Document 2qg9go5yR0p7xXOdLrJyRkBM7
FOR Oil PONT USE ONLY
AR226-2915
cc:
' } Hasten
E. I. dq Pont de Nemours and Co., Inc.
Laboratory for Toxicology and Industrial Ellkton Road. P. 0. Box 50,
.Newark, Delaware 19714
Medicine
HASKELL LABORATORREYPORT NO. 143-84
MR NO
o?|8l1|1n s
SUMMARY: .Groups of 25 male fcr1:CO rats were exposed to 0.62, 2.5 or 10 mg/iB
air. A control group was exposed simultaneously to air only. FornrTacs per group, exposure was 6 hours/day, 5 days/week for 2 weeks. After the 10th exposure, blojodand urine samples were collected for clinical
analysis, and 5 rats per group were sacrificed for pathological examination. Remaining rats were held for 14 days post exposure and were given the same clinical and pathological ex|am1nations. The additional 15 rats per group were exposed 6 hours/day for 1, 5'n 6 or 10 exposures. These rats were serially sacrificed throughout the test to obtain blood and urine samples for total
fluoride analysis,
i
Nonsignificant effects were observed in rats exposed to either 0.62 or 2.5 ing/in throughout the test.
At 10 mg/m , three rats died after being exposed to 1-3 exposures.
Pathological examination revealed severe pulmonary congestion, edema and hemor rhage. The deaths appear to be an acute response to the chemical because the
rats showed no clinical sign^ prior to dying, and because the pathologic findings were similar to those found in acute testing. After 10 exposures, one of 5 rats examined pathologically showed nilcroscopic edema, focal hemorrhage, and erxthrophagocytosis by alveolar macrophages. Finally, rats exposed to 10 nig/is had significantly elevated mean lung weights both after 10 exposures and after 14 days recovery. Except for the deaths and the lung effects, no adverse clinical!signs, body weight, clinical chemical or patho logical effects were obser d.
4
Both 0.62 and 2.5 mg/m' are "na-effect" concentrations under the conditions of this test* All 10 ing/in a11 observed effects were localized in the lungs. No other ouaans^pU'ssues appear to be affected by repeated Inhalation exposure to;
Company Sanitized. Does not contain TSCA<SS
I.
_ _ _ INTRODUCTION;
A 4-ftour Approximate
mg/m' of partlculatel
determine the. effect
Witratlon |s extremely toxic on an acute Inhalation basis, (ALC) for this material Is 42 The purpose of this study was to
nhalatlon of sublethal concentrations
II. PROCEDURE:
A. Animals; Young ac|u1t male Cr1:CD* rats were received from Charles River Breeding Laboratories, Kingston, New York. Rats were housed singly In S-xll-xT'" suspende steelmesh cages In rooms maintained
at 50 t 101 relative humidity and 74 ^ 2F on a 1?/12 hour light/ dark cycle. Rats Jwereassigned a unique identification number
which corresponded to a numbered card on the outside of the cage. Except during exposures, Purina Certified Rodent Chow* (15002 and water were avail ablle ad llbltum. Rats were quarantined for 1 week
prior to testing. . Rats were weighed and observed twice during the
quarantine period.;
B. Exposure Protocol;i Groups of 25 rats, 8 weeks old and weighing between 220-258 grams, were restrained 1n perforated, stainless s- t- eel* cyli*n--d*-e._rs- , tLat_ .^s-. w_e_r_e exp.o-_s_e-d--n o,s_ e. -o_n1 t*-o- d-<e_s_ig_n- conceRtra-
tlons of 0.50. 2.5, or 10 mg/m3of"--__--_--__--articulate. A control
group was exposed simultaneously '.air only. For 10 rats per group, exposure was 6 hours/day, 5 days/week for 2 weeks. Five rats per group were sacrificed after the 10th exposure, while 5 rats per group were a1Towedlto recover for 14 days post exposure. Rats were weighed and observed dally throughout the exposure and recovery periods, weekends Included when deemed necessary by the rats'
condition.
,
The remaining!15 rats per group were exposed 6 hours/day for 1, 5, 6 or 10 exposures. These rats were serially sacrificed throughout the exposure and recovery periods to obtain blood and urine samples for total fluoride analysis.
