Document DvVpwnnwzBE12OEn4MBy2mz2B
AR226-2927
FOR DUPONT USE ONLY
Subchronic Inhalation Toxicity of
Haskell Laboratory Report No. 182-85
I MR No,
Haskell
E. I. du Pont de Nemours and Co., Inc.
Laboratory for Toxicology and Industrial
P. 0. Box 50, Elkton Road Newark, Delaware 19714
Medicine
Date Issued: May 8, 1985
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Subchronic Inhalation Toxicit
Summary
Three groups of 20 male Cri:CD(SD)BR rats wefi_xposed 6 houj
days/week
lU^in ^{iH^UIB--^ Wter the
Blood and
for 2 weeks to 7.6, 58 or 480 mg/m air. A control group was exposed simuTtaneousiytoair only. exposure period, rats were observed for up to 12 weeks of recovery. urine samples were collected for clinical analysis from 10
rats/group at the end of the exposure period and on the 14th and 41st days of
recovery, and from 5 rats per group on the 84th day of recovery. Five rats
per group were killed for pathologic examination after the 10th exposure and
on the 14th, 41st and 84th days of recovery. In addition, at each sacrifice,
blood samples were collected from each rat to be analyzed for fluorine
concentration.
Mean body weights for rats exposed to
significantly lower than controls from the of recovery. No other significant adverse any rats throughout the test.
480 mg/m of||^BRwere 2nd exposure through the 17th day" clinical signs were observed in
ofpU^ Clinical analyses after 10 exposures revealed several, hematologic and
clinical chemical changes in rats exposed to 480 mg/m
Hematologic
changes included elevated erythrocyte count, hemoglobin concentration and
hematocrit, and depressed mean corpuscular hemoglobin and mean corpuscular
hemoglobin concentration. Clinical chemical changes included elevated
alkaline phosphatase activity, urea nitrogen concentration, urine volume and
urine pH, and depressed serum cholesterol concentration and urine osmolality.
These changes were absent after 14 days of recovery. No adverse clinical
chemical or hematologic changes were observed in rats exposed to 7.6 or 58
mg/m .
Pathologic examination showed compound-related changes in the livers and kidneys of rats exposed to 480 mg/m . The liver effects included elevated liver weights after the 10th exposure and after 14 days of recovery, and minimal to moderate fatty change in the centrilobular hepatocytes at a11 4 sacrifices. Microscopic examination of the kidneys showed minimal to mild nephrosis of tubular epithelium of the cortex after 10 exposures. This change was absent after 14. days of recovery. No adverse gross or microscopic effects were observed in rats exposed to 7.6 or 58 mg/m .
Blood fluorine analyses indicated that 99%-100% of the total fluorine in the blood of test rats was present as organic fluorine. Total blood fluorine concentrations in rats killed after the 10th exposure ranged from 10 ppm to 150 ppm. Blood clearance of total fluorine during the recovery period appeared to be biphasic, with a rapid decline in blood fluorine concentra
tions over the first 2 weeks of recovery (approximate half-life of 9 days),
followed by a gradual decline over the remaining 10 weeks (approximate
half-life of 25 days). After 84 days of recovery, blood fluorine
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concentrations for rats exposed to 7.6 mg/m3were indistinguishable from controls. However, fluorine concentrations for rats exposed to 58 mg/m and
rats exposed to 480 mg/m- were still significantly elevated.
JU^ No significant adverse effects were observed in rats exposed to 7.6 or
58 mg/m of
The 58 mg/m level is considered the "no-effect" exposure
concent rat ionunoer the conditions of this test.
Work by:
-/^v^^ / ^ ^ ^ TrUnomas A.Keqge-iman Technician
^1 3 I ^
^t^k T.. LlAQ^lyL-V^YY^-A^. Robert T. Turner Technician
^/s.
/<&<
Supervised by:
1 OLJL^/N^ 0 . r0^-'i^-r__
Laura A. Kinneyr
Chemist
S/ 3 / 8S
Study Director:
fJo^JLCC^L^^L 5"/ S /8S'
Nancy T. Chromey, (Ph.D.
Section Supervisor Acute Investigations
Approved by:
/.S
Manager, Toxicology
Acknowledgements: study.
LAK:HLR 9.4
Bruce A. Burgess also participated in the conduct of this
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Haskell Laboratory Report No. 182-85 Haskell No. 15,388
Material Tested:
Sponsor:
Polymer Products Department
E. I. du Pont de Nemours and Co., Inc.
Wilmington, Delaware
Material Submitted by:
Polymer Products Department
E. I. du Pont de Nemours and Co., Inc.
Wilmington, Delaware
Test Facility:
Haskell Laboratory for Toxicology
Industrial Medicine
E. I. du Pont de Nemours and
Elkton Road, P. 0. Box 50
Newark, Delaware 19714
Co.,
and
Inc.
Study Initiated/Completed: 7/9/84 - 10/12/84
There are 154 pages in this report. Distribution:
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TABLE OF CONTENTS
Page
Introduction
6
.......................... Materials and Methods
6
..................... Results and Discussion
9
. . . . . . . . . . . . . . . . . . . . . Conclusion
13
........................... Figure I - Growth Curve
14
.................... Figure II - Blood Flourine Elimination
15
. . . . . . . . . . . . . Appendix I - Daily Atmosphere Characterization
16
. . . . . . . . Appendix II - Mean Body Weights
17
................ Appendix III - Mean Organ Weights
22
. . . . . . . . . . . . . . . Appendix IV - Mean Organ-to-Body Weight Ratios
27
. . . . . . . . . Appendix V - Pathology Report No. 19-85
32
. . . . . . . . . . . . Appendix VI - Clinical Pathology Report No. 24-84
79
. . . . . . . Appendix VII - Blood Fluorine Analytical Report
136
................... Appendix VIII - Blood Fluorine Statistics
153
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INTRODUCTION
4-hour
ALC
for^_J_^_Rlroasw gtroeaxtiecritythaonn
an acute -, 2100 mg/m
I The purpose of this study was" to determTnethe toxic effects of
lalation of sublethal concentrations ofJ----ftF
MATERIALS AND METHODS
A. Animals
Young adult male Cri:CD(SD)BR rats were received from Charles River Breeding Laboratories, Kingston, New York. Each rat was assigned a
unique 6-digit identification number which was recorded on a card affixed to the cage. Rats were quarantined for one week prior to testing, and
were weighed and observed twice during the quarantine period. During the
test, rats were housed in pairs in 8" x 14" x 8" suspended, steel-mesh cages in rooms maintained at 23-60% relative humidity and 21-26C on a
timer-controlled 12 hour/12 hour light/dark cycle. The rat assigned the lower number in each cage was identified by a slash in the right ear.
Rats' tails and cage cards were color-coded with water-insoluble markers so that individual rats could be identified after exposure. Except
during exposure, Purina Certified Rodent Chow #5002 and water were available ad libitum.
B. Exposure Protocol
Four groups of 20 rats, 8 weeks old and weighing between 210 and 265 grams, were restrained in perforated, stainless steel cylinders with
conical nose pieces. Rats were grouped by computer randomization such
s that the groups' initial mean body weights were similar (p>0.99). Three were exposed to design concentrations of 5, 50 or 500 mg/m of in air. A control group was exposed to air only. Exposure was nose-only, 6 hour/day, 5 days/week for 2 weeks. Five rats per group were
randomly selected and killed after the 10th exposure, and after 14, 41 and 84 days of recovery. Rats were weighed and observed daily throughout the exposure period and for 14 days post exposure (weekends excluded), then were weighed and observed weekly and on the morning prior to sacrifice for 17 to 84 days post exposure.
C. Test Material
Physical Form: Purity:
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Composition:
Synonyms:
Stability:
The test material was assumed to be stable throughout the exposure phase of the study. The test material is hydroscopic, and readily
absorbs water when exposed to moist air.
Therefore, the amount of contact of the test material with room air was minimized throughout the test.
D. Atmosphere Generation
of|B|in Dust atmospheres
air were generated with a 2-stage,
vertical glass generator^/\ round flask served as a dust reservoir. A
cyclone-shaped flask, inserted above the reservoir, served as an elutriator. A motorized stirring rod with plastic paddles agitated dust in the generator. Air introduced at the reservoir blew dust particles
upward to the elutriator. Air introduced at the elutriatorsweDt dust
particles into the exposure chamber. The concentration ^JIBB10 the
atmosphere was controlled by varying the 2 airflows.
E. Analytical
The atmospheric concentrations ofB)lwere determined daily at
approximately 30-minute intervals for eacn exposure chamber by drawing calibrated volumes of chamber atmosphere through preweighed glass fiber
filters. Filters were weighed on a Cahn model 26 Automatic
Electrobalance. The atmospheric concentration of particulate was
determined from the filter weight differential before and after sampling.
Particle size distributions (mass median aerodynamic diameter and percent respirable) were determined with a Sierra model 210 cascade impactor1. Particle size samples were collected 2 times per week per
exposure chamber. During most exposures, chamber temperatures were
monitored with mercury thermometers, relative humidities were measured
with a Bendix model 566 psychrometer, and chamber oxygen contents were monitored with a BioMarine model 225 oxygen analyzer.
F. Pathology
Five rats per group were randomly selected and killed by chloroform asphyxiation after the 10th exposure and on the 14th, 41st and 84th days
of recovery for gross and histopathologic examinations. Organs and tissues examined were the heart, lungs, nasal cavities, mesenteric lymph
nodes, trachea, liver, pancreas, esophagus, stomach, duodenum, jejunum,
ileum, cecum, colon, rectum, kidneys, urinary bladder, bone marrow
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(sternal), spleen, thymus, thyroid, testes, epididymides, adrenal glands,
brain and eyes.
G. Organ and Body Weight Analyses
Mean body weights for test rats were compared to controls during the
exposure and recovery periods. In addition, at each sacrifice, mean
organ weights and organ-to-body weight ratios were calculated for the
lungs, liver, spleen, kidneys, testes and thymus. cally analyzed by a one-way analysis of variance.
Data were statisti
Test rats were
compared with controls by least significant difference and Dunneft's tests when the ratio of variance (F) indicated a significant
among-to-within group variation. Significance was judged at the 0.05
probability level.
H. Clinical Pathology
Urine samples were collected overnight from 10 rats per group after the 9th exposure and on the 13th and 40th days of recovery, and from 5 rats per group on the 83rd day of recovery. The 10 rats were selected such that the 5 rats per group designated to be killed the next day and the 5 rats per group designated to be killed at the next sacrifice were sampled. Samples were analyzed for volume, osmolality, pH, blood, sugar, protein, bilirubin, urobilinogen and ketone. Each specimen was noted for color and transparency, and the sediment from each sample was examined microscopically.
Blood samples were collected from the tails of 10 rats per group (same rats as above) after the 10th exposure and on the 14th and 41st
days of recovery, and from 5 rats per group on the 84th day of recovery. Samples were analyzed for erythrocyte count, hemoglobin concentration,
mean corpuscular volume, platelet count, leukocyte count, and relative numbers of neutrophils, band neutrophils, lymphocytes, atypical lymphocytes, eosinophils, monocytes and basophils. Hematocrit, mean
corpuscular hemoglobin and mean corpuscular hemoglobin concentration were
calculated from the erythrocyte data. In addition, serum activities of alkaline phosphatase. alanine aminotransferase and aspartate aminotransferase, and serum concentrations of urea nitrogen, creatinine, total protein and cholesterol were also measured.
I. Blood Fluorine Analysis
At each sacrifice, vena cava blood samples were collected from 5 rats per group in "h'thium-heparinized tubes. Samples were lyophilized by S. R. Laas, Polymer Products Department, Experimental Section, and were
analyzed by E. Kissa, Chemicals and Pigments Department, Jackson
Laboratory. Four control samples (1 collected after the 10th exposure and 3 collected after 14 days recovery) and 4 high group samples (3 collected after the 10th exposure and 1 collected after 14 days recovery)
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were analyzed for both total fluorine and ionic fluorine. Organic fluorine was calculated from the difference between the total and ionic fluorine values. Remaining samples were analyzed for total fluorine only.
J. Records Retention
A11 raw data (including tissue slides and paraffin blocks) and final reports will be stored in the archives of Haskell Laboratory for Toxicology and Industrial Medicine, Newark, Delaware, or in the DuPont
Hall of Records, E. I. du Pout de Nemours and Co., Wilmington, Delaware.
RESULTS AND DISCUSSION
A. Exposure Conditions
Chamber temperatures ranged between 25-31C, relative humidities
ranged from 55-66%, and chamber oxygen contents were maintained at 21%.
Particles size analyses indicated that atmospheres ranged between 80-89%
respirable with mass median aerodynamic diameters between 4.7-6.3 urn for the design concentration of 5 mg/m , and between 51-72% respirable with
mass median aerodynamic diameters of 6.5-9.8 urn for the design concen trations of 50 and 500 mg/m . Overall mean atmospheric concentrations
are presented in Table I. presented in Appendix I.
Daily atmospheric characterization data are
Table I Mean Atmospheric Concentrations of
Design Concentration
5 mg/m' 50 mg/m, 500 mg/m-
Q
Analyzed Concentration (mg/m )
Mean
S. D.
Range
7.6
58
480
8.1
38
210
0-50 0 - 230
20 - 1200
8
Represents mean, standard deviation and range of all samples from all exposures.
The large variations in atmospheric concentrations, and the
relatively low respirability and large mass median aerodynamic diameters, were due to the hydroscopicity of the test material. The test material
was "sticky" and tended to agglomerate in the generator and the chamber,
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causing the particles to be large and the atmospheres to be difficult to
control.
B. Clinical Observations
i
Mean body weights for rats exposed to 7.6 or 58 mg/m were indistinguishable from controls throughout the test. Rats exposed to 480 mg/m had significantly depressed body weights compared to controls
throughout the exposure period and for the first 17 days of recovery. A growth curve is attached as Figure I. Mean body weights are presented in
Appendix II.
During exposures, rats in all groups (including controls) exhibited red nasal and ocular disclfarges, effects common in rats under restraint. During the recovery period, 1 control rat had a red ocular discharge on the 14th day of recovery, and 1 control rat had brown-stained fur from the 46th to 59th days of recovery. One rat exposed to 480 mg/m had hair loss from the hip from the llth to 31st days of recovery. No other adverse clinical signs were observed in any rats throughout the test.
C. Pathology
No adverse gross or microscopic effects,-wera-obsenved at any
sacrifice in rats exposed to 7.6 or 58 mg/m of [jfly'J
3
Rats exposed to 480 mg/m had compound-related changes in the liver and kidneys. Liver changes included elevated liver weights and/or liver-to-body weight ratios after the 10th exposure and after 14 days of recovery, and fatty change in centrilobular hepatocytes which persisted for 84 days of recovery. After 10 exposures, the fatty change was of minimal severity, and affected hepatocytes contained small numbers of fine lipid vacuoles. However, after 14 days of recovery, the fatty
change was mild to moderate, and hepatocytes were moderately distended
with numerous lipid vacuoles. After 41 and 84 days of recovery, the fatty change was mostly minimal, although affected hepatocytes appeared similar to those at 14 days recovery.
i
Rats exposed to 480 mg/m had minimal to mild nephrosis in the kidneys after the 10th exposure. This lesion was characterized by foci
of cholesterol-like clefts, regenerative tubular epithelial cells and occasional necrotic epithelial cells in the cortex. This lesion was absent after 14 days recovery. '
In addition to the liver and kidney changes, rats exposed to 480 mg/m had depressed spleen weights and spleen-to-body weight ratios, and elevated testis weights after 10 exposures. These changes were absent after 14 days recovery.
Several statistically-significant organ weight changes were observed that were not considered compound related. Rats exposed to 7.6 mg/m had
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elevated thymus weights on the 14th day of 1ung-tosbody weight ratios on the 84th day 58 mg/m and rats exposed to 480 mg/m had ratios on the 84th day of recovery. These
unrelated to treatment.
recovery and depressed
of recovery. Rats exposed to elevated spleen-to-body weight changes were believed to be
Mean organ weights and organ-to-body weight ratios are presented in
Appendices III and IV. The Pathology report is attached as Appendix V.
C. Clinical Pathology
No treatment-related clinical chemical or hematologic effects were observed in rats exposed to 7.6 or 58 mg/m throughout the test.
3
After the 10th exposure, rats exposed to 480 mg/m had several significantly altered hematologic and clinical chemical parameters. Hematologic changes included elevated red blood cell count, hemoglobin concentration and hematocrit, and depressed mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration. Clinical chemical changes included elevated alkaline phosphatase activity, urea nitrogen concentration, urine volume and urine pH, and depressed urine osmolality and serum cholesterol concentration.
Several of the clinical changes were consistent with the microscopic pathologic findings. The elevated alkaline phosphatase activity, and the elevated urea nitrogen concentration and urine volume could indicate changes in the liver and the kidneys, respectively. The mild polycythemic effect, indicated by the elevated red blood cell parameters, may have been the result of dehydration.
After 14 days of recovery, all of the above changes were absent. No other treatment-related changes were observed at any sacrifice. The Clinical Pathology report is attached as Appendix VI.
E. Blood Fluorine Analysis
A comparison of total fluorine with ionic fluorine indicated that, for control rats, organic fluorine was greater than 96% of total fluorine, and for rats exposed to 480 mg/m0, organic fluorine was greater than 99.9% of total fluorine. Mean total fluorine concentrations for
each sampling interval are presented in Table II. Reported values are
averages of 5 samples.
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Table II
Total Fluorine Concentration (ppm)8 Mean (S.D.)
Exposure Concentration
Controls7.6 mg/m-
58 mg/m" 480 mg/m"
After 10
Exposures
After 14
Days Recovery
After 41
Days Recovery
After 84
Days Recovery
2.0 (1.5) 10 (1.4)
42 (7.9) 150 (26)
0.92 4.0
13
40
(0.20) (0.58)
(2.0) (8.6)
0.86 1.8 7.2
17
(0.30) (0.29)
(1.3) (3.2)
0.40 0.61
2.2 4.4
(0.17) (0.084)
(1.2) (1.1)
a
ug total fluorine per g blood
Mean total fluorine concentrations after the 10th exposure increased with increasing exposure concentration. However, the increase in fluorine was not directly proportional to exposure concentration: a 10-fold increase in exposure concentration did not result in a 10-fold increase in blood fluorine concentration.
Elimination of fluorine from the blood appeared to be biphasic, with a rapid decline in blood fluorine over the first 14 days of recovery, followed by a gradual decline over the remaining 10 weeks. During the first phase of elimination, the average half-life of total fluorine in blood was approximately 9 days. The clearance rate during the first phase appeared to be dose-dependent: the higher the initial blood concentration, the faster the test material was cleared. The half-life for rats exposed to480 mg/m was 7.5 days, while the half-life for rats exposed to 7.6 mg/m was 10.4 days.
During the second phase of elimination, the clearance rate appeared
to be similar for all exposure concentrations. The average half-life of
fluorine in blood during the second clearance phase was approximately 25
days.
A statistical coniDan^on of the test groups with controls indicated that rats exposed tofflRhad significantly elevated total fluorine concentrations at the-first 3 sampling intervals. After 84 days of recovery, blood values for rats exposed to 7.6 mg/m were indistinguish able from controls. However, blood fluorine concentrations for rats
exposed to 58 or 480 mg/m were still significantly elevated.
All reported half-lives were determined graphically. A blood
fluorine elimination curve is attached as Figure II. Fluorine
concentrations for individual rats and mathmatical expressions of the
observed fluorine eliminations are presented in Appendix VII. The statistical comparisons of total fluorine concentrations at.each sampling interval are presented in Appendix VIII.
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CONCLUSION
No significant adverse effects wereiObserved in rats exposed to 7.6 or 58 mg/m throughout the test. The 58 mg/m level is considered the "no effect" concentration under the conditions of this test.
Rats exposed to 480 mg/m of^B^yiad significant adverse effects in the liver and the kidneys. The liver cnanges persisted for 84 days of recovery. The kidney changes were absent after 14 days of recovery.
Blood fluorine concentrations for rats exposed toJd^were dose-depend ent and significantly elevated compared to controls for the first 6 weeks of recovery. Fluorine concentrations returned to normal after 12 weeks of
recovery for rat's exposed to 7.6 mg/m only. 'EThm' nation of blood fluorine
was biphasic, with a rapid decline in blood fluorine over the first 2 weeks
of recovery followed by a gradual decline over the remaining 10 weeks.
Calculation described in Sierra Instuments, Inc., Manual 7-79-210IM, Instruction Manual: Series 210 Cascade Impactors and Ambient Preseparators.
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^
S
220.00
^
0.00
00
-------- CONTROLS
B------B 7.6 MB/CM
DAYS
-0 58 MG/CM -A 480 MB/CM
ON
TEST
cm = cubic me.ter
0.00
CONTROLS
7.8 H6/CM
20.00
40.00
80.00
DAYS
0------0 58 H6/CM A------A 480 MG/CM
POST
EXPOSURE
cm = cubic meter
80.00
Exposure No.
APPENDIX I
DAILY ATMOSPHERE CHARACTERIZATION OF'
Concentration
Mean
S.D.
0
(mg/m )
Range
% Respirable
3
A. Design Concentration of 5 mg/m
1
6.9
7.0
2-26
2
16
17
0-50
3
8.2
7.2
0-25
80
4
8.3
6.5
0 - 20
5
8.1 8.8 0-32
83
6
5.3 4.6 0-13
7
5.4
3.7
2-11
84
8
6.5 4.3 2-14
9
5.5
2.9
1 - 10
89
10
5.2 3.0 0-10
B. Design Concentration of 50 mg/m
1
63
27
24 - 120
60
2
55
46
16 - 180
3
78
57
8 - 230
4
64
34
0 - 120
55
5
47
21
12 - 100
6
61
54
0 - 150
51
7
58
25
20 - 110
8
60
35
8 - 120
72
9
45
10
28 - 62
10
48
43
17 - 170
0
C. Design Concentration of 500 mg/m
1
520
290
20 - 920
70
2
400
95
180 - 570
3
420
98
190 - 550
4
430
220
150 - 730
64
5
450
150
180 - 620
6
470
110
310 - 690
61
7
480
200 '240 - 870
8
400
240
80 - 870
60
9
580
240
280 - 960
10
650
250
200 - 1200
MMD (urn)
6.3 4.7 5.3 4.7
8.5 8.9 9.8 6.5
6.9 7.8 7.9 8.0
Mass median aerodynamic diameter.
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APPENDIX II
MEAN BODY WEIGHTS
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^\ MEAN BODY WEIGHTS (GRAMS!
i,388 - EXPOSURE PERIOD
GROUP
CONTROL
7.6 MG/CM
58 MG/CM 480 MG/CM
ANOVA(l) TREND(2) L8D(3) DUNNETT(4) BARTLETT(5)
INTERVALS IN TEST DAYS
1.
2.
3.
232 .7 234 .4 235 .4 235 .8
0.778 0.316 6.4858 7.8220 0.177
237.1 235.4 240.2 229.6+
0.028* 0.116 6.9935 8.4344 0.356
242.6 240.1 242.8 231.0#
0.011* 0.012* 7.8406 9.4560 0.277
4.
247 .4 245 .1 245 .6 229 5#
0.001* 0.001* 8.0042 9.6533 0.313
5.
250.8 251.8 252.6 234.3#
0.001* 0.001* 8.4181 10.1525 0.403
GROUP
CONTROL
7.6 MG/CM
58 MG/CM 480 MG/CM
ANOVA(l) TREND(2) LSD(3) DUNNETT(4 ) BARTLETT( 5)
INTERVALS IN TEST DAYS
8.
9.
10.
270 .1 270 .0 269 .5 250 .5#
0.001* 0.001* 9.4285 11.3711 0.336
277.0 277.6 273.1 249.6#
0.001* 0.001* 9.9104 11.9522 0.543
280.9 279.0 277.5 247.8#
0.001* 0.001* 10.3550 12.4884 0.532
11.
284.9 284.3 282.4 250.3#
0 .001* 0 .001* 10. 6629 12. 8598 0 .258
12.
289.4 288.1 285.0 246.7#
0.001* 0.001* 11.3664
13.7324 0.125
(1) P VALUE of F-TEST from ONE-FACTOR ANALYSIS OF VARIANCE.
(* indicates P value less than 0.05)
(2) P VALUE OF TEST FOR LINEAR TREND OVER GROUPS.
(* indicates P value less than 0".05) (3) LEAST SIGNIFICANT DIFFERENCE - given a significant (alpha=0.05) F RATIO, any two means differing by more than the LSD are significantly different with a false positive (alpha) error rate'of 0.05. (4) DUNNETT TEST - any treatment mean differing from the control mean by more
than the DUNNETT statistic is significantly different from the control mean
with a variable-wise false positive (alpha) error rate of 0.05.
(5) BARTLETTS TEST FOR EQUAL VARIANCE P VALUE.
+ SIGNIFICANTLY DIFFERENT (P<0.05) from CONTROL GROUP by LSD. a SIGNIFICANTLY DIFFERENT (P<0.05) from CONTROL. GROUP by DUNNETT TEST and LSD.
cm = cubic meter
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-JMEAN BODY WEIGHTS (GRAMS) 0 TO 2 WEEKS POST EXPOSURE
GROUP
CONTROL
7.6 MG/CM
58 MG/CM 480 MG/CM
ANOVA(l) TREND(2) LSD(3) DUNNETT(4) BARTLETT(5)
INTERVALS IN TEST DAYS
15.
16.
17.
309 .9 305 .8 300 .5
263 Oft
0.001* 0.001* 14.3258 17.4059 0.533
312.9 309.5 304.3 266.9#
0.001* 0.001* 14.7224 17.8877 0.466
323.0 319.2 312.5 278.3#
0.001* 0.001* 15.0779 18.3197 0.602
18,
325.9 323.3 315.9 284.2ft
0.0(31* 0.001* 15.6897 19.0630 0.536
19.
330.3 326.1 318.3 287.9ft
0.001* 0.001* 15.7935 19.1891 0.516
GROUP
CONTROL
7.6 MG/CM
58 MG/CM 480 MG/CM
ANOVA(l) TREND(2) LSD(3) DUNNETT(4) BARTLETT(5)
INTERVALS IN TEST DAYS
22.
23.
24.
354 .1 349 .6 339 .0 312 7#
0.001* 0.001* 17 .8518 21 .6900 0.440
359.3 353.6 343.2 315.5#
0.001* 0.001* 18.0962 21.9869 0.428
364.2 359.4 349.5 322.9ft
0.001* 0.001* 19.0094 23.0965 0.440
25.
371.1 365.9 352.7 328.7ft
0.001* 0.001* 19.6318 23.8526 0.373
26.
373.8 363.3 356.3 331.6ft
0.001* 0.001* 18.8130
22.8-578 0.220
(1) P VALUE of F-TEST from ONE-FACTOR ANALYSIS OF VARIANCE. (* indicates P value less than 0.05)
(2) P VALUE OF TEST FOR LINEAR TREND OVER GROUPS.
(* indicates P value less than 0.05) (3) LEAST SIGNIFICANT DIFFERENCE - given a significant (alpha=0.05) F RATIO, any two means differing by more than the LSD are significantly different with a false positive (alpha) error rate, of 0.05. (4) DUNNETT TEST - any treatment mean differing from the control mean by more
than the DUNNETT statistic is significantly different from the control mean
with a variable-vise false positive (alpha) error rate of 0.05.
(5) BARTLETTS TEST FOR EQUAL VARIANCE P VALUE.
+ SIGNIFICANTLY DIFFERENT (P<0.05) from CONTROL GROUP by LSD. # SIGNIFICANTLY DIFFERENT (P<0.05) from CONTROL GROUP by DUNNETT TEST and LSD.
cm = cubic meter
19 Company Sanitized. Does not contain TSCA CBI
MEAN BODY WEIGHTS (GRAMS) "TO 12 WEEKS POST EXPOSURE
GROUP
CONTROL
7.6 MG/CM
58 MG/CM 480 MG/CM
ANOVA(l) TREND(2) LSD(3) DUNNETT(4) BARTLETT(5)
INTERVALS IN TEST DAYS
29.
36.
43.
389.9 381.0 371.1 347.2#
0.022* 0.003* 27.7810 33.8025 0.606
421.6 415.3 404.2 384.4+
0.125 0.022* 32.7937 39.9017 0.468
447.4 445.5 432.1 411.8+
0.161 0.034* 34.9541 42.5303 0.352
50,
472.1 472.4 459.7 438.6
0.258 0.067 38.4790 46.8193 0.352
53,
481.6 475.4 464.8 444.6
0.254 0.054 39.1459 47.6307 0.210
GROUP
CONTROL
7.6 MG/CM
58 MG/CM 480 MG/CM
ANOVA(l) TREND(2) LSD(3) DUNNETT(4) BARTLETT(5)
INTERVALS IN TEST DAYS
58.
