per gram
liver and blood of mice. Mote; only one animal in
"control-24 hours" group.
- 11 Company Sanitized. Doss not contain TSCA CB1