C. Test Material: TCFTtT;------ Composition:
Contaminants:
Synonyms:
Other Codes: Submitted by:
'Chemicals i P''gments Dept. Jackson Laboratory
- 2-
Company Sanitized. Does not contain TSCA CB|
0. Generation: Liquid--------nspumped Into a Spraying Systems9
Nebulizer. Air Introducedw the nebulizer aerosol 1zed the test material, and swe^t the aerosol scream through a cyclone. The cy clone removed large particles by Inertia! Impactlon, while aero dynamic particles passed through the cyclone and Into the exposure
chamber.
E. Analytical; At 20 to 40 minute Intervals, calibrated volumes of chamber atmosphere were dram through pre-welghed, glass-fiber
filters. Filters jwere weighed on a Cahn 26 Automatic Electrobalance. Atmospheric concentration was determined from the filter
weight differential before and after sampling.
Chamber temperatures were monitored with thermometers. Parti cle size (mass median diameter) and percent of resplrable panicu late were determined with a Sierra Cascade Impactor. Relative humidity was measured with a Bendix* Model 566 Psychrometer.
F. Clinical Measurements: Overnight urine samples were collected from 10 rats per group {after the 9th exposure, and from 5 rats per group after the 13th day'of recovery. Samples were analyzed for volume, osmotallty, pH, bipod, sugar, protein, blllrubin, uroblllnogen, and ^ ketone. Each samppe was noted for color and transparency, and the sediment from each I sample was examined microscopically. Unused portions of the samples were saved for subsequent fluorlde analysis.
Blood samples:were collected from the jugular vein from 10 rats per group aft^r the 10th exposure, and from 5 rats per group after the 14th day-of recovery. Samples were analyzed for erythrocyte count, hemoglobin concentration, mean corpuscular volume, platelet count, Teukocyte count, and relative numbers of neutrophtis, band neutro^hlls, lymphocytes, atypical lymphocytes, eosinophlls, monocytes artd basophlls. Hematocrit, mean corpuscular hemo globin, and mean corpuscular hemoglobin concentration were calcula
ted from the erythfrocytic data. Serum activities of alkaline
phosphatase and al^nlhe aminotransferase, and serum concentrations of urea nitrogen, Creatlnlne, total protein and cholesterol were also measured.
G. Pathology; Five rats from each group were sacrificed after the
luth exposure and dfter the 14th day of recovery for gross and
;
hrstopathologle examination. The heart, nasal cavities, lungs,
}
trachea, liver, pancreas, esophagus, stomach, duodenum, jejunum,
|
lleuro, cecum, colon, kidneys, urinary bladder, sternebrae with bone
|
marrow, spleen, thyjmus,thymic lymph nodes, mesenteric lymph nodes,
i
thyroid, testes, epidldymldes, adrenal glands, parathyroid, brain, and eyes were examl'ned microscopically.
Company Samfaed. Does not conlain TSCACBI
H. Organ and Body Height Analysis; At each sacrifice, mean organ weights and orgai^-to-body weight patios were calculated fop the heart, liver, lungs, kidneys, spleen, thymus and testes.
i
I. Blood and Urine Fluortde Analysis; Overnight urine samples were collected from 3 to 10 rats per group after the 1st, 5th, 6th, and
9th exposures and 3rd, 6th and 13th days of recovery for analysis of total fluorlde. The following collection scheme was used:
o after 1, 5, and 6 exposures and 3 days of
recovery " 6 rats per group
o after 9th Iexposure - 10 rats per group o after 6d^ys recovery - 3 rats per group o after 13 days recovery - 5 rats per group
Samples from each group were pooled In pairs (except for the odd sample per group:on days 6 and 13 of recovery). Samples collected following 6 exposures and after 3, 6, and 13 days recovery were not analyzed.
Vena cava blood samples were collected from 3 to 5 rats per group after the ^st, 5th; 6th, and 10th exposures, and after the 3rd. 7th, and 14fh days of recovery. Samples were collected from the 5 rats per group sacrificed for pathologic examination after the 10th exposure and 14th day of recovery, and from 3 rats per group at the remaining Intervals. Blood samples were analyzed Individually (samples collected after the 6th exposure and after the 3rd. 7th and 'l^th days of recovery were not analyzed).
Urine and blood samples were analyzed for total fluorlde by combustion In an oxyhydrogen torch. Samples were ana1yzJ by E. Ktssa, Chemicals and Pigments Department, Jackson Laboratory.
III. RESULTS
A. Exposure Data: Mean exposure concentrations were 0.62. 2.5 and 10 lug/in compared fo design concentrations of 0.50, 2.5 and 10 mg/m ;
respectively. O^lly concentrations are presented In Table I.