64.
71.
505.4 499.4 488.8 457.2
0.494 0.159 70.4257 87.3718 0.590
521.2 514.4 503.2 477.0
0.642 0.229 77.1268 95.6854 0.389
545.2 538.0 524.2 493.2
0.559 0.183 81.7306 101.3970 0.496
78.
561.8 555.4 543.8 514.2
0.677 0.257 87.9705 109.1384 0.359
85.
572.2
570s. 2
556.8 529.2
0.742 0.314 91.8318 113.9288 0.237
GROUP
INTERVALS IN TEST DAYS
92.
96.
CONTROL
7.6 MG/CM
58 MG/CM 480 MG/CM
ANOVA(l) TREND(2) LSD(3) DUNNETT(4) BARTLETT(5)
cm = cubic meter
583.6 582.6 577.0 539.8
0.742 0.355 96.5097 119.7323 0.270
586.2 575.4 567.6 532.6
0.627 0.228 90.1122 111.7954 0.424
2Q
Company Sanitized. Does not contain TSCA CBI
(1) P VALUE of F-TEST from ONE-FACTOR ANALYSIS OF VARIANCE.
(* indicates P value less than 0.05)
(2) P VALUE OF TEST FOR LINEAR TREND OVER GROUPS.
(* indicates P value less than 0.05) (3) LEAST SIGNIFICANT DIFFERENCE - given a significant (alpha=0.05) F RATIO,
any two means differing by more than the LSD are significantly different with a false positive (alpha) error rate of 0.05. (4) DUNNETT TEST - any treatment mean differing from the control mean by more than the DUNNETT statistic is significantly different from the control mean with a variable-wise false positive (alpha) error rate of 0.05.
(5) BARTLETTS TEST FOR EQUAL VARIANCE P VALUE. +. SIGNIFICANTLY DIFFERENT (P<0.05) from CONTROL GROUP by LSD. # SIGNIFICANTLY DIFFERENT (P<0.05) from CONTROL GROUP by DUNNETT TEST and LSD. cm = cubic meter
f) -f Company Sanitized. Does not contain TSCA CBI
APPENDIX III
MEAN ORGAN WEIGHTS
- 22 Company Sanitized. Does not contain TSCA CBI
MEAN ORGAN WEIGHTS (GRAMS) RATS SACRIFICED AFTER 10 EXPOSURES
GROUP CONC.
FINAL WT.
LUNGS
LIVER
CONTROL
7.6 MG/CM
58 MG/CM 480 MG/CM
290.4( 289.6( 285.4( 248.0(
0.000) 0.936)
0.617) 0.001)#
TEST - HOMOGENEITY TEST - TREND BARTLETT'S TEST
0.001 0.001 0.369
GROUP CONC.
SPLEEN
1.329( 1.260( 1.302( 1.148(
0.000) 0.373)
0.723) 0.029)
0.123 0.051 0.159
KIDNEY
10.086( 10.258( 10.80K
11.312(
0.000) 0.770) 0.233) 0.050)
0.178 0.034 0.375
TEST IS
CONTROL
7.6 MG/CM
58 MG/CM 480 MG/CM
0 ,598( 0 .542( 0 .541( 0 .360(
0.000) 0.335)
0.322) 0.001)#
TEST - HOMOGENEITY TEST - TREND BARTLETT'S TEST
0.003 0.001 0.767
GROUP CONC.
THYMUS
2.216( 2.329(
2.364(
2.145(
0.000)
0.395)
0.268) 0.587)
0.330 0.666 0.920
2.849( 2.807(
2.727( 2.742(
0.000) 0.731)
0.324) 0.386)
0.720 0.306
0.630
CONTROL
7.6 MG/CM
58 MG/CM 480 MG/CM
0.547( 0.638(
0.547( 0.442(
0.000) 0.285)
0.998) 0.221)
TEST - HOMOGENEITY TEST - TREND BARTLETT'S TEST
0.171 0.138 0.636
Values in parentheses -
P VALUE OF STUDENT T TEST COMPARISON OF TREATMENT MEAN TO CONTROL MEAN.
+
-
SIGNIFICANTLY DIFFERENT (P<0.05) FROM CONTROL GROUP BY LSD
# - SIGNIFICANTLY DIFFERENT (P<0.05) FROM CONTROL GROUP BY LSD
DUNNETT'S TEST
AND
HOMOGENEITY - P VALUE OF F TEST OF WHETHER GROUP MEANS ARE EQUAL.
TREND - P VALUE OF F TEST OF WHETHER THERE IS DOSE-RELATED CHANGE IN GROUP MEANS.
BARTLETT'S TEST - P VALUE OF TEST OF HOMOGENEITY OF VARIANCE
cm = cubic meter
''"'i 7
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MEAN ORGAN WEIGHTS (GRAMS) RATS SACRIFICED AFTER 14 DAYS RECOVERY
GROUP CONC.
FINAL WT.
LUNGS
LIVER
CONTROL
7.6 MG/CM
58 MG/CM 480 MG/CM
376.0( 361.0( 350.6( 337.0(
0.000)
0.367) 0.135) 0.028)
TEST - HOMOGENEITY TEST - TREND BARTLETT'S TEST
0. 143 0. 024 0. 267
GROUP CONC.
SPLEEN
1.635(
1.566( 1.486(
1.459C
0.000) 0.399)
0.081) 0.042)
0. 154 0. 028 0. 480
KIDNEY
13 .924( 12 .423( 12 917( 18 .836(
0.000) 0.464) 0.622) 0.026)+
0. 021 0. 028 0. 002
TEST IS
CONTROL
7.6 MG/CM
58 MG/CM 480 MG/CM
0.804( 0.718(
0.629( 0.698(
0.000) 0.283) 0.038) 0.190)
TEST - HOMOGENEITY TEST - TREND BARTLETT'S TEST
0. 200 0. 116 0. 943
GROUP CONC.
THYMUS
2.808( 2.822( 2.693(
2.660(
0.000) 0.933) 0.494) 0.379)
0. 692 0. 285 0. 351
3 .228( 2 .918( 3 .060( 3 050(
0.000) 0.133) 0.404)
0.376)
0. 491 0. 534 0. 123
CONTROL
7.6 MG/CM
58 MG/CM 480 MG/CM
0.619(
0.76K 0.59K 0.587(
0.000)
0.033)+ 0.648)
0.600)
TEST - HOMOGENEITY TEST - TREND BARTLETT'S TEST
0.034 0.182 0.554
Values in parentheses -
P VALUE OF STUDENT T TEST COMPARISON OF TREATMENT MEAN TO CONTROL MEAN.
+
-
SIGNIFICANTLY DIFFERENT (P<0.05)' FROM CONTROL GROUP BY LSD
# - SIGNIFICANTLY DIFFERENT (P<0.05) FROM CONTROL GROUP BY LSD
DUNNETT'S TEST
AND
HOMOGENEITY - P VALUE OF F TEST OF WHETHER GROUP MEANS ARE EQUAL.
TREND - P VALUE OF F TEST OF WHETHER THERE IS DOSE-RELATED CHANGE IN GROUP MEANS.
BARTLETT'S TEST - P VALUE OF TEST OF HOMOGENEITY OF VARIANCE
cm = cubic meter
24c ompany Sanitized. Does not contain TSCA CBI
MEAN ORGAN WEIGHTS (GRAMS) RATS SACRIFICED AFTER 41 DAYS RECOVERY
GROUP CONC.
FINAL WT.
LUNGS
LIVER
CONTROL
7.6 MG/CM
58 MG/CM 480 MG/CM
470 .2(
465 0( 454 .0( 442 .8(
0 .000) 0 .840) 0 .531)
0 .295)
TEST - HOMOGENEITY TEST - TREND BARTLETT'S TEST
0.712 0.262
0.208
GROUP CONC.
SPLEEN
1 .815( 1 -67K 1 .684( 1 724(
0.000) 0.193) 0.235)
0.403)
0.537
0.450 0.228
KIDNEY
18 .64K
17 .815( 17 .603( 18 .262(
0.000)
0.694) 0.622) 0.857)
0.958 0.839 0.586
TESTIS
CONTROL
7.6 MG/CM
58 MG/CM 480 MG/CM
0.773( 0.723( 0.728(
0.743(
0 .000) 0 .507)
0 .551) 0 .688)
TEST - HOMOGENEITY TEST - TREND BARTLETT'S TEST
0.904 0.719 0.234
3 .517( 3 344(
3 336( 3 187(
0. 000) 0. 551) 0. 532) 0. 261)
0.719 0.282
0.651
3 .246( 3 .126( 3 .176(
3 .19K
0.000)
0.514) 0.701)
0.762)
0.928 0.840 0.808
GROUP CONC.
THYMUS
CONTROL
7.6 MG/CM
58 MG/CM (180 MG/CM
0.633( 0.708( 0.579( 0.596(
0.000) 0.280) 0.436) 0.591 )
TEST - HOMOGENEITY TEST - TREND BARTLETT'S TEST
0.265 0.277 0.108
Values in parentheses -
P VALUE OF STUDENT T TEST COMPARISON OF TREATMENT MEAN TO CONTROL MEAN.
+
-
SIGNIFICANTLY DIFFERENT (P<0.05) FROM CONTROL GROUP BY LSD
# - SIGNIFICANTLY DIFFERENT (P<0.05) FROM CONTROL GROUP BY LSD
DUNNETT'S TEST
AND
HOMOGENEITY-- P VALUE OF F TEST OF WHETHER GROUP MEANS ARE EQUAL. TREND - P VALUE OP F TEST OP WHETHER THERE IS DOSE-RELATED
CHANGE IN GROUP MEANS.
BARTLETT'S TEST - P VALUE OF TEST OF HOMOGENEITY OF VARIANCE
cm = cubic meter
25
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- MEAN ORGAN WEIGHTS (GRAMS) S SACRIFICED AFTER 84 DAYS RECOVERY
GROUP CONC.
FINAL WT.
LUNGS
LIVER
CONTROL
7.6 MG/CM
58 MG/CM 480 MG/CM
586.2( 575.4( 567.6( 532.6(
0.000) 0.803) 0.668) 0.225)
TEST - HOMOGENEITY TEST - TREND BARTLETT'S TEST
0. 627 0. 228 0. 424
GROUP CONC.
SPLEEN
2.008( 1.582( 1.953( 1.942(
0.000) 0.031) 0.766) 0.719)
0.112 0.765 0.235
KIDNEY
21.936( 21.614( 20.026( 20.215(
0.000) 0.889)
0.415) 0.461)
0.783 0.363
0.4-84
TEST IS
CONTROL
7.6 MG/CM
58 MG/CM 480 MG/CM
0.749( 0.802( 0.944(
0.875(
0.000) 0.647) 0.106)
0.287)
TEST - HOMOGENEITY TEST - TREND BARTLETT'S TEST
0. 373 0. 170 0. 015
GROUP CONC.
THYMUS
3.952( 3.730( 3.52K 3.690(
0.000) 0.539) 0.241) 0.469)
0. 685 0. 386 0. 491
3.210( 3.454( 3.355(
3.204(
0.000) 0.129) 0.357) 0.970)
0. 322 0. 812 0. 092
CONTROL
7.6 MG/CM
58 MG/CM 480 MG/CM
0.709(
0.68K 0.676( 0.540(
0.000) 0.816) 0.789) 0.181)
TEST - HOMOGENEITY TEST - TREND BARTLETT'S TEST
0.519 0.199 0.927
Values in parentheses -
P VALUE OF STUDENT T TEST COMPARISON OF TREATMENT MEAN TO CONTROL MEAN.
+ - SIGNIFICANTLY DIFFERENT (P<0.05)FROM CONTROL GROUP BY LSD
# - SIGNIFICANTLY DIFFERENT (P<0.05) FROM CONTROL GROUP BY LSD
DUNNETT'S TEST
AND
HOMOGENEITY - P VALUE OF F TEST OF WHETHER GROUP MEANS ARE EQUAL. TREND - P VALUE OF P TEST OF WHETHER THERE IS DOSE-RELATED
CHANGE IN GROUP MEANS.
BARTLETT'S TEST - P VALUE OF TEST OF HOMOGENEITY OF VARIANCE
cm = cubic meter
26
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APPENDIX IV MEAN ORGAN-TO-BODY WEIGHT RATIOS
- 27 Company Sanitized. Does not contain TSCA CBI
MEAN ORGAN-TO-BODY WEIGHT RATIOS TS SACRIFICED AFTER 10 EXPOSURES
GROUP CONC.
LUNGS
CONTROL
7.6 MG/CM
58 MG/CM 480 MG/CM
0.458( 0.436( 0.456( 0.464(
0.000) 0.330)
0.925) 0.800)
TEST - HOMOGENEITY TEST - TREND BARTLETT'S TEST
0. 620 0. 601 0. 369
GROUP CONC.
KIDNEY
CONTROL
7.6 MG/CM
58 MG/CM
480 MG/CM
0.763( 0.803( 0.827( 0.868(
0.000) 0.292) 0.097) 0.011)
TEST - HOMOGENEITY TEST - TREND BARTLETT'S TEST
0.068 0.010 O.b56
LIVER
3. 472( 3. 534( 3. 782( 4. 573(
0.000) 0.686) 0.055)
0.000)#
0.000 0.000 0.034
TESTIS
0.982(
0.973(
0.957( 1.106(
0.000)
0.851)
0.577) 0.012)#
0.014 0.021
0.482
SPLEEN
0.206( 0.187( 0.189(
0.144(
0 .000) 0 .289) 0 .327). 0 .002)#
0. 012 0. 003 0. 341
THYMUS
0.188( 0.222(
0.190( 0.176(
0.000)
0.249) 0.947) 0.674)
0.435 0.457 0.049
Values in parentheses - P VALUE OF STUDENT T TEST COMPARISON
OP TREATMENT MEAN TO CONTROL MEAN.
+
-
SIGNIFICANTLY DIFFERENT (P<0.05) PROM CONTROL GROUP BY LSD
ff - SIGNIFICANTLY DIFFERENT (P<0.05) FROM CONTROL GROUP BY LSD
DUNNETT'S TEST
AND
HOMOGENEITY - P VALUE OF F TEST OF WHETHER GROUP MEANS ARE EQUAL. TREND - P VALUE OF F TEST OP WHETHER THERE IS DOSE-RELATED
CHANGE IN GROUP MEANS.
BARTLETT'S TEST - P VALUE OF TEST OP HOMOGENEITY OF VARIANCE
cm = cubic meter
28 Company Sanitized. Does not contain TSCA CBI
MEAN ORGAN-TO-BODY WEIGHT FIAT I OS RATS SACRIFICED AFTER 14 DAYS RECOVERY
GROUP CONC.
LUNGS
CONTROL
7.6 MG/CM
58 MG/CM 480 MG/CM
0.435( 0.434(
0.424( 0.434(
0.000) 0.941)
0.510) 0.943)
TEST - HOMOGENEITY TEST - TREND BARTLETT'S TEST
0.897 0.800
0.267
GROUP CONC.
KIDNEY
CONTROL
7.6 MG/CM
58 MG/CM 480 MG/CM
0. 747( 0. 781( 0. 768( 0. 790(
0 .000) 0 .301) 0 .517) 0 .190)
TEST - HOMOGENEITY TEST - TREND BARTLETT'S TEST
0.564 0.259 0.923
LIVER
3.697(
3.437( 3.685( 5.502(
0.000)
0.484) 0.975) 0.000)#
0. 000 0. 000 0. 233
TEST IS
0.858( 0.807(
0.876( 0.914(
0.000) 0.410)
0.763) 0.357)
0.374 0.225
0.238
SPLEEN
0.213( 0.199(
0.179( 0.206(
0.000) 0.407)
0.061) 0.667)
9. 251 0. 444 0. 002,
THYMUS
0. l65(
0. 212( 0. 168( 0. 175(
0.000) 0.015)
0.833) 0.566)
0.055
0.815 0.565
Values in parentheses - P VALUE OF STUDENT T TEST COMPARISON
OF TREATMENT MEAN TO CONTROL MEAN.
+ - SIGNIFICANTLY DIFFERENT (P<0.05) FROM CONTROL GROUP BY LSD # - SIGNIFICANTLY DIFFERENT (P<0.05) FROM CONTROL GROUP BY LSD
DUNNETT'S TEST
AND
HOMOGENEITY - P VALUE OF F TEST OF WHETHER GROUP MEANS ARE EQUAL. TREND - P VALUE OF F TEST OF WHETHER THERE IS DOSE-RELATED
CHANGE IN GROUP MEANS. BARTLETT'S TEST - P VALUE OF TEST OF HOMOGENEITY OF VARIANCE
cm = cubic meter
2r~7 Company Sanitized. Does not contain TSCA CBI
MEAN ORGAN-TO-BODY WEIGHT RATIOS RATS SACRIFICED AFTER 41 DAYS RECOVERY
GROUP CONC.
LUNGS
CONTROL
7.6 MG/CM
58 MG/CM 480 MG/CM
0 .387( 0 .360( 0 .371(
0 .390(
0.000) 0.202)
0.452) 0.870)
TEST. - -HOMOGENEITY TEST - TREND
BARTLETT'S TEST
0.430 0.742 0.208
GROUP CONC.
KIDNEY
CONTROL
7.6 MG/CM
58 MG/CM 480 MG/CM
0 .749( 0 .720( 0 735(
0 718(
0.000) 0.555)
0.784) 0.517)
TEST - HOMOGENEITY TEST - TREND BARTLETT'S TEST
0.902 0.606 0.759
LIVER
3.975(
3.797( 3.858( 4.126(
0.000) 0.601)
0.730) 0.656)
0.770 0.632 0.259
TEST IS
0.692( 0.676(
0.700( 0.722(
0.000) 0.656) 0.829) 0.432)
0.657 0.343
0.719
SPLEEN
0. 165( 0. 156( 0. 159( 0. 169(
0.000)
0.576) 0.679) 0.815)
0.840 0.788
0.995
THYMUS
0.134(
0.153( 0.127( 0.135(
0.000)
0.129) 0.516) 0.980)
0.180 0.499 0.274
Values in parentheses -
P VALUE OF STUDENT T TEST COMPARISON OF TREATMENT MEAN TO CONTROL MEAN.
+
-
SIGNIFICANTLY DIFFERENT (P<0.05) FROM CONTROL GROUP BY LSD
# - SIGNIFICANTLY DIFFERENT (P<0.05) FROM CONTROL GROUP BY LSD
DUNNETT'S TEST
AND
HOMOGENEITY - P VALUE OF F TEST OF WHETHER GROUP MEANS ARE EQUAL.
TREND - P VALUE OF F TEST OF WHETHER THERE IS DOSE-RELATED CHANGE IN GROUP MEANS.
BARTLETT'S TEST - P VALUE OF TEST OF HOMOGENEITY OF VARIANCE
cm = cubic meter
J (J Company Sanitized. Does not contain TSCA CBI
MEAN ORGAN-TO-BODY WEIGHT RATIOS RATS SACRIFICED AFTER 84 DAYS RECOVERY
GROUP CONC.
LUNGS
CONTROL
7.6 MG/CM
58 MG/CM 480 MG/CM
0. 344( 0. 273( 0. 345( 0. 368(
0.000) 0.010)# 0.963) 0.336)
TEST - HOMOGENEITY TEST- - TREND BARTLETT'S TEST
0.008 0.079 0.424
GROUP CONC.
KIDNEY
CONTROL
7.6 MG/CM
58 MG/CM 480 MG/CM
0.676( 0.649( 0.620(
0.694(
0.000) 0.522)
0.196) 0.687)
TEST - HOMOGENEITY TEST - TREND BARTLETT'S TEST
0.345 0.867
0.003
LIVER
3.739( 3.755(
3.506( 3.788(
0 .000) 0 .948) 0 .354) 0 .843)
0.649 0.8 97 0.088
TESTIS
0.550( 0.602(
0.595( 0.61K
0.000) 0.124)
0.180) 0.073)
0.266 0.099
0.376
SPLEEN
0.128( 0.139(
0.165(
o'.mc
0.000) 0.342)
0.004)# 0.010)#
0.012 0. 663 0.152
THYMUS
0.120( 0.120( 0.118( 0.099(
0.000) 0.995) 0.916) 0.271)
0.617 0.282 0.438
Values in parentheses - P VALUE OF STUDENT T TEST COMPARISON
OF TREATMENT MEAN TO CONTROL MEAN.
+
-
SIGNIFICANTLY DIFFERENT (P<0.05) FROM CONTROL GROUP BY LSD
# - SIGNIFICANTLY DIFFERENT (P<0.05) FROM CONTROL GROUP BY LSD
DUNNETT'S TEST
AND
HOMOGENEITY - P VALUE OF F TEST OF WHETHER GROUP MEANS ARE EQUAL. TREND - P VALUE OF F TEST OF WHETHER THERE IS DOSE-RELATED
CHANGE IN GROUP MEANS. BARTLETT'S TEST - P VALUE OF TEST OF HOMOGENEITY OF VARIANCE
cm = cubic meter
51
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APPENDIX V
PATHOLOGY REPORT NO. 18-85
32 Company Sanitized. Does not contain TSCA CBI
ss^ffT' EV. iiiBZ
E5TJBUSHEDIB02
E. 1. DU PONT DE NEMOURS & COMPANY
INCORPORATED
HASKELL LABORATORY FOR TOXICOLOGY AND INDUSTRIAL MEDICINE
t'.O. BOX 50, ELKTON ROAD
NEWARK, DELAWARE 19711 CENTRAL RESEARCH AND DEVELOPMENT DEPARTMENT
PATHOLOGY REPORT NO. 19-85
SUBCHRONIC INHALATION STUDY IN MALE Crl;CD(SD)BR RATS
APRIL 4, 1985
Summary
inhalation for 10 days were examined grossly and selected tissues were weighed and/or examined microscopically. Compound-related lesions consisting of fatty change in centrilobular hepatocytes of the liver and nephrosis of tubular epithelial cells of the cortex of the kidneys occurred in high dose animals. The fatty change was most severe in animals killed 14 days
following the last exposure. A slight degree of fatty change was still
present in the liver of 2 of 5 animals killed after 84 days of recovery. The kidney lesion was only noted in the animals killed on the last day of exposure. The no-effect-level for histopathology was the design
concentration of 0.05 mg/L.
Introduction This report will^summarize the results of inhalation exposure of male
Crl:CD(SD)BR rats tof----^------ll------Jfor 10 days. Treatment groups
were as follows;
35
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Design Chamber Concentration of
I
0 (Control)
II
0.005 (Low Dose)
III
0.05 (Intermediate Dose)
IV
0.5 (High Dose)
Animals were exposed "nose only" to the compound 6 hours/day, 5
days/week for -2 weeks. Five animals from each group were killed and examined at each of 4 different time periods - on the last day of exposure and 14, 41 and 84 days following the last exposure. Organ weights were determined for lungs, liver, spleen, kidneys, testes and.thymus. Selected tissues were
processed and examined for histopathology .
Results
Table I contains the gross observations made at necropsy. Tables
II, IV and V summarize the microscopic observations for rats with 0, 14, 41
III, and 84 days recovery, respectively. Table VI contains microscopic
observations for Individual animals.
Compound-related lesions occurred in the liver and kidneys of high dose animals. Fatty change occurred in centrilbbular hepatocytes of the liver in 4 of '1 ,raCs killed on-the loot day of exposure, 5 of 5 rats killed on days 14 and 41 post-exposure and 2 of 5 rats killed on day 84 post-exposure. Diffuse fatty change of minimal severity occurred in the animals killed on the last day of exposure. Affected hepatocytes contained small numbers of fine lipid vacuoles without being appreciably enlarged. At 14 days recovery, the fatty
change was moderate in one animal and mild in the other four. Affected
hepatocytes were moderately distended by numerous lipid vacuoles. At 41 days recovery, the lesion was mild in one animal, minimal in three and only
present in a few scattered hepatocytes In one animal. Eighty-four days following the last exposure, the lesion was minimal in one animal and only present in a few scattered hepatocytes In one animal. Affected hepatocytes at 41 and 84 days post-exposure were simlliar in appearance to those at 14 days post-exposure.
Minimal to mild nephrosis occured in the kidneys of all five high dose animals killed on the last day of exposure. The lesion was characterized by foci of cholesterol-like clefts, regenerative tubular epithelial cells and
Liver, kidneys, lungs, heart, spleen, thymus, pancreas, adrenal glands,
thyroid gland, trachea, esophagus, brain, stomach, duodenum,- jejunum,
ileum, cecum, colon, rectum, mesenteric lymph node, testes, epidldymldes,
urinary bladder, sternum, bone marrow, eyes, nose and all gross lesions.
^5 4 Company Sanitized. Does not contain TSCA CBI
occasional necrotic epithelial cells in the cortex of the kidneys. The lesion was not present after 14 days of recovery.
Conclusion
Compound-related lesions consisting of fatty change in the liver and
nephrosis in the kidneys occurred, in animals exposed to a design
concentration of 0.5 mg/L offlj^^Hfor 10 days. A slight degree of fatty
change was still present in the^Rver of 2 of 5 animals after 84 days of
recovery. The kidney lesion was not evident after 14 days of recovery. The no-effect-level for histopathology was the design concentration of 0.05 mg/L.
Acknowledgement
Pathology supervisory personnel associated with this study'.were Joan A. Wolfe (Histology) and Bobby L. Moore (Necropsy).
TWS/WCK/wfd
TWS 1.6
Report by: ^W^CP^. \^. VJ^CP^^TI
Theodore W. Slone, Jr. D.V.M.
