Document 6B1D66Qo1RnopEvqw7ovOZ684
Copies to:
AR226-2750
E. I. du Font de Nemours and Company
Haskell Laboratory for Toxicology and Industrial Medicine
HASKELL LABORATORY REPORT NO. 253-79
Material Tested Ainmonium PerEluorooctanoate
Haskell
No.
12,037
Other
I: a Codes
Sample Ready
for Testing
1/5/78
INHALATION SUBACUTE
I f Material Subm HHUPlastic Produc
client, Washington We -ks
Introduction; Existing data|
'indicate that Ammonium perflnorooct'.anoatt
enlargement following acute i ^posure via inh'Slation or oral routes. This experiment was"des1
effect" level.
ause ied t
Procedure; Houseline aiT^(-2 K./min) was passed through a cyclone-head dust generator connected to
r_e_s_er_v_oi_r which concaine_d_H_R^ The resulting airborne particulate was passed into a 30 1 battery j
The atmospheric concentration of|]pB6j^nthe exposure chamber was monitored at 30-min interval fiber filters (type AE, 47 mm). The paniculate concentration was determined by weight gain of the
size was determined on a Brink cascade Impactor.
SixtyChR-CD'" albino male rats (20/group) were exposed to design level atmospheric concentra 0.08 mg/K.||^._K Rats were exposed, head only, for 5 consecutive days, 6 hr per day. Affter 5 days, a 2-day recovery (weekend) which was followed by 5 daily, consecutive 6-hr exposures.
All rats were weighed and observed daily (except weekends) during the exposure and recovery p
Laboratory Chow and water were available ad 1tbitum at all times other than during actual exposure
Clinical laboratory examinations were performed on 10 rats from each group at 0, 14, and 28 (details in Appendix B). After a total of 10 exposures, 5 rnta from each of the 3 groups were pat at 0, 14, 32 and 42 days post-exposure (details in Appendix C). Select organs were weighed: absolu weights were calculated.
On the 5th and 9th dayo of exposure, 10 rats were selected from each group for eye examinatio
Company Sanitized. Does
HLR #253-79
- 2
Results:
Acmosplieric|----^
Concentrations
W<0_______ Atjii.' < pheric t S.D.
0.0 (control) 0.008
0.080
0.0 0.011 t 0.005
0.083 0.017
Mean Mas 3
Median Diameter ^ S.I), (u)
0.0 1.63 t 0.70 4.47 t 3.41
Weight Gain; Racs exposed cogBl^showed a suppression of body weight throughout the test. The group was more severely affected during exposure (loss of body weight) and for 14 days of recove
Clinical Observations; During each exposure, sporadic cases of blinking, pawing, chewing and re
discharge were seen in all groups.
Clinical Pathology: Some rats exposed tolflUdust displayed elevated alkaline phosphatase acti were seen in glutamic-pyruvic cranaaminase and glutamic-oxalacetic transaminase after 0, 14 and days. The incidence was related to dose; higher activities were found at the higher exposure le
.only the latter activity at 0.083 mg/H was statistically different from controls. ^^f--------
Pathology: Pathologic evaluations showed,cloudy swelling or granular degeneration of hepatocyte of rata (5 of 5 examinrd) exposed ti^----Q|or 10 days with no recovery. Thia effect, was not see ^ longer recovery period. No other compound-related histologic changes were noted. VIPWMH------
[Appendix C.)
Organ/Body Weinhts; Various organ weight effects were evident in rats exposed t seen after 32 or 48 recovery days and in the absence of related hiatologic abi compound-related (Appendix D).
The dose-related increase in liver weights correlated with existing dat
described above.
These e ItTes were n
and
Eye Examinations;
9
No corneal, iricic or conjunctival effects were seen in any of the rats exam
exposure days (Appendix E).
-irorn^. -^Hi^- P^
-
3 -
Summary; Groups of 20_niale rats were exposed, head only, to particulate atmospheres of 0, 0.01,1 or perfluorooctanoatejimn 6 hr /day, S days/wk for 2 wka with 42 days recovery.
Rats exposed tofJJUshowed a dose-related suppression of body woi^lit.
Rats exposed Co|Cflhad dose-related elevations of plasma enzyme activities for up to 28 days
injury or dysfunction war suggested.
Liver degeneration was detected at the end of the 2-week exposure period in all examined rats liver effect was not detected after 14, 32 or 42 days of recovery.
Eye examinations revealed no compound-related effects.
GTH:scg
Report No. 253-79 .Date Issued; July 20. 191
Report by:
;-<-- >c_ Sflbrg
Toxi
Approved by;
j.^^T..Lajl JJ. 1I
Gerald Chief, Acute In
o
Sanded. Does" compa^
(.6rj t4TO 13-JUL-7
APPENDIX A
<ssssss>
450.
GROUTH CURVE-AnPIONIUn PERFLUOROOCTANOATE RATS
^ ^ 1
1 1
1,
1
1
f
1 1
1
1
1
1t i.
.^ .L
. 1
I1 .1
t 1
. 1
. 1
I1 1
1
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0) 400.
<
Ct
0
>-^ --
350. -
0
1--
UJ
>- 300.
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0
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x
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150.
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- .,
&.
,.. ^--^--.--(^.^--^--?..--y--,--^.^-----,--^--y--r- i i i -^r--r--r--r--r
10.
20.
30.
40.
50.
DAYS ON TEST \ ^s.n^.o
APPENDIX B
SUBACHTE INHALATION OF AMMOBltM PERFLUOROOCTAMOATE BM^||
Haskell Laboratory No..12037
Clinical Laboratory Report
Samples of urine were collected overnight (16 hours) from groups
8,of ten rats that were exposed nine times for four hours per day, five
*
per week over a two-week period to 0 mg/L, 0.008 ag/L or 0.08 mg/L
use. Blood was taken from the tail of these rats after the tenth
'
ure. Fourteen and 28 days after the last exposure blood and urine
(24 hour) samples were again collected from the animals.
The examination of the blood and urine included the following:
Hematology: Erythrocyte count (RBC), hemoglobin (Hb), hemaeocrit
(Ht), total leukocyte count (WBC), relativ; number of oeucrophils Oieut),
lymphocytes (Lymph), eosinophils (Eosib), oonocytes (Mono) and basophils
(Baso). The indices, mean corpuscular volume (MCV), mean corpuscular hsasoglobic (MCH) and mean corpuscular hemoglobin concentration (MCHC), were
calculated from these data.