Chamber temperatures ranged between 22-27C. Relative humidity ranged from 31-61li
4 -
^""PanySanina
Exposure
__No.
1 2 3 4 5 6 7 8 9 10
Overall*
Table 1: Atmospheric Concentrations Design Concentration - 0.50 mg/m
Partlculate Concentration
(mg/tn3)8
Mean
S.D.
Range
Resplrable
Mass Median
Diameter
of Resplrable PartlcuTate (urn)
0.64 0.28 0.047-0.97
0.74 0.43 0.21 -1.7
0.46 0.45 0.013-1.3
91
1.3
0.58 0.14 0.30 -0.80
0.66 0.34
0 -1.3
0.54 0.53 0.15 -1.6
89
1.4
0.62 0.55 0.12 -1.9
0.74 0.32 0.19 -1.1
0.64 0.56 0.15 -1.5
92
1.6
0.62 0.40 0.27 -1.5
0.62 0.41
0 -1.9
Design Concentration - 2.5 ing/in
^^
Mass Median
Exposure
No
1 2 3 4 5 6 7 8 9 10
Particu1ate Concentration (ing/in3)"
Mean
S.D*
Range
2.6 0.55 1.8 -3.5
2.6 0.69 1.7 -4.3
'.4
1.2
0.19-4.7
2.5 0.71 1.5 -3.8 2.3 0.85 1.3 -3.8 2.2 0.58 1.6 -3.4
2.8 0.67 1.5 -39
1.2 0.70 0.38-2.2
3.5 1.4 . 2.5 -7.6
2.9 0.65 2.2 -4.6
l h Resplrable0
93
93
91
Diameter of Resplrable
Paniculate (um)-
1.8
1.8
1.6
Overall'1
2.5 0.99 0.19-7.6
comb1ne&HH--------------9 a^at^cltlat(^oocwtratlon represents
.^^^^^HH ^concentrations.
^^^^^^^^^^^^^^^^^^w
'l^^eTgn1 ^^rartlcles with aerodyn amic diameter less than 10 urn.
. Calculated for resplrable portion of atmosphere.
lean and standard deviation of all samples from all exposures.
1
- 5 Company Sanffized. Does not contain TSCA CB|
Exposure No.
1 2 3 4 5 6 7 8 9 10
Overalld
Table 1: Atmospheric Concentrations (cont'd)
3
Design Concentration - 10 ma/m
Part1(;u1ate Ciagcentr.ill on
(mg/in"^"
Mean
S.D.
Range
8.9 2.3
8.9 2.0
13
3.2
12
3.1
10
2.0
11
2.4
10
3.3
11
3.0
9.8 2.2
8.5 1.7
6.6 - 14 5.7 - 12
10 - 21
5.8 - 16 8.1 - 14 7.1 - 14 6.4 - 18 7.4 - 17 6.3 - 13 5.8 - 11
10
2.9
5.7 21
Resplrable
91 92 92
Mass Median
Diameter of Respirable Partlculate (urn)"
2.0
2.1
2.1
-nt ration represents conibinedj^
^^^^^^^Jponcentrations.
I*
ByTieTgn^T^frticles with aerodynamic diameter less than 10 urn.
.-
j Calculated for respirable portion of atmosphere.
Mean and standard deviation of all samples from all exposures.
B. Clinical Signs; Mean body weights for test rats were indistin
guishable from controls throughout the test (Figure I, Appendix I).
Except for 1 rat exposed to 2.5 mg/m which had brown disco lored fur and hair loss on the head during the recovery period. clinical signs for rats exposed to 0.62 and 2.5 mg/m^ were indis tinguishable from controls*
At 10 mg/m , 1 rat was found dead the morning after the first
exposure, 1 rat died during the 3rd exposure, and 1 rat was found dead the morning after the 3rd exposure. No adverse clinical signs were observed In these rats before they died, or in surviving rats at any time.
C. Clinical Pathology : No treatment-related clinical chemical or hematologic effects were observed at any expc jre oncentration at either sacrifice.
6 - cwl!"^^^^.
Rats exposed to 2.5 rng/m showed a statistically significant
Increase In erythrocyte count and decrease In mean corpuscular hemoglobin after 10 exposures. These changes were not interpreted
as being biologically significant or treatment-related because the changes were not dose-related, and were within the range of expected biological variation.
p
0. Pathology ; No adverse gross or microscopic effects were seen in rats exposed to either 0.62 or 2.5 mg/m at either sacrifice.