Diplomate A.C.V.P. Staff Pathologist
Approved by;
UL^/A^L/ C '/ffffJt/My
IffTiliam C. Krauss, D.V.M. Manager, Pathology Division
35 Company Sanitized. Does not contain TSCA CBI
-
4 -
KEY TO TABLES
Mode of Death SD = Sacrificed by design
Tissue Accounting Code N = No change observed L = Change observed 0 = No tissue present
I = Insufficient tissue present for evaluation
Lesion Grades P = Change present, severity not graded 1 = Minimal degree of change present 2 = Mild degree of change present 3 = Moderate degree of change present 4 = Marked degree of change present - = Lesion not present
56 Company Sanitized. Does not contain TSCA CBI
- 5
C J1 H-153|
*
TABLE I GROSS ]?/. riON SUBC1HIIONIC - MALE RATS
Animal
Number
Days on
Test
Recovery Days
Group I - Control
376825
12
0
376839
12
.0
376840
12
0
376870
12
0
376873
12
0
376835
26
376841
26
14
'
14
376849
26
14
376863 l
26
14
376872
26
14
376801
53
41
376836
53
41
376837
53
^1
376847
53
41
376878
53
41
376807
96
84
376829
96
84
376834
96
84
Mode of Death
Observation
SD
No abnormalities detected
SD
No abnormalities detected
SD
No abnormalities de&eeted
SD
No abnormalities detected
SD
Mandibular Lymph Nodes - large,
slight
SD
No abnormalities detected
SD
Lungs - discoloration, red, gray,
patchy areas
SD
No abnormalities detected
SD
Urinary Bladder - dilatation, (1.0
cc)
SD
Medias final Lymph Node -
discoloration, red
SD
No abnormalities detected
SD
Liver - large
Lungs - discoloration, white patchy
areas
SD
No abnormalities detected
SD
No abnormalities detected
'
SD
No abnormalities detected
SD
No abnormalities detected
SD
No abnormalities detected
SD
No abnormalities detected
37
Company Sanitized. Does not contain TSCA CBI
6 -
Mg-15388,
*
TABLE I
GROSS P LTHOLOGY^^^^^
IRHALA'riON SUBCHI IONIC - MALE RATS
Part 2
Animal
Number
Days on
Test
Recovery Days
Mode of Death
Observation
376861
96
84
SD
No abnormalities detected
376869
96
84
SD
Lungs - discoloration, dark red foci,
2 mm in diameter), scattered
Group II - Low Dose
376804
12
0
376806
12
0
376818
12
0
376823
12
0
376844
12
0
*
376810
26
14
376822
26
14
376852
26
14
376876
26
14
376881
26
14
376800
53
41
376848
53
41
376856
53
41
SD
No abnormalities detected
SD
No abnormalities detected
SD
No abnormalities detected
SD
Lungs - foci, red, 2 mm), several
SD
Renal Pelvis - dilatation, right,
slight
SD
Lungs - foci, red, 2 mm in
diameter), few
SD
Lungs - discoloration, pale
SD
No abnormalities detected
SD
Lungs - focus, brown, (1 mm in
diameter)
Testes - small, left, (wt. = 0.688
grams)
SD
No abnormalities detected
SD
Thymus - discoloration, red patchy
areas, slight
SD
Lungs - foci, red, few, 2 mm in
diameter)
SD
Liver - discoloration, pale
58
Company Sanitized. Does not contain TSCA CBI
-
7
r jH-15388 *
TABLE I
-- -- ^ 1 ^ GROSS P/ LTHOLOGY ^
INHAL AT][ON SuBCH IONIC - MALE RATS
Part 3
Animal
Number
Days on
Test
Recovery Days
Mode of Death
Observation
376866
53
41
SD
Lungs - foci, dark red, lower right
lobe, 2 mm in diameter), few
Thymus - foci, dark red, (1 mm in
diameter), several
376871
53
41
SD
No abnormalities detected
376827
96
84
SD
No abnormalities detected
376831
96
84
SD
Lungs - foci, black, (2 mm in
diameter), caudal lobe
376862
96
84
SD
No abnormalities detected
376877
96
84
SD
No abnormalities detected
376882
96
84
SD
No abnormalities detected
Group III - Intermediate Dose
376805
12
0
SD
376821
12
0
SD
376838
12
6
SD
376851
12
376867
12
0
SD
0
SD
376812
26
14
SD
376813
26
14
SD
376830
26
14
SD
No abnormalities detected
No abnormalities detected
Renal Pelvis - dilatation, right,
moderate
No abnormalities detected
Perlocular - chromodacryorrhea, right, slight
Thymus - discoloration, red patchy
areas
Lungs - focus, dark red, 1 mm in diameter), postcaval lobe
No abnormalities detected
No abnormalities detected
59 Company Sanitized. Does not contain TSCA CBI
-
8 -
m 1 H-15388
TAIiL E I GROSS I'ATHOLOCT
nc)N SUBClIRom^^ws^Svs
Part 4
Animal
Number
Days o a
Test
Recovery Days
Mode of Death
Observation
376857
26
14
SD
Lungs - foci, red, right lower lobe,
two, 1 mm in diameter)
376874
26
14
SD
No abnormalities detected
376803
53
41
SD
No abnormalities detected
376808
53
41
SD
Liver - large
Lungs - foci, red, few, 1 mm In
diameter)
376811
53
41
SD
Lungs - foci, dark red, diffuse, . 2
mm In diameter)
376843
53
41
SD
Lungs - focus, dark, (2 mm In
diameter), lower right lobe
376860
53
41
SD
Thynus - discoloration, red patchy
*
areas
376817
96
84
SD
No abnormalities detected
376846
96
84
SD
No abnormalities detected
376855
96
84
SD
No abnormalities detected
376864
96
84
SD
No abnormalities detected
376875
96
84
SD
No abnormalities detected
Group IV - High Dose
376820
12
0
376828
12
0
376854
12
0
376859
12
0
SD
SD
SD
SD
No abnormalities detected
No abnormalities detected No abnormalities detected
Lunge - discoloration, white patchy areas, scattered
40
Company Sanitized. Does not contain TSCA CBI
9 -
EJ H-15388,
TABLE I ^ GROSS PATHOLOGY a
Part 5
Animal Number
Days on
Test
Recovery Days
Mode of Death
Observation
376879
12
376819
26
376824
26
376833
26
376858
26
*
376880
26
376814
53
376815
53
376832
53
376850
53
376853
53
376816
96
376826
96
0
SD
Oral Cavity - discharge, clear
Perineum - stain, brown
Whole Body - thin
14
SD
Liver - discoloration, lobular
patterns prominent
Lungs - discoloration, pale
14
SD
Liver - foci, 1 mm in diameter),
diffuse, dark Lungs - foci, red, scattered, ( < 1
nun in diameter)
Thymus - foci, red, multiple, ( < 2 nun in diameter)
14
SD
No abnormalities detected
14
SD
No abnormalities detected
14
SD
41
SD
41 . SD
:
41
SD
Liver - discoloration, lobular patterns prominent
Lungs - foci, red, 2 mm in diameter), few
No abnormalities detected
Liver - large Thyfflus - discoloration, dull red,
left lobe
Lungs - discoloration, dark red foci, (< 2 mm), scattered
41 SD . No abnormalities detected
41
SD
No abnormalities detected
84
SD
No abnormalities detected
84
SD
Lungs - foci, red, brown, (1 mm in
diameter), scattered
Company Sanitized. Does not contain TSCA CBI
W J H-15388.
-
10 -
TABLE I GROSS PATHOLOGY
Part 6
Animal
Number
Days on Test
Recovery Days
Mode of Death
Observation
376842
96
84
SD
Lungs - foci, red, (1 mm in
diameter), scattered
376845
96
84
SD
Liver - hernia, through diaphragm
3768&8 . 96
84
SD
No abnormalities detected
42
Company Sanitized. Does not contain TSCA CBI
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UN-15388 TISSUES/OBSERVATIONS
TA3LE V:[
f SUBCHRONIC 1INHALATION STUB " POLYMER PROI)UCTS CIEPAF(TMEhIT SPEI:IES: R(AT
SEX: MALE
GROUP: r
DC)SE: CONT ROL
ANIMAL NUMBER:
MODE OF DEATH: DAYS ON TEST; DAYS ON RECOVERY:
376 376 376 376 376 376 376 376 376 825 839 840 870 873 835 841 849 863
SD SO SD SD SD SD SD SD SD
12 12 12 12 12 26 26 26 26
0
0
0
0
0 14 14 14 14
THYROID GLAND CVST ULTIMOBRANCHIAL CYST
TRACHEA
ESOPHAGUS
BRAIN
STOMACH
DUODENUM
JEJUNUM
ILEUM
CECUM
COLON NEMATODE, LUMEN
RECTUM NEMATODE. LUMEN
MESENTERIC LYMPH NODE
URINARY BLADDER
TESTES
ATROPHY. ATROPHY,
SEMINIFEROUS SEMINIFEROUS
TUBULES, TUBULES,
BILATERAL UNILATERAL
EPIDIDYMIDES
SPERM GRANULOMA
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
0
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
0
N
N
N
N
N
N
'* N
N
0
N
0
N
N
N
L
N
N
N
N
N
-
-
-
1
N
N
N
N
N
N
N
N
N
EYES
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----3 HN-153BS
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TISSUES/OBSERVATIONS
TABLE VI
^ SU6CHRONIC INHALATION STUDY ^
POLYMER PRODUCTS DEPARTMENT SPECIES: RAT
SEX; MALE
GROUP: I
DOSE: CONTROL
ANIMAL NUMBER:
MODE OP DEATH: DAYS ON TEST: DAYS ON RECOVERY:
376 376 376 376 376 376 376 376 376 625 839 840 870 873 835 841 849 863
SD SD SD SD SD SD SD SD SD
"
12 12 12 12 12 26 26 26 26
0
0
0
0
0 14 14 14 1
STERNUM
N
N
N
N
N
N
N
N
N
. BONE MARROW
N
N
N
N
N
N
N
N
N
NOSE
INFLAMMATION. ACUTE, MUCOSA/SUBMUCOSA, RESPIRATORY EPITH. INFLAMMATION, ACUTE. MUCOSA/SUBMUCOSA, VENTRAL MEATUS INFLAMMATION. FOCAL. SUBACUTE, MAXILLOTURBINATE INFLAMMATION, SUBACU1'E, MULTIFOCAL, RESPIRATORY TURBINATES SOUAMOUS METAPLASIA, FOCAL. RESPIRATORY EPITHELI UM SQUAMOUS METAPLASIA, RESPIRATORY EPITHELIUM
OTHER MANDIBULAR LYMPH NODE: HYPERPLASIA, LYMPMOID
L
N
1
-
1
N
N
N
-
N
N
-
-
L
N
1
0
0
0
0
L
0
0
0
0
2
HN-1538E
TABLE VI
SMBCHRONIC INHALATION STUDY 0
POLYMER PRODUCTS DEPARTMENT SPECIES: RAT
SEX; MALE
GROUP.- I
DOSE; CONTROL
TISSUES/OBSERVATIONS
ANIMAL NUMBER:
MODE OF DEATH: DAYS ON TEST: DAYS ON RECOVERY:
376 376 376 376 376 807 829 834 661 869
SO SD SO SD SD
' 96 96 96 96 96 84 84 84 84 84
LIVER
FATTV CHANGE. DIFFUSE. CENTRILOBULAR FATTY CHANGE, FOCAL, MEDIAN LOBE FATTY CHANGE. INDIVIDUAL HEPATOCYTES,SCATTERED.CENTRILOBULAR INFLAMMATION, SUBACUTE. MULTIFOCAL NECROSIS, ACUTE. INDIVIDUAL HEPATOCVTES, CENTRILOBULAR NECROSIS. COAGULATIVE. ACUTE, FOCAL/MULTIFOCAL NECROSIS. COAGULATIVE. SU8ACUTE, MULTIFOCAL
KIDNEYS
CHOLESTEROL CLEFTS/REGENERATIVE TUBULES/INDIV. CYST, FOCAL GLOMERULONEPHROPATHY, CHRONIC HYDRONEPHROSIS, UNILATERAL PROTEIN DROPLETS. PROXIMAL TUBULES
CELL
NECROSIS
LUNGS HEMORRHAGE. SUBACUTE. FOCAL/MULTIFOCAL
HISTIOCVTOSIS. FOCAL/MULTIFOCAL INFLAMMATION. SUBACUTE. FOCAL/MULTIFOCAL LYMPHOCVTIC INFILTRATE, MULTIFOCAL. PERIVASCULAR POLYMORPHONUCLEAR INFILTRATE, MULTIFOCAL, PERIVASCULAR
HEART MYOOEGENERATION, POCAL/MULTIFOCAL, MVOCARDIUM
PANCREAS
ATROPHY. FOCAL. LOBULE INFLAMMATION,CHRONIC.INTERSTITIAL.WITH PIGMENTED MACROPHAGES
THVMUS HEMORRHAGE. ACUTE. MULTIFOCAL
SPLEEN
ADRENAL GLANDS DEGENERATIVE FOCUS
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HN-15388
TABLE VI
0 0 SBBCHRONIC INHALATION STUDY POLYMER PRODUCTS DEPARTMENT SPECIES: RAT
SEX; MALE
GROUP:
DOSE: CONTROL
TISSUES/OBSERVATIONS
STERNUM
ANIMAL NUMBER:
MODE OF DEATH: DAYS ON TEST; DAYS ON RECOVERY:
376 376 376 376 376 807 829 834 861 869
SD SD SD SD SD
96 96 96 96 96 84 84 84 84 84
N
N
N
N
N
BONE MARROW
N
N
N
N
N
NOSE
INFLAMMATION. INFLAMMATION.
INFLAMMATION,
ACUTE, ACUTE, FOCAL.
MUCOSA/SUBMUCOSA, RESPIRATORY EPITH.
MUCOSA/SUBMUCOSA, VENTRAL MEATUS SUBACUTE, MAXILLOTURBINATE
INFLAMMATION, SUBACUTE, MULTIFOCAL, RESPIRATORY TURBINATES
SQUAMOUS METAPLASIA. FOCAL. RESPIRATORY EPITHELIUM SDUAMOUS METAPLASIA, RESPIRATORY EPITHELIUM
N
N
N
N
N
OTHER MANDIBULAR LVMPH NODE: HVPERPLASIA. LVMPMOID
END OF GROUP I
TABLE VI
TISSUES/OBSERVATIONS
ANIMAL NUMBER;
MODE OF DEATH; DAYS ON TEST: DAYS ON RECOVERY:
376 376 376 376 376 376 376 376 376 804 806 818 823 844 810 822 852 876
. SD SD SO SO SO SD SD SD SO
)2 12 12 12 V2 26 26 26 26
0
0
0
0
0 14 14 14 14
LIVER FATTY CHANGE. DIFFUSE, CENTRILOBULAR
N N L L L N N N L N FATTY CHANGE. FOCAL. MEDIAN LOBE
FATTY CHANGE. INDIVIDUAL HEPATOCVTES , SCATTERED , CENTRI LOBULAR INFLAMMATION. SUBACUTE. MULTIFOCAL
NECROSIS. ACUTE. INDIVIDUAL HEPATOCVTES, CENTRILOBULAR
- - - - - - - - - NECROSIS. COAGULATIVE, ACUTE. FOCAL/MULTI FOCAL
NECROSIS. COAGULATIVE, SUBACUTE. MULTIFOCAL
N---.-N--_--NI1--N-,-N---N-----N----N--,-N--- "
KIDNEYS
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--
CVST. FOCAL
GLOMERULONEPHROPATHY, CHRONIC
HYORONEPHROSIS, UNILATERAL
N-------L---N-----L---N----N-----L_---L----_ PROTEIN DROPLETS. PROXIMAL TUBULES
. LUNGS
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HISTIOCYTOSIS. POCAL/MULTI FOCAL INFLAMMATION, SUBACUTE, FOCAL/MULTIFOCAL
- - - - - - - ' - - - LYMPHOCYTIC INFILTRATE, MULTIFOCAL. PERIVASCULAR
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-N PANCREAS
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INFLAMMATION,CHRONIC.INTERSTITIAL,WITH PIGMENTED MACROPHAGES
THYMUS
N- -N-N-N-N-N-N-N-N- HEMORRHAGE, ACUTE. MULTI FOCAL
SPLEEN
N-N-N-N-N-N-N-N-N- ADRENAL GLANDS
N- '-N-N-N-N-N-N-N-N- DEGENERATIVE FOCUS
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MN-15388
TABLE VI
I SJLIBCHRONIC INHALATION STUDY
POLYMER PRODUCTS DEPARTMENT SPECIES: RAT
TISSUES/OBSERVATIONS
SEX; MALE
GROUP;
ANIMAL NUMBER:
MODE OP DEATH:
DAYS ON TEST: DAYS ON RECOVERY;
II
DOSE;' LOW
376 376 376 376 376 376 376 376 376 3
804 806 B1S 823 844 810 822 852 876 8
: SO SD SD SD SD SD SD SD SD
12 12 12 12 12 26 26 26 26
0
0
0
0
0 14 14 14 14
STERNUM
BONE MARROW
I
N
I
I
N
N
N
N
N
NOSE
INFLAMMATION. ACUTE. MUCOSA/SUBMUCOSA. RESPIRATORY EPITH. INFLAMMATION, ACUTE. MUCOSA/SUBMUCOSA, VENTRAL MEATUS INFLAMMATION. FOCAL. SUBACUTE, MAXILLOTURBINATE INFLAMMATION, SUBACUTE, MULTIFOCAL, RESPIRATORY TURBINATES SQUAMOUS METAPL'ASIA, FOCAL. RESPIRATORY EPITHELIUM SOUAMOUS METAPLASIA. RESPIRATORY EPITHELIUM
OTHER MANDIBULAR LYMPH NODE: HYPERPLASIA, LYMPHOID
N
N
N
N
N
L
N
N
N
1
0000000000
r wHN-153S8_
TISSUES/OBSERVATIONS
TABLE VI
,_ ^UBCHRONIC INHALATION STUDY
POLYMER PRODUCTS DEPARTMENT SPECIES: RAT
SEX: MALE
GROUP;
ANIMAL NUMBER:
MODE DAYS DAYS
OF DEATH: ON TEST: ON RECOVERY;
II
376
027 SD 96 84
376
B3) SD
96
84
376
862
SD
96 84
DOSE: LOW
376
877
SD
96 84
376
882
SD
96 84
LIVER
FATTY CHANGE. DIFFUSE, CENTRILOBULAR
FATTY CHANGE. FOCAL. MEDIAN LOBE
FATTY CHANGE. INDIVIDUAL HEPATOCVTES, SCATTERED, CENTRILOBULAR
----_-_-_- INFLAMMATION, SUBACUTE, MULTIFOCAL
NECROSIS. ACUTE, INDIVIDUAL HEPATOCYTES, CENTRILOBULAR
- - - - - NECROSIS. COAGULATIVE, ACUTE, FOCAL/MULTI FOCAL
NECROSIS. COAGULATIVE, SUSACUTE. MULTIFOCAL
.-
-- -- -- -- -- KIDNEYS
CT\
CHOLESTEROL CLEFTS/REGENERATIVE TUBULES/I NDIV. CELL NECROSIS
4^,
CYST. FOCAL
GLOMERULONEPHROPATHY. CHRONIC
- - - - - HYDRONEPHROSIS, UNILATERAL
- - - - - PROTEIN DROPLETS. PROXIMAL TUBULES
- - - - - LUNGS
HEMORRHAGE. SUBACUTE, FOCAL/MULTI FOCAL HISTIOCVTOSIS, FOCAL/MULTIFOCAL INFLAMMATION, SUBACUTE, FOCAL/MULTIFOCAL LVMPHOCYTIC INFILTRATE, MULTIFOCAL, PERIVASCULAR POLYMORPHONUCLEAR INFILTRATE. MULTIFOCAL, PERIVASCULAR
HEART
--------------------
MYODEGENERATION, FOCAL/MULTIFOCAL. MYOCARDIUM
PANCREAS ATROPHY, FOCAL, LOBULE
INFLAMMATION,CHRONIC,INTERSTITIAL.WITH
THYMUS HEMORRHAGE,
ACUTE.
MULTIFOCAL
SPLEEN
ADRENAL GLANDS
DEGENERATIVE
FOCUS
PIGMENTED
MACROPHAGES
----- '"'-
--.--_
3 MN-15388
TISSUES/OBSERVATIONS
^uu^imw^&k' 1. 1ii min i A U11 J 1 UL.
^POLVMERPRf0131JCTS CIEPAF!TMEI SP!E(C:[ES: E[AT
SEX: MALE
GROU P
ANIMAL NUMBER:
MODE OF DEATH:
DAYS ON TEST: DAYS ON RECOVERY:
II
DOSE'.: L(
376 376 376 376 376 B27 831 862 877 882
. SD 5D SD SD SD
96 96 96 96 96 84 84 84 84 84
THYROID GLAND CVST
ULTIMOBRANCHIAL CYST
N
0
N
N
0
TRACHEA ESOPHAGUS
N
N
N
N
N
N
N
N
N
N
BRAIN
N
N
N
N
N
STOMACH
N
N
N
N
N
DUODENUM
N
N
N
N
N
JEJUNUM
N
N
N
N
N
ILEUM
N
N
N
N
N
CECUM
N
N
N
N
N
'COLON NEMATODE, LUMEN
N
N
N
N
N
RECTUM NEMATODE, LUMEN
N
N
L
N
N
P
MESENTERIC LYMPH NODE
N
N
N
N
N
.
URINARY BLADDER
N
N
N
N
' N
TESTES ATROPHY, ATROPHY,
SEMINIFEROUS TUBULES. SEMINIFEROUS TUBULES,
BILATERAL UNILATERAL
EPIDIDYMIDES
SPERM GRANULOMA
N
N
N
N
N
N
N
N
N
N
EYES
N
N
N
N
N
r 6 ) HN-15368
TISSUES/OBSERVATIONS STERNUM
TABLE VI
,SUBCHRONIC INHALATION STUDY ^
' POLYMER PRODUCTS DEPARTMENT ' SPECIES: RAT
SEX: MALE
GROUP: II
ANIMAL NUMBER:
MODE OF DEATH: DAYS ON TEST: DAYS ON RECOVERY:
376 827
. SD
96
84
376 83)
SD
96 84
376 862
SD
96 84
DOSE: LOW
376 376 877 882
SD SD
96 96 84 84
N
N
N
N
N
BONE MARROW
N
N
N
N
N
NOSE
.
N
L
N
N
N
INFLAMMATION. INFLAMMATION, INFLAMMATION,
ACUTE,
ACUTE, FOCAL.
MUCOSA/SUBMUCOSA, RESPIRATORY EPITH.
MUCOSA/SUBMUCOSA, VENTRAL MEATUS SUBACUTE, MAXILLOTURBINATE
-
-
-
-
-
- - - - - INFLAMMATION. SUBACUTE, MULTIFOCAL. RESPIRATORY TURBINATES
SOUAMOUS METAPLASIA. FOCAL. RESPIRATORY EPITHELIUM
.-)--- C^
SOUAMOUS METAPLASIA, RESPIRATORY EPITHELIUM
-
-
-
-
0^
OTHER
- - - - - MANDIBULAR LYMPH NODE: HVPERPLASIA, LYMPHOID
0 0 0 0 0 *** END OF GROUP II
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TABiLE VI
HN-15388
TISSUES/OBSERVATIONS THYROID GLAND
CVST ULTIMOBRANCMIAL CYST TRACHEA ESOPHAGUS BRAIN STOMACH
SEX:
f SUBCHRONIC l NHALA1-ION STUC POLYMER PROD UCTS C1EPAF!TMEf' SPEC IES: P!AT
MALE
GROUP: III
ANIMAL NUMBER;
MODE OF DEATH: DAYS ON TEST: DAYS ON RECOVERY:
376
805
. SO
12
0
376 821
SO
12
0
DOSE:: If.ITERUflEDlyt-TE
376 376 376 376 376
838 851 867 612 813
SO SO SO SO SD
12 12 12 26 26
0
0
0 14 14
376 830
SD
26
14
0
0
H
N
N
N
N
L
P
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
DUODENUM
JEJUNUM ILEUM
CECUM
' COLON NEMATODE, LUMEN
RECTUM NEMATODE, LUMEN
MESENTERIC LYMPH NODE
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
0
0
N
N
N
.
URINARY BLADDER
TESTES ATROPHY, ATROPHY,
SEMINIFEROUS SEMINIFEROUS
TUBULES, TUBULES,
BILATERAL UNILATERAL
EPIDIDVMIDES
SPERM GRANULOMA
EYES
N
N
N
H
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
NNNNNNNNN
TABLE VI
S>UU_BBCCHHRROONNIC INHALATION STUDY _ _
c w HN-15388 . ------------- TISSUES/OBSERVATIONS
POLYMER PRODUCTS DEPARTMENT
'
SPECIES: RAT
'
SEX:
MALE
GROUP: III
ANIMAL NUMBER;
MODE OP DEATH;
DAYS ON TEST:
DAYS ON RECOVERY:
376 805
SD
12
0
376 821
SD
12
0
DOSE: INTERMEDIATE
376 376 376 376 376
838 851 867 812 813
SD SD SO SD SD
12 12 12 26 26
0
0
0
1-4
14
376 830
SO
26 14
376 857
SD
26
14
STERNUM
ONNINNNNNN BONE MARROW
ONNINNNNNN NOSE
INFLAMMATION. ACUTE. MUCOSA/SUBMUCOSA. RESPIRATORY EPITH.
N . N N N N N ' N N N INFLAMMATION, ACUTE, MUCOSA/SUBMUCOSA. VENTRAL MEATUS
INFLAMMATION, FOCAL, SUBACUTE. MAXI LLOTURBINATE
INFLAMMATION. SUBACUTE. MULTIFOCAL, RESPIRATORY TURBINATES
--- ----_------------------ 0\ SQUAMOUS METAPLASIA. FOCAL, RESPIRATORY EPITHELIUM SQUAMOUS METAPLASIA. RESPIRATORY EPITHELIUM
- \) OTHER
0-0-0-0-0-0-0-0-0- MANDIBULAR LYMPH NODE: HYPERPLASIA, LYMPHOID
'
%
TABLE VI
^ S.UBCHRONIC IMMOLATION STUDY ,,
^POLVMERPRODUCT^DEPARTME^r SPECIES: RAT
TISSUES/OBSERVATIONS
SEX:
MALE
GROUP; III
ANIMAL NUMBER;
MODE OF DEATH:
DAYS ON TEST: DAYS ON' RECOVERY:
DOSE: INTERMEDIATE
376 376 376 376 376 6)7 846 855 864 875
SD SD SD SD SD
96 96 96 96 96 84 84 84 84 84
LIVER
"
N
L
N
N
N
FATTY CHANGE. DIFFUSE. CENTRILOBULAR
-
-
-
-
_
FATTY CHANGE, FOCAL, MEDIAN LOBE FATTY CHANGE, INDIVIDUAL MEPATOCYTES,SCATTERED,CENTRILOBULAR INFLAMMATION, SUBACUTE, MULTIFOCAL
NECROSIS. ACUTE, INDIVIDUAL HEPATOCVTES, CENTRILOBULAR NECROSIS. COAGULATIVE. ACUTE, FOCAL/MULTIFOCAL NECROSIS. COAGULATIVE, SUBACUTE, MULTIFOCAL
KIDNEYS
-
-
-
.
----- -
,
-
-
-
---------- N
N
N
L
N
^1
CHOLESTEROL CLEFTS/REGENERATIVE TUBULES/INDIV. CELL NECROSIS
Q
CYST. FOCAL
-
-
-
P
-
GLOMERULONEPHROPATMY, CHRONIC
-
-
-
1
-
HYDRONEPHROSIS. UNILATERAL
- - - - - PROTEIN DROPLETS, PROXIMAL TUBULES
LUNGS
- - - - - HEMORRHAGE, SUBACUTE. FOCAL/MULTI FOCAL
HISTIOCYTOSIS. FOCAL/MULTIFOCAL
INFLAMMATION, SUBACUTE. POCAL/MULTIFOCAL
'
- - - - - LYMPHOCVTIC INFILTRATE, MULTIFOCAL, PERIVASCULAR
POLVMORPHONUCLEAR INFILTRATE. MULTIFOCAL. PERIVASCULAR
L
L
L
N
N
-
-
-
_
_
,
-
-
-
_
-
-
_
_
-
1 1 ) - - HEART
N
N
N
N
N
MYODEGENERATION, FOCAL/MULTIFOCAL, MYOCAROIUM
-
-
-
-
_
PANCREAS ATROPHY. FOCAL, LOBULE INFLAMMATION,CHRONIC.INTERSTITIAL,WITH PIGMENTED MACROPHAGES
THYMUS HEMORRHAGE. ACUTE. MULTIFOCAL
SPLEEN
ADRENAL GLANDS DEGENERATIVE FOCUS
L
N
N
L
N
-
-
-
]
-
1
-
-
- .-
N
N
N
N
N
----- N
N
N
N
N
N"
N
N
N
N
-----
HN-153B8
TISSUES/OBSERVATIONS
THYROID GLAND CYST ULTtMOBRANCHIAL
TRACHEA
CYST
SEX:
TABLE VI
gUBCHRONIC INHALATION STUDY
POLYMER PRODUCTS DEPARTMENT
SPECIES: RAT
MALE
GROUP: III
ANIMAL NUMBER:
MODE OF DEATH." DAYS ON TEST; DAYS ON RECOVERY:
DOSE: INTERMEDIATE 376 376 376 376 376
817 846 855 864 875
SO SO SD SO SO
96 96 96 96 96 84 84 84 84 84
N
0
I
0
N
ESOPHAGUS BRAIN
N
N
N
N
N
N
N
N
N
N
STOMACH
N
N
N
N
N
DUODENUM
N
N
N
N
N
JEJUNUM
N
N
N
N
N
ILEUM
N
N
N
N
N
CECUM
N
N
N
N
N
COLON NEMATODE.
LUMEN
RECTUM NEMATODE
LUMEN
MESENTERIC LYMPH NODE
URINARY BLADDER
TESTES
ATROPHY. ATROPHY.
SEMINIFEROUS SEMINIFEROUS
EPIDIDYMIDES
SPERM GRANULOMA
EYES
TUBULES, TUBULES,
BILATERAL UNILATERAL
N
N-
N
N
N
N
N
N
N
N
N
N
N
N
N
I.I N
I
N
N
N
N
N "'"'N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
MN-15388
TISSUES/OBSERVATIONS STERNUM
TABLE VI
,SUBCHRONIC INHALATION STUDY
POLYMER PRODUCTS DEPARTMENT
SPECIES: RAT
SEX; MALE
GROUP: III
ANIMAL NUMBER;
MODE OP DEATH:
DAYS ON TEST: DAYS ON RECOVERY:
DOSE: INTERMEDIATE
376 376 376 376 376 817 846 855 864 875
SD SD SD SD SD
96 96 96 96 96 84 84 84 84 84
N
N
N
N
N
BONE MARROW
N
N
N
N
N
NOSE
INFLAMMATION, ACUTE. MUCOSA/SUBMUCOSA. RESPIRATORY EPITH. INFLAMMATION. ACUTE. MUCOSA/SUBMUCOSA, VENTRAL MEATUS INFLAMMATION, FOCAL, SUBACUTE. MAXILLOTURBINATE INFLAMMATION. SUBACUTE, MULTIPOCAL, RESPIRATORY TURBINATES SOUAMOUS METAPL-ASIA. FOCAL, RESPIRATORY EPITHELIUM SOUAMOUS METAPLASIA, RESPIRATORY EPITHELIUM
OTHER
MANDIBULAR LYMPH NODE: HYPERPLASIA, LYMPHOID
* END OF GROUP III
N
N
N
N
N
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.HN-15368.