Chemistry: Alkaline phosphatase (AP), glutamlc-pyruvic crans-
aminase (GPT), glutamic-oxalacetic transaminase (GOT), ganma-glucamyi
cranspeptidase (gGTP), bilirubin (BILRN), urea nitrogen (BUN) and total protein (TPROT).
Urinalysis: A measure of the volume (VOL), osmolality (mOs) and pH; a seai-quantitative test for sugar; protein and urobilinogen (UROBL); a test for blood and bilirubin; a microscopic examination of the sediment
from pooled speeiaess.
The data were analyzed by a one-way analysis of variance (AOV) to
compare the exposed animals with the controls at each sampling interval and by a nested AOV for the three sampling intervals. Significance was Judged at the 0.05 probability level.
Results;
The results of the clinical
are sumnarized in Table 1, and for Measurements on individual animals
attached to this report.
laboratory measurements or observations
th statistical analyses in Table 2. are listed in the computer print-out
Company Sanitized. Does not contain TSCA CBI
Higher
than
normal
activity wasfound
cclfKlust
for the plasma enzymes AP, after the last .exposure and
GPT
and
GOT
in
some
rats exposed The incidence
of
elevated
enzyme
activity
was
re
14 and 28 days later. lated tothe dose, occurring
more
frequently
in
the racs exposed to 0.08 indicated that only
mg/LmQlusc.
The
statistical analysis, however,
exposed to 0.08 mg/L was
significantly
the Sbl activity of the rats
elevated.
Increased
activity
of
these
enzymes
is
associated with liver injury
study with dogs
or dysfunction.
A
similar
effect
was
seen
in
an-earlier QKHMUCl)'
single non-lethal oral dose
By
These retcsQultsB,Ck
chat were given a
Chat
the
livers
of
rats, exposed inhalation that the effect may persist
for
dthuesrte, fomraey , besugagffeesctted by the exposure and
28 days or longer.
(1) Effect;^
Dogs.
on the Livers of Rats and
O/^fc 6. K'S^^L.
Report by; uW-a1l.t.e..r, aB. Koniecki
Clinical Chemist
WBK:JRB:ljo Date: October 19-.
178
Approved by: -^L^fL ^L\^j.
JoHn R. Barnes
Chief .^Clinical Pathology Section
Does 1:31 caniain TSCA C'sti CoilipAi^ Saiiii.u.fcc.
TA11LE 1
SUCMAKY OP CLINICAL LABORATORY MEASURED EXPOSED TO AMMOMIUM PERFLUOROOCTAMOAT
Teat
0 mft/L
Recovery
I*
26
UeHAIOLCCX
Erythrocytes X
HeLglobtngX
Heortocrit 1
MCVH' MCH ng
,IO,,'/,BB*i
5s .8R66
IS.l
^
"
26
o6 'W30 ^8
46 72
23
o6 t2>5 IA-9 '-7 75
24
MCHC %
33
32
32
Leukocytes X 10/r
Nentrophlls H
Lyophocycus 1 Eolilnuphlla 1
15.115 18 81
0.8
17.76 22
75
1.2
15.73
18
7t 2.7
Honncytua I
Basophlla 1.
C11EM1STBY AP 1U
GPT IU
GOT IU g-CTF IU
Blllrubin Hi Ure* altrogeo RX
Tofl Protein gX
IIH1HALYSIS
1.0
2.1
3.4
. 201 226 270
23
23
25
0 0 068
68
1.7
. 6 2O.J 16
0.9 0.6
21
1.0
0.3
18
6.6
6.7
6.7
Volume al
7
18
14
Oaoolallty OB
pit
blood, niwber polt!-'
Sugcr, number biiw.nuti Protein, nuaber i'inor--1
Uroblllnogen, Ehrllch unit* Blllrubin, nuober positive HIcroicopIc, nuober bnonul
20I9
1327
1706
7.2
7.1
6.7
1.0
0000
00001.0 10001
.
0
Test
0.008 nin/L
Recovery
14
28
5.H7 14.7 45 77
25
33 10.77 19
79 .
0.6 1.2
0
fr.12 14.3 45 73
23
32 13.17 19 78
1.3 1.6
0
6.24 14.7
47 75 24
32
12.92
15
81
1.3 2.6
0
242 28 72 1.2
0.3
19
6.3
296 25 74
0.7 0.4 .
22
6.7
291 26 67
0.8 0.3
19
6.8
6
16
12
2337
1490
1818
7.7
6.9
7.3
0
0
0 0 1.0
1.0
0000 0
0
1
0
001 1
.
0
0.08 Test
5.99
l!>.2 46 76
25
33
13.44 20
78
0.8 1.6
0 0 244 27
72
1.1 0.4 20 6.6
8
1624
1
7.9
0
0000 0
1.0
Company Sanitized. Does net
Erythrocytes
Hemoglobin Hematocric
MCV
MC11 MCHC
LeukocyCes
Neutr.;nhlls Lymphocytes Eoslnophila Monocytes Basophlls
AP GPT GOfT
gGTP
Billrubin Urea nitrogen Total Protein
Urine VOL Urine mOs
TABU-: 2
SUMMARY OF STATISTICAL DATA F; RATIO OF VARIANCE
Tenth Exposure
0.5 1.3
1.1
0.8
1.7 0.1 7.A 0.4 0.7 0.2 0.7
0.0 4.4 1.4 1.5
1.3 3.0 4.8 1.9
2,0 7.4
14-Day PostExposure
1.5 1.7 1.5 2.0 0.0 2.9 4.4
l.b
2.7
0.5 1.2 0.0 2.0 0.8 1.1 0.6 2.1 1.4 0.3
0.3 0.9
28-Day PostExposure 1.0 1.7 0.7
0.2 0.5 0.4 2.2 1.0 2.9 4.9 2.0 0.0 1.0 1.4 5.4
1.8 2.5 1.8 0.4 0.8 1.0
All Data 0.7 2.2 1.8 0.3 1.4 0.4 5.2 0.5 1.4 2.9 1.2 0.0 2.3 2.1
2.7
1.6 6.1 3.2 0.1 0.6 1.0
C^pany Seized. Does net co
APPENDIX C
Inhalation Subacute - ChR-CD Rats
February 27. 1979
Summary and Conclusion
Sixty young adult male rats were divided equally into three groups with
II Group I serving as a negative control and exposed only to air. Groups
and
III were exposed to ammonium perfluorooctanategfHIIIyat concentrations of
0.01 and 0.08 mg/1 respectively, 6 hrs/day, 5 days/week for 2 weeks. On 0, 14,
32, and 42 days post-exposure, 5 animals from each group were sacrificed for
pathological evaluation. At necropsy, the animals were examined grossly, and
the following tissues or organs saved for hisiopathologic evaluation: external
ear, abdominal skin, trachea, lungs*, heart*, thyroid, adrenals, thymus*, mediastinal tissue, spleen*, sternebrae with bone marrow, stomach, small intes
tine, large intestine, liver*, kidneys*, testes*, epididymis, brain and eyes.