3
The 3 rats which died from exposure to 10 mg/m exhibited severe pulmonary congestion, edema and hemorrhage, which appeared
to be caused by damage to Type I pneianocytes and endothelial cells in the alveolar capillaries. The lung edema was both intraalveo-
1ar and interstitial, and was especially pronounced in the peri-
vascular and peribronchial regions. The intraalveolar edema we characterized by homogeneous eosinophilic protein^cA' ^ *luid and
fine fibrin. These deaths are considered to be an a>-ui.1 response
to a single exposure, rather than the result of successive
j
exposures, because the pathologic lesions seen are identical to
'
those found during acute studies, and because no changes in any
other organs were observed. The 10 dig/in exposure concentration
is considered to be a more "precise" ALC, based on the larger number of animals (25 versus 6 per group) and the longer exposure
duration (6- versus 4-hour exposures).
One of five rats examined after the 10th exposure showed
microscopic edema, focal hemorrhage, and erythrophagocytosis by
alveolar macrophages. Phagocytosis is a common clearance mechanism to remove foreign particulates, and erythrophagocytosis is phagocytosis of heinorrhagic materials. The erythrophagocytosis appears to be a recovery mechanism following an acut in'.ult, rather than a response to repeated insult. No other dunges were seen in any other rats either after the 10th expos.''e or the 14th day of
recovery.
E. Organ and Body Weight Analysis ; No biologically-significant organ weight changes were found in rats exposed to either 0 62 or 2.5 mg/m at either sacrifice.
Rats exposed to 10 ing/in had significant increases in mean lung weights compared to controls after both the 10th exposure and the 14th day of recovery. However, these changes were small, and were not significant on an organ-to-body weight basis. No other organ weight changes were found in this group at either sacrifice.
III). After 10 exposures, rats exposed to 0.62 mg/m had signifi
cantly decreased mean spleen weight. Thi? change is not considered
biologically significant as it was not obsei. l at higher concen trations (Appendices II and
Company Sanitized. Does not contain TSCA.CBS
F. Blood and Urinary Fluorlde Analysis:
III. 1. Data: Mean blood and UiInary fluorlde concentrations are
presented in Tables II and
Individual sample data are
reported In Appendix IV.
T^ble II; Blood Fluorlde Concentrations
Exposure
Concent ration ("g/'"3)
Control 0.62 2.P
10
Mean Blood Total
After 1
Exposure
0.2 + 0.2 0.2 + 0.3 0.3 7 0.3 0.3 7 0.3
Fluorlde Coneentratiodb (ug/g)'
After 5
After l6
Exposures
Exposures
b
0.2+0
0.9 + 1.0 0.5 7 0.2. 0.4 7 0.4"
0.1 + 0.1
0.37 0
0.3 7 0.1
0.47 0.1
Mean value's represent an average of 3 Individual blood
samples, except where indicated. Two samples only.
e III: Ur'ie Hupr e Concent i af.c.nj
Exposure Concentration
Cmg/m3)
Mean Urine Total Fluorlde Concentrations (ug/g)
After 1
After 5
After 9
Exposure
Exposures
Exposures
Control 0.62 2.5
10
0.8 + 0.2
1.070.5
1.1 7 0.3. 1.3 + 0.2
0.4 + 0.4
0.370.1
1.9 + 2.9 1.1 + 0.4
1.5 + 0.6
1.1 70.2
1.5 + 0.4 1.9 7 0.4
8 Mean values represent an average of 3 pooled urine samples, . except where Indicated.
Two samples only.
2. Discussion ; No significant dose-related Increases in blood or
lift njIrjL n uoM de concetttratlons wre observed after l.
or 9
or 10 exposures Further, blood fluorlde concentratii
Id not
significantly Increase Nith an Increasing number of expu.>ures.
Urinary fluorlde concentration after 5 exposures was lower than concentrations after I and 9 exposures. However, concentra tions after 1 and 9 exposures Mere similar. Although the decreased concentration after 5 exposures was statistically
8 - Company Sanitized. Does not contain TSCACBS
significant, this change Is Interpreted as being an artifact of analysis because concentrations after 1 and 9 exposures were not significantly different, and because no dose-related differences between test and control animals were observed at any time interval.