TISSUES/OBSERVATIONS
TABLE V][
I SUBCHRONIC I :NHALAT ION STUC
POLYMER PROCUCTS DlEPAFiTMErIT
SPEC:IES: R:AT
SEX: MAL E
GROUP;! IV
DOSE;; HI:GH
ANIMAL NUMBER:
MODE OF DEATH: DAYS ON TEST: DAYS ON R'ECOVERV:
376 376 376 376 376 376 376 376 37 B20 828 854 859 879 819 824 833 85
. SO SD SD SD SD SD SO SD S
12 12 12 12 12 26 26 26 2
0
0
0
0
0 14 14 14 1
THYROID GLAND CVST ULTIMOSRANCHIAL CYST
TRACHEA
ESOPHAGUS
BRAIN
STOMACH
N
N
N
0
I
N
N
N
L
-
-
-
-
-
P
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
DUODENUM
N
N
N
N
N
N
N
N
N
JEJUNUM ILEUM CECUM
N N N N.N N 0 N N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
"COLON NEMATODE, LUMEN
RECTUM NEMATODE, LUMEN
MESENTERIC LVMPH NODE
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
.
URINARY BLADDER
TESTES ATROPHY. ATROPHY.
SEMINIFEROUS SEMINIFEROUS
TUBULES, TUBULES,
BILATERAL UNILATERAL
EPIDIDVMIDES
SPERM GRANULOMA
N
N
N
N
" N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
EYES
NNNNNNNNN
HN-1S3BB^ TISSUES/OBSERVATIONS
'1:ABLE \ JI
SUBCHRONIC^ INHA.LA1ION
SPE CIES; FiAT
r :( STUC
SEX: MAL E
GROUP: IV
DOSE:; HI[GH
ANIMAL NUMBER:
MODE OF DEATH; DAYS ON TEST: DAYS ON RECOVERY:
376 376 376 376 376 376 376 376 3 820 S2S 854 S59 879 819 824 833 8
. SO SO SO SD SD SD SD SD
12 12 12 12 12 26 26 26
0
0
0
0
0 14 14 14
STERNUM
N
N
N
N
N
N
N
N
BONE MARROW
N
N
N
N
N
N
I
N
NOSE
INFLAMMATION.
INFLAMMATION. INFLAMMATION, INFLAMMATION,
ACUTE, ACUTE. FOCAL,
MUCOSA/SUBMUCOSA. RREESSPPIIRRAATTOORY EPITMH.
MUCOSA/SUBMUCOSA. V'ENTRAL M"--" MtEt=MATI UU,S?
SUBACUTE, MAXILLOTUIRBINATE
SUBACUTE. MULTIFOCAL, RESPIRATORY TURBINATES
SQUAMOUS METAPLASIA, FOCAL, RESPIRATORY EPITHEELLIIUUMM SQUAMOUS METAPLASIA, RESPIRATORY EPITHELIUM
OTHER MANDIBULAR LYMPH NODE: HVPERPLASIA, LYMPHOID
N
N
N
N
0
N
N
N
-
-
-
-
-
-
-
TABLE VI
^ _ajBCHRQNIC INHALATION STUDY _
HN-15388_
-"POLYMER PRODUCTS DEPARTMENT ^ SPECIES: RAT
SEX: MALE
GROUP: IV
DOSE; HIGH
TISSUES/OBSERVATIONS
ANIMAL NUMBER:
MODE OF DEATH: DAYS ON TEST: DAYS ON RECOVERY:
376 376 376 376 376 816 826 842 645 B6S
. SO SO SO SO SD
96 96 96 96 96 84 84 84 84 84
LIVER
L
L
N
N
L
FATTY CHANGE, DIFFUSE, CENTRILOBULAR
-
-
-
-
1
FATTY CHANGE, FOCAL, MEDIAN LOBE
-
_
-
-
-
FATTY CHANGE, INDIVIDUAL HEPATOCVTES.SCATTERED.CENTRILOBULAR -
,
-
-
-
INFLAMMATION. SUBACUTE. MULTIFOCAL
1
-
-
-
1
NECROSIS. ACUTE. INDIVIDUAL HEPATOCVTES. CENTRI LOBULAR NECROSIS. COAGULATIVE, ACUTE. FOCAL/MULTI FOCAL NECROSIS. COAGULATIVE. SUBACUTE, MULTIFOCAL
- - - - - KIDNEYS
"
N
L
N
L
N
----- J
CHOLESTEROL CLEFTS/REGENERATIVE TUBULES/INDIV. CELL NECROSIS
0^
CYST. FOCAL
GLOMERULONEPMROPATHV, CHRONIC
-
-
-
1
-
HYDRONEPHROSIS, UNILATERAL
- - - - - PROTEIN DROPLETS, PROXIMAL TUBULES
-
2
-
-
-
----- LUNGS
L
L
N
N
N
HEMORRHAGE. SUBACUTE, POCAL/MULTI FOCAL HISTIOCVTOSIS. FOCAL/MULTIFOCAL INFLAMMATION. SUBACUTE. FOCAL/MULTIPOCAL LVMPHOCYTIC INFILTRATE. MULTIFOCAL, PERIVASCULAR POLYMORPHONUCLEAR INFILTRATE, MULTIFOCAL. PERIVASCULAR
HEART MVOOEGENERATION. FOCAL/MULTIFOCAL, MYOCARDIUM
PANCREAS
-
,
-
-
-
-
,
-
-
-
)
_
-
-
-
----- N
N
L
N
N
-
-
,
-
-
----- N
N
N
L
N
ATROPHY. FOCAL, LOBULE
-
-
-
,
-
INFLAMMATION,CHRONIC,INTERSTITIAL,WITH PIGMENTED MACROPMAGES -
-
-
- -
THYMUS HEMORRHAGE. ACUTE. MULTIFOCAL
SPLEEN
ADRENAL GLANDS DEGENERATIVE FOCUS
N
N
N
N
N
----- N
N
N
N
N
N' N
N
N
N
-----
TABLE VI
SHRONIC INHALATION STUDY
POLYMER PRODUCTS DEPARTMENT SPECIES: RAT
TISSUES/OBSERVATIONS
THYROID GLAND CYST ULTIMOBRANCHIAL CYST
SEX: MALE
GROUP: IV
DOSE: HIGH
ANIMAL NUMBER:
MODE OF DEATH: DAYS ON TEST: DAYS ON RECOVERY:
376 376 376 376 376 616 B26 842 845 868
SD SO SD SD SD
96 96 96 96 96 84 84 84 84 64
L
0
0
0
L
P
P
TRACHEA
N
N
N
N
N
ESOPHAGUS
N
N
N
N
N
BRAIN
N
N
N
N
N
STOMACH
N
N
N
N
N
DUODENUM
N
N
N
N
N
JEJUNUM
N
N
N
N
N
ILEUM
N
N
N
N
N
CECUM
N
N
N
N
N
COLON NEMATODE. LUMEN
N
N
N
N
N
RECTUM NEMATODE, LUMEN
MESENTERIC LYMPH NODE
URINARY BLADDER
N
N
N
N
N
N
I
N
N. I
N
N
N
N ' N
TESTES
ATROPHY, ATROPHY.
SEMINIFEROUS SEMINIFEROUS
TUBULES. TUBULES,
BILATERAL UNILATERAL
EPIDIDYMIDES
SPERM GRANULOMA
N
N
N
N
L
1
N
N
N
N
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190 VOS1 uiEluoojou-saan'paziilues Auedluoo
ESTttUSHEDISO;
E. I. DU FONT DE NEMOURS 5t COMPANY
INCORPORATED
HASKELL LABORATORY FOR TOXICOLOGY AND INDUSTRIAL MEDICINE
P.O. BOX 50, ELKTON ROAD NEWARK, DELAWARE 19711
CENTRAL RESEARCH AND DEVELOPMENT DEPARTMENT CLINICAL PATHOL'OGY
REPORT NO.
24-84
MEDICAL RESEARCH PROJECT N0.|
HASKELL LABORATORY NO. 15388
FEBRUARY 28..1985
Summary.
Male Crl:CD(SD)BR rats were exposed, by inhalation, toj
lat concentrations of 0 (control), 0.0076, 0.058 an_d _0_.4_8 mg/L.
Compound-related effects observed in high-dose (0.48 mg/L) males at the 0-day recovery period included alterations in several hematologic and clinical chemical parameters. The hematologic changes included an increase in red blood cell count, hemoglobin and hematocrit and a decrease in mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration. The
clinical chemical changes included an increase in alkaline phosphatase, urea
nitrogen, urine volume and pH and a decrease in urine osmolality and serum cholesterol. These effects were not present at any of the subsequent recovery periods.
The 0.058 mg/L exposure concentration was interpreted to be a no-effect
dose level for the hematologic and clinical chemical parameters measured
under the conditions of this study.
Procedure
Four groups of 20 male Crl:CD(SD)BR rats were exposed, by inhalation, for six hours per day for 10 days to Telomer B sulfonic acid at concentra tions of 0 (control), 0.0076, 0.058 and 0.48 mg/L.
After the ninth exposure, an overnight (approximately 16-hour) urine specimen was collected from ten rats per group to measure volume (VOL), osmolality (OSMOL), pH and urobilinogen (UROBL); and to determine the presence of blood, sugar (glucose), protein, bilirubin and ketone (acetoacetic acid). The appearance (color and transparency) was recorded and the sediment from each specimen was microscopically examined.
After the tenth exposure (0-Day Rec), and at the 14-day recovery period (14-Day Rec) and 41-day recovery period (41-Day Rec), blood was taken from
the tail of ten rats per group for measurement of erythrocytes (RBC),
hemoglobin (Hb), mean corpuscular volume (MCV), platelets (PLAT), leukocytes (WBC) and relative numbers of neutrophils (Neut), band neutrophlls (Band), lymphocytes (Lymph), atypical lymphocytes (Alym), monocytes (Mono), eosinophils (Eosin) and basophlls (Baso). Absolute numbers of various types of leukocytes were calculated from the leukocytic data. Hematocrit (Ht), mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) were calculated from the erythrocytic data. Serum activities of alkaline phosphatase (ALP), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and concentrations of urea nitrogen (BUN), creatinine (GREAT), total protein (TPROT) and cholesterol (CHLOS) were also measured. After each sampl-ing time, five rat-s f-rom eachgroup were then
killed for pathologic evaluation.
Following an 84-day recovery period (84-Day Rec), the hematologic and
clinical chemical (serum and urine) measurements were repeated on the five
remaining rats in each group.
Statistics
Hematologic and clinical chemical data were statistically analyzed using
a one-way analysis of variance for each sampling time. When the F-test was significant, least significant difference (LSD) and Dunnett tests were used to compare the control" group and the groups exposed to Telomer B sulfonic acid. Significance was judged at the 5% probability level using Dunnett criteria.
Results
Results of hematoiogic and clinical chemical measurements are summarized
in Tables I, II and III, statistical analyses in Tables IV and V. Data for
individual animals are listed in the computer printouts attached to this
report. A legend, preceding the computer printouts, defines terms and
criteria used for urinalyses.
At the 0-day recovery sampling time, rats in the high-dose (0.48 mg/L) group had an increased erythrocyte count, hemoglobin and hematocrit. Mean corpuscular hemoglobin concentration was increased for the intermediate-dose (0.058 mg/L) rats and decreased for the high-dose rats. Decreased mean corpuscular hemoglobin and platelet count were observed for rats in the high-dose group. Serum alkaline phosphatase and serum aspartate aminotransferase activities and serum urea nitrogen concentration were increased for the high-dose rats. Rats in the high-dose group had decreased serum cholesterol concentration. Urine volume and pH were increased for rats in the high-dose group. Decreased urine osmolality was observed for the high-dose rats.
1
Company Sanitized. Does not contain TSCA CBI
At the 14-day recovery sampling time, rats in the high-dose group had
decreased hemoglobin, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration. Urine pH was decreased for the intermediate- and
high-dose rats.
At the 41-day recovery sampling time, rats in the high-dose group had a decreased erythrocyte count. The platelet count was increased for the high-dose rats. Decreased serum alanine aminotransferase activity was observed for rats in the low-(0.0076 mg/L) and high-dose groups.
At the 84-day recovery sampling time, rats in the intermediate- and
high-dose groups had increased leukocyte counts and absolute numbers of lymphocytes. The absolute number of neutrophils was increased for the high-dose rats. Serum urea nitrogen concentration was decreased for rats in the high-dose group.
Discussion and Conclusions
There was a statistically significant increase in red blood cell count,
hemoglobin, hematocrit, alkaline phosphatase, urea nitrogen, urine volume and pH in the high-dose animals at the 0-day recovery sampling time. At this time period, there was also a statistically significant decrease in mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, urine osmolality and serum cholesterol in the high-dose animals.
The other hematologic and clinical chemical parameters shown to be statistically significantly changed were within the range of expected biological variation and were not related to the administration of the
compound.
The 0.058 mg/L exposure concentration was interpreted to be a no-effect
dose level for the hematologic and clinical chemical parameters measured
under the conditions of this study.
DRH:bl
CP 3
2/28/85
Report by:^JLjML^.CL- ^-- /^Wt
Donna R. Holt
Technician
Approved by:
(1A^JJS^OjLJ^. I^ILS^C^
Charlotte M. Keenan Acting Coordinator
Clinical Pathology Section
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TESTS
RBC
x1o6/uL
Hb
g/dL
Ht
%
MCV
fL
MCH Pg
IEXPOSED
T ABLE I
SUMMAFlY OF HE:MATOLOG 1C FINE)INGS.FCRMALL RATS
BY INE1ALATIOK1 T0{11
(FOR 10
GRCUP
MEAKIS
^ E y m ANpTsTANDARE
IONS(SE>)
DAYS
DOSE
(rng/L)
0.0000 0.0076 0.0580 0 .4800
0 .0000 0 .0076 0 .0580 0 .4800
0 .0000 0 .0076 0.0580 0 .4800
0 .0000 0 .0076 0 .0580 0 .4800
0 .0000 0 .0076 0 .0580 0 .4800
0-DJ?lY REC
7.4K 0.57) 7.28( 0.54)
7.26( 0.47) 8.55( 0.24)
15.6( 15.3( 15.8( 16.5(
43.( 42.( 42.(
49. (
57.( 57.( 57.( 57.(
21.( 21.( 22.( 19.(
0.9) 0.5) 0.7) 0.7)
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1.) 1.) 1.) 1.)
SAMIPLING 1IME
14-D'AY REC
41-CAY REC
84-EIAY REC
7.12( 0.56) 7.09( 0.44) 7.48( 0.33) 7.17( 0.55)
7.92( 7.56(
7.59( 7.29(
0.45) 0.44)
0.52) 0.48)
8.15( 0.46)
7.7K 0.79) 8.49( 0.96) 7.84( 0.33)
15.8( 0.5) 15.9( 0.5) 16.0( 0.5)
14.8( 0.6)
15.5( 0.4) 15.5( 0.7) 15.5( 0.5) 15.0( 0.7)
16.0( 0.3) 15.5( 0.6) 15.8( 0.8)
15.1( 0.8)
41.( 2.) 40. ( 2.) 42. ( 1.) 40. ( 3.)
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41.( 1.) 39. ( 4.) 43.( 4.) 40.( 3.)
49. ( 1.) 51.( 2.) 51.( 2.) 51.( 2.)
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TESTS
ALP
U/L
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U/L
BUN
mg/dL
I I TABLE
SUMMARY OF CLINICAL ;HEMICAL FINDINGS FOR MALE RATS
EXPOSED BY INHALATION TOJ
GROUP MEANS At
BBHJ^ iitiraa'l noNsTsD) 10 DAYS
DOSE
(mg/L)
0.0000 0.0076 0.0580 0.4800
0.0000 0.0076 0.0580 0.4800
0.0000 0.0076 0.0580 0.4800
0.0000 0.0076 0.0580 0.4800
0-DA Y REC
191.( 62.)
199.( 206. (
325. (
52.) 49.) 48.)
37.( 5.) 39.( 7.) 44.( 11.) 44.( 8.)
87. ( 14.) 83.( 12.) 91.( 15.) 108.( 17.)
16.( 3.)
17.( 2.) 16.( 3.) 29. ( 4.)
<3AMiPLING TIME
T 1-D AY REC
4 1-D AY REC
171 .( 179 .( 196 .( 215 .( 35 .( 34 .( 36 .(
36 .( 76 .( 75 .( 79 .( 70 .( 17 .( 17 .( 17 .( 19 .(
58.) 56.) 38.) 59.)
4.) 7.) 5.) 5.)
11.) 10.) 15.) 11.)
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131 .( 151 .( 157 .( 152 .( 40 .( 32 .( 37 .( 33 .( 76 .( 73 .( 76 .( 77 .(
17 .( 17 .( 17 .( 17 .(
30.) 40.) 42.) 55.)
7.) 4.) 4.) 6.)
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84-D,AY REC
97. ( 134.C
126.( 120.(
37.) 41.) 56.)
73.)
34.( 5.) 29.( 5.) 43.( 25.)
35.( 11.)
66. ( 11.)
60. ( 6.) 83.( 35.)
71.( 17.)
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^"- ^0 vD ITt
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os
mf~'~-inio
>-
<
l o
=rcr>f"i^
inir>o\o
0000
. . . . <y> o '-- (M
in'o>'>
. . . . ttT- i(^y\-oina'-\
0^ td--s
M _3
0^000 0 t-- CO 0
OOlTtOO
0O^v-O0O0O0
OOlTlOO
0Ot^--0O0Q0O
OOlnco
QUO 0003- 0003- 0003-
'-^ oooo oooo oooo
W
E-i J
E-i
CO J
E-"
< T3
0 -J
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CC tlO
&. ^
X hO
E-"
U E
E-i hO
U E
88 Company Sanitized. Does not contain TSCA CBI
TESTS
VOL mL
OSMOL mOs 03
. '43
pH
UROBL
mg/dL
RATS
II T/IBLE I
EXSPU<13WSAERDY BOYF INCHLAILNAK'nSAoLN UfRoH^f--NAL'ysis FII^IDINGS IFO^RFOMARLE 10 GRC)UP MEA]US AND. cTAN ^ffiviAlJONS(SlD)
DAYS
DOSE
(mg/L)
0.0000 0.0076 0.0580 0.4800
0.0000 0.0076 0.0580 0.4800
0.0000 0.0076 0.0580 0.4800
0.0000 0.0076 0.0580 0.4800
0-D/IY REC
7.2( 3.7) 5.2( 1.6)
7.5( 3.3) 11.9( 2.5)
1714.( 1795.( 1610.( 850. (
296.)
350.) 389.) 171.)
7.3( 0.7)
6.8( 0.6) 7.0( 0.7) 8.3( 0.7)
0.9( 0.3)
0.9( 0.3) 1.0( 0.0) 0.6( 0.5)
SA(11PLI NG riME
14-r)AY REC
41-r)AY REC
84-E)AY REC
13.2( 12.4(
12.5( 12.0(
4. 3) 4. 5) 4. 5) 1. 8)
13.5( 4.9) 13.8( 5.0) 13.3( 4.6) 13.5( 7.0)
13.5( 17.4( 16.3( 17.0(
6.4) 13.7) 5.4) 9.0)
1447.(
1316.( 1566.( 1538.(
406 .) 411 .) 335.) 312.)
1895.(
1633.( 1821,,( 1626.(
370.)
373.) 523.) 467.)
1784.(
1602.( 1364.( 1446.(
756.)
663.) 361.) 551.)
8.K 0. 7)
7.6( 0. 5)
7.K 0. 6)
7.2( 0. 4)
7.2( 0.4)
7.3( 0.5) 7.0( 0.5) 7.0( 0.5)
7.4( 0.5)
7.0( 0.0) 7.4( 0.5) 7.2( 0.4)
1.0( 0. 0) 0.8( 0.4)
1.0( 0.0) 1.0( 0.0)
1.0( 0.0) 1.0( 0.0)
1.0( 0.0) 1.0( 0.0)
0.3( 0.4) 0.6( 0.5)
0.6( 0.5) 0.5( 0.5)
I I I TABLE
(continued)
SUMMARY OF CLINICAL URINE ANALYSIS FINDINGS FOR^MALERATS EXPOSED
BY INHALATION TOJi^------^------------------B^^ ^ DAYS
Sampling Time Pose (mg/L)
Measurement Blood
Number Positive
Sugar (Glucose) Number Positive
Protein
Number Abnormal
_> + 3
Bilirubin Number Positive
Ketone
Number Positive
Appearance (Color and Transparency)
Microscopic
Number Abnormal
0-Day Recovery 0 .0076 .058 .48 1/10* 3/10 1/10 0/10 2/10 3/10 1/10 3/10
0/10 0/10 0/10 0/10
6/10 3/10 2/10 3/10 9/10 8/10 10/10 0/10 0/10 0/10 0/10 0/10 4/10 1/10 1/10 0/10
14-Day Recovery 0 .0076 .058 .48 0/10 0/10 1/10 0/10 0/10 1/10 2/10 0/10 1/10 0/10 1/10 0/10
4/10 2/10 7/10 6/10 9/10 8/10 9/10 8/10 0/10 0/10 0/10 0/10 6/10 1/10 4/10 3/10
* Number of abnormal or positive findings/number of individual
specimens examined
90
Company Sanitized. Does not contain TSCA CBI
I I I TABLE
(continued)
SUMMARY OF CLINICAL URINE ANALYSIS FINDINGS FOR MALE RATS EXPOSED
n'i1 iiiihMiinii \i}f^mfmmwv\^\' 1111^1'
Sampling Time Dose (mg/L)
Measurement
Blood
Number Positive
Sugar (Glucose) Number Positive
Protein
Number Abnormal
2+ 3
Bilirubin Number Positive
Ketdtie
Number Positive
Appearance (Color and Transparency)
Microscopic Number Abnormal
41-Day Recovery 0 .0076 .058 .48
0/10 1/10 0/10 1/10 1/10 2/10 1/10 2/10 1/10 1/10 0/10 2/10
2/10 2/10 6/10 6/10 10/10 10/10 10/10 9/10 0/10 0/10 0/10 0/10 1/10 1/10 2/10 0/10
84-Day Recovery 0 .0076 .058 .48
3/5 4/5 3/5 5/5 3/5 3/5 3/5 5/5 2/5 0/5 0/5 0/5
2/5 2/5 1/5 0/5 4/5 3/5 3/5 4/5 0/5 0/5 0/5 0/5 0/5 2/5 0/5 1/5
91
Company Sanitized. Does not contain TSCA CBI
SUMMARY OF CHEMICAL
TABLE IV STATISTICAL ANALYSES OF HEMATOLOGIC AND CLINICAL
FINDINGS FOR MALE RATS EXPOSED BY INHALATION TO
Sampling Time
Statistic
0-Day Recovery
p*
Dunnett
Measurement Hematology
RBC Hb
Ht
MCVMCH MCHC
PLAT WBC
Neut Band
Lymph Alym Mono
Eos in
Baso
0.000
**
0.003
**
0.000
**
0-.755
0.000
**
0.000
**
0.007
**
0.748
0.280
0.404
0.673
0.358
0.407
0.112
1.000
Clinical Chemistry (Serum)
ALP
. 0.000
**
ALT
0.135
AST
0.003
**
BUN
0.000
**
CREAT
0.057
TPROT
0.120
CHLOS
0.000
**
Clinical Chemistry (Urine)
VOL
0.000
**
OSMOL
0.000
**
pH
0.000
**
UROBL
0.069
14-Day Recovery
p
Dunnett
0.270
0.000
**
0.353
&.-32-3
0.015
**
0.021
**
0.991
0.627
0.880
1.000
0.740
0.106
0.092 0.038
1.000
0.283 0.903 0.398 0.426
0.891 0.445 0.094
0.911
0.432
0.002
**
0.099
* = Value of p for F-statistic ** = Significantly different from controls at 57, level by Dunnett
criteria
92
Company Sanitized. Does not contain TSCA CBI
TABLE IV (continued)
SUMMARY OF STATISTICAL ANALYSES OF HEMATOLOGIC AND CLINICAL
CHEMICAL FINDINGS FOR MALE RATS EXPOSED BY INHALATION TO
Sampling Time
Statistic
41-Day Recovery
p
Dunnett
Measurement Hematology
RBC
Hb
Ht
MCV
MCH
MCHC PLAT WBC
Neut
Band Lymph Alym Mono
Eosin
Baso
0.045
**
0.170
0.053
0.789
0.100
0.179
0.014
**
0.289
0.259
0.404
0.472
0.168
0.412
0.316
0.554
Clinical Chemistry (Serum)
ALP
0.532
ALT
0.008
**
AST
0.933
BUN
0.980
GREAT
0.496
TPROT
0.511
CHLOS
0.686
Clinical
VOL OSMOL
pH UROBL
Chemistry
(Urine) 0.998 0.425 0.382 1.000
84-Day Recovery
p
Dunnett
0.313
0.165
0.207
0.375
0.302
0.050
0.335
0.000
**
0.000
**
0.418
0.005
**
0.611
0.552
0.500
1.000
0.727
0.487
0.355
0.048
**
0.299
0.412
0.227
0.904 0.704 0.455 0.585
93
Company Sanitized. Does not contain TSCA CBI
TABLE V
SUMMARY OF STATISTICALLY SIGNIFICANT HEMATOLOGIC AND CLINICAL CHEMICAL FINDINGS FOR MALE RATS EXPOSED BY INHALATION T0|
Sampling Time
0-Day Rec
Measurement Hematology
RBC Hb
-BfeMCH
MCHC PLAT WBC
Neut
Lymph
+IV
-t-IV
-t-I-V
+IV +111, IV -HV
Clinical
ALP ALT AST BUN
CHLOS
Chemistry (Serum) +IV
-f-IV
+IV IV
Clinical
VOL
OSMOL
pH
Chemistry (Urine) +IV + IV +IV
14-Day Rec
+IV +IV
4-IV
+III,IV
j> 1-Day jRec____84-Day Rec
-HV
+IV +11,IV
t-III.IV
HV
+III,IV
+IV
-t- = Significantly higher than controls by Dunnett criteria + = Significantly lower than controls by Dunnett criteria
Group
II III
IV
Designation and Dose Concentration = Low Dose (0.0076)
= Intermediate Dose (0.058) = High Dose (0.48)
(mg/L)
94
Company Sanitized. Does not contain TSCA CBI
LEGEND
TERMS AND CRITERIA USED IN URINALYSES
Abbreviations for Descriptive Terms Normally Used for Gross Evaluation of
Urine (other Abbreviations and Descriptive Terms may be used if they are more
applicable).
Y =
LY =
DY = A =
DA = G =
BL = R = C =
CL = PPT =
F =
FEC =
Yellow Light Yellow Dark Yellow
Amber
Dark Amber Green Bloody
Red
Clear Cloudy Precipitate
Feed
Feces
Abbreviations for Descriptive Terms Used for Microscopic Evaluation of Urine
TNTC
Epith = hpf =
Ipf =
RBC =
WBC =
(99-99) =
Epithelial Cells high power field low power field
Red Blood Cells
White Blood Cells
Too Numerous to Count
Definition of "Normal" and "Abnormal" Designations Used for Gross and
Microscopic Appearance of Urine
Appearance Color
Microscopic Red Blood Cells
Normal
Light to dark yellow or amber
Average of 0 to 4 red blood cells per high
power field
Abnormal
Color other than yellow or amber
Average of more than 4 red blood cells per high
power field
Casts
None observed
Average of more than 0
per low power field
Epithelial Cells
White Blood Cells
Average of 0 to 9 per
high power field
Average of 0 to 9 per
. high power field
Average of more than 9
per high power field
Average of more than 9
per high power field'
95
Company Sanitized. Does not contain TSCA CBI
15388
HASKELL CODE^QfQ
"
DEPARTMENT: POLYMER PRODUCTS
REPORT DATE: 17-OCT-84
GROUP: 1CM
DOSE: CONTROL
SAMPLE DATE: 07/20/84
ANIMAL?: 376825 376835 376839 376840 376841 376849 376863
376870 376872 376873
RBC
x10/uL 7.31 6.73 7.61 7.63 6.41 7.06 7.59 7.73 8.45 7.57
Hb
g/dL 15.2
15.1 15.9 15.5 14.0 15.0 15.6 16.1 17.5 15.7
Ht
%
42. 40. 43. 45. 37. 41. 44. 44. 50. 42.