The results of pathologic findings are summarized in Table I. As the
table shows, an apparent compound-induced toxic effect consisting of a cloudy
II III swelling or granular degeneration of hepatocytes was detected in the livers
of all five rats (5/5) in both Group
(0.01 mg/1) and Group
(0.08 mg/1)
at the end of the rwo-week exposure period. However, the hepatocoxic effect
was not detected after a 14-day or longer post-exposure recovery period. All
of the remaining pathologic findings listed in the cable are considered to be
spontaneous or the result of intercurrent disease.
* Organs weighed
HHCC:WCK:mjb
Report bv:
-7^ (Uj^. X^?. Bans H. C. Chen, D.V.M. Senior Research Pathologist
Approved bv:
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K_r--a--u--s--s, DT\ .VTT .M .
Chief, Pathology Section
Company Sanitszsd. Does not contain TSCA CBJ
TABU; i
BIIMMAIIY OF rATiioLOisic rmDnr.s IN HAI.E cim-cn BATn
EXPOSED TO /UMOHIUH rEnnjJOIlOOCTAHATE
Animal.No. R pViV.i
i
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0
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h i u h
ri
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pnetZBOBia, eirly jtage
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iiiiiiii . a ospbyifBA
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Bicro-grKBuloBa/foci of >m^nT-r heoonolejii
Livr: Cloudy veiling/
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TABLB I
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0.08
10
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1
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0.08
10
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1
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0.08
10
lit
2
No lesions I: VIsry i"lld chanRa ?!
not nvnl|nb4<> for lilntolnnlc rvniuntinn
2
Rllpht
1
2
-
i
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1
2
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-
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1
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p.
1---1.-- 1
-
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-
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change 5 Moderate ctiange r; IBlon present X
Company Sanitized. Does no
PAHT V
TABLE I
auwART or PA'nioKxnc FtNiiiNus in HME cim-cn RATS EXFOBEP TO W10HIW rERFUJUROOCTAMATE
?
Animal No.
0
R 216195
III
R ?1^19'
ni
B ?5ft19'5
in
R 25<W' .
HI
B ??<'.?97
ITI
R 216588
in
B 2Vi509
TTT
n 256590
ill
R 216191
III
R ?1?;592
III
|
li
8
0.08 0.00 0.08 0.08
o.oB 0.08
0.08 0.08
O.OB
0.08
1P.
8
8
?
J I1
10
52
10
12
10
52
10
52
10
52
10
!?
10
4S
10
iia
10
h3
10
li;?
I? a;
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Q
2 2 P 1 2 1 3 1 X 1
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1
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2
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Code: -! No leHoM
li Very nlld chanRe 2i Slight change 5l Moderate change r: Leclon preBent X:
the tIflBuc ott nvallnhftc for hIslnloRlr evd hint Inn
Company Sanitized. Does not conta
^'^^B"S
APPENDIX D
MEAN ABSOLUTE ORGAN AND BODY WEIGHTS
AMMONIUM PERFLUOROOCTANOATE VIA INHAL.
OF MALE RATS^I
<SUBACUTE-6;f||||^|
' .'-:" . ^ C -:?:'.
-ceuuE'-
I CONTROL
IIIII LOU LEVEL HIGH LEVEL
F RAT3CX1) LSD<2) DUNNETT(3) UHS < A)
-EItlAL-BU
273.6000 258.8000 239.0000+
6.125* 21.6130 24.7992 246.0000
.----.-.-G&QUE.
-KIDyEY.
J CONTROL
IIIII LOUI LEVEL HIGH LEVEL
2.5560 2.2840+
2.2:180-*
F RATIO<1) LSD<2)
DUNi<(ETT(3)
UMS < 4)
5.9205K
0.2269 0.2603 0,0271
<1> RATIO OF AMONG- TO UlTHIN-GROUP VARIATION--ONE-FHCTOR ANALYSIS' ^m^^i^l
^^lil^^;^ <2) LEAST SIGNIFICANT DIFFERENCE--GIVEN H SIGNIFICANT (ALPHA=0. OSy^.R^R^piaSpl"^^
ANY Tyn MEi^NR GIFFER1MG BY MORE THAN THE LSD ARE SI5NIFICATLY rsIFFERE^Tl^^^^ kITrh A VARIABLE-UISE FALSE POSITIVE (ALPHA) ERROR RATE OF 0.05.
m
THAN WTTi-i
"%^ DUNNETT
TEST--ANY
TREATMENT
MEA'l
H1FFEPINO
FROM
THE
CONTROL MEAN'S'Ka^^E;^!! THE CONTROL ^l^iljp ^III
THE HUNNETT STATISTIC IS SIGNIFICANTLY DIFFERENT FROM
--
A VARIABLE-UISE FALSE POSITIVE (ALPHA) ERROR RATE OF 0.05.
(-li kl; THIN-GROUP NE(4N SQUnKF . + SIGNTF-ICANfLV DIFFERENT <p<0.0'5> FROh CONTROL GROUP BY LSD.
< IG-'II-1CANTLY DIFFERENT (P<0.0^> FR'3n CONTROL GROUP BY DUNNETT TEST^^gjgl^;!;^ * S:1'NIFICANT AT THE 0,05 FROPAPIL :[ ! Y LEVEL.
*
MEAN RELAT IUE ORGAN AND BODY WEIGHTS3 TO AMMONIUM PER FLUOROOCTANOAT E VIA INHAL.
GBQUE------.------ ,,-- --HatF. tAatBt.*I--- ----------
I CONTROL
II LOU LEVEL HI HIGH LEVEL
P RATIO<1) LSD<2) DUNNETTO) UMS(4)
0.3548 0.3243 0.3254
1.725 0.0406 0.0466 0.0009
LUNGS-----
0.6206 0.5447+ 0.6083
4.569* 0.0587 0.0674 0.0018
F(SOURBAMCAULETER-Cfi^) TSRECEXOPVOERSEYD DAYISjy ;'.H
LIUER-----..SELEEN----
..?