Because no biologically-significant cnanges In either blood or urinary flourlde concentration were observed either among dose levels within each sampling Interval, or among sampling Intervals, analysis of the remaining samples (collected after the 6th exposure and ^fter 3, 6 or 7, and 13 or 14 days post
exposure) nas deemed unnecessary.
o f f V J IV. CONCLUSION; Repeated exposure to either 0.62 or 2.5 mg/m3 partkulate caused no adverse effects. At 10 mg/m , 3 of 25 rats died after being exposed to 1-3 exposures. AH effects observed at this concentration were localized In the lungs. No signs of systemic toxiclty were observed In any group under the conditions of this test.
Mackey, Joyce L. and Raymbnd M. Everett, "Clinical Pathology Report No. 1-84", MR-4932-001, H-15.048, February 9. 1984.
2
Lee, K. P. and J. 6. Aftosnhs, "Pathology Report No. 77-83", MR-4932-001, H-15,048, December 21, 1983.
3
'.
Data were statistically analyzed by a one-r;,' analysis of variance. Compa
rison of test rats with ^controls by least ^igmfiLant difference and
Dunnett test Is considered valid only when the ratio of variance (F)
Indicates a significant among-to-wlthin rroup variation. Significance is judged at the 0.05 probability level.
4
:
Data were statistically analyzed by a two-way analysis of variance using
logrlthmic values of concentrations. Significance is judged at the 0.05
probability level.
Co".Pa"ySa^e<,.o,esn,,con,a,nTSc
Work and Report by
^ ^ Supervised by:
P^^JJ^- ry P. Koechert
Technician
fn l
,L. aura
/^., L<
A. Kiriney
Chemist
Stfy Director:
/AW^Q{/^ y -Bruce y.^Burofss
_- ----i./T-.-.t -J ---a
Approved by:
j^jjia. tt^^A. ^
Gerald L. Kennedy; *]r. Section Supervisor
Acute Investigations
SCC:sg1:2.24 Date Issued: June 27, 1984 Study Inltlated/Cornpleted.
Number of pages In this report: 19
Manager, Toxicology Division
- 10
Company Sanitized. Does not contain TSCA CBj
FIGURE I
0.00
5.00
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10.00
15.00
TEST DAYS
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jii
^ '...-' 'f.
:;.s
;:3
h
1 - 13 -"';".
1
CiaiipanySanTiized.Does.no!Iconl^nTSCACBg
(P P VALUE of F-TEST froir ()NE-FACTAONRALYSIS OF VARIANCE.
<t iiidiL-dtrs P vdlu^ Itfss th<n 0.05) (2) P VALUE OF TEST FOR LINKAR TREND OVER 8ROUP8
( indicdbus P vdlu" lest thn O.OS) (3) LEAST SIGNIFICANT DIFFEKEHCE - 8ivn 9 sillftifi'-^t (lph3=O.OS F RftTIO ana two Bans differing bv i>i'< than t)r 1.10 ari* <i '.-.fi--<.i'.li li-'^erent
with a flc* positiv (flpha rr6p rat* of 6iOS
(4) DUNNETT TEST - nu treat ient aedn diffrfinjl Ci*'. tl.c i;rn;,i.jl an an by Mil
than the DUNNETT statistic ii siainlficantly difftMpt ficiai thy control e<" with 3 variable-Milie fdl'au Piaitlve (dictid) errijr I'-ii-f uf (5-^5.
. 7LETTS TEST FOR EOtJHl VARIANCE P yALOH. + oI6NIFICANTLY DIFFERENT (R'-O.OS) fPUB COWTROL 6?OUP ba L3D.
# SIGNIFICANTLY DIFFERENT (R<0.65 frw efiNTROl .^OUP ta 3U'<NETT TEST aw LS3.
14 Company Sanifized. Does no'l contain TSC.ft.CESI
c"^^k------AE--PEjNHDIE?8OARIIGNAN UEZGHTS ^|Hl5048 - AFTER 10 EXPOSURES
GF-OUP Fl NAL UT. HEART LUNG \
CONTROL
269. (
0.)
s0.?2<
0.00)
1.23( 0*09)
0.62 MS/X3
2A&.(
1.)
O.,88r 0.44)
1.20( 0,61)
":\
2.5 MG/M3
278. <
0.)
.O^K 0.78)
1.23( &.93)
10 ?16/M3
282. (
0.)
|ty87r; 0,32)
l..i4( O.G3H
- ,i
0^3 TEST - HOMOGEf'Em
0.304
0.041
TEST - TREND
0. 107
6^25
0.023
PARTLET-3 TEST
0. 581
. ;^<562
0.066
.y^-.