AVG.
S. D. S-. E.
7.409 0.570 0.180
15.56 0.90 0.28
42.7 3.3 1.0
SPECIES: RAT
BIRTH DATE: 05/14/84
MCV
MCH MCHC PLAT
fL
Pg g/dL X1Q3/UL
57.
21.
36.
1068.
58.
23.
38.
952.
56.
21.
37.
984.
58.
20.
35.
716.
58.
22.
38.
1030.
57.
21.
37.
1008.
58.
21.
35.
842.
57.
21.
37.
876.
58.
21.
35.
1044.
55. 21. 37.
774.
57.2 1.0 0.3
21.0 0.7 0.2
36.5 1.1 0.3
929.4 121.2 38.3
GROUP: 2M
DOSE: .0076 mg/L
SAMPLE DATE: 07/20/84
SPECIES: RAT
BIRTH DATE: 05/14/84
ANIMALS: 376804 376806 376810 376818 376822 376823 376844 376852 376876 376881
RBC
xlO^uL
7.37 7.32 6.75 6.26 6.81
7.35 7.61 7.33 7.90 8.05
Hb
g/dL 15.4 16.5 14.8 14.6 15.2 15.5 15.1 15.0 15.4 15.7
Ht
MCV
%
fL
42.
57.
42.
56.
40.
59.
36.
58.
41.
59.
42.
57.
43.
56.
43.
58.
44.
55.
47.
57.
MCH MCHC PLAT
Pg g/dL x1o3/uL
21. 37.
814.
23.
40.
1032.
22.
37.
758.
23.
40.
22. 38.
802. 984.
21. 37.
20.
35.
21.
35.
20.
35.
936. 728. 876. 776.
20.
34.
720.
AVG.
S. D. S. E.
7.275 0.542 0.171
15.32 0.53 0.17
42.0
2.7 0.8
57.2 1.3 0.4
21.1
1.3 0.4
36.6
2.0 0.6
842.6 109.5 34.6
96
Company Sanitized. Does not contain TSCA CBI
MR:
COMPOUND:^____
PERIOD: 0-DAY REC
SEX;
MALE
15388
HASKELL CODE:(JH
DEPARTMENT: POLYMER PRODUCTS
REPORT DATE: 17-OCT-84
GROUP: 3M
DOSE: .058 mg/L
SAMPLE DATE; 07/20/84
SPECIES: RAT
BIRTH DATE: 05/14/84
ANIMALS: 376805
376812 376813 376821 376830 376838 376851 376857 376867 376874
RBC
xlO^uL 8.00 7.04 7.27 6.70 7.30 6.95 7.25 7.90 6.60 7.61
Hb
g/dL 16.8 15.5 16.2 15.8 16.0 15.3 15.6 16.6 14.5 15.7
Ht
MCV
%
fL
46.
56.
41.
58.
43.
58.
39.
57'.
42.
57.
41.
58.
40.
55.
44.
56.
38.
57.
43.
56.
MCH MCHC PLAT
Pg g/dL X103/UL
21. 37.
22.
37.
722. 692.
22.
38.
724.
24.
41.
1164.
22.
38.
806.
22.
38.
836.
22.
39.
21.
38.
22.
38.
890. 804. 852.
21.
37.
722.
AVG.
S. D. S. E.
7.262 0.468 0.148
15.80 0.66 0.21
41.6 2.4 0.7
56.8 1.0 0.3
21.8 0.8 0.3
38.0 1.2 0.4
821.2 137.3 43.4
GROUP: 4M
DOSE: .480 mg/L
SAMPLE DATE: 07/20/84
SPECIES: RAT
BIRTH DATE: 05/14/84
RBC
Hb
Hfc
MCV
ANIMALS: xiO^uL g/dL
%
fL
376819
8.67 16.6
49.
56.
376820
8.65 16.1
50.
57.
376824
8.18 16.1
48.
58.
376828
8.90 17.4
51.
57.
376833
8.21 15.8
48.
58.
376854
8.67 17.9
53.
61.
376858
8.58 16.6
49.
57.
376859
8.30 16.3
48.
58.
376879
8.74 17.0 51.
57.
376880
8.63 15.6
48.
55.
MCH
MCHC
PLAT .
Pg g/dL X103/UL
19.
34.
19.
32.
20.
34.
20.
34.
19.
33.
21.
34.
19.
34.
20.
34.
20.
34.
18.
33.
690. 590. 808. 524. 670. 864. 766. 806. 846. 722.
AVG.
S. D. S. E.
8.553 16.54 49.4 57.4 19.4 33.5
0.240 0.72
1.8
1.6
0.7
0.6
0.076 0.23 0.6 0.5 0.2 0.2
728.6 111.5 35.3
97 Company Sanitized. Does not contain TSCA CBI
HASKELL NUMBER;_15388
HASKELL CODE^B
____BIBMMB1^ 3-DAY REC
DEPARTMENT! POLYMER PRODUCTS
REPORT DATE: 17-OCT-84
MALE
GROUP: 1CM
DOSE: CONTROL
SAMPLE DATE: 07/20/84
SPECIES: RAT
BIRTH DATE: 05/14/84
ANIMALS: 376825
376835 376839 376840 376841 376849 376863
376870 376872 376873
WBC
X1Q3/UL
13.6 14.8
8.9 10.5 13.3 16.0 10.5
9.1 18.5
9.5
Neufc
WBCxjE
2992. 3700. 2136. 1785. 1330. 3520. 2100. 1092. 1295. 2280.
Band WBCx?
0. 0. 0. 0. 0. 0. 0. 0. 0. 0.
Lymph WBCx?
9792. 10508.
6141. 7875. 11172. 11680. 7560. 7735. 16095. 6365.
Alym WBCx?
408. 148. 89. 210. 266. 160. 105.
0. 185. 95.
Mono WBCx?
408. 444. 534. 525. 532. 640. 735. 182. 740. 665.
Eos in
WBCx?
0. 0. 0. 105.
0. 0. 0. 91. 185.
95.
Baso WBCx?
0. 0. 0. 0. 0. 0. 0. 0. 0. 0.
AVG.
S. D. S. E.
12.47 3.28 1.04
2223.0 0.0 919.6 0.0 290.8 0.0
9492.3 166.6 540.5 47.6
0.0
3032.7 112.3 169.6 66.6 0.0
959.0 35.5 53.6 21.1
0.0
GROUP: 2M
DOSE: .0076 mg/L
SAMPLE DATE: 07/20/84
SPECIES: RAT
BIRTH DATE; 05/14/84
ANIMALS: 376804 376806 376810 376818 376822 376823 376844 376852 376876 376881
WBC
a ^O3/!! L
9. 5 11. 1 13. 0
13.6 13. 2 10. 1 13. 0 10. 4 15. 0 8. 3
Neut
WBCx?
2185. 4107. 2730. 1904. 3300. 1717. 3770. 1456. 4050. 1162.
Band VIBCxf,
0. 0. 0. 0. 132.
0. 0. 0. 0. 0.
Lymph
WBCxjt
6270. 6327. 8580. 11288. 9372. 7373. 8710. 8528. 9750. 6640.
Alyn WBCx?
285. 222. 390. 136. 132. 404. 130. 104. 600.
0.
Mono WBCx?
665. 444. 1040. 272. 132. 505. 390. 208. 600. 498.
Eos in
WBCx?
95. 0.
260.
0. 132. 101.
0. 104.
0. 0.
Baso WKCx%
0. 0. 0. 0. 0. 0. 0. 0. 0. 0.
AVG.
S. D. S. E.
11.72
2. 14 0.68
2638.1
1107.9
350.4'
13.2 41.7 13.2
8283.8 240.3 475.4 69.2 0.0
1636.5 180.1 260.5 86.4
0.0
517.5 57.0 82.4 27.3 0.0
98
Company Sanitized. Does not contain TSCA CBI
MR:
COMPOUND:
PERIOD: SEX:
0-DAY REC MALE
15388
HASKELL CODE:Jf||
lt DEPARTMENT: POLYMER PRODUCTS
REPORT DATE: 17-OCT-84
GROUP: 3M
DOSE: .058 mg/L
SAMPLE DATE: 07/20/84
SPECIES: RAT
BIRTH DATE: 05/14/84
ANIMALtf: 376805 376812 376A13 376821 376830 376838 376851 376857 376867 376874
WBC
xlO^uL 6.6
14.4 14.4 11.7 10.4 9.4 12.7 12.5 11.0 9.9
AVG.
S. D. S. E.
11.30 2.39 0.76
Neut WBCxj6
1122. 2160. 1872. 2106. 1768. 1598. 3302. 2000. 1980. 1386.
Band WBCxjE
0. 0. 0. 0. 0. 0. 0. 0. 0. 0.
1929.4 0.0 583.3 0.0 184.5 0.0
Lymph
WBCx?
4884. 11376.
11-376. 9009. 7280.
7332. 8636. 9500. 8470. 7722.
Alym WBCx?
66. 144. 432. 117. 416.
94. 254. 125. 330.
99.
Mono WBCx?
528.
720. 576. 468. 832. 376. 381. 750. 220. 693.
Eosin WBCx?
0. 0. 144.
0. 104.
0. 127. 125.
0. 0.
Baso WBCx?
0. 0. 0. 0. 0. 0. 0. 0. 0. 0.
8558.5 207.7 554.4 50.0 0,0 1952.8 139.3 195.6 65.2 0.0 617.5 44.1 61.9 20.6 0.0
GROUP: 4M
DOSE; .480 mg/L
SAMPLE DATE: 07/20/84
SPECIES; RAT
BIRTH DATE: 05/14/84
ANIMAL//: 376819 376820 376824 376828 376833 376854 376858 376859 376879
376880
WBC
X1Q3/UL
10.9 8.5 16.7 9.8 13.5 11.1 12.7 14.0 9.0 17.8
Neut WBCxjC
2180. 1700. 2338. 1862. 2160. 3663. 2667. 2800. 2070. 2848.
Band WBCx?
0. 0. 0. 0. 0. 0. 0. 0. 0. 0.
Lymph WBCx?
7739. 6545. 13360. 7546. 10800. 6105. 9144. 10220. 6390. 13884.
Alym WBCx?
218. 85.
167. 98. 0.
222. 127. 140. 180. 178.
Mono WBCx?
763. 170. 835. 294. 540. 1110. 762. 840. 360. 890.
Eosin WBCx?
0. 0. 0. 0. 0. 0. 0. 0. 0. 0.
Baso WBCx?
0. 0. 0. 0. 0. 0. 0. 0. 0. 0.
AVG.
S. D. S. E.
12.40 3.14 0.99
2428.8 0.0 579.0 0.0 183.1 0.0
9173.3 141.5 656.4 0.0 0.0 2833.1 67.6 301.4 0.0 0.0
895.9 21.4 95.3 0.0 0.0
99
Company Sanitized. Does not contain TSCA CBI
----fHn DAY
MALE
HASKELL REC
NUMBER;_15388
HASKELL CODE;^
DEPARTMENT: POLYMER PRODUCTS
REPORT DATE: 17-OCT-84
GROUP: 1CM
DOSE: CONTROL
SAMPLE DATE: 07/20/84
SPECIES: RAT
BIRTH DATE: 05/14/84
ANIMALS:
376825 376835 376839
J9*776<H0H4|/0V 376841 376849 376863
376870 376872 376873
ALP
U/L 130. 339. 237. 137. 161. 184. 183.
211. 140. 185.
ALT
U/L
35. 44. 42. 46. 33. 31. 32. 37. 37. 32.
AST
U/L
75. 96. 71. 9T. 73. 68. 93. 98. 95. 109.
BUN
mg/dL 16. 16. 13. 15. 14. 14. 23. 19. 16. 15.
CREAT
mg/dL
0.54 0.59 0.53 6.56 0.56 0.55 0.41 0.46 0.56 0.66
TPROT
g/dL
5.9 6.0 6.2 6.0 5.6 5.8 5.9 6.0 5.5 5.9
CHLOS
mg/dL
62. 60. 64. 60. 62. 81. 40. 54. 40. 45.
AVG.
S. D. S. E.
190.7 62.1 19.6
'36.9 5.4
1.7
86.9 14.0 4.4
16.0
2.9 0.9
0.542 0.068 0.021
5.88 0.20 0.06
56.7 12.8 4.0
--- GROUP: 2M
DOSE:
SAMPLE DATE: 07/20/84
ANIMALS:
376804 376806 376810 376818 376822 376823 376844 376852 376876 376881
ALP
U/L
98. 166. 177. 265. 262. 242. 153. 211. 206. 207.
ALT
U/L
35. 46. 43. 41. 41. 54. 33. 28. 35. 37.
AVG.
S. D. S. E.
198.7
52.0 16.4
39.3 7.4 2.3
.-0-07.6..n.g./-L
--.--. SPECIES: RAT
BIRTH DATE-.:.-- 05/14/84
AST
U/L
69. 90. 72. 82. 77. 106. 70. 92. 93. 77.
BUN
mg/dL 17. 20. 18. 16. 17. 16. 12. 20. 14. 18.
CREAT
mg/dL
0.58 0.52 0.59 0.59 0.59 0.65 0.66 0.67 0.54 0.56
TPROT
g/dL 6.3 6.0 6.0 6.5 6.0 5.8 6.1 5.8 6.1 5.3
CHLOS
mg/dL
62. 47.
CO -3J.
69.
52. 50.
U^
TJf 34. 41. 34.
82.8
12.1
3.8
16.9 2.4
0.7
0.595 0.051 0.016
5.99 0.32 0.10
48.6 11.0 3.5
00 Company Sanitized. Does not contain TSCA CBI
LwJH------MHHO HASKELL MOMBER;
0-DAY REC MALE
15388
HASKELL CODE:^a
DEPARTMENT: POLYMER PRODUCTS REPORT DATE: 17-OCT-84
GROUP: 31
DOSE:
SAMPLE DATE; 07/20/84
ANIMALS: 376805
376812 376813
37682.1
376830 376838 376851 376857 376867 376874
ALP
U/L
299..
127. 229. 228. 210. 240. 204. 187. 141. 199.
ALT
U/L
71. 43. 43. 40. 35. 40. 50. 46. 39. 33.
AVG.
S. D. S. E.
206.4 49.1 15.5
44.0 10.7 3.4
.058mg/L
SPECIES: RAT
BIRTH DATE: 05/14/84
AST
U/L 116.
72. 83.
7B.
102. 105. 96. 99. 79. 76.
BUN
mg/dL
15. 13. 15. 16. 19. 14. 14. 24. 12. 17.
CREAT
mg/dL
0.67 0.53 0.70
0.-68
0.55 0.72 0.61 0.63 0.61 0.59
TPROT
g/dL
6.3 6.1 6.2 6.4
5.9 6.4 6.7 5.8 5.6 6.0
CHLOS
ng/dL
47. 61. 53. 50. 48. 49. 50. 42. 49. 52.
90.6 14.9 4.7
15.8 3.4 1.1
0.629 0.063 0.020
6.14 0.33 0.10
^9.9 4.8 1.5
GROUP: 4M
DOSE:
SAMPLE DATE: 07/20/84
ANIMALS: 376819 376820 376824 376828 376833 376854
376858 376859 376879 376880
ALP
U/L 372. 287. 324. 322. 351. 334. 263. 254. 328. 411.
AVG.
S. D. S. E.
324.6 48.0 15.2
ALT
U/L 47. 45. 41. 62. 50. 50. 38. 35. 38. 37.
44.3 8.3 2.6
.480 mg/L
SPECIES: RAT
BIRTH DATE: 05/14/84
AST
U/L 124. 123. 93. 137. 91. 94. 99. 94. 101. 124.
BUN
mg/dL
27. 25. 34. 29. 31. 23. 28. 25. 36. 32.
CREAT
mg/dL
0.70 0.62 0.71 0.29 0.74 0.76 0.71 0.60 0.62 0.68
TPROT
g/dL
6.1 5.9 6.4 6.1 5.4 6.3 6.2 6.0 7.1 6.9
CHLOS
mg/dL
32. 18. 19. 19. 20. 16.
18.
9. 18. 16.
108.0 28.9' 0.643 6.24 18.6 17.0 4.2 0.135 0.49 5.5 5.4 1.3 0.043 0.15 1.7
10
Company Sanitized. Does not contain TSCA CBI
( I f MR:
I
HASKELL NUMBER; 15388
COMPOUND: f^^^^--------------------9D1EPARTMENT:
HASKELL CODE:Cft
POLYMER PRODUCTS
PERIOD: 0-DAY REC
REPORT DATE; 17-OCT-84
SEX:
MALE
GROUP: 1CM
DOSE: CONTROL
SAMPLE DATE: 07/20/84
SPECIES: RAT
BIRTH DATE; 05/14/84
ANIMALS: 376825 376835 376839 376840 376841 376849 376863 376870 376872 376873
VOL
mL
5.8 6.1 5.4 5.5 7.9 6.7 3.5 17.0 7.8 6.3
OSMOL
mOs
1862. 1641. 2028. 1739. 1552. 1901. 1593. 1002. 1879. 1944.
BLOOD
-
+
-
SUGAR
-
+
-
+
-
PRO
TEIN
+1
+2
+1 +1 +1 +1
+2
+
+1 +1
pH BILI- UROBL Ke-
ROBIN mg/dL tone
7.0 -
1.0 +1
7.0 +1
1.0 +1
7.0 +1
1.0 +1
8.0 -
1.0 +
8.0 -
1.0 +
8.0 +1
1.0 +1
6.0 +1
1.0 +
8.0 -
0.1 -
7.0 +1
1.0 +
7.0 +1
1.0 +1
AVG.
S. D. S. E.
7.20 1714.1 3.67 296.2 1.16 93.7
7.30 0.67 0.21
0.91 0.28 0.09
GROUP: 2M
DOSE: .0076 mg/L
SAMPLE DATE: 07/20/84
SPECIES: RAT
BIRTH DATE: 05/14/84
ANIMALS: 376804 376806 376810 376818 376822 376823 376844 376852 376876 376881
AVG.
S. D. S. E.
VOL OSMOL BLOOD
mL m0s
4.6 1966. 5.1 1607. 7.4 1641. 4.6 1926. + 5.0 1666. 4.2 2130. + 7.7 1664. 2.2 1868. +
6.5 1090. -'
4.4 2388. -
5.17 1794.6 1.64 350.5 0.52 110.8
SUGAR
-- -
+ + +
-
PRO
TEIN +2
+1 +1 +1 +1 +1 +1 +1 +1 +1
'
pH BILI- UROBL Ke-
RUBIN mg/dL tone
6.0 +1
1.0 +
8.0 +1
1.0 +
7.0 -
1.0 +1
7.0 -
1.0 +
7.0 -
1.0 +1
6.0 -
1.0 -
7.0 +1
1.0 +1
7.0 -
0.1 -
7.0 -
1.0 +
6.0 -
1.0 +1
6.80 0.63 0.20
0.91 0.28 0.09
02
Company Sanitized. Does not contain TSCA CBI
CODE:^^ 15388
to DEPARTMENT:
HASKELL POLYMER PRODUCTS
REPORT DATE: 17-OCT-84
GROUP: 34
DOSE: .058 mg/L
SAMPLE DATE: 07/20/84
SPECIES: RAT
BIRTH DATE: 05/14/84
ANIMALS: 376805 376812 376813 376821 376830 376838 376851 376857 376867 376874
VOL
fflL
5.0 7.3 6.2 8.3 6.7 5.0 9.0 7.1 4.6 16.0
OSMOL
m0s
2062.
W. 1763.
1398. 1471. 1976. 1322. 1669. 2080. 821.
BLOOD
-
+
-
SUGAR
! -
+
-
PRO
TEIN +2
+1 +1 +1 +1 +1 +1 +1 +1
+
PH BILI- UROBL Ke-
RUBIN mg/dL tone
7.0 -
1.0 +1
8.0 -
1.0 +
7.0 -
1.0 +
7.0 +1
1.0 +
8.0 -
1.0 +
6.0 -
1.0 +1
7.0 +1
1.0 +
7.0 -
1.0 +1
6.0 -
1.0 +
7.0 -
1.0 +
AVG.
S. D. S. E.
7.52 1609.6 3.31 389.0 1.05 123.0
7.00 0.67 0.21
1.00 0.00 0.00
GROUP: 4M
DOSE; .480 mg/L
SAMPLE DATE: 07/20/84
SPECIES: RAT
BIRTH DATE: 05/14/84
ANIMALS: 376819 376820 376824 376828 376833
376854 376858 376859 376879 376880
VOL
mL
11.0 9.1 12.0 16.0 15.0 11.0 10.0 8.7 14.0 12.0
OSMOL
m0s
1039. 955. 944. 886. 730.
1099. 537. 861. 725. 723.
BLOOD
-
SUGAR
+ +
-
+
-
PRO
TEIN
+1 +1 +1
+
+1 +1
+
+1 +1
+
PH BILI- UROBL Ke-
RUBIN mg/dL tone
8.0 -
0.1 -
9.0 -
0.1 -
8.0 +1
1.0 --
7.0 -
0.1
8.0 -
. 1.0
9.0 +1
1.0 -
8.0 -
0.1
9.0 +1
1.0 --
9.0 -
1.0
8.0 -
1.0 -
AVG.
S. D. S. E.
11.88 2.45 0.78
849.9 171.0
54.1
8.30
0.64
0.67
0.46
0.21
0.15
05 Company Sanitized. Does not contain TSCA CBI
5388
HASKELL CODE^jR
DEPARTMENT: POLYMER PRODOCTS
REPORT DATE: 17-OCT-84
GROOP: 1CM
DOSE: CONTROL
SAMPLE DATE: 07/20/84
SPECIES: RAT
BIRTH DATE: 05/14/84
ANIMALS: 376825 376835 376839
376MO' 376841 376849 376863 376870 376872 376873
RBC
/hpf 0-0
0-0 0-0 0-0 0-0 0-0 0-0 0-2 0-0 0-0
WBC
/hpf 4-8
5-10 0-2 5-8 8-10 0-4 0-1 10-20
1-3 5-10
Epith /hpf
0-3 0-2 1-2 0-3 2-4 0-2 0-1
1-3 0-1
0-2
Cast
/Ipf
0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0
APPEARANCE
Y CL PPT FEED DY CL PPT FEED Y CL PPT FEED. LY CL PPT FEED DY CL PPT FEED DY CL PPT FEED DY C PPT Y CL PPT FEED Y C PPT FEED DY CL PPT FEED
GROUP; 2M
DOSE: .0076 fflg/L
SAMPLE DATE: 07/20/84
SPECIES: RAT
BIRTH DATE: 05/14/84
ANIMALS: 376804
376806 376810 376818 376822 376823 376844 376852 376876 376881
RBC
/hpf 0-0 0-0 0-0 0-0 0-0 0-2 0-0
0-1 0-0 0-0
WBC
/hpf
1-4 1-3 20-30 0-2 2-4 5-8 1-2 0-2 0-1 0-2
Epifch
/hpf
0-1 0-1 3-6 0-1 0-1 0-2 0-0 0-2 0-0 0-1
Cast
/Ipf
0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0
APPEARANCE
DY CL PPT FEED Y CL PPT FEED DY CL PPT FEED DY C PPT LY C PPT Y C PPT Y C PPT FEED DY C PPT LY CL PPT Y C PPT
04 Company Sanitized. Does not contain TSCA CBI
15388
HASKELL CODE: OK
DEPARTMENT: POLYMER PRODOCTS
REPORT DATE: 17-OCT-84
GROUP: 31
DOSE: .058 mg/L
SAMPLE DATE: 07/20/84
SPECIES: RAT
BIRTH DATE: 05/14/84
ANIMALS: 376805 376812 376813 376821 376830 376838 376851 376857 376867 376874
RBC
/hpf
0-0 0-0 0-1 0-0 0-0 0-0 0-0 0-0 0-3 0-0
WBC
/hpf
5-10 3-6 1-3 4-6 1-4 0-3 0-2 0-2 2-4 0-3
Epith /hpf 1-4
0-2 1-2 0-1 0-3 0-1
1-2 0-1 0-2 0-1
Cast
/Ipf
0-0 0-0 0-0
0-0 0-0 0-0 0-0
0-0 0-0 0-0
APPEARANCE
Y CL PPT FEED ' Y CL PPT FEED Y C PPT Y CL PPT FEED Y C PPT FEED DY CL PPT FEED Y C PPT FEED Y C PPT FEED DY CL PPT PEED LY CL PPT FEED
GROUP: 4M
DOSE: .480 mg/L
SAMPLE DATE: 07/20/84
SPECIES: RAT
BIRTH DATE: 05/14/84
ANIMALS: 376819 376820 376824 376828 376833 376854 376858 376859 376879 376880
RBC
/hpf 0-0 0-0 0-0
0-1 0-0 0-0 0-0 0-0 0-0 0-0
WBC
/hpf
1-3 0-4 0-1 0-2 1-4 1-3 0-1 2-4 0-2 1-3
Epith /hpf 1-2
0-2 0-1 0-1
1-2 0-2 0-2 2-4 0-1 2-4
Cast
/Ipf
0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0
APPEARANCE
DY CL PPT Y CL PPT FEED Y CL PPT FEED LY CL PPT FEED Y CL PPT FEED DY CL PPT LY CL PPT A CL PPT Y CL PPT LY CL PPT
05 Company Sanitized. Does not contain TSCA CBI
5388
HASKELL CODE;(jB
'
DEPARTMENT: POLYMER PRODUCTS
REPORT DATE; 17-OCT-84
GROUP: 1CM
DOSE: CONTROL
SAMPLE DATE: 08/03/84
ANIMAL#: 376801 376835 376836
376837 376841 376847 376849
376863 376872 376878
RBC
xloS/uL
6.73 6.49 7.63 7.75 6.39 7.93 7.27 7.28 7.26 6.51
Hb
g/dL
15.2 16.4 16.0 16.0 14.8 15.8 15.8 15.9 16.4 16.0
Ht
%
39. 39. 43. 43. 38. 42. 42. 41. 42. 38.
AVG.
S. D. S- E.
7.124 0.561 0.177
15.83 0.49 0.16
40.6
2.0 0.6
SPECIES: RAT
BIRTH DATE: 05/14/84
MCV
MCH MCHC PLAT
fL
P6 g/dL x1o3/uL
57.
23.
39.
940.
59.
25.
43.
1262.
56.
21.
37.
1138.
54.
21.
38.
944.
59.
23.
39.
1190.
52.
20.
38.
1158.
58.
22.
38.
56.
22.
39.
954. 998.
57.
23.
39.
864.
58.
25.
42.
1360.
56.6 2.2 0.7
22.4 1.7 0.5
39.2 1.8 0.6
1080.8 163.4 51.7
GROUP: 2M
DOSE: .0076 mg/L
SAMPLE DATE: 08/03/84
SPECIES: RAT
BIRTH DATE: 05/14/84
RBC
Elb
Hfc
MCV
ANIMAL#: 3doS/uL g/d,L
% fL
376800
7.25 16. 2
41.
56.
376810
6.68 15. 0
40.
59.
376822
6.23 16. 1
37.
58.
376848
6.74 15. 5
38.
57.
376852
7.49 16. 4
44.
58.
376856 376866 376871 376876 376881
7.72 16. 3
43.
55.
7.03 16. 3
40.
56.
7.43 15. 8 . 42.
55.
7.20 15. 1
39.
54.
7.18 16. 3
41.
57.
MCH MCHC PLAT
Pg g/dL 3d03/uL
22.
40.
1118.
23.
38.
888.
26.
44.
1330.
23.
40.
1042.
22.
38.
1078.
21.
38.
936.
23.
41.
1162.
21.
38.
972.
21.
39.
1048.
23.
40.
1066.
AVG.