"v^,
:|$iDyEX-^
'
4.7259 4.9997 5.9226+
02075
0.1665+ 01455+
" ;b.9348;| 0.8920% 0.9292:^
4.316* 0.9299 1.0670 0.4554
17,638i;
0.0232 0.0266 0.0003
0.273^ 0.1372^
0.1574;H 0.0099;|
;5
,6
^
"'??
.^'
.
-GE:OUE.----.---------- IESIIS----- IciXdua------
';
III CONTf.OL
1.0253
0.2418
;;
LOU LEVEL
1.0059
0.1808+
HI HIGH LEVEL
1.1105
0.1438+
"I^^-^^^1^ ^^^ri^^"^^'^^^^^"0' F RATIO(1)
1.836
7*713*
LSD < 2)
0.1266
0.0549
DUNNETTO)
0.1452
0.0629
in3<4)
0.0084
0.0016
,1, ..TIO OP ^ONO- TO W1THIN-GR03P ^I.TION-ONE-F.CTO. ^LYSIS 0? ^I.NCE
<2> L^ST S^IFIC^T
^
---- or o.cs.
^ S ^ ^ ^ ^ z ^ ^ ^^^O^O^OL^r <3, BU^TT TEST-.HV TP..TMENT ^
^^ ^
^ S ^ ^ ^ ^ S S (4 UITHIN-GROUP MEAN SQUARE.
^ ^ '- 0--
, cin.TFTnANTLY DIFFERENT (P-::0.05.) FROM CONTROL GROUP BY LSD.
SIONIFIC.NTLY DIFFERENT <P<0.05> FROM CONTROL GROUP BY DUNNETT TEST.
SIGNIFICANr AT THE 0.05 PROBABILITY LEVEL.
M^L .-:.^,..fc^.,a-^jaiSa^a^^
Con^ Saniti^d. Does not contain TSCAC6L
MEAN ABSOLUTE ORGAN AND BODY WEIGHTS OF MALE RATS EXPOSED TO
AMMONIUM PERFLUOROdCTANOATE VIA INHAL. (SUBACUTE-14 RECOVERY DAYS)
G&OLP
I CONTROL
IIIII LOU LEVEL HIGH LEVEL
F RATIOd)
LSD(2) DUNNETTO) UhS(4)
Elbli&L U - - - - -..HE^fil- -.--.- LL1UGS----
341.2000 341.0000 303.9000
1.1660 1.1720 1.0480
1.8480
1.6900 1.6640
2.604 41.1241 47.1867
890.6333
1.810 0.1601 0.1838 0.0135
1.226 0.2771 0.3180 0.0405
LIUE6 -
14.4980 16.0560 15.0360
0.684 2.9474 3.3819 4.5750
SilLEEhl ^8
- ^ 'i:-
'
.^Q
.
7
5
'
0
0'-^i^
0 .6260^
6 .58601
;
^3
3.0291^
0 .151.4ii 0 . 173'7^
"0 .Ol2.iw
i
... -.-..GROUE-..-..-..-....- , -- -......-.KIDNEY--..,..-.- . -- .T1.1C--Ci3TI-TAi6.3; " -- -- -..-.-lyjcuus.--. -
I fOMTROL LOU) LEVEL
IIIII HIGH LEVEL
F RATIOd)
LS-JLI < ? )
DUNNETT(3) UMS<4)
2.8520 3.0060 2.6360
1.793 0.4278 0.4908 0.0964
3.2760 3.1580 2.5840+
3.949* 0.5740 0.6586 0.1735
0.6040 0.6520 0.6020
0.250 0.1743 0.2000 0.0160
(1) RATIO OF AMONG- TO U:l THIN-GROUP VARIATION--ONE-FACTOR ANALYSIS OF VARIANCE
(2^ LEAST SIGNIFICANT IHFFERENCE--GI*.'EN A SIGNIFICANT <ALPHA=0.05) F RATIO, ANY TUO MEANS DIFFERING BY MORE THAN THE LSD ARE SIGNIFICATLY DIFFERENT
UTTH A VARIABLE-UISE FALSE POSITIVE (ALPHA) ERROR RATE OF 0.05.
<3)
THAN WITH
DUNNETT TEST--ANY TREATMENT MEAN DIFFERING FROM THE CONTROL MEAN BY MORE THE DUNNETT STATISTIC IS SIGNIFICANTLY DIFFERENT FROM THE CONTROL MEAN
A UARIABLE-UISE FALSE POSITIVE (ALPHA) ERROR RATE OF 0.05.
(4) UI THIN-GROUP MEAN SQUARE.
+ SIGNIFICANTLY DIFFERENT (P<0.05) FROM CONTROL GROUP BY LSD. * SIGNIFICANTLY DIFFERENT (P<0.05) FROM CONTROL GROUP BY DUNNETT TEST. :: *" SIGNIFICANT AT THE 0.05 PROBABILITY LEVEL. Comply Sanitized- Ooeso^cor!faiti,;ISi|ACB^
J - ''--ssssssssK-Sfe
MEAN RELATIVE ORGAN AND BODY UEIGHTS FOR MALE RATS EXPOSED TO AMMONIUM PERFLUOROOCTANOATE VIA INHAL. (SUBACUTE-14 RECOVERY DAYS)
-GBQUE,
I CONTROL
IIIII LOU LEV;EL HIGH L-EVEL
F RATIO(l) LSD(2)
DUNNETT<3) UMS(4)
UlTAC-T
0.3420 0.3438 0.3458
0.029 0.0339 0.0389 0.0006
LUNGS
0.5392 0.4965 0.5514
1.952 0.0637 0.0731 0.0021
---- LIUEE
sifLEEtsl----
-K3;lh!Ey-a
.: '";.
' -
-^
4.2487 4,7164 4.9095t '
0.21BO
0.1838+ 0.1925+
:
W.83A&IJ
OS. 8837.;
0*8647 a
:
^i
3.350 0.5720
0.6563 0.1723
5.090*0,0243
0*0279 0.0003
'
.0.62411
^0920?
O^IOSS^
^.0045'
.BKOUE-
-iE3iis.--.---iyYaus-
I CONTROL LOU LEVEL
IIIII HIGH LEVEL
F RAT 10(1) LSIK2)
DUNNETT(3)
UIMS<4)
0.9658 0.9263 0.8528
1.004 0.1763 0.2023 0.0164
0.1773 0.1916 0.2003
0.408 0.0560 0.0642 0.0017
(1) RATIO OF AMONG- TO UITHIN-GROUP VARIATION--ONE-FACTOR ANALYSIS OF VARIANCE
(2) LEAST SIGNIFICANT DIFFERENCE--GIVEN A SIGNIFICANT (ALPHA=0.05) F RATIO?