^OiJP
'i
LIVEfi;
SP1-EEN
KIDNEY
CO?(TROL
0.62 MG/M3 2.5 MG/rt3
10 MG/H3
'^Sr - HOMOGEMEin'
TEST - '?,?.t;i, RA''<TLETTS -fr.Sr
Jh-;TJP
8,76( 8,70(
?.42<
^.39(
O.OO)'
0.93) 0.35)
C.2-3;
0. - >75
/
'^0. 1.53
;:
fS9
'..
.
7ESTIS
^*9^
Q.'5^..
(hitr^
. ;.^4N?'.
:. '!; '.''' ''i ^"\"
0.00) 0.02X o.^s) 0.74)
;; .o;,^?
''
'0^3
.'".: ^.^w
1
-^^l.'s
2.16(
2.2K 2.33( 2.20(
0.90) 0.73) 0.2A) 0.78)
0,685
0.607 0.331
CONTROL
O.oS H-3/M3
?.? MO/13
10 Me/":-.
:2:.S6< 263<
2:. 38; 2.7S<
0.00^ 0.62)
0.0-2)
0.10)
^.^7;'-: 6^<
0^4?("
6.i3<
0.00) 0.07) 0.39)
0.7'-?
L:Sr - -OriOGENEi.TY
72'iT - T^NL r('>'.rLl;TT:j -F.5I
0.( 8? ;.<38 0.341
/: 0.%63
O,^?
-' 0.^6
vd!uc. i;. parentheses -
P VALUE )F;.STUDENT, t ^EST COhP-ARISON F TSSATHlNf^e^i^tO^liONTRrOtEL^N.
;-E-=SS=S3SS=
!3;i.'E'llT/ - P ^IUJE ?? ? TEST OF ^FTHER |S^tf- MEANS AtE 3UAL.
TREND -
.
P ^ALIE OF F ^ST |}F yHETNEft.TMfii^E.^'^OSE-SELATEC
^rif-ii^E IN GROUP MKAKS:.
''. , .;.'.'.
EAST; En3 TEST - :'- 'yAU'E ^ TE^r OF HiStlOOFi.itiyy rp VARlnHCE
F^ < - SIGtiIF'TCANTl-V ^'FER^NT (P-<0.0:S) FftW COffiTROL GS.'C.L'F SY LS:i
* - SIGMIFICAMTLf tilp!-ft|SNT ;P<O.OS
.Cfi'HtROl. tiROUP BY LSO AND
ri)HNt-:TT"; "EST
15 - Company Sanitized. Does not contain TSCA CBI
GROUP
MEAN ORGAN UEIOHTS
^151048 - AFTER 14 DAYS RECOVERY
PIN tL Ut.
HEART
LUNO
CUMTSQL
0.&2 HG/M3
2.5 M6/M3 i0 MG/M3
TEST - HOM06ENE ITY
TKST - TREND 6ARTLSTTS TEST
GROUP
354. (
0.)
364. (
0.)
356. (
L.)
362. (
l.>
0.8 is
Oio tl .,
0.^ 1
LtVES
l.t4<
117<
l.l^<
l.i6,<
".OO)
0.35) 0.79)
o.ri)
-6.940 : e.aoA
6.33<&
sfiMM
CONTROL
0.62 ME/M3 2.5 hC/H3 10 i^/M3
13.43t 14.03( 13.38( 13.7^
0.00)
0.761 0. ?9)
0^6)
^T '-. r
HO.^GEf^''Tf - T^'.D
^?ILETT5 TEST
QROUP
Oi-f' 9
0.9' 3
0..2; 9
.,,,..
E8Tt3;
0fr3<
0.6g< C-.^2( O.?l<
0.00) 0.56) 0.86) 0.08)
e2^?
'a* KB
- - | |^%rH^ius
1 .46(
I .34( I .46( I .61(
0.00) 0.19) 0.94) O.ODt
0. 035 0. 044 0. 222
KID HEY
2 .67( 2 86( 2 .93(
.j .87<
0.00)
0.17) 0.06) 0.15)
0,255
0.127 0.817
CONTR01.
>.c2 MO/13 S.5 tiG/!13 ;r, M.3/M3
3.12( 3.10(
3.C4( :?.Ut
0.0( 0.83)
^.41) 0.91)
^ASSt
0.7^
3.,3?<
0.71(
0.00) 0.40)
O.&A)
0.32)
K-ST - KI.-IOGE^F. :'y I!:-'.! - Tr;i-:NC?^PT!.F7''? F.Tj'-
C-.8;i8
"..'.i3
07i>i
0:42'i
'6.578 0.676
T^:'SST-:.e^SS=--;:;S s = s ssasascsilsssissasai RS&3sxsicaeafs=;=zf=5=s^ 55
'-&.'.;,.& >'. i-aper.i 'l^-s L6 - P '.^LliE CF Sm?Nt T ft:ST CCMPARISC N
01'. T^^^THE NT MftN TO CDNTROL MEAN.