S. D. S. E.
7.095 0.441 0.140
15. 90
0.52 0. 17
40.5 2.1 0.7
56.5 1.6 0.5
22.5 1.4 0.5
39.4
2.0 0.6
1064.0 124.7 39.4
06 Company Sanitized. Does not contain TSCA CBI
5388
I
. HASKELL CODE:^BI)
DEPARTMENT: POLYMER PRODUCTS
REPORT DATE: 17-OCT-84
GROOP: 3M
DOSE: .058 mg/L
SAMPLE DATE: 08/03/84
SPECIES: RAT
BIRTH DATE: 05/14/84
ANIMALS:
376803 376808 376811 376812 376813 376830 376843 376857 376860 376874
RBC
xlO^uL
7.54 7.66 7.99 7.16 7.07 7.57 7.29 7.90 7.05 7.54
Hb
g/dL 16.1 16.3 16.2 16.6 15.7 16.2 15.3 16.6 15.3 15.8
Ht %
41. 42. 44. 42. 41. 43. 40. 44. 40. 42.
MCV
fL 54.
55. 54. 58. 57. 57. 54. 55. 56. 55.
MCH
P6
.21. 21. 20. 23. 22. 21. 21. 21. 22. 21.
MCHC
g/dL
39. 39. 37. 40. 39. 38. 38. 38. 38. 38.
PLAT
X103/UL 1064. 1126. 768. 1300. 878. 1060. 1026. 1134. 1282. 1050.
AVG.
S. D. S. E.
7.477 0.329 0.104
16.01
0.47 0.15
41.8 1.5 0.5
55.5 1.4 0.5
21.4 0.8 0.2
38.3 0.8 0.2
1068.8 161.8 51.2
GROUP: 4M SAMPLE DATE;
I >OSE:
08/03/ 84
.480 mg/L
SPECI ES; RA T
BIRTH DATE: 05/14/84
ANIMALS: 376814 376815 376819 376824 376832 376833 376850 376853 376858 376880
RBC
xlO^uL
7.52 7.32 6.83 6.18 6.76 7.25 7.71 8.01 7.40 6.70
Hb
g/dL 15.2 14.7 14.5 14.0 14.9 15.3 15.6 15.4 15.2 13.6
Hfc
%
41. 40. 38. 35. 37. 44. 43. 43. 43. 37.
MCV
fL 54. 54. 56. 56. 55.
60. 55. 53. 57. 54.
MCH
PS
20. 20. 21. 23. 22. 21. 20. 19. 21. 20.
MCHC
g/dL 37. 37. 38. 40. 40. 35. 36. 36. 35. 37.
PLAT
X103/UL
1052. 1140. 900. 1146. 1078. 1256. 1036. 1120. 1074. 998.
AVG.
S. D. S. E.
7.168 0.546 0.173
14.84 0.64 0.20
40.0 3.1 1.0
5S.4
2.0 0.6
20.8 1.0 0.3
37.2 1.7 0.6
1080.0
QC
3J'
7 1
30.3
107 Company Sanitized. Does not contain TSCA CBI
( f j MR:
COMPOUND:!
PERIOD: '14-DAY
SEX;
MALE
HASKEL1 . REC
NUMBE:R;
153188
HASICELL CODE^fl
DEPABTMElIT: POL}fMER PRODUCTS REPORT DlITE: 17--OCT-84
GROUP: 1CMI
DOSE: CONTRO L
SAMPLE DATE: 08/0 3/84
SPECIES: RAT
BIRTH DA'FE: 05/'14/84
ANIMALS: 376801 376835 376836 376-837 376841 376847 376849 376863 376872 376878
ALP
U/L 166. 307. 151. 10T. 168. 201. 207. 128. 139. 139.
ALT
AST
BUN GREAT TPROT CHLOS
U/L
U/L mg/dLi mg/dL g/dL mg/dL
39.
71. 22. 0.63
6.2
63.
39. 103.
16. 0.68
6.4
67.
32.
70.
15. 0.60
6.5
63.
38.
77.
12. 0.55
7".4
76.
35.
78.
19. 0.58
7.5
72.
29.
75.
18. 0.49
5.4
64.
37.
59.
16. 0.64
5.7 101.
28.
71. 21. 0.60
5.7
61.
37.
83.
18. 0.54
5.8
61.
35-
77
16. 0.56
5.8
87.
AVG.
S. D. S. E.
170.7
57.7 18.2
34.9 4.0 1.3
76.4 11.3
3.6
17.2
3. 0 1. 0
0.587 0.055 0.017
6.24 0.72 0.23
71.5 13.2 4.2
GROUP: 2M
DOSE: .0076 mg/L
SAMPLE DATE: 08/03/84
SPECIES: RAT
BIRTH DATE: 05/14/84
ALP
ALT
AST
BUN GREAT TPROT CHLOS
ANIMALS:
U/L
U/L
U/L mg/dL mg/dL g/dL mg/dL
376800 219.
39.
72.
16. 0.53
6.0
50.
376810 127.
32.
70.
15. 0.60
6.3
64.
376822 261.
46.
70.
20. 0.69
6.6
64.
376848
87.
24.
98.
17. 0.57
6.1
65.
376852 137.
30.
81.
15. 0.59
6.2
66.
376856 145.
31.
76.
16. 0.56
6.2
55.
376866 176.
28.
59.
17. 0.61
6.8
86.
376871 180.
36.
67.
16. 0.61
6.3
50.
376876 242.
39.
79.
19. 0.63
5.7
51.
376881 219.
39.
75.
15. 0.49
5.2
65.
AVG.
S. D. S. E.
179.3
55.8 17.6
34.4 6.6 2.1
74.7 10.3 3.3
16. 6 1. 6 0. 5
0.588 0.055 0.017
6.14 0.45 0.14
61.7 10.8 3.4
08 Company Sanitized. Does not contain TSCA CBI
| f MR:
&
HASKEL1
^
COMPOUND:!^^^^^^^^^^^^^^--
PERIOD: TCDA^EC^
SEX:
MALE
B l iJ NUMBEIL-
15388
HJISKELL (;ODE:1
DEPAR'IMENT: P()LYMER I'RODUCTS1
REPOR'r DATE: 16-OCT-fi4
GROUP: 1C(4
DOSE: CONTR01
SAMPLE DA'FE: 08/03/84
SPECI1ES: RAT
BIRTH DATE: O!5/14/84
ANIMALS; 376801 376835 376836 376837 376841 376847 376849 376863 376872 376878
WBC
x1o3/uL
9.9 12.4 14.4 13.8 14.1 15.5 14.9 10.6 11.6 13.8
AVG.
S. D. S. E.
13.10 1.88 0.60
Neufc WBCx?
1287. 3720. 3168. 4002. 2961. 1860. 3725. 2332. 1624. 1104.
Band WBCx;(
0. 0. 0. 0. 0. 0. 0. 0. 0. 0.
2578.3 0.0 1078.5 0.0 341.0 0.0
Lymph
WBCxf,
8514. 8680. 11232. 9798. 11139. 13485. 11026. 8268. 9976. 12558.
Alym WBCx{6
0. 0. 0. 0. 0. 0. 0. 0. 0. 138.
Mono WBCx?
0. 0. 0. 0. 0. 155.
0. 0. 0. 0.
Eosin
WBCx?
99.
0. 0. 0.
0. 0.
149.
0. 0. 0.
Baso WBCx?
0.
0. 0. 0. 0. 0. 0. 0. 0. 0.
10467.6 13.8 15.5 24.8 0.0 1743.6 43.6 49.0 53.6 0.0 551.4 13.8 15.5 16.9 0.0
GROUP: 2M
DOSE: .0076 mg/L
SAMPLE DATE: 08/03/84
SPECIES: RAT
BIRTH DATE; 05/14/84
ANIMALS: 376800
376810 376822 376848 376852 376856
376866 376871 376876 376881
WBC
x1o3/uL 14.7 13.1 13.8 16.7 10.4 16.4 12.0 18.0 13.2 8.3
Neut WBCx?
5292. 2882. 3174. 1169. 1560. 2460. 1680. 2160. 5148. 1660.
Band
mcx%
0. 0. 0. 0. 0. 0. 0. 0. 0. 0.
Lymph WBCx;6
9261. 9563. 10488. 15030. 8528. 13612. 10320. 15660. 7788. 6474.
Alyn WBCx?
147. 131.
0. 167.
0. 0. 0. 0. 0. 0.
Mono WBCx?
0. 524. 138. 167. 208. 164.
0. 0. 132. 83.
Eosin
WBCx?
0. 0. 0. 167. 104. 164.
0. 180. 132. 83.
Baso WBCx?
0. 0. 0. 0. 0. 0. 0. 0. 0. 0.
AVG. S. D. S. E.
13.66 2.97 0.94
2718.5 0.0 1456.0 0.0 460.4 0.0
10672.4 44.5 141.6 83.0 0.0 3099.0 72.2 154.7 77.0 0.0
980.0 22.8 48.9 24.4 0.0
109 Company Sanitized. Does not contain TSCA CBI
A f l MR:
H
COMPOUND:'
PERIOD: 14-DAY
SEX:
MALE
HASKELL REG
1 ] :ODE:0(|| NuMBElfl:
15388
H.ASKELL (
DEPAR'IMENT: P(3LYMER 1PRODUCT;3 REPOR'r DATE; 16-OCT-)34
GROUP: 3M
DOSE: .058 m(/L
SAMPLE DA'IE: 08/03/84
SPECIJ3S: RAT
BIRTH DATE: 0'5/14/8,4
ANIMALtf:
376803 376808 376811 376812 376813 376830 376843
376857 376860 376874
WBC
x1o3/uL
11.3 24.4 10.6 21.2 10.7 12.2 15.2 12.4 21.2
8.2
AVG.
S. D. S. E.
14.74 5.55 1.75
Meut WBCx?
2260. 4148. 2014. 3392. 1712. 1586. 4104. 3100. 5936. 1640.
Band WBCx?6
0. 0. 0. 0. 0. 0. 0. 0. 0.
'
0.
2989.2 0.0 1427.8 0.0 451.5 0.0
Lymph WBCx?
8588. 19764.
8480. 17808.
8881. 10126. 11096. 8804. 14840. 6478.
Alym WBCx?
113.
0. 106.
0. 107. 122.
0. 248. 212.
0.
Mono WBCx?
226. 244.
0. 0. 0. 244.
0. 248. 212.
82.
Eosin
WBCx%
113. 244.
0. 0. 0. 122.
0. 0. 0. 0.
Baso WBCx?
0. 0. 0. 0. 0. 0. 0. 0. 0. 0.
11486.5 90.8 125.6 47.9 0.0 4450.2 90.9 118.1 84.5 0.0 1407.3 28.7 37.4 26.7 0.0
GROUP: 4M
DOSE: .480 mg/L
SAMPLE DATE: 08/03/84
SPECIES: RAT
BIRTH DATE: 05/14/84
ANIMALS: 376814 376815 376819 376824 376832 376833
376850 376853 376858
376880
WBC
x1o3/uL
16.7 17.3 11.6 16.7 11.5 12.2 19.0 13.8 12.6
17.7
Meut Band WBCx? WBCx?
2672. 2422. 2552. 4008. 2300. 2684.
4180. 3036. 2394. 2478.
0. 0. 0. 0. 0. 0. 0. 0.
'
0. 0.
Lymph WBCx?
13861. 14705.
9048. 12358.
9085. 9272. 14440. 10764. 9450. 15045.
Alym WBCx?
0. 173.
0. 0. 0. 122. 190.
0. 378. 177.
Mono WBCx?
167.
0. 0. 334. 115. 122. 190. 0. 378.
0.
Eosin
WBCxjt
0. 0. 0. 0. 0. 0. 0. 0. 0. 0.
Baso WBCx?
0. 0. 0. 0. 0. 0. 0. 0. 0. 0.
AVG.
S. D. S. E.
14.91
2.85 0.90
2872.6 0.0 676.5 0.0 213.9 0.0
11802.8 104.0 130.6
0.0
0.0
2548.0 127.8 139.8 0.0 0.0
805.7 40.4 44.2 0.0 0.0
110 Company Sanitized. Does not contain TSCA CBI
-DAY MALE
HASKELL NUMBER; J5388
HASKELL CODE^Wl
"^~--------------"" DEPARTMENT: POLYMER PRODUCTS
REC
REPORT DATE: 17-OCT-84
GROUP: 3M
DOSE: .058 mg/L
SAMPLE DATE: 08/03/84
SPECIES: RAT
BIRTH DATE: 05/14/84
ANIMALS: 376803 376808 376811 376812 376813
376830 376843 376857 376860 376874
ALP
U/L 185. 236. 171. 11T. 252. 200. 209. 178. 213. 196.
ALT
AS T
BUM CREAT 'rPROT (:HLOS
U/L
U/ L nig/dL mg/dL g/dL rng/dL
40.
104
22. 0.56
6.5
52.
36.
72
17. 0.53 6.9 84.
36.
81
17. 0.66 6.5 68.
42.
69
15. 0.59 6.6 70.
37.
74
18. 0.63 6.3 54.
27.
79.
19. 0.57
5.5 48.
36.
56
14. 0.62 4.0 56.
43.
107
21. 0.53
6.3
57.
31.
73
15. 0.57 6.4 71.
32.
79
13. 0.54 6.4 67.
AVG.
S. D. S. E.
195.6 37.5 11.9
36.0 5.0 1.6
79.4 15 .5 4.9
17.1
2.8 0.9
0.580 0.044 0.014
6.14 0.83 0.26
62.7 11.2 3.6
GROUP: 4M
DOSE: .480 mg/L
SAMPLE DATE: 08/03/84
SPECIES: RAT
BIRTH DATE: 05/14/84
ALP
ALT
AST
BUN CREAT TPROT CHLOS
ANIMALS:
U/L
U/L
376814 210.
46.
376815 277.
31.
376819 234.
38.
376824 233.: 41.
376832 139.
38.
376833 239.
35.
376850 122.
33.
376853 247.
32.
376858 150.
27.
376880, 294.
36.
U/L mg/dL mg/dL
64.
16. 0.60
61.
16. 0.64
88.
19. 0.49
68. 27. 0.72
90.
16. 0.58
65.
18. 0.69
60.
16. 0.58
63.
22. 0.58
77.
19. 0.62
65.
17. 0.50
g/dL
6.4 6.8 6.9 7.5 6.5 6.9 6.4 6.3 5.9 5.9
mg/dL
73. 63. 63. 58. 55. 65. 44. 46. 66. 60.
AVG.
S. D. S. E.
214.5
58.7 18.6
35.7 5.4 1.7
70.1 11.0 3.5
18.7
3.7 1.2
0.600 0.073 0.023
6.55 0.49 0.16
59.2 8.8 2.8
111 Company Sanitized. Does not contain TSCA CBI
i -- MR:
RHASKEL1,, NUMBER; 15388
HASKELL COI)E:(JWO
COMPOUND :fl^^^^--------------------DE^PARTMENT: POLYMER PRODUCTS
PERIOD: 14-DAY REC
REPORT DATE: 17-OCT-84
SEX:
MALE
GROUP: 1CM
DOSE: CONTROL
SAMPLE DATE: 08/03/84
SPECIES: RAT
BIRTH DATE: 05/14/84
ANIMALS: 376801 376835 376836
376837 376841 376847 376849 376863 376872 376878
VOL
mL
5.4 13.8 10.2
17.6 14.3 11.8 18.6 8.9 17.9 13.9
OSMOL
mOs
2496. 1371. 1608. 1061. 1300. 1573. 1367. 1344. 1147. 1201.
BLOOD
-
-
SUGAR
-
-
PRO
TEIN +2 +2 +2
+1 +1 +3 +1 +2 +1 +1
pH BILI- UROBL Ke-
RUBIN mg/dL tone
7.0 +1
1.0 +
8.0 -
1.0 +
8.0 -
1.0 -
9.0 -
1.0 +
8.0 -
1.0 +
9.0 +1
1.0 +1
8.0 +1
1.0 +
9.0 +1
1.0 +
7.0 -
1.0 +
8.0 -
1.0 +
AVG.
S. D. S. E.
13.24 1446.8 4.25 406.4 1.35 128.5
8.10 0.74 0.23
1.00 0.00 0.00
GROUP: 2M
DOSE: .0076 mg/L
SAMPLE DATE: 08/03/84
SPECIES: RAT
BIRTH DATE: 05/14/84
ANIMALS; 376800 376810 376822 376848 376852 376856 376866 376871 376876 376881
AVG.
S. D. S. E.
VOL
mL
12.9 22.8 11.0
8.1 10.0 8.2 15.4 8.0 13.9 14.0
OSMOL
m0s
1603. 642.
1455. 932. 834.
1874. 1151. 1694. 1332. 1640.
BLOOD
-
12.43 1315.7 4.54 411.3 1.44 130.1
SUGAR
+
-
PRO
TEIN +2
+1 +1 +1
+
+2 +1 +1 +1 +1
pH BILI- UROBL Ke-
RUBIN mg/dL tone
7.0 -
1.0 +1
8.0 -
1.0 +
8.0 -
0.1 +
8.0 -
0.1 -
7.0 -
1.0 +
8.0 -
1.0 +1
8.0 -
1.0 -
7.0 +1
1.0 +1
8.0 -
1.0 +
7.0 +1
1.0 +1
7.60 0.52 0.16
0.82 0.38 0.12
12
Company Sanitized. Does not contain TSCA CBI
| MR:^JB
HASKEL1L NUMBER; J5388
HASKELL COI)E:(JB
COMPOUND: fi--------------||------------|D3EPARTMENT: POLYMER PRODUCTS
PERIOD: 14-DAK HEC
REPORT DATE: 17-OCT-84
SEX:
MALE
GROUP: 3M
DOSE: .058 mg/L
SAMPLE DATE: 08/03/84
SPECIES: RAT
BIRTH DATE: 05/14/84
ANIMALft: 376803 376808 376811 376812 376813 376830 376843 376857
376860 376874
AVG.
S. D. S. E.
VOL
mL
7.0 9.9
12.2 19.0
9.0 12.2 11.0 12.8 10.0 21.7
OSMOL
mOs
1998. 1894.
14J.3. 1063.
1707. 1573. 1682. 1532. 1785. 957.
BLOOD
-
-
+
-
12.48 1566.4 4.53 334.9 1.43 105.9
SUGAR
-
-
+
-
+
PRO
TEIN
+1 +1
+3 +2 +2 +2 +2 +2 +1 +2
pH BILI- UROBL Ke-
RUBIN mg/dL tone
7.0 -
1.0 +
6.0 +1
1.0 +1
8.0 +1
1.0 +
7.0 -
1.0 -
7.0 +1
1.0 +
7.0 +1
1.0 +
7.0 +1
1.0 +
8.0 +1
1.0 +1
7.0 +1
1.0 +1
7.0 -
1.0 +
7.10 0.57 0.18
1.00 0.00 0.00
GROOP; 4M
DOSE: .480 mg/L
SAMPLE DATE: 08/03/84
SPECIES: RAT
BIRTH DATE: 05/14/84
ANIMALS: 376814 376815 376819 376824 376832 376833 376850 376853 376858 376880
VOL
mL
10.0 10.2 10.5 15.0 14.1 13.0 12.7 10.0 11.9 12.3
OSMOL
m0s
1570. 1754. 1775. 1303. 1413. 1272. 1705. 1957. 912. 1722.
BLOOD
-
SUGAR
-
PRO
TEIN +1 +1 +1 +2 +1 +1 +2 +2
+1 +1
pH BILI- UROBL Ke-
RUBIN mg/dL tone
7.0 +1
1.0 +
7.0 +1
1.0 +
7.0 7.0 +1
1.0 + 1.0 +
7.0 8.0 -
1.0 + 1.0 -
7.0 +1
1.0 +
7.0 +1 8.0 -
1.0 + 1.0 -
7.0 +1
. 1.0 +
AVG.
S. D. S. E.
11.97 1538.3 1.78 311.7 0.56 98.6
7.20 0.42 0.13
1.00
0.00 0.00
113 Company Sanitized. Does not contain TSCA CBI
^5388
HASKELL CODE:(|R
DEPARTMENT: POLYMER PRODUCTS
REPORT DATE: 17-OCT-84
GROUP: 1CM
DOSE: CONTROL
SAMPLE DATE: 08/03/84
SPECIES: RAT
BIRTH DATE: 05/14/84
ANIMALS: 376801
376835 376836
376837 376841 376847 376849 376863 376872 376878
RBC
/hpf 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0
WBC
/hpf 3-5 10-20 10-15 10-20
10-20 10-20 4-6 4-8 10-20 5-8
Epifch
/hpf
0-1
0-2 1-2 1-3 2-4 2-4 0-1 4-6 0-2 0-2
Cast
/Ipf
0-0 0-0 0-0 0-0 0-0 0-0 0-0
0-0 0-0 0-0
APPEARANC E
Y C Y CL PPT FEED Y CL PPT FEED Y CL PPT FEED Y CL PPT FEED DY CL PPT FECES Y CL PPT DA CL PPT FECES Y CL PPT FEED Y CL PPT
GROUP: 2M
DOSE: .0076 mg/L
SAMPLE DATE: 08/03/84
SPECIES: RAT
BIRTH DATE: 05/14/84
ANIMALS: 376800 376810 376822 376848 376852 376856 376866 376871 376876 376881
RBC
/hpf 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0
0-0
WBC
/hpf 4-6 3-5 3-6
0-1 0-0 1-5 4-8 0-2 3-6 8-12
Epith /hpf
2-3 0-2 0-3 0-2 0-0 0-0
1-4
0-1 1-2 1-3
Cast
/Ipf
0-0 0-0 0-0
0-0 0-0 0-0 0-0 0-0
0-0 0-0
APPEARANCE
DY CL PPT FEED Y CL PPT FEED DY CL PPT FEED Y CL PPT Y CL DY CL PPT FEED Y CL PPT Y CL Y CL PPT DY CL PPT FECES
114 Company Sanitized. Does not contain TSCA CBI
14-DAY
MALE
HASKELL REC
NUMBER;
J5388
HASKELL CODE:QR
DEPARTMENT: POLYMER PRODUCTS
REPORT DATE: 17-OCT-84
GROUP: 3M
DOSE: .058 mg/L
SAMPLE DATE: 08/03/84
SPECIES: RAT
BIRTH DATE: 05/14/84
ANIMALS: 376803 376808 376811 376812 376813 376830 376843 376857 376860. 376874
RBC
/hpf 0-0 0-0 0-0 0-0 0-0
0-1
0-0 0-0 0-0 0-0
WBC
/hpf
10-15 2-4 1-3 3-6 4-6 5-10 4-8 10-15 3-5 5-10
Epith /hpf
0-3 0-2 0-1 0-2 0-2 1-3 0-1 1-2 0-2 2-4
Cast
/Ipf
0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0
0-0
APPEARANCE
Y CL PPT DY CL PPT FEED DY CL PPT FEED DY CL PPT FEED Y CL PPT DY CL PPT FEED Y CL PPT Y CL PPT FEED Y CL PPT FEED DY CL PPT FEED
FECES
GROUP: 4M
DOSE: .480 mg/L
SAMPLE DATE: 08/03/84
SPECIES: RAT
BIRTH DATE: 05/14/84
ANIMALS: 376814
376815 376819 376824 376832 376833 376850 376853 376858 376880
RBC
/hpf 0-0 0-0
0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0
WBC
/hpf 4-8
10-20
3-5 1-3 0-2 4-8 5-10 5-10 0-1 0-3
Epith /hpf 1-3
0-3 0-2 0-1 0-1 0-2 1-2 1-3 0-1 0-2
Cast
/Ipf
0-0 0-0 0-0 0-0 0-0
0-0 0-0 0-0 0-0 0-0
APPEARANCE
Y CL PPT Y CL PPT FEED Y CL PPT FEED Y CL PPT FEED Y CL PPT FEED Y CL PPT FEED DY CL PPT FEED DY CL PPT FECES Y CL PPT Y CL PPT FEED
115 Company Sanitized. Does not contain TSCA CBI
MR: COMPOUND:!
PERIOD: SEX:
41-DAY
MALE
R_EC_
388
HASKELL CODE:^H
DEPARTMENT: POLYMER PRODUCTS
REPORT DATE: 27-FEB-85
GROUP: 1CM
DOSE: CONTROL
SAMPLE DATE: 08/30/84
ANIMALi?: 376801
376807 376829
37683.4 376836
376837 376847 376861 376869 376878
RBC
x1o6/uL
7.55 7.25 8.34
7-.5Q
7.78 8.09 8.70 8.28 7.62 8.06
Hb
g/dL 15.4 15.1 16.0 15.1 15.1
15.5 15.8 15.8 15.4 16.1
Hfc
%
43. 39. 44. 40. 41. 43. 46. 43. 42. 45.
AVG. S. D. S. E.
7.917 0.451 0.143
15.53 0.38
0.12
42.5 2.1 0.7
SPECIES: RAT
BIRTH DATE: 05/14/84
MCV
MCH MCHC PLAT
fL
Pg g/dL x103/uL
57.
20. 36.
1008.
53.
21. 39.
1020.
52.
19.
37.
694.
53.
20.
38.
1000.
53.
19.
37.
974.
53.
19.
36.
968.
52.
18.
35.
882.
52.
19.
37.
1054.
54.
20.
37.
1122.
55.
20.
36.
782.
53.4 19.6 36.6 1.6 0.8 1.1 0.5 0.3 0.4
950.4 129.3 40.9
GROUP: 2M
DOSE: . 0076 mg/L
SAMPLE DATE: 08/30/84
SPECIES: RAT
BIRTH DATE: 05/14/84
ANIMAL)?;
376800 376827 376831 376848 376856 376862 376866 376871 376877 376882
RBC
x1o6/uL
7.36 6.90 7.26 7.14 8.00 7.77 7.68 7.53 7.55 8.44
Hb
g/dL 15.4 15.9 15.1 15.3 15.6 15.6 15.6 14.6 15.1 17.2
Ht
MCV
%
fL
41. 55.
39.
56.
40. 54.
40.
55.
43. 53.
42. 54.
42. 54.
41.
53.
39,
51.
46.
55.
MCH MCHC PLAT
Pg g/dL x103/uL
21. 38.
23.
41.
21.
38.
21.
39.
20. 37.
20. 37.
20. 37.
19.
36.
1158. 1236. 1266. 1094. 904. 1086. 994. 1046.
20.
39.
20.
37.
920. 1038.
AVG.
S. D. S. E.
7.563 0.443 0.140
15.54 0.69 0.22
41.2
2.3 0.7
54.0 1.4 0.4
. 20.6 1.0 0.3
37.8
1.3 0.4
1074.2 121.0 38.3
116 Company Sanitized. Does not contain TSCA CBI
MR:Q^BR
COMPOUND^
PERIOD: 41-DAY
SEX:
MALE
i-1ASKELL B;EC
NUMBER:
15388
HASKE:LL CODE\r
1 DEPAfETMENT: POLYM:ER PRODUCTS
.REPOF!T DATE : 27-F:EB-85
GROUP: 3M
SAMPLE DA'rE:
DOSE:
08/30i/84
. 058 mg/L
SPECIE S: RAT BIRTE1 DATE: 05/14,/84
ANIMALS: 376803 376808 376811 376817 376843 376846 376855 376860 376864 376875
RBC
x1o6/uL
8.45 7.51 7.33 7.96 7.75 7.96 7.83 7.44 6.59 7.10
Hb
g/dL 16.4 15.4 15.7 15.3 15.3 16.0 15.8 14.8 15.1 15.5
Ht
MCV
%
fL
45. 53.
41. 53.
39. 53.
42.
52.
42. 53. 44. 55.
41.
52.
44. 59. 37. 56. 39. 55.
MCH MCHC PLAT
Pg g/dL X103/UL
20.
37.
1142.
21.
38.
1108.
22.
40.
1004.
19.
37.
1244.
20.
37.
1064.
20.
36.
852.
20.
38.
1144.
20.
34.
1398.
23.
41.
1066.
22.
40.
964.
AVG.
S. D. S. E.
7.592 0.520 0.164
15.53 0.46 0.15
41.4
2.5 0.8
54.1
2.2 0.7
20.5 1.2 0.4
37.7 2.1 0.7
1098.6 150.9 47.7
GROUP: 4M
DOSE: . 480 mg/L
SAMPLE DATE: 08/30/84
SPECIES: RAT
BIRTH DATE: 05/14/84
ANIMALS: 376814 376815 376816 376826 376832 376842 376845 376850 376853 376868
RBC
xlO6/^
7.00 8.06 7.26 7.52 7.47 7.38 6.32 7.07 7.77 7.00
Hb
g/dL 15.3 16.1 14.4 15.1 15.1 14.9 13.4 15.8 15.2 15.1
Hfc
MCV
%
fL
39.
55.
43. 53.
38. 52.
41. 53.
40.
53.
41. 55.
36.
56.
39.
55.
4'1.
52.
39.
56.
MCH MCHC PLAT
Pg g/dL X103/UL
22.
39.
1134.
20.
37.
1544.
20.
38.