ANY TWO MEANS DIFFERING BY MORE THAN THE LSD ARE SIGNIFICATLY DIFFERENT
UITH A UARIABLE-UISE FALSE POSITIVE (ALPHA) ERROR RATE OF 0.05.
(3)
THAN
WITH
DUNNETT TEST--ANY TREATMENT MEAN DIFFERING PROM THE CONTROL MEAN BY MORE
THE DUNNED STATISTIC IS SIGNIFICANTLY DIFFERENT PROM THE CONTROL MEAN
A VARIABLE-UISE FALSE POSITIVE (ALPHA) ERROR RATE OF 0.05.
::
<4) UITHIN-GROUP MEAN SQUARE.
:
+ SIGNIFICANTLY DIFFERENT (P::0.05) FROM CONTROL GROUP BY LSD.
* SIGNIFICANTLY DIFFERENT <P<0.05> FROM CONTROL GROUP BY DUNNETT TEST.
'M.&TI TTV i FUEL. '-C-^o(m^p'^a"n^yBS.aSfit^itMSf^fl-iafef'cg.e-aQ-a^'^^W^^r'.C^t^'eM^aHsaala
5W6B
^S ' -^f'.- '}':v'^^'y;^^.^'iW"?-it'ii^sa<"Ti'e?t'^.M^^';y1i:
"^i-aa i
'^|
-M MEAN
ABSOLUTE
ORGAN
AND
BODY
UEIOHT s
OF MALE RATS <8UBACUTE-32
VIA AMMONIUM PERFLU OROOCTANOA rE
INHAL *
-
^
n&niip
I CONTROL
IIIII LOU LEVEL HIGH LEVEL
F RATIO(l) LSD(2)
DUNNETT(3)
1MS(4)
EIH6L-BU- -
367.2000 361*6000 351.6000
0.494 34.6587 39.7681 632.6000
----UE6RI-- - --LUNGS------ LlUEfi-,:
1.1100
1.1260 1.1340
1.7940
1.6840 1.7600
12.244^ :'
^^a-^r
12.5760;
0.054 0.1628
0.1868 0.0140
0.575 0.2289 0.2626 0.0276
. 0.099' ;::.^fc?rf?.*'?i3!^
1.6240 1.8634
.;^105A
1.3889 "''^ig 004^1
^.'^'fgl . .^i^
.
------------------- --
-.GSQUE-
I CONTROL
111 'I LOU LEVEL
II HIGH LEVEL
- -- .- KIDNEY--
2.6740 2.8200 2.6660
.Tj.Ct-"aCxT^TBC---
3.0520 3.2400 3.1060
----IUXBUS---
0.5900 0.5220 0.6340
.,:'' '.;
''"M^i
:.' i^ag
' ----;%:1^|
III F RATIO(l)
0.279
0.891 0.3159
1.816 0.1290
LSD(2) DUNNETT(3)
0.3058 0.5803
0.3625
0.1480
^.'.';^
^N
UwMnaS\(4 )/
0-.._13_ 4. 7
0.0526
0.0088
.^'^
':s ^s
VARIATION--ONE-FACTOR
A--N..A. LYSIS
.
^OrF.
;v|ii[ANCE:| "-. ^. ^.?
'
'n^t-.a'AMr'C"^
. . ,, (1) RATIO OF AMONG- TO UITHIN-GROUP
(2) LEAST SIGNIFICANT DIFFERENCE--GIVEN LASDSIGARNEIFISCIAGNNTIFIC(AALTPLHYA=D0I.F0F5E)REFNTRA^Hlb !3
AUNITYH TMAO VMAERAIANSBLDE-IFUFIIESREINFGALSBEY MPOORSEITITVHEAN (ATHLPEHA) ERROR RATE OF 0*05^
TREATMENT
MEAN
DIFFERING
FROM
THE
CONTROL
MEAN
BYltWRE
MEi?iN
T(H3A) N DTHUENVNADERTUITANNBTELETETS-UTS--ISTAEANTYFISATLSICE PISOSSITIGIVNEIFIC(AALNPTHLAY) DERIFRFOERRERNATTEFROOFM 0T.0HE5. CONTROL ' ;:;|
WITH A
: I
(4) UITHIN-GROUP MEAN SQUARE. + SIGNIFICANTLY DIFFERENT (P<0.05) FROM CONTROL GROUP BY LSD. * SIGNIFICANTLY DIFFERENT (P<0.05) FROM CONTROL GROUP BY DUNNETT TEST. ,
.':!!i
-. -t
TSCACBJ Company Sanitized. Does not contain
.;;ii.a,:a5^,^S.,^,.,,.-..
HP
'^'T^SJB ORGAN
AND
BODY
WEIGHTS
FOR
MALE
RATS EXPQsi&^IS^SI RECOVERY; Bilt^iil
MEAN RELATIVE PERFLUOROOCTANOATE VIA
INHAL.
(SUBACUTE-32
"
.'-
Vi -:'. -^A^-w-.Kg^S^
TO AMMONIUM
._-.----GBQUE:----_-
I CONTROL
IIIII LOk) LEVEL HIGH LEVEL
F RATIO<1) LSD(2) DLINNETTO) UMS<4)
-UEAKI--
0.3028 0.3104 0.3221
1.379 0.0255 0.0293 0.0003
0.4884 0.4662 0.5004
1.449 0.0443 0.0509 0.0010
3.3384 3,4328 3.5735
1.472 0.3004 0.3447 0.0475
0.1789 0.1661 0.1704
0.765 0.0231 0.0265 0*0003
'^M m^
'.:W3r4tg
. W ^ i -.SfF567;;! '
' . ; . ^ ':'"'":';^KS?:i'-3" ^r-s.
; -^6s3s
.;:.;>31&3_ ;8. -0. .4. 1
..;^w'^i2--6"r^ ';.;.,!,<&!,, .. ,, ,':^t
-?
.IESIIS-
.laXBUS--
.--.---GEs.aUE:--.---------.
I COMTI-<01. LOU LfcyiE-.L
II HTGH L&'yFL
0.8336 0.8991 0.8849
0.1627
0.1439 0.1810
III F RATIO(1)
LSD'2)
1.067 0.1029 0.1180
1.913 0.0413 0.0474
DUMNETT(3) UUIM">SS(44,>>
0.-.0.^0-5-_6
0.000'? VARIATION--ONE-FACTOR ANALYSIS OP VARIANCE.