^C.IOGF.^TTY - P VAL UE OF F TS5T OF KI-IETNfcR'BRWP flEAMS ARE E QLJAL.
"?->1D '> ;ALUE JF F -ISl (IF WHETMRl TM^RE'iS &OSE-RELATED :HW ; L-^3U-' 'E^^.
^'..cTr:; ;c!?' - F- -Al.i;' ;;^ ^ES' OF H-3HOOeNEITY OF VARIAHCE
ssasss
<
-
3l'"-NlFICAN TLY llIF'-n^T
t"-. 0?' '"gi GONT'i-Ol. 3ROUP BT i SD
- SIGMFICAN 71.' OIPPEPEhT (P<0, ftS) FRflH CONTROL GROUP BY L SD ANL;
'J'-'f.flETT'S if ST
- 16 - Company Sanitized. Does not corstaisiTSCACBB
I
6KWF
APPBHDIX III
OROAN-TO-BODY UEIOMT RATIOS
ltl5048 - AFTER 10 EXPOSURES
HEART
LUNG
LIVER
C.UHfRQl.
0.62 M6/M3 ^.5 MO/H3
10 MO/M3
rESf - HOMOGENEITY
TEST " TRENP SAhTLETIS TEST
fi?.n'jp
0.34( 0.33(
<5.33(
0.3K
0*00) 0.46) 0.24) 0.03)
0*13 6
0*0; 5 0*5; 1
iPLEeN
0<4i< 04S(
0.4< 0.48(
0.00) 0.92) 0.54)
0.44)
O.S7A
0.545' o.syy
KIfiHEY
3.24( 3.26( 3.38' 3.39(
0.00) 0.91) 0.41) 0.38)
O.?l7 0.289 0.038
TESTIS
CONTROL
0.62 M8/M3 :.5 MG/M3
O MB/H3
TEE7 - HGr'^E.'lEITY TEST - TR^ SORT .ETTS rESf
=il<l]:.iP
0.18< 0.1S(
0.1?( ;.17<
0.00) 6.02)
0.690.72)
3-(<A3
^'iS 0.3(1
T lYlUS"
0.80<
0,8I(
0.84( 0.7fl(
0.00) 0.4A)
0.405 0.52)
5.413
0.566
0.23]i6
0.93( 0.99(
1.04( 0.99(
0.00) 0.47)
0,16) 0.53)
}.544
0.406 0.362
:C!<TROL
'62 HR/f3
:.5 MG/M3
10 tiG/1.'!
*EST - HC^CEFNEITY
^r'r.T - TPENP
^K-RT'-ETTS '^S;r
0.22( 0.26< 0.20( 0.20(
0.01 0.06
0.5-.'
0.&0) ')34)+
0.21) 0.40)
''AliJi'S in .-a "b,.LhffhKS ~
:ccs=3=sssr==3==;fli" sss====s==s===e5sss-a P VALUE UFSTUBENT T TRST COMPARISGN
TREATMEMT HEAM TS CfiKTRGL MEAN.
;'!0^'.^^?><e:TY - P VALUE SP P .ST 3F UMETHEft (SROUP iEAK9 AKE EG'JAL.
TRCM- -
P VALUE OF F TEST
UHE-MEfi THERE fS tOiBE-RFLATED
CHA^E 1-< r.ROUP C.eA^
RTLETTS T??T - P '/-ALCe 3F|r?3T OP -SOtiCGErtEir-i OF l-ARIANCE
* - 3IN;F;CAMTLY 01 FFEAE^T?f."..-55 Fi3ti :5NTROL GROUP BY i;^
- SIONIFI:ANTLY OIPFERE NT (?<O.OS) FR3H CONtROLGROUP BY LSI- -^I-
DUMNETT'3 'EBT
17 -
eon^ny Sanl^d. Does nolco^nTSC&C^
W.MP
M
ORGAN-TO-BODY KEIOHT RATIOS
#15048 - AFTER 14 CAYS RECOVERY
HEART
LU N6
LIVER
CONTROL
0.62 HC'MJ
;'.; MS/rt3 10 MS/M3
-13T HOMOGENEITY rES; - rfffcNI; PARLETT' T^ST
'iKG-JP
0.32( 0.32<
0.?2<
0.32(
0.00)
<).'7)
0.92)
3.87-.