1294.
20.
37.
986.
20.
38.
1060.
20.
36.
1080.
21.
38.
1168.
22.
41.
1224.
20.
37.
1088.
21.
38.
1080.
AVG.
S. D. S. E.
7.285 0.480 0.152
15.04 0.74 0.23
39.6 2.0 0.6
54.0 1.6 0.5
20.7 0.9 0.3
37.9 1.2 0.4
1165.8 159.2 50.4
H7 Company Sanitized. Does not contain TSCA CBI
H i MR:
COMPOUND:___
PERIOD: 41-DAY REC
SEX:
MALE
5388
HASKELL CODE
DEPARTMENT: POLYMER __ PRODUCTS
REPORT DATE: 27-FEB-85
GROUP: 1CM
DOSE: CONTROL
SAMPLE DATE: 08/30/84
SPECIES: RAT
BIRTH DATE: 05/14/84
ANIMAL//: 376801 376807 376829
37'6'83'4"
376836 376837 376847 376861 376869 376878
WBC
x1o3/uL 11.8 9.1 12.3 12.9 11.5 13.9 12.2 10.1 13.2 13.9
Neut WBCx%
1416. 1274. 1968. 2064. 1380. 3892. 1952. 1414. 2904. 2641.
Band WBCxl
0. 0. 0. 6. 0. 0. 0. 0. 0. 0.
Lymph
WBCxt
10384. 7462. 10086. 10836. 10005. 10008. 10004. 8080. 9900. 10981.
Alym WBCxt
0. 91.
0. 0. 0. 0.
122. 101. 132.
0.
Mono WBCx%
0. 91. 123.
6.
115.
0. 0. 303.
132. 139.
Eosin
WBCx%
0. 182. 123.
0. 0. 0. 122. 202.
132. 139.
Baso WBCx%
0. 0. 0. 0. 0. 0. 0. 0. 0. 0.
AVG.
S. D. S. E.
12.09 1.56 0.49
2090.5 0.0 838.6 0.0 265.2 0.0
9774.6 44.6 90.3 90.0 0.0 1127.7 58.6 96.4 81.4 0.0 356.6 18.5 30.5 25.8 0.0
GROUP: 2M
DOSE: .0076 mg/L
SAMPLE DATE: 08/30/84
SPECIES: RAT
BIRTH DATE: 05/14/84
ANIMAL//: 376800 376827 376831 376848 376856 376862 376866 376871 376877 376882
WBC
x1o3/uL
15.7 19.3 13.2 15.4 14.0 13.4 10.0 13.3 11.8 17.0
. AVG.
S. D. S. E.
14.31
2.65 0.84
.Neut WBCx?
3768. 4632. 2772. 2464. 2800. 3350. 1400. 3458. 2360. 2210.
Band WBCx?
0. 0. 0. 0. 0. 0. 0. 0. 0. 0.
2921.4
0.0
912.7
0.0
288.6 0.0
Lymph
WBCxiE
11618. 14282. 10164. 12782. 10500. 9916. 8500. 9576. 9086. 14110.
Alym
WBCxit
157. 0.
132. 0.
140. 134.
0. 0. 118.
0.
Mono
WBCx^E
157. 193.
0. 0. 420.
0.
100. 266. 118. 680.
Eosin
WBCx%
0. 193.
0. 154. 140.
0. 0. 0. 118.
0.
Baso WBCx%
0. 0. 132.
0. 0. 0. 0. 0. 0. 0.
11053.4 2055.8
650.1
68.1 72.4 22.9
193.4 216.4
68.4
60.5 80.2 25.4
13.2 41.7 13.2
1 18 Company Sanitized. Does not contain TSCA CBI
f l f MR:
1
COMPOUND:{
PERIOD: 41-DAY
SEX:
MALE
^ HASKEL LJtUMBER :
9 3 REG
15388
H.ASKELL CODE:f|
DEPARTMENT: P OLYMER PRODUCT
REPORT DATE: ,27-FEB-,85
GROUP: 3M
DOSE: .058 mig/L
SAMPLE DA'iFE: 08/30/84
SPECIES: RAT
BIRTHI DATE: 0'5/14/84
ANIMALtf: 376803 376808 376811 376817 376843 376846 376855 376860 376864 376875
WBC
xi03/uL
9.4 22.2
7.8 18.9 12.4 9.7 17.8 24.2 15.8 14.4
Neut WCx% 1316. 4662. 1482. 3402.
4.7-1.2.
1552. 2492. 6776. 2528. 2448.
Band WBCx?
0. 0. 0. 0. 0. 0. 0. 0. 0. 0.
Lymph
WBCx?
7990. 17094. 6084. 14742. 7440. 7857. 13884. 16940. 12166. 11376.
Alym WBCx%
0. 0. 78. 378.
0. 0. 712. 242. 158. 144.
Mono WBCx%
0. 0. 0. 189. 124. 194. 356. 242. 790. 432.
Eosin
VBCx%
94. 222. 156. 189. 124.
97. 356.
0.
158.
0.
Baso WBCxiE
0. 222.
0. 0. 0. 0. 0. 0. 0. 0.
AVG. S. D. S. E.
15.26 5.56 1.76
3137.0 0.0 1762.2 0.0 557.3 0.0
11557.3 4067.7 1286.3
171.2 227.8
72.0
232.7 245.7
77.7
139.6 105.3
33.3
22.2 70.2 22.2
GROUP: 4M
DOSE: .480 mg/L
SAMPLE DATE: 08/30/84
SPECIES: RAT
BIRTH DATE: 05/14/84
ANIMAL//: 376814 376815 376816 376826 376832
376842 376845 376850 376853 376868
WBC
xi03/uL
11.1 12.5
22.0 15.0 9.5 16.6 20.8 18.4 9.8 12.3
AVG.
S. D. S. E.
14.80
4..50
1.42
Neut Band
VBCxl WCx%
1776.
0.
1500.
0.
6600.
0.
2700. 150.
1045.
0.
4316.
0.
7280.
0.
5704.
0.
1666.
0.
2214. .
0.
3480.1 2311.2
730.9
15.0 47.4 15.0
Lymph WBCx!6
9213. 10625. 14740. 11250. 8265. 11786. 12688. 11224. 7938. 10086.
Alym VBCx%
0. 250.
0. 300.
190.
0. 208. 368.
98. 0.
Mono
WCx%
111. 125.
0. 450.
0. 332. 416. 552.
98. 0.
Eosin
WBCx%
0. 0. 660.
150.
0. 166. 208. 552.
0. 0.
Baso
VBCx%
0. 0. 0. 0. 0. 0. 0. 0. 0. 0.
10781.5 141.4 208.4 173.6 0.0 , 2057.9 140.2 209.2 243.2 0.0
650.8 44.3 66.1 76.9 0.0
n9 Company Sanitized. Does not contain TSCA C81
f l i MR:
COMPOUND:! PERIOD: 41-DAY
SEX:
MALE
HASKEL1L REC
NUMBE R: 1538.8
HAS KELL CODE:fB|^
S
EPARTME;NT: EPORT D.ATE:
POLYMER PRODUCTS
27 -FEB-85
GROUP: 1Ch1
DOSE: CONTRO:L
SAMPLE DA1E: 08/3!0/84
SPEICIES: RAT
B IRTH DA"TE: 05/ 14/84
ALP
ALT
AST
BUN CREAT TPROT CHLOS
ANIMAL//:
U/L
U/L
U/L mg/dL mg/dL g/dL mg/dL
376801 131.
44. 96.
17. 0.68 6.0 53.
376807 121.
36.
67.
20. 0.66
6.6
71.
376829 125.
39.
80.
18. 0.70 6.8
62.
376834
91.
28.
75.
17. 0.65
5.4
63.
376836 166.
37.
81.
15. 0.60 5.6
62.
376837 100.
35.
56.
16. 0.62 6.9
71.
376847 172.
42.
68.
15. 0.65 6.3
58.
376861 173.
43.
78.
16. 0.57 6.5
56.
376869 125.
54.
68.
20. 0.68 6.7
93.
376878 104.
46.
91.
19. 0.67 6.1
85.
AVG.
S. D. S. E. ,
130.8 30.1
9.5
40.4 7.1 2.2
76.0 11.9 3.8
17.1 0.648 1.9 0.040 0.6 0.013
6.29 0.51 0.16
67.3 12.8 4.0
GROUP: 2M
DOSE: .0076 mg/L
SAMPLE DATE: 08/30/84
SPECIES: RAT
BIRTH DATE: 05/14/84
ANIMAL//: 376800 376827 376831 376848 376856 376862 376866 376871 376877 376882 .
ALP
U/L
197. 134. 174. 99. 102. 219. 156. 139. 120. 173.
ALT
AST
BUN CREAT TPROT CHLOS
U/L
U/L mg/dL mg/dL g/dL mg/dL
36. 101.
31.
77.
39. 65.
31. 68.
37.
66.
28. 78.
31. 63.
35.
71.
28.
61.
28.
84.
16. 0.66 6.0 47.
19. 0.64 6.4 55.
19. 0.61 . 6.6
70.
16. 0.63
6.1
60.
15. 0.64 5.3 52.
17. 0.75
6.9
95.
18. 0.72 7.3 102.
17. 0.69
6.5
58.
19. 0.66
6.3
64.
17. 0.81
6.7
89.
AVG. S. D. S. E.
151.3 39.8 12.6
32.4 4.1 1.3
73.4 12.2 3.8
17.3 0.681 1.3 0.062 0.4 0.020
6.41 0.54 0.17
69.2 19.2 6.1
20
Company Sanitized. Does not contain TSCA CBI
MR:[1
COMPOUND:)
PERIOD: 41-DAY
SEX:
MALE
HASKELL REC
NUMBE R: 1538 8
HASKELL CODE(^
^ s EPARTMEMT: POLYMER PRODUCT; EPORT D.ATE: 27 -FEB-85
GROUP: 3M
DOSE: .058 m g/L
SAMPLE DA'TE: 08/:50/84
SPEICIES: RAT
BIRTH DA'TE: 05/ 14/84
ANIMAL//: 376803 376808 376811 376817
376843 376846 376855 376860 376864 376875
ALP
U/L
117. 224. 138. 127. 182. 147. 155. 144. 230. 106.
ALT
AST
BUN CREAT TPROT CHLOS
U/L
U/L mg/dL mg/dL g/dL mg/dL
35. 100. . 23. 0.78
40.
87.
18. 0.62
32.
75.
18. 0.64
41.
73.
18. 0.59
38.
65.
17. 0.59
41.
83.
14. 0.74
36.
95.
15. 0.69
30.
60.
15. 0.68
41.
62.
19. 0.71
33.
64.
18. 0.67
5.8 41. 5.8 75.
5.3 55. 5.6 64. 5.8 48. 6.4 88. 6.7 88. 6.5 81. 7.2 102. 6.4 70.
AVG.
S. D. S. E.
157.0 42.4 13.4
36.7 4.1 1.3
76.4 14.3 4.5
17.5 0.671
2.4 0.063 0.8 0.020
6.15 0.58 0.18
71.2 19.3 6.1
GROUP: 4M
DOSE: .480 mg/L
SAMPLE DATE: 08/30/84
SPECIES: RAT
BIRTH DATE: 05/14/84
ANIMAL//: 376814 376815 376816 376826 376832 376842 376845 376850 376853 376868
ALP
U/L
171. 227. 216. 120.
74. 187. 113. 90. 201. 125.
ALT
AST
BUN GREAT TPROT CHLOS
U/L
U/L mg/dL mg/dL g/dL mg/dL
38.
76.
20. 0.71
5.9
69.
22.
71.
16. 0.54 6.0 56.
43.
73.
14. 0.55 6.0
46.
32.
76.
17. 0.66
5.6
53.
26.
80.
17. 0.66 5.4
68.
37. 102.
23. 0.67
6.1
50.
38.
87.
16. 0.63 6.4 87.
31.
65.
15. 0.67
6.4
57.
30.
65. 19. 0.59
6.4
71.
31.
71.
17. 0.78
6.7
70.
AVG. S. D. S. E.
152.4 54.7 17.3
32.8 6.3 2.0
76.6 11.1 3.5
17.5 2.5 0.8
0..646
0.073 0.023
6.09 0.40 0.13
62.7 12.4 3.9
12
Company Sanitized. Does not contain TSCA CBI
15388
HASKELL CODE(fl^
h' DEPARTMENT: POLYMER PRODUCTS
REPORT DATE: 27-FEB-85
GROUP: 1CM
DOSE: CONTROL
SAMPLE DATE: 08/30/84
SPECIES: RAT
BIRTH DATE: 05/14/84
ANIMAL//: 376801 376807 376829 376834 376836
376837 376847 376861 376869 .76878
VOL
mL
10.0 7.8 15.0 8.0 13.0 24.0 12.4 17.0 16.5 11.5
OSMOL
m0s
1961. 2420. 2280. 1967. 1877. 1164. 2170. 1537. 1915. 1655.
BLOOD
--
-- -- -- -
SUGAR
--
+
-
PRO
TEIN
+1 +3 +2 +1 +2 +1 +2 +2 +2
+2
pH BILI- UROBL Ke-
RUBIN ing/dL tone
7.0 +1 7.0 +1
.0 +1 .0 +1
7.0 -
.0 +1
7.0 -
.0 +
7.0 -
.0 +
8.0 -
.0 +
7.0 -
1.0 +1
8.0 -
1.0 +
7.0 --
1.0 +
7.0 -
1.0 +
AVG. S. D.
S. E.
13.52 1894.6 4.88 369.7 1.54 116.9
7.20 0.42 0.13
1.00 0.00 0.00
GROUP: 2M
DOSE: .0076 mg/L
SAMPLE DATE: 08/30/84
SPECIES: RAT
BIRTH DATE : 05/14/84
ANIMAL//: 376800 376827 376831 376848
376856 376862 376866 376871 376877 376882
AVG.
S. D. S. E.
VOL
mL
16.0 15.0 10.5 9.0 11.0 9.0 22.5 11.5 11.5 22.0
OSMOL
m0s
1608. 1365. 1889. 2126. 1761. 2064. 1389. 1536. 1726. 865.
BLOOD SUGAR
--
+3
--
-- -
--
+
-- -- -
+
-- '
--
-
PRO
TEIN +2 +2 +2 +2
+1 +3 +2 +1 +2 +1
13.80 1632.9
5.00 372.8 1.58 117.9
pH BILI- UROBL Ke-
RUBIN mg/dL tone
7.0
1.0 +1
7.0 7.0 +1
1.0 + 1.0 +
7.0
1.0 +
7.0 7.0 +1
1.0 +1 1.0 +
8.0
1.0 +
7.0
1.0 +1
8.0
1.0 +1
8.0 -
1.0 +
7.30 0.48 0.15
1.00 0.00 0.00
22 Company Sanitized. Does not contain TSCA CBI
MR:(r'1HASKELL
NUMBER:
15388
.
HASKELL CODE:(H
coMpomm:(^^^^------|^^^1 DEPARTMENT : POLYMER PRODUCTS
PERIOD: 41-DAY REC
REPORT DATE: 27-FEB-85
SEX:
MALE
GROUP: 3M
DOSE: .058 mg/L
SAMPLE DATE: 08/30/84
SPECIES: RAT
BIRTH DATE: 05/14/84
ANIMAL//: 376803 376808 376811 376817 376843 376846 376855 376860 376864 376875
VOL
mL
6.5 11.0 12.0 17.0 10.0 18.5 19.5 18.0 12.0 8.5
OSMOL
mOs
2420. 2362. 1939. 1534. 2338. 1258.
981. 1344. 1773. 2260.
BLOOD
-- -- -
SUGAE!
+
--
-
PRO
TEIN +2 +2 +2
+1 +2 +1 +1 +1 +2 +2
pH BILI- UROBL Ke-
RUBIN mg/dL tone
7.0 +1
1.0 +
7.0 +1 7.0 +1
1.0 +1 1.0 +
7.0 -
1.0 +1
6.0 +1
1.0 +
8.0 -
1.0 +1
7.0 -
1.0 +
7.0 -
1.0 +
7.0 +1
1.0 +
7.0 +1
1.0 +2
AVG.
S. D. S. E.
13.30 1820.9 4.60 522.8 1.45 165.3
7.00 0.47 0.15
1.00 0.00 0.00
GROUP: 4M
DOSE: .480 mg/L
SAMPLE DATE: 08/30/84
SPECIES: RAT
BIRTH DATE ; 05/14/84
ANIMALS:
376814 376815 376816 376826 376832 376842 376845 376850 376853 .76868
VOL
mL
12.0 11.5 15.0 15.0 16.0 4.6 30.5 12.5 6.8 11.0
OSMOL
mOs
1646. 1808. 1105. 1555. 1232. 2292. 956. 1883. 2336. 1446.
BLOOD
--
+
-- -- -
SUGAR
-
+ +
-- -
PRO
TEIN +2 +2 +3 +2 +1 +2
+1 +1
+3 +1
pH BILI- UROBL Ke-
RUBIN mg/dL tone
7.0 +1
1.0 +1
7.0 +1
1.0 +1
8.0 +2
1.0 +1
7.0 -
1.0 +1
7.0 -
1.0 +
6.0 +1
1.0 +
7.0 -
1.0 +
7.0 +1
1.0 +1
7.0 +1
1.0 -
7.0 -
1.0 +1
AVG.
S. D. S. E.
13.49 1625.9 6.97 466.7 2.20 147.6
7.00 0.47
0.15
1.00 0.00 0.00
23 Company Sanitized. Does not contain TSCA CBI
MR:
_ _ _ COMPOUND;
PERIOD:
SEX:
MALE
?388
HASKELL CODE:W\
DEPARTMENT: POLYMER PRODUCTS
REPORT DATE: 27-FEB-85
GROUP: 1CM
DOSE: CONTROL
SAMPLE DATE: 08/30/84
SPECIES: RAT
BIRTH DATE: 05/14/84
ANIMAL//: 376801 376807 376829 37-6834 376836 376837 376847 376861 376869 376878
RBC
/hpf
0-0. 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0
WBC
/hpf 3-5
10-15 2-4 0-2 3-5 4-6 0-4 4-8 0-3 0-3
Epith /hpf 1-3
0-3 0-2 0-1 1-3 1-2 0-2 0-3 0-2 2-3
Cast
/Ipf
0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0
APPEARANCE
Y CL PPT FEED
Y CL PPT FEED
Y CL PPT FEED
Y CL PPT FEED
Y CL PPT FEED
Y CL PPT FEED
Y CL PPT FEED
DY CL PPT FEED
Y CL PPT FEED
Y CL PPT
GROUP: 2M
DOSE: .0076 mg/L
SAMPLE DATE: 08/30/84
SPECIES: RAT
BIRTH DATE: 05/14/84
ANIMAL//: 376800 376827 376831 376848 376856 376862 376866 376871 376877 376882
RBC
/hpf 0-0 0-0 0-0 0-0 0-0 7-10 0-0 0-0 0-0 0-0
WBC
/hpf
0-0 0-3 1-2 0-2 0-2 2-4 1-2 1-3 2-3 0-1
Epith /hpf
4-6 3-5 4-6 6-8 5-7 7-9 2-4 1-3 1-2 2-4
Cast
/Ipf
0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0
APPEARANCE
Y CL PPT FEED Y CL PPT FEED Y CL PPT FEED Y CL PPT FEED Y CL PPT FEED DY CL PPT FEED Y CL PPT FEED Y C PPT FEED Y CL PPT FEED Y CL PPT FEED
24 Company Sanitized. Does not contain TSCA CBI
MK:(------
COMPOUND:
PERIOD:
SEX:
MALE
HASKEI-L
NUMBE;R: 153'88
HASKELL CODE:(^)
R
DEP.ARTMENT: POLYMER PRODUCTS
REPIORT DATE: 27-FEB-85
GROUP: 3M
DOSE:; .058 irlg/L
SAMPLE DA'FE: 08 /30/84
SiPECIES: RAT
IBIR'I-H DATE: 05/14/84
ANIMAL//: 376803 376808 376811
37-6817 376843 376846 376855
376860 376864 376875
RBC
/hpf 0-3
0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0
WBC
/hpf 4-6
1-2
3-5 1-2 0-2 5-10 2-4 10-20 5-8 0-4
Epifch
/hpf
0-2 0-2 1-2 0-1
0-1 0-3 0-2 1-4 0-3 0-3
Cast
/Ipf
0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0
AlPPEARANCE
Y CL PPT FEED Y C PPT FEED Y CL PPT FEED Y CL PPT FEED Y C PPT FEED Y CL PPT FEED Y CL PPT FEED Y CL PPT FEED Y CL PPT FEED Y C PPT
GROUP: 4M
DOSE: .480 mg/L
SAMPLE DATE: 08/30/84
SPECIES: RAT
BIRTH DATE: 05/14/84
ANIMAL//: 376814 376815 376816 376826 376832 376842 376845 376850 376853 376868
RBC
/hpf 0-0
0-0 0-1 0-0 0-1
0-0 0-0 0-0 0-0 0-0
WBC
/hpf
1-2 0-2 1-2 1-2 0-0 0-1 1-2 0-1 1-2 0-1
Epifch
/hpf 4-6
1-2 1-3 3-5 0-1 0-2 1-3 1-2 3-5 1-3
Cask
/Ipf
0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0 0-0
APPEARANCE
Y CL PPT FEED Y CL PPT FEED DY CL PPT FEED Y CL PPT FEED Y C PPT Y C PPT LY CL PPT FEED Y CL PPT FEED Y C PPT Y C PPT
FECES
125 Company Sanitized. Does not contain TSCA CBI
MR: COMPOUND: PERIOD; SEX:
84-D_A_Y_R_E_C
MALE
^5388
HASKELL CODE^^|
DEPARTMENT: POLYMER PRODOCTS
REPORT DATE: 17-OCT-84
GROOP: 1CM
DOSE: CONTROL
SAMPLE DATE: 10/12/84
RBC
Hb
Ht
ANIMALS: x10/uL g/dL
%
376807
7.80 16.1
40.
376829
8.60 16.1
42.
376834
8.31 15.7 41.
376861
8.51 16.5 41.
376869
7.54 15.8 39.
AVG.
S^ D. S. E.
8.152 0.462 0.206
16.04 0.31 0.14
40.7 1.2 0.5
SPECIES: RAT
BIRTH DATE; 05/14/84
MCV
MCH MCHC PLAT
fL
P8 g/dL xlO^uL
50. .21.
40.
1120.
48.
19.
39.
1288.
49.
19.
38.
1154.
48.
19.
40.
f120.
51.
21.
41.
1356.
49.2 1.3 0.6
19.7 1.0 0.4
39.4 1.1 0.5
1207.6 108.1 48.3
GROUP: 2M
DOSE: . 0076 ing/L
SAMPLE DATE: 10/12/84
SPECIES: RAT
BIRTH DATE; 05/14/84
ANIMALS: 376827 376831 376862 376877
376882
RBC
xlO^uL 7.08 7.54 6.91
8.21 8.81
Hb
g/dL 15.4 16.2 14.8 15.2 16.0
AVG.
S. D. S. E.
7.710 0.795 0.355
15.52 0.58 0.26
Ht %
38. 40. 35. 39. 45.
39.5 3.6 1.6
MCV
fL 53.
53. 51. 47. 51.
51.0 2.4
1.1
MCH MCHC PLAT
Pg g/dL x1o3/uL
22.
41.
1434.
22.
41.
1324.
22.
42.
1446.
19.
39.
1074.
18.
36.
826.
20.3 1.8 0.8
39.6 2.5 1.1
1220.8 266.6 119.2
126
Company Sanitized. Does not contain TSCA CBI
15388
HASKELL CODE:f9)
"L DEPARTMENT: POLYMER PRODUCTS
REPORT DATE: 17-OCT-84
GROUP: 34
DOSE: .058 mg/L
SAMPLE DATE: 10/12/84
SPECIES: RAT
BIRTH DATE: 05/14/84
ANIMALff:
376817 376846 376855 376864 376875
RBC
x10/uL 9.52 8.42 9.26 7.12 8.12
Hb
g/dL 15.9 16.5 16.5 14.6 15.6
Ht
MCV
% fL
47.
49.
43.
51.
46.
49.
38.
52.
43.
53.
MCH
MCHC
PLAT
Pg g/dL x1o3/uL
17.
34.
1022.
20.
38.
1162.
18.
36.
1180.
21.
39.
1312.
19.
36.
1028.
AVG.
S. D. S. E.
8.488 0.958 0.429
15.82 0.79 0.35
43. 5
3. 7 1. 6
50.8 1.8 0.8
18.7 1.5 0.7
36.5 2.0 0.9
1140.8 120.6 53.9
GROUP: 4M
DOSE: .480 mg/L
SAMPLE DATE: 10/12/84
SPECIES: RAT
BIRTH DATE: 05/14/84
ANIMALS:
376316 376826 376842 376845 376868
RBC
x10/uL 7.53 7.90 8.13 7.47 8.18
Hb
g/dL 14.9 14.7 15.6 14.1 16.2
Ht
MCV
.%
fL
37.
49.
39.
49.
43.
52.
40.
53.
43.
53.
MCH MCHC
PLAT
Pg g/dL x1o3/uL
20.
40.
1208.
19.
37.
1174.
19.
37.
894.
19.
36.
20.
38.
972. 926.
AVG.
S. D. S. E.
7.842 15.10 40.5 51.2 19.3 37.4 1034.8
0.330 0.82
2.5
2.0
0.5
1.7
145.8
0.148 0.36
1.1
0.9
0.2
0.7
65.2
127 Company Sanitized. Does not contain TSCA CBI
15388
HASKELL CODE:^||
DEPARTMENT: POLYMER PRODUCTS
REPORT DATE: 17-OCT-84
GROUP; 1CM
DOSE; CONTROL
SAMPLE DATE: 10/12/84.
SPECIES: RAT
BIRTH DATE: 05/14/84
ANIMALS; 376807
376829 376834
376861 376869
WBC
xlO^uL 11.9 10.9 13.0 10.4 12.0
AVG.
S. D. S. E.
11.64 1.02 0.45
. Neut Band WBCx!( WBCxj?
2142.
0.
1744.
0.
1560.
0.
1872.
0.
1320.
0.
1727.6 0.0
311.1 0.0
139.1
0.0
Lymph
WCx% 8449. 8938. 11050. 8112. 10320.
Alym WCx%
476. 109. 130.
0. 120.
Mono WBCxjE
714. 109. 130. 104.
0.
Eosin
WBCxjt
119.
0. 130. 312. 240.
Bago
WCx%
0. 0. 0. 0. 0.
9373.8 167.0 211. 4 160.2
0.0
1259.2 180.5 285. 5 120.1
0.0
563.1 80.7 127. 7 53.7
0.0
GROUP: 2M
DOSE: .0076 mg/L
SAMPLE DATE: 10/12/84
SPECIES: RAT
BIRTH DATE: 05/14/84
ANIMALtf: 376827 376831 376862 376877 376882
WBC
xloS/uL 13.3 13.5 15.5 10.1 12.8
AVG.
S. D. S. E.
13.04 1.94 0.87
Neut
WBCx%
2926. 2700. 2325. 1111. 1536.
Band WBCxj6
0. 0.
0. 0. 0.
2119.6 0.0 772. 5 0.0
345. 5 0.0
Lymph WBCx%
9709. 10125. 12710.
8787. 10752.
Alym WBCx%
133. 270. 155.
0. 384.
Mono WBCxjE
399. 270. 310. 101. 128.
Eoain
WBCx?
133. 135.
0. 101.
0.
Baso WBCx%
0. 0. 0. 0. 0.
10416.6 188.4 241.6 73. 8
0.0
1467.4 145.4 125.4 68.7 0.0
656.3 65. 0 56.1 30.7 0.0
28 Company Sanitized. Does not contain TSCA CBI
HASKELL
NUMBER:
J.5388
HASKELL CODE:fl|
DEPARTMENT! POLYMER PRODUCTS
REPORT DATE: 17-OCT-84
GROUP: 3M
DOSE: .058 mg/L
SAMPLE DATE: 10/12/84
SPECIES: RAT
BIRTH DATE: 05/14/84
ANIMALS: 376817 376846 376855 376864 376875
WBC
xlO^uL
17.1 18.1 16.5 12.2
21.4
AVG.
S. D. S. E.
17.06
3.31 1.48
Neufc WBCxf,
3420. 3620. 2805. 2196. 2568.
Band WBCx?
0. 0. 0. 0. 214.
2921. 8 591. 9 264.7
42. 8 95. 7 42.8
Lymph WBCx?
12996. 13937. 13365.