.1) RATIO OF AMONG- TO UITHIN-GROUP
(ALPHA=0.05) F RATIQ.-
LEAST
SIGNIFICANT
DIFFERENCE--GIVEN
M SIGNIFICANT LSD ARE SIGNIFICATLY
DIFFERENT
THE
;
.2)
DIFFERING
BY
MORE THAN
POSITIVE (ALPHA)
ERROR
RATE
OF
0.05.
Alo N1:1/ l-l iUftCi VMAEFAIMNSBLE-UISF- FALSE
CONTROL MEAN BY MOF.-E
DLINNFTT
TEST--ANY
TREATMENT
MEAN
DIFFERING FROM THE DIFFERENT FROM
THE
CONTROL
MEAN
0)UTH:[ATHN TAHEV: ADRLIiANtNfELTET-USISTEATFISALTSICE PISOSSITIGIVNEIFIC(AALNPTHLAY) ERROR RATE OF 0.05. i ,
(4) UITHTH-GR-01JP MEAN SQUARE.
'
DIFFERENT (P<0.05) FROM CONTROL GROUP BY LSD.
+ SIGNii-](:p)N(|..'r
CONTROL GROUP BY DUNNETT TEST.
< Sir-mFICANTLY DIFFERENT (P<0.05) FROM
S^.Oo.no.co^TSC.CB,
Company
....-aK.l.iaiiiil-fea^^!?,
' "
' '
' ...-.-...,----'-"^^"-p--"^^-- -.^^^ai.s^s^g^
E ^ ^ AMMMEOANNIUMABSPEORLFULTUEOROOROGACNTANAONDATEBODVYIA WIENIGHHATLS. O(SFUMBAALCEUT-R42ATSREC^^j|
____-GE;OUE--------------EHit61--BU-
I CONTROL
IIIII LOU LEVEL HIGH LEVEL
F RATIO(l)
LSEK2) DUNNETT(3) UM3(4)
427.8000 409.8000 372.8000*
3.4A9 46.3909 57.22^B 1133.3667
.UE6&I-
1.3460 1.2420 1.1640
3.078 0.1604 0.1840 0.0135
-LUaGS------
1.9080 1.8920 1.8480
0.035 0.3275 0.3758 0.0565
JjEOUE-
_KIDblE^-
-ICSIIS-- ...lU^CtiUS--
I CONTROL LOW LEVEL
iIIn HIGH LEVEL
F RATIO(1) LSD(2) DUNNETT': 3)
kiM&'<4)
3.2100 3.2220 2.8500
1.241 0.5846 0.6708 0.1800
3.3000 3.2560 3.2100
0.235 0.2862 0.3284 0.0431
0.6040 0.5920 0.5440
0.540 0.1331 0.1527 0.0093
(1; RATIO OF AMONG- TO UITHIN-GROUP VARIATION--ONE-FACTOR ANALYSIS^ CH||ip|:IAN;l
A STGMIFIC:(">NT (ALPHA=.0.05) F^IIN^O' '
(2)
ANY
LEAST SIGNIFICANT DIFFERENCE--GIVEN TWO MEANS DIFFERING BY MORE THAN THE
L&E!
fSRE
SIGNIFICATLY Or
DIFFERED
"^M
yi-"!-! A VARIABLE UISE FALSE POSITIVE (ALPHA) ERROI- RATE
0.05.
(3)
THAN
UITH
DUNNETT
TEST--ANY
TREATMENT
MEAN
DIFFERIf.'Q
FF<OM
THE CONTROL MEAN ^Y^CiW
PROM THE CONTROL; .MEAn
ATHEVADRUIANBNELTET-USISTEATFIASLTSICE PISOSSITIGIVNEIFIC(AALNPTHLAY) DE.R' RF-OFRERER.NA'Tl E OF 0-05.
^^l
;^
(4) UIITHIN-GROUP MEAN SQUARE. + SIGNIFICANTLY DIFFERENT <P<0.05) FROM CCN f i":OL GROUP BY LSI:'.
^.^A
* SIGNIFICANTLY DIFFERENT (P<-0<05> FRCiM C(!?-T^a!. O.ROUP BY HUNNET't ;"ESI^||,
Coinpany s^^'^^^Sl
--
^ MY||
MEAN RELATIVE ORGAN AND BODY UEI6HTS (SFUORRACMUALTEE--4R2ATSRECEOXPVOERSEYD UA PERFLUOROOCTANOATE VIA INHAL.
TO AMMONIUM
"^Mn
; SfS^
: '.jg
-- - G&QUE ----- --------UE6EI-- --
1 CONTROL
IIIII LOU LEVEL HIGH LEVEL
F RATIO(1) LSD(2) DUNNETT(3)
UMS(4)
0.3162 0.3029 0.3125
0.405 0.0333 0.0382 0.0006
-LUNGS-
0.4451 0.4629 0.4950
1.530 0.0629 0.0722 0.0021
--.HUEK- .
3.8684 3.7516 3.6035
0.573 0.3807 0.4368 0.0763
SELEEH--...--. .SWsISUl^^-^.H,^i .
0.1847 0*1613
0.1.875
'^.719<SJl| .^0.7855|| ;!'y^,7&2QSj
2.089 0.0307
0.0352 0.0005
-[Q^ ^^Rifi
; . : r;;U SO^-SS
"0.0904!^ ':' 0.1037-1
0.0043l
.bKOUE-
.IESIIS-
.lU^ttUS-
I CONTROL
0.7745
0.1422
i LOW LEVEL
0.7982
0.1451
II HIGH LEVEL
0.8630
0.1456
^
III F RATIO<D
2.687
0.027
LSIK2) D'-INNE-TT (3)
0.0861 0.0988
0.0345 0.0396
UMS(4)
0.0039
0.0006
W)O1F\J \ AifMONG- TO UITHTN-GROIJP VARIATION--ONE-FACTOR ANALYSIS OF VARIANCE;
(1) l':ATIO
A SIGNIFICANT <ALPHA=0.05) F RATIO ;;
(2)
LEAST
SIGNIFICANT
DIFFERENCE--GIVEN
BY MORE THAN THE
LSD
ARE
SIGNIFICATLY
DIFFERENT
AUNITYH TUAO VMAERAIANSBLDEI-FWFIESREINFGALSE POSITIVE (ALPHA) ERROR RATE OF 0*05.