0.9( 5
0.9 i
0.5SO
SF-LESM
0.41 (
0.*2( 0^-tt
0^(
0.00) 0.76) 5.87)
0.13)
0.3i?
,6.1^8 8*9Sl
KIDNEY
3.84( 3.85(
3.7&<
3.79(
0.90) 0.94) 0.70)
0.82)
0.9&5
0.721 0.509
TESTIS
C0^7'!;L
O.A2 MG-'.13
2.5 KG/*!.7 1C -"iSj//^.i1S^
T -iCMC-32';<[-TT'r
T - r^END rLcTT? 'EST
L'P
0.13^
O.l8(
o.irc 0V>.2fc3j;i
0.00) O.S3) 0.;'5
V.4,4
C.25'
O.I3?
O..'1!
TI'tMa.S
o.y:6( 0.78<
0.8^ \0n.?/'n^
0.00) 0.56) 0.14)
vv..-fl^3'i
O.S:00
0.301 ,0^19
0.89( 0.85( 0.86(
OU.Sf6i(t
0*00) 0.43)
0.47) 0V.3544J)
0.343
0.568 0.089
Trc.;! : .-:r;/;-3
1;/M3 '../.M3
r 3.
'S^' - TRE",'
BA^TL;-"'? .;;'.
c.'.e< ',.; 9 (
0.17(
o,^^^
0,(i<
-.'.49) O.A3)
0.36)
5.183
..'U :.,35^
^;i-;i i
...re!-.;.ri4.-s -
P y|fil.UE3P STUS^<t'T t?.^' .:/,FftRI50H CF ImATWir sgAK TO celtir^o^-);(.
I '' ' ' ' : . . ; :-:.-::^!;
i^^i-^F^^in - ' vrtL'JE PF F 'FST,-''F i.'-fE rME^'eftOy^P^^S ^RE EG-AL,
-.-??;[!- ? -rtil;E GF ,- T.:3T L^j^ffTr:S f|-Sft rS:36^-P='' ^Cr
-A'-'iE 1^ 3ft:;UF- -::^"1?.
: ,, , . .
tr^:"; rSST h -^.Jl; :'
- a'-' r-^EMTt-.^ ARIANCE
3IGMIFI!';^TLY DI.^tREN - E-ICNiFIC^NTLr DI"?R6.S
"jMETT's rrsr
i:?<C',OS) fROH CliNTSieL GRQW BY LSfi
^<0.6S) FROS CONTROL GROUP BY LSB AND
- 18 -
.co^^^081
,.-,^a.Po^01
APPEWJM BLOOO AND URINE fUl!ffi ^llEEltTRATIONS
Table I - Blood tffi6iili^ljuarla*.^n6tatratlon (Ufl/^
Exposure Concenteatlon
-J"aZ2
Controls
A
^
e
P
J
I
XBi
f, t
s
u
e
?
,
0
0.4 0,3
Adfeer S.fMoftsures
.
,.
,,,
0.2 0.2
After 10 Exposures
0
0.1 0.1
0.62
0.6
0.8
0.3
0
0
0.3
O.I
2.fl
0.3
!^' 2.5
0*6
0
0.2
^ -.
0.3
0.3
*2
0.4
^
10
0.2
^
0.4
Q
<U ;:----
;,
0.4 0.3
Table U - UCli-tlUl F1jliS>rfte 66ff<a*ntrat1ofts ("g/a)'
y-.
%5
Exposure
I Concenteatlon (ma/m3) Control
After I Ex,i.s.u, fi
1.0 0.6 0.7
A^r^ fetsures
0,2
^1 04
After 10.Exposures
2.1b 0.9 1.4
0.62
0.5
02
1.1
1.2
0,S
0.9
1.4,
;s^
1.2
2.5 0,8 / . 'M..: 1.4
1*3 1.1
-:I'.MT\;.:
1.2 2.0
10
i;.""
^
l ^^ : ' N M :
1.2
-
2,3
1*4
1.5
*
2.0
a All samples represent pool ed specimens fNM 2 rats. EXC(ept where ^ Indicated, each sample tfijt analyzed once.
Average of 2 values fron itaAple analyxed (n duplicate.
19
Company Sanitized. Does not contain TSCACB1