9638. 15408.
Alym WBCx^
0. 181.
0. 122. 1070.
Mono WBCx?
342. 0.
330. 244. 1712.
Eosin
WBCx?
342. 362.
0. 0. 428.
Baso WBCx?
0. 0. 0. 0. 0.
13068.8 274.6 525. 6 226.4 0.0
2126.6 451.5 677. 3 209.1
0.0
951.0 201.9 302.9 93.5 0.0
GROUP: 4M
DOSE: .480 mg/L
SAMPLE DATE: 10/12/84
SPECIES: RAT
BIRTH DATE: 05/14/84
ANIMAL)?:
376816 376826 376842 376845 376868
WBC
xiO^uL 24.2 17.9 23.1 18.0
17.1
AVG.
S. D.. S. E.
20.06 3.32 1.48
Neufc WBCx%
7260. 3938. 5775. 6300. 3078.
Band WBCx?
0. 0. 0. 0. 0.
5270.2 0.0 1721.6 0.0 769.9 0.0
Lymph WBCxjt
15972. 12351. 15708. 10800. 13338.
Alym WBCx5(
242. 716. 231. 360. 342.
Mono WBCx?
0. 537. 1386. 360. 342.
Eosin
WBCx?
726. 358.
0. 180.
0.
Baso WBCx?
0. 0. 0. 0. 0.
13633.8 378. 2 525.0 252. 8
0.0
2209.8 197. 5 519.1 303. 4
0.0
988.3 88. 3 232.1 135. 7
0.0
129 Company Sanitized. Does not contain TSCA CBI
G------------------------------A :Q| MR: 1----R____HASKELL NUMBER;
COMPOUND:
PERIOD: SEX:
W-DK^EC
MALE
153 88
HASKELL CODE
DEPARTMENT: POLYMER PRODUCTS REPORT DATE: 17-OCT-84
GROUP: 1CM SAMPLE DATE:
DOSE:
10/12/84
ANIMALff:
376807 376829 376834 376861 376869
AVG.
S. D. S. E.
ALP
U/L 84. 78. 66. 161. 96.
97.0 37.4 16.7
ALT
U/L 35. 40. 29. 37. 27.
33.6 5.5 2.4
CONTROL
SPECIES: RAT
BIRTH DATE: 05/14/84
AST
0/L
65. 81. 69. 64. 49.
BUN
mg/dL 21. 16. 17. 21. 24.
CREAT
mg/dL 0.61 0.59 0.64
0.59 0.71
TPROT
g/dL 4.6 7.4 6.4 6.9 7.0
CHLOS
mg/dL 119. 198. 75. 64. 132.
65.6 11.5 5.1
19.7
3.5 1.6
0.628 0.050 0.022
6.46 1.10 0.49
117.5 53.3 23.8
GROUP: 2M SAMPLE DATE:
DOSE:
10/1,;2/84
ANIMAL)?:
376827 376831 376862 376877 376882
AVG.
S. D. S. E.
ALP
U/L 110. 136. 190. 83. 150.
133.8 40.5 18.1
ALT
U/L 30. 35. 32. 26. 23.
29.2 4.8 2.1
.0076 mg/L
SPECIES; RAT BIRTH DATE: 05/1J4/84
AST
U/L 60. 68. 65. 53. 56.
BUN
mg/dL 21. 19. 19. 20. 18.
CREAT
mg/dL 0.65 0.64 0.74 0.65
0.77
TPROT
g/dL 6.4 7.2 7.3 7.1 7.2
( MLOS
nig/dL 73. 94.
118. 83. 94.
60.4 6.2 2.8
19.5 1.0 0.4
0.690 0.060 0.027
7.04 0.36 0.16
92.3 16.9
7.5
50 Company Sanitized. Does not contain TSCA CBI
HASKELL
NUMBER:
^15388
HASKELL CODE:QB!
DEPARTMENT: POLYMER PRODUCTS
REPORT DATE: 17-OCT-84
GROUP: 3M
DOSE: .058 mg/L
SAMPLE DATE: 10/12/84
SPECIES: RAT
BIRTH DATE: 05/14/84
ANIMALS: 376817 376846 376855 376864 376875
ALP
U/L 84. 156. 92. 211. 89.
ALT
AST
BUN CREAT TPROT CHLOS
U/L
U/L mg/dL mg/dL g/dL mg/dL
33.
70.
87. 145.
26.
70.
40.
66.
30.
65.
23. 0.67 16. 0.62 19. 0.74 19. 0.65 18. 0.67
6.9 71. 6.8 96.
7.3 99. 7.4 124. 6.9 81.
AVG. S. D.
S. E.
126.4
55.7 24.9
43.2 25.0 11.2
83.2 34.6 15.5
19.2
2.7 1.2
0.670 0.044 0.020
7.06
0.27 0.12
94.4 20.1
9.0
GROUP: 4M
DOSE; .480 ing/L
SAMPLE DATE: 10/12/84
SPECIES: RAT
BIRTH DATE: 05/14/84
ALP
ALT
AST
BUN CREAT TPROT CHLOS
ANIMALS:
U/L
U/L
U/L mg/dL mg/dL g/dL mg/dL
376816 171.
49.
71.
14. 0.55
7.3
79.
376826
64.
25.
61.
16. 0.65
7.0
77.
376842 224.
43.
97.
19. 0.71
6.4 49.
376845
70.
36.
74.
15. 0.63
6.7
93.
376868
72.
23.
53.
14. 0.67 7.0
78.
AVG. S. D.
S. E.
120.2 73.1 32.7
35.2 11.2
5.0
71.2 16.6
7.4
15.4 2.1 0.9
0.642 0.059 0.027
6.88 0.34 0.15
75.0 16.1
7.2
15'! Company Sanitized. Does not contain TSCA CBI
MR: f------
COMPOUND:)
PERIOD: SEX:
84-DAY MALE
HASKEL L
NUMB ER:
J53!88
HAS?:ELL COE
DEPARTME)IT: POLKMER PRCDUCTS
REPORT DjATE: 17-OCT-84
GROUP: 1CI4
DOSE: CONTRI3L
SAMPLE DA'FE: 10/ 12/84
SPECIES: RAT BIRTH DA'rE: 05/114/84
ANIMALS: 376807 376829 376834 376861 376869
AVG.
S. D. S. E.
VOL
mL
6.4 10.5 19.5 21.0 10.0
OSMOL
m0s
2636. 2348.
763. 1337. 1836.
BLOOD
-
+ +
-
+
SUGAR
+
-
+ +
-
PROTEIM +3 +2
+
+2 +3
13.48 1784.0
6.40 756.5 2.86 338.3
PH BILI- UROBL Ke-
RUBIN mg/dL tone
7.0 +1
1.0 +1
7.0 +1
0.1 +1
8.0 -
0.1 -
8.0 -
0.1 +
7.0 -
0.1 +
7.40 0.55 0.24
0.28 0.40 0.18
GROUP: 2M
DOSE: .0076 mg/L
SAMPLE DATE: 10/12/84
SPECIES: RAT
BIRTH DATE: 05/14/84
ANIMALS: 376827 376831 376862
376877 376882
VOL
mL
41.0 ' 8.4
10.2 9.4
18.0
OSMOL
m0s
721. 2070. 1849. 2272. 1100.
BLOOD
+
+1 +1
-
+
SUGAR
+1
-
+1
-
+
PRO
TEIN
+1 +2
+2 +2
+1
PH BILI- UROBL Ke-
RUBIN mg/dL fcone
7.0 7.0 +1 7.0 +1 7.0 -
7.0 -
0.1 1.0 + 1.0 + 1.0 +1 0.1 -
AVG.
S. D. S. E.
17.40 1602.4 13.73 662.8 6.14 296.4
7.00 0.00 0.00
0.64 0.49 0.22
32 Company Sanitized. Does not contain TSCA CBI
15388
HASKELL COOE:(|BB
DEPARTMENT! POLYMER PRODUCTS
REPORT DATE: 17-OCT-84
GROUP: 3M
DOSE: .058 mg/L
SAMPLE DATE: 10/12/84
SPECIES: RAT
BIRTH DATE: 05/14/84
ANIMALS: 376817 376846 376855 376864 376875
VOL
mL
13.0 14.0 25.0 18.0 11.5
OSMOL
mOs
1448. 1398. 778. 1421. 1773.
BLOOD
-
+ + +
-
SUGAR
-
+ + +
-
PRO
TEIN +2
+1 +1 +1
+2
PH BILI- UROBL Ke-
RUBIN mg/dL fcone
8.0 -
1.0 +1
7.0 -
0.1 +
7.0 -
7.0 8.0 +1
0.1 1.0 1.0 +1
AVG.
S. D. S. E.
16.30 1363.6 5.43 361.3 2.43 161.6
7.40 0.55 0.24
0.64 0.49 0.22
GROUP: 4M
DOSE: .480 mg/L
SAMPLE DATE: 10/12/84
SPECIES: RAT
BIRTH DATE: 05/14/84
ANIMALtf: 376816 376826 376842 376845 376868
AVG.
S. D. S. E.
VOL
mL
18.5 18.5
5.7 30.0 12.5
OSMOL
mOs
1292. 1372. 2348.
839. 1381.
BLOOD
+ + +
+1
+
SUGAR
+ +
+1
+ +
PRO
TEIN
+1 +2
+2
+1 +1
17.04 1446.4 8.96 551.2 4.01 246.5
PH BILI- UROBL Ke-
RUBIN mg/dL fcone
8.0 7.0 7.0 7.0 7.0 -
0.1 + 1.0 +1 1.0 + 0.1 0.1 +
7.20 0.45 0.20
0.46 0.49 0.22
35 Company Sanitized. Does not contain TSCA CBI
15388
HASKELL CODEflj
DEPARTMENT: POLYMER PRODOCTS
REPORT DATE: 17-OCT-84
GROUP: 1CM
DOSE: CONTROL
SAMPLE DATE: 10/12/84
SPECIES: RAT
BIRTH DATE: 05/14/84
ANIMALtf: 376807 376829 376834 376861 376869
RBC
/hpf 0-0
0-1 0-1 0-0 0-1
WBC
/hpf
4-6 1-3 3-6 5-8 1-2
Epith /hpf 1-3
0-2 0-1 1-2 0-3
Cast
/Ipf
0-0 0-0 0-0 0-0
0-0
APPEARANCE
Y CL PPT Y CL PPT LY CL PPT Y CL PPT FEED Y CL PPT
PECES
GROUP: 2M
DOSE: .0076 mg/L
SAMPLE DATE: 10/12/84
SPECIES: RAT
BIRTH DATE: 05/14/84
ANIMALff: 376827 376831 376862 376877 376882
RBC
/bpf 0-2
0-1 0-2 0-3 0-1
WBC
/hpf 5-10 4-8 3-5
10-20 0-2
Epith /hpf
3-5 0-2 1-2 4-8 0-1
Cast
/Ipf
0-0 0-0 0-0
0-0 0-0
APPEARANCE
LY CL PPT FEED DY CL PPT FEED DY CL PPT FEED Y CL PPT FEED Y CL PPT FEED
134 Company Sanitized. Does not contain TSCA CBI
HASKELL NUMBER:
15388
HASKELL CODE:(|B>
DEPARTMENT: POLYMER PRODOCTS
REPORT DATE: 17-OCT-84
GROOP: 3M
DOSE: .058 mg/L
SAMPLE DATE: 10/12/84
SPECIES: RAT
BIRTH DATE: 05/14/84
ANIMALS: 376817 376846 376855 376864 376875
RBC
/hpf 0-0
0-1 0-2 0-0 0-0
WBC
/hpf 0-3 5-8 3-4 2-4 1-3
Epith
/hpf 0-2 3-5 0-2 3-6 1-2
Cast
/Ipf
0-0 0-0 0-0 0-0 0-0
APPEARANCE
Y CL PPT FEED Y CL PPT FEED
Y CL PPT FEED Y GL PPT Y CL PPT
GROUP: 4M
DOSE: .480 mg/L
SAMPLE DATE: 10/12/84
SPECIES: RAT
BIRTH DATE: 05/14/84
ANIMAL)?:
376816 376826 376842 376845 376868
RBC
/hpf
1-2 0-3 0-1 0-3 0-2
WBC
/hpf 0-3 4-8 0-3 10-15 2-4
Epith
/hpf
1-3 1-4 0-2 3-6 1-2
Cast
/Ipf
0-0 0-0 0-0 0-0 0-0
APPEARANCE
Y CL PPT Y CL PPT FEED Y CL PPT Y CL PPT FEED FECES Y CL PPT
55
Company Sanitized. Does not contain TSCA CBI
APPENDIX VII
BLOOD FLUORINE ANALYTICAL REPORTS
-136-
Company Sanitized. Does not contain TSCA CBI
ESTAfitlSHEO 1802
E. I. DU PONT DE NEMOURS S COMPANY
.INCORPORATED
WILMINGTON, DELAWARE 19898
CHEMICALS AND PIGMENTS DEPARTMENT JACKSON LABORATORY
October 18. 1984
TO:
y
FROM:
L. A. Kinney CR&D, Haskell Lab.
E. Kissa ,^*-^ -<^^<-
C&P, Jackson Lab.
FLUORINE IN BLOOD
We have analyzed--tat blood samples of the inhalation subchronic
blood sampireswereanaTyzedfortota^fluorine by the oxyhydrogen torch method and four samples for ionic (inorganic) fluorine by our analyte addition method. The difference between total fluorine and ionic (inorganic) fluorine is organic fluorine. The ionic fluorine values were found to be so low that the difference between total and organic fluorine is insignificant in this study.
The amount of organic fluorine in^^od, Cb> was found to increase
exponentially with the increasingflfm; oncentration in air, Cg
(/ FiT" ; g-- . D. 1 ^ e--x--p--re-*s_s---ed---Aa-s_:-
~
^
n
c. = k c
The values of the coefficient, k, and to a lesser extent, the values
of the exponent n. decreased with the increasing recovery time.
(Table I).
137 Company Sanitized. Does not contain TSCA CBI
.Page 2 October 18. 1984
L. A. Kinnev
TABLE I
ORGANIC FLUORINE IN RAT BLOOD
Exposure Coonne^. of
B^jnaZm3!
ppm Organic Fluorine in Blood*
2-Weeks
6-Weeks
Initial
Recovery
Recovery
0
7.6 58.0 480.0
2.0 10.2 42.0
147.0
0.9 4.0 13.0 40.5
0.9 1.8 7.2 16.6
*Average values for blood samples of five rats.
2.87 1.31 0.67
n
0.64 0.56 0.54
During the recovery period the logarithm of organic fluorine content of blood decreased with the square root of the recovery time (Fig. 2), suggesting that fluorine is eliminated by a diffusion controlled
process: log (Ct/Co) = kctO.5
where c^ is the organic fluorine concentration at time t, Cg the initial'organic fluorine concentration, and kjc the recovery
coefficient.
TABLE II
DESORPTION RATE OF FLUORINE FROM BLOOD
Eoxf o(If--lBu--re--CinoAneir.
(mg/m3)____
Recovery time (weeks)
Needed for the Fluorine
Values to Return to Normal
k,
(1 ppm or less) Values
0
7.6
58 480
-0.31
11
-0.32
26
-0.39
31
The value of the desorption coefficient k^ for human blood differs
probably from that of cat blood, but the desorption mechanism may be similar.
The inorganic (ionic) fluorine in rat blood increased slightly, but
perhaps significantly,
If the slight increase
as a result of exposure toftHj^(Table III).
was significant, the ionic ^Luorine returned
to normal values in a relatively short time.
]38
Company Sanitized. Does not contain TSCA CBI
^^k-UUCJ- JL U , J. 7 01
L. A. Kinnei
;ure Jconc,
in Air
(mq./m3)
0
0
0
0
480 480 480 480
TABLE III
INORGANIC (IONIC) FLUORINE IN RAT BLOOD
Recovery Time
(Weeks)
Organic Fluorine
(PPnO
1.4 0.7 1.1 0.7 140.0 112.0 168.0 41.2
Inorganic Fluorine
(ppm)
0.016 0.025 0.019 0.007 0.055 0.034 0.063 0.020
Rat No.
376 840 376 849 376 835 376 841 376 854 376 828 376 879 376 858
The remaining 56 blood
if the significance of
samples will
the apparent
be
io
n
an ic
al
f
yz
lu
ed
ori
f n
o e
r
e
i l
o e
n v
ic at
i
flu
on
obryi
nfleB.
f,
_ u
exposure has to be established.
^^^
The total fluorine values of the sixty blood samples analyzed are
given in Table IV.
EKissa/jve
0524J
39
Company Sanitized. Does not contain TSCA CBI
uccooer 1B, 1984
L__A^ Kinney___
FLUORINE IN BLOOD
TABLE IV
TOTAL FLUORINE IN RAT BLOOD OF THE INHALATION SUBCHBONIC STUDY ON
TOTAL FLUORINE (PPM)
!roup I - Control
II - Low
[I - Inter.
V - High
Cone.
in Air
0 ins/in3
7.6 ing/m3
58 mg/m3
480 ing/in3
!nitia;L
Rat
Number PPIP F
376839 376870 376840 376873 376825
376804 376844 376806 376823 376818
376805 376838 376851 376821 376867
376854 376879 376828 376820 376859
1..5 1.,7
1.4 4.6 1.0
10. 8 7. 6
10. 5 10. 8 11. 1
44. 3 46. 0 44. 4 47.4 28. 0
140. 0 168. 0 112. 0 176. 0 138. 0
Avg.
2.0
Avg.
10.2
Avg.
42.0
Avg. 147
2-Weel:s R(icovrery Rat Number EESn F
376872 1..0 376849 0. 7
376835 1.1
376841 0.7 376863 1.1
376810 3. 4 376876 4. 4 376852 3. 4 376822 4. 0 376881 4. 7
376874 376812 376813 376857 376830
15. 1 12. 9 10. 3
11. 8 14. 9
376858 376824 376880 376833 376819
41. 2 34. 7 33. 6 37. 9
55. 0
Avg.
0.9
Avg.
4.0
Avg.
13.0
Avg.
40.5
6-Weeks Rec;overy Rat
Number PPn F
376801 376836 376837 376878 376847
376871 376800 376848 376866 376856
376808 376811 376803 376843 376860
376815 376814 376853 376850 376832
0,,8 1.,3
0.5 0.7 1.0
1.6 1.4 2. 0 2. 1 1. 7
8. 2 8. 6 5. 3 6. 9
7. 0
16. 8
11.. 1
17. 7 18. 7 18. 8
Avg.
0.9
Avg.
1.8
Avg.
7.2
Avg.
16.6
:jve
24J
140 Company Sanitized. Does not contain TSCA CBI
/^^ ^
Fig. 1. Concentration of organic fluorine in blood as a function
of(m^;oncentratlon in air.
41
Company Sanitized. Does not contain TSCA CBI
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ESTABUSHEO IB02
E. 1. DU PONT DE NEMOURS & COMPANY
INCORPORATED
WiLMINGTON, DELAWARE 19898
CHEMICALS AND PIGMENTS DEPARTMENT JACKSON LABORATORY
December 19, 1984
TO:
^L. A. Kinney
/^CR&D. Haskell Lab.
FROM:
E. Kissa ^e*^ ^^yc^
C&P, Jackson Lab.
FLUORINE IN BLOOD
The rat blood samples of the twelve-weeks recovery period
have been analyzed for fluorine (Table I). This completes
.hefluorine data of the inhalation subchronic study on
To compare the recovery rate of fSrelated fluorine in
blood to that of perfluorooctanoic acid the data have to
be fitted to a kinetic expression that permits the
calculation of rate constants or rate coefficients. This is. however, not straightforward, because the elimination of fluorine from blood does riot obey simple kinetics. The decrease of the organic fluorine concentration in blood during the recovery period of the recent inhalation
subchronic study on TBSA can be represented as a reasonable approximation with the equation
log (Ct/Co) = kr t0.5.
(1)
where c^ is the organic fluorine concentration in blood at time t.
CQ the initial organic fluorine concentration in blood, and k^ the
recovery coefficient. (Fig. 2 in Kissa to Kinney, October 18, 1984.)
143 Company Sanitized. Does not contain TSCA CBI
December 19, 1984 L. A. Kinne\
- FLUORINE IN BLOOD
The average fluorine values of the 12-veeks recovery period are slightly lower than these calculated by this equation from the
recovery data of the first six weeks.
Initial Fluorine
Cone. in Blood PPIP______
Fluorine Cone. after 12-weeks Recovery
_Pr_e_d_ic_te_d_______Efin_____F_ou_n_d____
10.2
42.0 147.0
0.90 3.2 6.6
0.40 2.2 4.4
The recovery coefficients are slightly higher for the 0 to 12 weeks reco've.r'y..P^lod than those calculated for the 0 to 6-weeks r-fr&overy
period, but the correlation with equation (I) is still reasonable:
ExDpsure Cone.
ofj----Tin Air
(mq./m^
Linear Correlation Coefficient
ffor log c vs. t0-5) 0-6 weeks 0-12 weeks
Recovery Coefficient kg 0-6 weeks 0-12 weeks
0.9991 0.995 0.9998
I reported in ORBi^mO that the
period of a perfluorooctanoic acid
first-order kinetics.
0.993 0.992 0.995
-0.31
-0.32 -0.39
-0.35 -0.36 -0.43
decay of fluorine during recovery
feeding study approximates
log Ct/Co = krt
(2)
The log c vs. time plot (Fig. 1) shows considerable curvature indicating that the removal of fluorine from blood is more rapid at the beginning of the recovfijjv time than predicted by equation (2).
The first-order plot of|^|Rjdata also shows curvature (Fig. 2).
Conceivably the rate at which a fluorocompound is eliminated from blood is not the same for different[aBE}teloiaes. Their diffusion
rates are likely to vary with their chain length. It is also
possible that the adsorptive bond of the fluorochemical in blood may vary. The less strongly bonded molecules may be eliminated at a faster rate and leave the more strongly held fluorochemical molecules back. Since perfluorooctanoic acid is homogeneous, this type of a mechanism is needed to explain its decreasing coefficient of the-elimination rate. Perhaps perfluorooctanoic acid dissolved in blood is eliminated from blood at a fast rate. but perfluorooctanoic acid bound to protein in blood at a slower rate,
perhaps together with the protein on which it is adsorbed. Whatever
the true mechanism, the expected result is a decrease of the recovery rate (fluorine elimination rate) coefficient with increasing time.
144 Company Sanitized. Does not contain TSCA CBI
WWUtUVl. if, i101
FLUORINE IN BLOOD
The average fluorine removal rate coefficient k^ during a time interval At can be calculated from the equation
ft - ^a-
<3^
where Ac is the average fluorine concentration decrease and Cg
the average fluorine concentration during time interval At. It
follows that
log (Ac) = log k^ + z log Cg
(4)
At
A plot ofQHUrecovery data according to the equation (4) yields
straight lines with the average z value of one. However, the log
k^. and consequently, the k^' values are not constant, but
de wi
cre th
ase
my
with expla
the natio
in n
cr of
e
asing curva
t
rec ure
o
ve in
r
y
f
i
tine
rst
o
( r
T d
a e
b r
l
e p
l
I
o
I
t
)
s
,
in accord (Fig. 3 and
4).
Hence
log (Ct/Co) = ktt
(5)
where k^ is the time dependent rate coefficient at time t.
l^data The question remains, why does the ^^^dl
fit equation (5) and
also, as a reasonable approximation, equation (1). Since the left
side of the equations is the same. the right side has to be the same
function of time. This is the case when
kt = kr/tV.
(6)
where y is an exponent. If y = 0.5
kt = kr/tO-5'
(7)
and the equation (5) becomes equation (1)
log (c,/c,) = _^= k,t0-5.
(8)
Although the time intervals ofUm^recovery data are not suited for
redefining the time dependence oftne rate coefficients, the kf
values seem to vary approximately with the square root of time.
(Table III).
45
Company Sanitized. Does not contain TSCA CBI
uecemoer if, i^yi
.L. A. Kinney
FLUORINE IN BLOOD
In summary, the elimination of organic fluorine from blood can be described by a time dependent rate coefficient ki and an exponent z, that is approximately equal to one. A logarithmic plot
log (Ac/At) = log k^ + z log Cg
(9)
or regression analysis using a pocket calculator, yields k^.
A comparison of^flBRtand perfluorooctanoic acid decay in blood suggests that k^ values of anionic fluorosurfactants in blood may
not be largely different. However,[fHQis much less volatile than
perfluorooctanoic acid and poses therefore a lesser environmental
problem.
EK:jve Attach.
0564J
146 Company Sanitized. Does not contain TSCA CBI
TABLE I
FLUORINE IN BLOOD AFTER A 12-WEEK RECOVERY PERIOD
Exposure
Control : (0 ng/m3)
Low:
(7.6 mg/m3)
Intermediate; (58 mg/n3)
High: (480 mg/m3)
Rat
Number
376869 834 829 807 861
376877 862 882 831 827
376875 864 817 855 846
376826 845 868 816 842
Fluorine
PPP
0.54 0.54 0.17 0.49 0.26
0.53 0.72 0.64 0.64 0.52
1.37 1.91 1.18 2.13 4.23
5.89 3.22 4.12 5.21 3.47
Average
Fluorine
PPP
0.40
0.61
2.16
4.38
147 Company Sanitized. Does not contain TSCA CBI
TABLE II
KINETICS OF FLUORINE ELIMINATION FROM RAT BLOOD
Recovery Period
(weeks)___
0-2 2-6 6-12
Fluorochemical
(inhan^ion)
Rate
Coefficient
__kt____
0.36 0.17 0.16
Average
Exponent
z
1.10 1.03 1.07 1.07
0-2
Perfluorooctanoic
0.73 .
0.92
2-6
Acid (feeding)
0.33
1.03
Average
0.98
Recovery Period (weeks)
0-2 2-6 6-12
TABLE III
RATE COEFFICIENTS AS A FUNCTION OF TIME
Average Recovery Time
(weeks)
Square Root of Average Recovery
Time_____
Found
0.36 0.17 0.16
Rate Coefficients Perfluorooctanoic
Calc.* _Fo_u_n_d AcCida_lc_._* __
0.18 0.12
0.73 0.33
0.37
* Calculated by the equation (7)
EK:jve Attach. 0564J
148 Company Sanitized. Does not contain TSCA CBI
n:
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5?i
55
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51
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^ ^ ^ / ^a ^
152
Company Sanitized. Does not contain TSCA CBI
APPENDIX VIII
BLOOD FLUORINE STATISTICS
153 Company Sanitized. Does not contain TSCA CBI
^ MEAN BLOOD FLOURINE CONCENTRATIONS
^TC?sinLog(ppm) + 1) H# 14,930
GROUP
0 DAYS POST EXPOSURE
14 DAYS POST EXPOSURE
41 DAYS POST EXPOSURE
CONTROL
7.6 MG/CM
58 MG/CM 480 MG/CM
1.243K 2.0028( 2.6159(
3.161-2 (
0.000) 0.000)# 0.000)# 0.000)#
TEST - HOMOGENEITY TEST - TREND BARTLETT'S TEST
0.000 0.000 0.034
0.9546(
1.596K 2.1095( 2.6001(
0.000)
0.000)# 0.000)# 0.000)#
0.000 0.000 0.818
0.9122( 1.2408(
1.8513( 2.2129(
0.000) 0.000)#
0.000)# 0.000)#
0.000 0.000 0.425
GROUP
84 DAYS POST EXPOSURE
CONTROL
7.6 MG/CM
58 MG/CM 480 MG/CM
0 .560K 0 .7820(
1 .2889( 1 6300(
0.000) 0.054) 0.000)ft 0.000)#
TEST - HOMOGENEITY TEST - TREND BARTLETT'S TEST
0.000 0.000 0.088
Values in parentheses -
P VALUE OF STUDENT'S T TEST COMPARISON OF TREATMENT MEAN TO CONTROL MEAN.
+
-
SIGNIFICANTLY DIFFERENT (P<0.05) FROM CONTROL GROUP BY LSD
# - SIGNIFICANTLY DIFFERENT (P<0.05). FROM CONTROL GROUP BY LSD AND
DUNNETT'S TEST
HOMOGENEITY - P VALUE OF F TEST OF WHETHER GROUP MEANS ARE EQUAL.
TREND - P VALUE OF F TEST OF WHETHER THERE IS DOSE-RELATED CHANGE IN GROUP MEANS.
BARTLETT'S TEST - P VALUE OF TEST OF HOMOGENEITY OF VARIANCE
154
Company Sanitized. Does not contain TSCA CBI