DUNNETT
TEST--ANY
TREATMENT
MEAN
DIFFERING
PROM
THE CONTROL MEAN BY MORE FROM THE CONTROL MEAN
TU(H3ITA) HN TAHEVADRUIANBNELTET-WSISTEATFISALTSICE PISOSSITIGIVNEIFIC(AALNPTHLAY) DERIFRFOERRERNATTE OF 0.05* .
(4) UITH1N-GROUP MEAN SQUARE. + SIGNIFICANTLY DIFFERENT (P<0.05) FROM CONTROL GROUP BY LSD. * SIGNIFICANTLY DIFFERENT (P<0.05) FROM CONTROL GROUP BY DUNNETT TEST*
Co^pani"*1' S:i an"is^c. Dcs'"s-' wnos;,ic^amnlwain TSCA CB'.'
Procedure: Sixty ChR-CD young adult male rats were divided in^|;(
three groups of 20 rats each and exposed (head-only) six houa;^^^^
day,
five
days
per week
for
a
total
of
10
exposures over
a
two-;'^?]!
|'
week period to O.OC, 0.01 or 0.08 mg/1 octanoic acid, perfluoro-^f
ammonium salt paniculate. for eye examination on the
Ten rats were selected from each grolig 5th and 9th days of exposure. ObseirvtG-;
;
tions of the cornea, iris and conjunctiva were made with a hand-"^; :
slit lamp and a biomicroscope after using Fluor-i-strip stain, ^ ';:
Results: The results of the eye examinations for each rat are
;
presented in Tables
II III. halation to octanoic
I,
acid,
and
When rats were exposed by in-^;l;
perfluoro-, ammonium salt particulate;at^
^^ 0.01 ag/1, two of ten rats at five days and five of ten rats at
ni ex
ne po
s
da ed
y
s
to
h
ad
0.0
d 8
r
ied
mg/
1
r
ed
of
di
t
sh
es
t
b
ro
m
w
a
n
te
disc
rial,
h
arg
two
e
a
of
r
oun ten
d
r
the ats
ir
h
a
e d
ye d
s. rie
d
IW
^
I
ie
^
n
reddish brown discharge at five days and five of ten had brown dits-y
charge^and one had dried reddish brown discharge at nine days. ; ^
This discharge (chromodacryorrhea) is often seen in animals under
stress. No corneal or iritic effects were seen in these rats.
:
No corneal, iritic or conjunctival effects were seen in the control;
rats at any time.
Summary; No significant ocular effects were seen in rat eyes when
examined after the fifth and ninth exposures to octanoic acid,
perfluoro-, ammonium salt.
Report by;
^fcua-^ fjlLs
Doris F. Edwards Toxicologist
Approved by:
^^fGYera^ld,^^i.. Kennedy
Chief, Acute Investigations Section
>DFE;scg
ite Issued:
*^
June 2r, 1979
contain T5CACB1
Company San^d. Doa..,ot
-.--;. --.'tMSiiJ?.'-^.
-r?-wyw/-^f.a
-
TABLE I ^ Conttrol (0.0 mcr/U H-12.037
;f
143 CSW
spaci-iy araa
^i
Csaiuse-sy/a
fdsw
silaaasia
diaei.ar;*
riaor-t.-a^i?9
Steals e5 esr-.sa
3S Csfxea ape-sy
W
Csaluaes.i.va rdas3 CSCW1.S i-ie.-.Arg*
Tiao.c-i.-atri?5 3-esi.e ci ear-in*
Is50
-
Cassfti
opteisy
&c--
1?-3
Caajuas^va c*daaa ctMBoaia disc!&f9
Fluec-i-atr;.?3
3&3aic =S e3ra
.6351
Caca-- Bpc:.=y ara
^s.
Caa^'sacs^v rdaa eifBoai.j
Aiacirrg*
riaor-i-ttr:.?' Siesic e; saraw
;63S2
&
^
tezaea o?acs.t7
r*a
Iri.*
Cony-nc^iTa c!a* sisjmosi.j
dijehAf;*
?laor-s.-^i.p*
Steals e5 cara
S ftJiys a/'4
i* -3-
3
0
0
0
3
0
0
a
3
0
1
3
9
0
3g ?
te
v 9 11r/
9/1
0
3
3
3
3
3
0 3
0
ng
3 0 0
3
ag
0
3
a
0
3 0.
3
0
3
3
0
0
0
0
0
0
0
0
0
9
a
3
0
Q
0
0
0
5
=? nq
-
n^
te -3-- L a
0
3
0
0
0
3
0
0
3
0
3
0
3
0
0
3
0
3
0
3
r.g n?
u
a
3
0
0
0
0
0
-
0
-
cg
to
a
0
0
0
0
9
3
0
C
0
0
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3
a
n9
~~3. ."
S
S
0
3
0
3
.
0
3
ii
3
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3
3
ee
0
3
3
0
3
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0
0
0
0
3
0
.
0
-
?
M
3.
Q
a
C
0
3 0 -
-
3
0
3
0
3
0
a ^
" ?
^dried reddish brown 2 brown
/ v a*e
S&y 9
a3*/1y0
a
236333
.CasaM 8p*ci=y
f--
;si.s Csniwess-ya
rds* eiuaosij iie&s?e
riaor-*.-esi?9
3iic af eoKr*.
0 0'
a
a
0
C
0
0
3
0
0
0
0
0
0
0
0
0
0
sag
** --3----
0 0 0
9 3 3 0
-.-?
23S3S
esraea spass.s?
f a 2ri.
Canjaaesi.va
rdjrs ehjBosi^ die&r;
riaoE-i-xsrs.?'
BtqmiT o; ears**
5
3
0
0
0 0
0
Q
0
0
0
0
*
0
' any
3
8
3
3
0
C
a
9
0
0
Q
0
*
0
CM^
2363S5
Casa* opACi-ly rft
=i8
eaajuaeciva ?da*
ehoexij
iie&s?c
yluoE-l.-t'ssi?3
Blaaie of esss
1
'
0
9
0
0
0
S
0
0
0
0
9
9
0
0
0
^
0
a
-
0
Q
0
0
0
e
0
-
0
a9
*
' --sr~ -
Wf
. a,
2363S6
C5Za opae^sy
f--
2si
Csa}ueei7a ;das e&csaclj .
iisebkz;*
Masr-i-scri?* aisaie af csrsea
9. 0
a
0
0 0
0
5
0
0
3
0
a
0
0
0
0
0
3
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0
0
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-
0
* B-?
"
"* -3---- ^
3*?
""A
:33S7
f Cora-- opMisy
;ris
e
0
0 Q
0
0
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Q
0
2
0
0
Canjuac'si-yi
fds*a.
eiiool die!tr;
3
0
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0
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0
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ylaes-I.-sss'i?9
-
0
-
0
leoie ef earaaa
Mg if ?
Cowanysa"-"--"083^co,*""^"'
u
- en LJ
-I
Bu m "i
i- r
o r " n i
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ill M
!{ )! S ^
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ii' n >i 9 r !rn' (Buf PIi -'PHi M
lNr
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l| r H r
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n
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in -
w <1
II
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M
r <
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n 1|
r
pit
r 11
|i (*
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Hi "1
P' 1-
u i:
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n
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W&gr2;J{ n i4
n. n ii Uii
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t "
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n!-ofiLif' SR8
ii
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p H
C- 1-'
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a c u< o n p >
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{ i
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u
iiifiuliu 5 0
r1-
p(i
b
U
M
n 11
* !" i. "
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a ".
n 0 o *(
li-au
r Nn
r
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1 f tt;
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K.
8 !' f p^
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u
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n i k u ii
I" II M >< M r
>
jli dl u
<
11 >1
.' "
V
I
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U 0
Ltd CJ
0 C' 0
< 0 0
C 0 LJ
"M 0
i rjcjocj
0 LJ U
a
c- _*
I <
| | 00 0
*.ll
o
LJO a
C 0 U L> o u
I | 1 000
u
U
0 <11
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t' 1 1 0 0 L)
ano e
Hi 9
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I'OOUUO
S;
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000
QOO
|'l 1 ICJOO
11
M
U f-* U J
<n
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000' 000
f OCJ
a0 1
1U
Jl 1
0 00 0
000 000
I'
1 1 |3 0 U
n
'M OOOO
0
U 0
000
000 (> 1 0
>1
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1a0 0
0- 00
U
0
0 0
jlrfsji
u^ s
s"
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{J
C
a
a
;
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';
'i
u^ ^m iigjij^il thiij^ij jhifsil
^m !s
s
s
^lutt
y"-
: s ",,
lilll?' ^
y<11*
' ' "" .S " """
" ""
o oo
' ' "fl"
fl ,?"
.- '
l>
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t!
^ J( ,,
00" ,,,,,,
" c."
,, ^^
; "OCT
S{ J tl
" .* ,,"
I
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" " ,,0 ,0^0
. , . ooo
^ ^ ^^
.-I I . "o
JJ g'
1 ^,. ^,,,.,,
o o
^
^
,, o ^- ^_ ^
... ooo ooo
,, ^ o ooo o oo
. . ..
^1 yj; ^
I *4*1"
ooo ^- ^^
o oo
^- ^-^-
P 000 00
U. ^ 00
<" ..
'
0
0
^j...^ .0. ,,",,",," ," H
TABLE III - (0.08 mq/L) H-12,037
?.K
236339
Cam**
ooaex;-/ c
;ri
Casluacsiva cda*e eaBOlj discharge
?luor-s.-t=;.?*
SicstC oi caw*
23B389
CS?3
op*etsy
?*
lrt
Cott3uae^i ?&& chaoiJ dj.sehax;
yiaor-i-sss:.?*
3iea-e o5 earr-ae
236390
f * SaraM opaeisy
Sri Canluae'si.v
rdas
ehifasis
Aics&r5 lBBS-i.-SSS.?9
aicsie ofi easaaa
236391
CaraM
afsew
uw
-S3.S
Caaiaaes-ya
;SS;^
&ie!iu?
Tiaas-i.-w.?9 3iea-e at assess.
2363S2
essa-- e?acl.w
;*
Zf^x
Can^ttce^iv ?&r cMnoi Aiea;?
y-aos-s.-*^:.?*
a-ggis a; ecra
1 reddish brown
5 ia?
a/'T4 "
0
0
Q
a
0
0
0
0
0
0
Q' 01
0
0
ns ?
/^ 3 &iy 8
f
0
0
0
s
0
0
0
0
0
11 1'
0
"
sag -- BB'S"
0
0
a
0
0
0
0 0 0
-
.-
--
9 0 0
0
asg
0
0
0
0
0
0
0
0
x- s-
^ 0
&?
0
0
0
9
0
0
0
0
0
0
0
0
0
n?
0
0
3
a
0
0
0
0
0
0
0
0
0
B<?
g
a
o
a
o
0
0
01
- tt"?
"I" a
0
0
0
3
0
;
0
0
Q
a
0
0
0
- a?
0
0
3
3
0
0
3
8
1 , ;,
-
0
.
" s*^
0
C
;
C
3
0
0
C
0
0
r
-^
0
- =;
tec
SVS^VS
236393
Cars-- optc^ey
f
Sri.
Cocjuaesi-.-a ecda*-- chaaoi.
Aiaeluu;*
FlKac-l-Kri.?'
Biaaic of esraaa
236394
Caea** opacity
r-- 2ria
Csajcaesl.v
fdaes*
ebcaos.Lj dlCB;;B
rlues-i-rcsi.?
Siesta o eacaa
23S3SS
Cssaoa opacisy se
Iris
Caajuae^iv rdna
ehsoB&
6char9
riaor-i-ats.l.p*
Bigaic ei earai
236396
Cessea
opacity
aea
w
CoajBacsiva
r6rj
c6--oi 4ie6af9
yiaas-i-fvsif9
3iesie of co^aa*
236397
Cara
aycisy
6?S6
iria
Ceajueefivx ?da* ehooi
6iebzf
riaer-i-tssip9
lleBie oi esrs
5 day
a/V
s
0
0
0
0
0
0
0
0
0
0
0
0
0
a9
&
3
9 iliy
a/;.c
b
C
Q
C
C
g
0
0
0
0
0
^
i f
-
0
* nag
5
0
0
0
0
0
0
a
a
C
0
0
0
0
* ?
0 0'
s
s
0
0
0
0
0
0
0
0
0
a;
&
a
0
0
0
0
0
0
C
0
0
0
o1
0
-
0
a
3.
0
a
9
Q
0
0
0
3
0
0
0
0
c
&0
&
;
0
0
0
0
0
0
0 0
g
0 o*
0
?
L
a
0
(
0
(
0
0 0 0
-
c
r
0 c
a
s
0
0
0
G
0
3
0
0
3
0
0
0
0
"
n<?
a
a
e
c
c
3
0
a
0 j
0
0
c
^
a
Company Sanitized. Docs notcontain TSCj&A -fCBB'1I.,